[Senate Hearing 109-816]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 109-816

                               NOMINATION

                                   OF

                 ANDREW VON ESCHENBACH AND PAUL DECAMP

=======================================================================

                                HEARING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS
                          UNITED STATES SENATE

                       ONE HUNDRED NINTH CONGRESS

                             SECOND SESSION

                                   ON

ANDREW VON ESCHENBACH, OF TEXAS, TO BE COMMISSIONER OF FOOD AND DRUGS, 
                DEPARTMENT OF HEALTH AND HUMAN SERVICES

  PAUL DeCAMP, OF VIRGINIA, TO BE ADMINISTRATOR OF THE WAGE AND HOUR 
                     DIVISION, DEPARTMENT OF LABOR

                               __________

                             AUGUST 1, 2006

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions


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          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

                   MICHAEL B. ENZI, Wyoming, Chairman

JUDD GREGG, New Hampshire            EDWARD M. KENNEDY, Massachusetts
BILL FRIST, Tennessee                CHRISTOPHER J. DODD, Connecticut
LAMAR ALEXANDER, Tennessee           TOM HARKIN, Iowa
RICHARD BURR, North Carolina         BARBARA A. MIKULSKI, Maryland
JOHNNY ISAKSON, Georgia              JAMES M. JEFFORDS (I), Vermont
MIKE DeWINE, Ohio                    JEFF BINGAMAN, New Mexico
JOHN ENSIGN, Nevada                  PATTY MURRAY, Washington
ORRIN G. HATCH, Utah                 JACK REED, Rhode Island
JEFF SESSIONS, Alabama               HILLARY RODHAM CLINTON, New York
PAT ROBERTS, Kansas

               Katherine Brunett McGuire, Staff Director

      J. Michael Myers, Minority Staff Director and Chief Counsel

                                  (ii)



























                            C O N T E N T S

                               __________

                               STATEMENTS

                        TUESDAY, AUGUST 1, 2006

                                                                   Page
Enzi, Hon. Michael B., Chairman, Committee on Health, Education, 
  Labor, and Pensions, opening statement.........................     1
Kennedy, Hon. Edward M., a U.S. Senator from the State of 
  Massachusetts, opening statement...............................     7
Hutchison, Hon. Kay Bailey, a U.S. Senator from the State of 
  Texas..........................................................    10
Von Eschenbach, Andrew, nominee to be Commissioner of Food and 
  Drugs, Department of Health and Human Services.................    11
    Prepared statement...........................................    14
DeCamp, Paul, nominee to be Administrator of the Wage and Hour 
  Division, Department of Labor..................................    16
    Prepared statement...........................................    18

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Letters of support:
        Mark B. Leahy, Medical Device Manufacturers Association..     3
        Michael J. Fitzpatrick, The Nation's Voice on Mental 
          Illness (NAMI).........................................     3
        Stephen J. Ubl, Advanced Medical Technology Association 
          (AdvaMed)..............................................     4
        Anthony J. Dennis, OMERIS................................     5
        Edwin A. Mirand, New York State Cancer Programs 
          Association, Inc.......................................     6
        Charles A. Reinwald, Cancer Cure Coalition...............     6
    Letters submitted by Senator Clinton:
        Michael O. Leavitt.......................................    35
        Andrew von Eschenbach....................................    36
    Response by Andrew C. von Eschenbach to questions of:
        Senator Enzi.............................................    53
        Senator Kennedy..........................................    66
        Senator Gregg............................................    78
        Senator Burr.............................................    85
        Senator DeWine...........................................    86
        Senator Ensign...........................................    93
        Senator Hatch............................................   100
        Senator Sessions.........................................   102
    Additional questions of Senator Sessions for Andrew C. von 
      Eschenbach.................................................   103
    Response by Andrew C. von Eschenbach to questions of:
        Senator Dodd.............................................   104
        Senator Harkin...........................................   116
        Senator Mikulski.........................................   117
        Senator Jeffords.........................................   120
        Senator Bingaman.........................................   120
        Senator Murray...........................................   129
        Senator Reed.............................................   136
        Senator Clinton..........................................   139
    Additional questions of Senator Clinton for Andrew C. von 
      Eschenbach.................................................   152

                                 (iii)


























 
          NOMINATION OF ANDREW VON ESCHENBACH and PAUL DeCAMP

                              ----------                              


                        TUESDAY, AUGUST 1, 2006

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 10 a.m., in room 
SD-430, Dirksen Senate Office Building, Hon. Mike Enzi, 
chairman of the committee, presiding.
    Present: Senators Enzi, Alexander, Isakson, Ensign, Hatch, 
Kennedy, Dodd, Harkin, Mikulski, Murray, Reed and Clinton.
    Also present: Senator Hutchison.

                   Opening Statement of Senator Enzi

    The Chairman. Good morning, and welcome to the confirmation 
hearing for Dr. Andrew von Eschenbach, to be the Commissioner 
of the Food and Drug Administration and Mr. Paul DeCamp, to be 
the Wage and Hour Administrator of the Department of Labor. 
Both nominees are superbly qualified for these positions, and I 
look forward to their testimony and responses today.
    The FDA has a very broad and critical mission in protecting 
the public health. Dr. von Eschenbach, you'll be in charge of 
an Agency that regulates $1 trillion worth of products a year. 
The FDA ensures safety and effectiveness for all drugs and 
biological products, such as vaccines, medical devices, and 
animal drugs and feed. It also oversees the safety of a vast 
variety of food products, as well as medical and consumer 
products, including cosmetics.
    As Commissioner of the FDA, you'll be responsible for 
advancing the public health by helping to speed innovations in 
its mission areas and by helping the public get accurate, 
science-based information on medicines and foods. As a 
physician, I know you take this mission to heart.
    I'm pleased that we are now ready to hear Dr. von 
Eschenbach's plan to take charge, to take action, and to take 
responsibility for leading the FDA in the best interests of 
public health. We've met several times during your tenure as 
Acting Commissioner, and discussed a variety of issues, 
including drug safety, advisory committees, and citizen 
petitions. At those meetings, I've been impressed by your 
dedication to solving problems, and your focus on patient care, 
and your knowledge. One item we've discussed many times is the 
application to make the Plan B emergency contraceptive 
available without a prescription. You made a major announcement 
about that yesterday, and I'm going to ask you to go over that 
in some detail later this morning.
    The FDA has been without a confirmed Commissioner for all 
but 18 months out of the last 5\1/2\ years. I think we all can 
agree we need a strong leader at the FDA right now, and one who 
has a mandate to act. We must be forward-looking. There are 
many items before the FDA that require the immediate attention 
of an FDA Commissioner vested with full authority. But that 
authority flows directly from the act of Senate confirmation. 
Without a Senate-confirmed leader, we can't expect the FDA to 
be as effective as we need it to be. I urge my colleagues to 
consider this as we move forward.
    I look forward to working with you, Senator Kennedy, and 
with members of the committee, to protect and promote the 
public health and to maintain the FDA's status as one of the 
world's strongest regulatory agencies. We've been working in a 
very bipartisan way to get a bill that we think will do that. A 
confirmed commissioner would be very helpful in that.
    Also on this morning's agenda is the nomination of Paul 
DeCamp to be the Wage and Hour Administrator. This position 
within the Department of Labor is a pivotal one in 
administering and enforcing some of our most important 
workplace laws. The Wage and Hour Division is an integral part 
of the Department's largest administrative component, the 
Employment Standards Administration. The Wage and Hour Division 
is responsible for administering the minimum wage, overtime 
pay, and child labor provisions of the Fair Labor Standards 
Act. This statute has enormous reach, covering some 110 million 
full-time and part-time workers.
    In addition to the Fair Labor Standards Act, the Wage and 
Hour Division is responsible for the administration and 
enforcement of a number of other important workplace laws, 
including the Family and Medical Leave Act, the Migrant and 
Seasonal Workers Protection Act, and the three major statutes 
governing wage and hour standards for government contracts: the 
Davis-Bacon Act, the McNamara-O'Hara Service Contract Act, and 
the Walsh-Healy Public Contracts Act.
    The Wage and Hour Administrator oversees many of the laws 
that protect our Nation's greatest resource: our workers. The 
President's nominee for this important position, Paul DeCamp, 
is currently serving in the Department of Labor as senior 
policy advisor to the Assistant Secretary of Labor for 
Employment Standards.
    Before assuming his current position at the Department of 
Labor, Mr. DeCamp had a distinguished career in a private legal 
practice, where he specialized in labor and employment issues, 
with a special emphasis on wage and hour matters. He has also 
written extensively on a number of Fair Labor Standards Act 
issues. The combination of practical front-line experience and 
demonstrated intellectual interest in the workings of the Wage 
and Hour Administration will be invaluable as he assumes his 
position of leading the division.
    Following an outstanding career at Harvard College and 
Columbia Law School, Mr. DeCamp was selected for a clerkship 
with U.S. Circuit Judge Alan E. Norris of the Sixth Circuit 
Court of Appeals. Judge Norris has recommended Mr. DeCamp to 
this committee without reservation, praising his intellectual 
abilities, his practicality, balance, and impartiality in 
resolving difficult legal issues. He and others who have 
written to the committee in support of Mr. DeCamp's nomination 
praise his judgment, unbiased analysis of legal issues, 
attention to detail, and his ability to lead others.
    Mr. DeCamp, it'll be your responsibility to build upon your 
record and experience to effectively administer laws that are 
so critical to American workers and businesses. I have 
confidence in your ability to do so.
    I would note that the committee has received a number of 
letters in support of both these worthy nominees. These letters 
of support will be included in the record.
    [The information previously referred to follows:]

   Medical Device Manufacturers Association (MDMA),
                                            Washington, DC,
                                             July 27, 2006.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
835 Hart Senate Office Building,
Washington, DC 20510.

Hon. Edward M. Kennedy,
Ranking Member,
Committee on Health, Education, Labor, and Pensions,
644 Dirksen Senate Office Building,
Washington, DC 20510.
    Dear Chairman Enzi and Senator Kennedy: On behalf of the Medical 
Device Manufacturers Association (``MDMA'') and the entrepreneurial and 
innovative medical technology companies we represent, I wish to convey 
strong support for the speedy confirmation of Dr. Andrew von Eschenbach 
to be the Commissioner of the Food and Drug Administration. A rapid 
confirmation process is critical to ensuring the public health and 
safety of the Nation's citizens.
    As a representative of the innovative sector of the medical 
technology industry, MDMA has worked with Dr. von Eschenbach during his 
tenure at the FDA. He has always proven an able leader and has fought 
tirelessly to uphold the FDA's mission.
    MDMA believes Dr. von Eschenbach, as both a physician and a cancer 
survivor, is uniquely suited to lead FDA. With rapidly developing 
technologies and advancements in medicine it is imperative that FDA 
have a Commissioner who possesses not only the appropriate professional 
training, but also the courage, dedication and integrity necessary to 
lead the Agency. Dr. von Eschenbach is clearly qualified to be just 
such a Commissioner. We endorse Dr. von Eschenbach and encourage the 
Senate to act quickly to confirm him.
            Sincerely,
                                            Mark B. Leahey,
                                                Executive Director,
                          Medical Device Manufacturers Association.
                                 ______
                                 
        National Alliance on Mental Illness (NAMI),
                                  Arlington, VA 22201-3042,
                                                     July 31, 2006.
Hon. Mike Enzi,
Hon. Edward M. Kennedy,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, DC 20510.
    Dear Chairman Enzi & Senator Kennedy: On behalf of the 210,000 
members and 1,200 affiliates of the National Alliance on Mental Illness 
(NAMI), I am writing to urge support for the nomination of Andrew C. 
von Eschenbach, M.D. as Commissioner of the Food and Drug 
Administration (FDA). As the Nation's largest organization representing 
individuals with severe mental illnesses and their families, NAMI is 
pleased to support this important appointment.
    In NAMI's view, Dr. von Eschenbach brings unique qualifications to 
the important position of FDA Commissioner. He has an enormous 
background as a clinician and researcher and is well qualified to lead 
the FDA. His resume speaks volumes to his professional accomplishments 
as a leader in medical research. He most recently served as the 
Director of the National Cancer Institute as Chief Academic Officer at 
the M.D. Anderson Cancer Center in Houston. He has gained perspective 
as a patient advocate, serving as President of the American Cancer 
Society, before joining NCI and being recognized with the National 
Health Care Humanitarian Award by the Patient Advocate Foundation in 
2005.
    NAMI urges you and your colleagues on the Senate HELP Committee to 
act swiftly on this important nomination. It is critically important 
that the FDA have a strong leader in place to address challenges faced 
by the Agency with respect to speeding access to newer and more 
effective treatments for Americans living with chronic disabling 
illnesses.
            Sincerely,
                            Michael J. Fitzpatrick, M.S.W.,
                                                Executive Director.
                                 ______
                                 
 Advanced Medical Technology Association (AdvaMed),
                                 Washington, DC 20005-3814,
                                                     July 31, 2006.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
428 Dirksen Senate Office Building,
Washington, DC 20510.

Hon. Edward M. Kennedy,
Ranking Member,
Committee on Health, Education, Labor, and Pensions,
317 Russell Senate Office Building,
Washington, DC 20510.
    Dear Chairman Enzi: On behalf of the Advanced Medical Technology 
Industry (AdvaMed) and our member companies, I am writing in support of 
the nomination of Dr. Andrew von Eschenbach to be Commissioner of the 
Food and Drug Administration.
    Dr. von Eschenbach is an excellent choice to head the FDA. He has 
had an outstanding career as a physician, researcher, and administrator 
in both the public and private sectors. As a physician, he has treated 
cancer patients for almost 30 years. As a researcher, he has published 
more than 200 articles and books and was the founding director of M.D. 
Anderson's Prostate Cancer Research Program. As an administrator, he 
has served as Vice President for Academic Affairs at M.D. Anderson and 
has had a dynamic tenure as the head of the National Cancer Institute. 
He has also served as the president-elect of the American Cancer 
Society.
    It is critically important to our industry and to the Nation that 
the position of FDA Commissioner be filled. Strong leadership is 
essential if the FDA is to most effectively fulfill its mission of 
assuring that the food Americans eat is safe and healthful, that the 
drugs they take are safe and effective, and that the medical devices 
they rely on for cures and treatment are safe and effective and 
represent the latest and best that our industry can offer. Experience 
has shown that a permanent director confirmed by the Senate is 
necessary to assure that the Agency has the authoritative leadership it 
needs to respond promptly and effectively to all the challenges it 
faces.
    Prompt confirmation of Dr. von Eschenbach is especially important 
in view of the issues that are currently facing the FDA. Next year, 
both the medical device and drug user fee programs must be renewed by 
Congress, and the agreements between industry and the FDA that will be 
the starting point for the reauthorization are being negotiated right 
now. The critical path initiative, which offers so much potential for 
speeding the development and approval of safe and effective products, 
is just getting off the ground and needs a strong advocate. The 
challenge of determining how FDA can most effectively conduct post-
market surveillance to assure the safety and effectiveness of approved 
products is an issue that needs strong leadership from the top. The 
continuing challenges of food safety and preparation for a pandemic or 
bioterrorist attack need a strong FDA voice.
    AdvaMed member companies produce the medical devices, diagnostic 
products and health information systems that are transforming health 
care through earlier disease detection, less invasive procedures and 
more effective treatments. Our members produce nearly 90 percent of the 
health care technology purchased annually in the United States and more 
than 50 percent purchased annually around the world. AdvaMed members 
range from the largest to the smallest medical technology innovators 
and companies.
    We respectfully urge you to support Dr. von Eschenbach's prompt 
confirmation. Thank you for considering this request.
            Sincerely,
                                            Stephen J. Ubl,
                                                 President and CEO.
                                 ______
                                 
                                            OMERIS,
                                   Columbus, OH 43212-1155,
                                                    August 2, 2006.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
428 Dirksen Senate Office Building,
Washington, DC 20510.

Hon. Edward M. Kennedy, Ranking Member
Committee on Health, Education, Labor, and Pensions,
317 Russell Senate Office Building,
Washington, DC 20510.
    Dear Chairman Enzi: On behalf of Omeris, Ohio's bioscience 
membership and development organization, and our member companies, I am 
writing in support of the nomination of Dr. Andrew von Eschenbach to be 
Commissioner of the Food and Drug Administration.
    Dr. von Eschenbach is an excellent choice to head the FDA. He has 
an outstanding career as a physician, researcher, and administrator in 
both the public and the private sectors. As a physician, he has treated 
cancer patients for almost 30 years. As a researcher, he has published 
more than 200 articles and books and was the founding director of M.D. 
Anderson's Prostate Cancer Research Program. As an administrator, he 
has served as the president-elect to the American Cancer Society.
    It is critically important to our industry and to the Nation that 
the position of the FDA Commissioner be filled. Strong leadership is 
essential if the FDA is to most effectively fulfill its mission of 
assuring the food Americans eat is safe and healthful, that the drugs 
they take are safe and effective, and that the medical devices they 
rely on for cures and treatment are safe and effective and represent 
the latest and best that our industry can offer. Experience has shown 
that a permanent director confirmed by the Senate is necessary to 
assure that the Agency has the authoritative leadership it needs to 
respond promptly and effectively to all the challenges it faces.
    Prompt confirmation of Dr. von Eschenbach is especially important 
in view of the issues that are currently facing the FDA. Next year, 
both the medical device and drug user fee programs must be renewed by 
Congress, and the agreements between industry and the FDA that will be 
the starting point for the reauthorization are being negotiated right 
now. The critical path initiative, which offers so much potential for 
speeding the development and approval of safe and effective products, 
is just getting off the ground and needs a strong advocate. The 
challenge of determining how FDA can most effectively conduct post-
market surveillance to assure the safety and effectiveness of approved 
products is an issue that needs strong leadership from the top. The 
continuing challenges of food safety and preparation for a pandemic or 
bioterrorist attack need a strong FDA voice.
    Omens members, Ohio's bioscience companies, help revitalize our 
State's economy while developing critical tools, treatments, and 
technologies that benefit the world. Omens is a focal point for the 
bioscience and biotechnology community, providing networking and 
educational events, continually developing web-based resources, 
addressing public policy, and analyzing resource and funding issues.
    We respectfully urge you to support Dr. von Eschenbach's prompt 
confirmation. Thank you for considering this request.
            Sincerely,
                                  Anthony J. Dennis, Ph.D.,
                                                   President & CEO.
                                 ______
                                 
  New York State Cancer Programs Association, Inc.,
                                         Buffalo, NY 14263,
                                                    August 3, 2006.
To: Senate Health, Education, Labor, and Pensions Committee
From: Dr. Edwin A. Mirand, Secretary-Treasurer, NYSCPA

Subject:  Nomination of Dr. Andrew von Eschenbach as Permanent 
Commissioner of Food and Drug Administration

    The New York State Cancer Program Association, Inc. supports the 
nomination by President Bush as permanent Commissioner of Food and Drug 
Administration (FDA) Dr. Andrew von Eschenbach.
    Dr. von Eschenbach's experience as a researcher and physician will 
provide the FDA with a better focus to confront the challenges and new 
opportunities facing the Agency. Dr. von Eschenbach will lead the 
Agency and strengthen the credibility of its decisionmaking process.
              
                             Edwin A. Mirand, Ph.D., D.Sc.,
                                                         Secretary.
                                 ______
                                 
                             Cancer Cure Coalition,
                             Palm Beach Gardens, FL, 33410,
                                                    August 9, 2006.
Dr. Andrew Von Eschenbach, M.D.,
Acting Commissioner,
U.S. Food and Drug Administration,
Rockville, MD 20857-0001.
    Dear Dr. Von Eschenbach: I am President of the Cancer Cure 
Coalition, a nonprofit Foundation dedicated to the cure and prevention 
of cancer. We join with the Biotechnology Industry Organization's (BIO) 
call for a swift confirmation of your appointment as Commissioner of 
the FDA. We believe it important that a permanent director be in charge 
of this vitally important public health Agency and we believe that you 
have the special experience and ability required to deal with the 
complex problems confronting it.
    We believe that the long period where this Agency has lacked a 
permanent director has led to a slow down in its decisionmaking and a 
possible fearfulness to approve new scientific breakthroughs. We think 
that this is holding back important new treatments for life threatening 
illnesses and in particular those for cancer.
    One major example of this is the delay in approving Advexin, a P53 
gene tumor suppressor now in Phase III of clinical trials for treating 
head and neck cancer. This therapy was first developed at the M.D. 
Anderson Cancer Center in Texas and then was licensed to Introgen Corp. 
which continued its development. Although being tested for only head 
and neck cancer this gene therapy has already shown its ability to 
successfully treat many other types of cancer as well.
    The P53 gene is naturally present in the body and it stops cell 
division when DNA damage occurs. When the P53 gene is damaged or does 
not function normally genetic mutations can occur in dividing cells 
leading to the accumulation of malignant cells and potential cancer 
growth.
    What makes this gene therapy even more promising is the recent 
development by Genzyme Corp. of a new diagnostic test that detects 
specific mutations in the P53 gene.
    This allows the gene therapy treatment to be targeted to those 
patients most likely to respond to this therapy. Genzyme's test is a 
significant improvement over the florescent in-situ hybridization. 
(FISH) technology currently in use.
    What is especially troubling about the FDA's delay in approving 
this therapy is that a similar gene therapy was approved in China 3 
years ago. The product Gendicine is produced by SiBiono Corp. of 
Beijing, China. It was tested for head and neck cancer and it was 
approved after only 3 years of testing. It is now being used to treat 
other cancers as well. Some doctors in China view it as a scientific 
breakthrough comparable in importance to the discovery of penicillin. 
Cancer patients are now visiting China to get this therapy and SiBiono 
has recently started licensing it to cancer centers outside of China.
    Dr. Peng Zhaohui who founded SiBiono was trained in the United 
States and I suspect he brought back to China information on this 
therapy that was developed in the United States. I think we have reason 
to be concerned about our country falling behind other nations in the 
development and use of new therapies. This is causing economic harm to 
our country as well as deficiencies in our treatment of critically ill 
patients.
    ``This is a wake-up call to America'' said Mark Kay, president of 
the American Society of Gene Therapy and Director of The Stanford 
University School of Medicine. ``We need to look at some of the 
regulatory hurdles, and the funding issues right now, funding for 
biomedical research is really hurting, and it's short sighted to think 
this doesn't hurt our economy in the long run.''
    I know from your opening statements at your confirmation hearing 
that you well understand the importance of the FDA and its need for 
strong and permanent leadership. I am looking forward to your taking on 
that role and in your leading the FDA in finding ways to streamline its 
regulatory processes to make them more efficient and to respond to the 
opportunities and challenges of science and technology.
    We hope that the Senate will promptly approve your appointment.
            Sincerely,
                                       Charles A. Reinwald,
                                                         President.
                                 ______
                                 

    The Chairman. I thank both nominees for their willingness 
to serve, and for their attendance and attention today.
    I would now turn to Senator Kennedy for purposes of his 
opening statement.

                  Opening Statement of Senator Kennedy

    Senator Kennedy. Thank you very much, Mr. Chairman. And 
thank you for having these hearings.
    Just, sort of, to frame this hearing, particularly with 
regards to the head of the FDA, the Food and Drug 
Administration is perhaps the most important health Agency that 
we have in the United States of America, and probably in the 
world. Centers for Disease Control may be a close-to-second. 
Obviously, NIH has an extraordinary role to play. But the Food 
and Drug Administration, as you appropriately pointed out, has 
such influence and responsibility to the American families, in 
terms of its leadership.
    I really deplore the fact that we have not had a permanent 
chair for that Agency--only 18 months out of the last 5 years--
and an acting head cannot do the job and make the difficult 
judgments and decisions. And we have seen an Agency that's in 
trouble. That is why we have to give very, very careful 
consideration. We have a number of important policy issues 
today to examine with the nominee.
    But this Agency is really in trouble, and some would even 
say, in crisis. At a time, we are on the brink of the life-
science century--life-science century, with all the 
possibilities that this has, in terms of new drugs, and the 
possibilities of using the information technology that you and 
I have talked about that can bring drugs onto the market 
faster--but we need to have an Agency that has the support of 
an administration, that has the support of the Congress, and is 
going to follow the--wherever the science is going to lead it. 
So, this is an important, extremely important, hearing and I 
welcome this.
    I welcome these nominees, Dr. von Eschenbach and Mr. 
DeCamp, and congratulate them on receiving their nominations. 
These are two positions worthy of the serious consideration, 
and we are looking forward to the course of the hearings.
    I've always been a strong supporter of the Cancer 
Institute. I admire Dr. von Eschenbach's leadership there, 
especially on issues on genomics and nanotechnology. As a 
survivor of cancer himself, and physician for patients with 
cancer, he has brought an important patient-centered 
perspective to the Institute, and he'll bring it to the Food 
and Drug Administration, as well.
    In the controversies over antidepressants and suicide 
behavior in children, the withdrawal of Vioxx, the Agency's 
refusal to approve the sale of Plan B over-the-counter, we've 
seen the FDA struggling with difficult scientific questions, 
inadequate resources and authority, and unfair pressures to 
ignore science. FDA needs a strong commissioner to deal with 
these and other issues, to refocus the Agency, enable it to 
make decisions based solely on science, developed after an open 
and unencumbered scientific debate, not on ideology or 
political expediency. So, the pending decision on the Plan B is 
a test case of the FDA's integrity.
    Yesterday, Dr. von Eschenbach announced that FDA would not 
pursue the rulemaking the administration had previously claimed 
was needed to respond to this application in favor of a more 
informal negotiation with the manufacturer. If this step leads 
to a swift and clear decision, I applaud it, but we must make 
certain that the administration does not use it as yet another 
delaying tactic.
    Serious concerns have been raised about the degree to which 
political pressures influence FDA's actions on Plan B, and I 
urge Dr. von Eschenbach to use the upcoming negotiations to 
begin to allay those concerns, and not to raise them anew.
    Sadly, Plan B is not the only example in which the 
Administration has pressured FDA to value political 
consideration over the statutes under which it operates and the 
science before it. Recent survey of the Union of Concerned 
Scientists presents serious evidence of problems at the Agency. 
The majority of the Agency's scientists who responded 
disagreed, or strongly disagreed, that FDA's leadership 
consistently stands behind scientific staff or managers who 
propose science-supported decisions, even though they may be 
politically controversial.
    FDA has long been regarded as the gold standard in 
regulatory work, but that will continue to be the case only if 
it makes independent science-based decisions in both fact and 
appearance.
    Under Dr. von Eschenbach's leadership, we expect FDA to 
make decisions solely on the basis of science and in the best 
interest of the public health. I hope he will assure us that 
FDA management will no longer reject the views of Agency 
scientists or actively discourage them from voicing their 
concern.
    Next year will be an important year for the FDA. Four 
reauthorizations will come before this committee. We'll need 
the Agency's assistance to enact them. Senator Enzi and I are 
preparing to introduce a drug safety bill, which will require 
the Agency and companies to develop a strategy to consider the 
post-approval safety of a drug. And I hope we'll have Dr. von 
Eschenbach's support for that effort and the support of all at 
the Agency.
    We also have the opportunity to consider another 
nomination, Paul DeCamp, to be Administrator of the Wage and 
Hour Division, Department of Labor. This vital position is 
charged with enforcing many of our most critical worker 
protections, including minimum wage, overtime, child labor 
protections, Fair Labor Standards Act, the leave requirements, 
family and medical leave, the prevailing wage requirements, the 
Davis-Bacon Act, and Service Contract Act.
    The actions of the Wage and Hour Administrator affect the 
lives of every worker in America. It ensures that men and women 
who work overtime will be able to rely on overtime pay to make 
ends meet. He protects working teenagers from being forced to 
use dangerous equipment that can threaten their health or 
safety. He ensures that parents who need to care for sick 
children can meet their family needs and still return to their 
jobs. He defends vulnerable employees, such as migrant workers 
and day laborers, when they are exploited by unscrupulous 
employers.
    Unfortunately, this administration has showed a troubling 
lack of commitment to protecting workers' rights in these 
areas. They've adopted regulations that could deny overtime 
rights for as many as 6 million workers. They've made 
sweetheart deals that let repeat offenders, like Wal-Mart, off 
the hook for violating child labor laws year after year, and 
they've refused to raise the minimum wage for hardworking 
people living below the poverty line. And they've failed to 
protect the rights of hardworking men and women rebuilding the 
Gulf Coast.
    So, the nomination of Mr. DeCamp raises troubling 
questions. His record clearly demonstrates--question whether--
his real commitment to workers' rights, which is necessary to 
fulfill these important laws. His extensive record of 
publication shows--does not support the goals of the statute, 
in many of the statutes he'll be responsible for enforcing. 
He's advocated change in current law to drastically reduce the 
number of employees entitled to overtime pay, and suggested 
that those who work overtime, but are denied overtime pay by 
their employers, do not deserve the remedies these laws 
provide. So, his record in the private practice is equally 
disturbing. And we're very concerned about the alarming number 
of men and women in the Gulf Coast area who were not paid, and 
the working conditions they had there, which was a part of the 
responsibility that he had when he was in the Department.
    So, I look forward to those questions, and I thank the 
Chair.
    The Chairman. Thank you, Senator Kennedy.
    Senator Kennedy and I would join in welcoming Dr. von 
Eschenbach's wife, Madelyn, who's here with us today. Would 
you--thank you. And I would mention that Mr. DeCamp's wife gave 
birth to a baby last week; and so, is at home taking care of 
that baby. So, we congratulate you.
    In a moment, I'll ask Senator Hutchison to take a moment to 
introduce Dr. Eschenbach. And, following the introductions, 
we'll hear the testimony of both nominees, beginning with Dr. 
Eschenbach. After both of the nominees have offered their 
testimony, we'll begin with the first of two rounds of 
questions by the members who are present and wish to make 
inquiry of one or both of the nominees. Should any member have 
additional questions remaining after the two rounds, these 
additional questions can be submitted in writing to the 
nominees after the conclusion of today's hearing. I would ask 
that that be expeditious. The record will remain open for 10 
days.
    Senator Hutchison.

                     Statement of Senator Hutchison

    Senator Hutchison. Thank you very much, Mr. Chairman.
    I'm very pleased to introduce my constituent, Dr. Andy von 
Eschenbach. He is a person that I have known for a long time, 
and I know he is the highly qualified person that we are 
looking for in this very important job.
    I listened to both the opening statements, and I agree that 
this is perhaps the most important of our medical agencies, 
because it not only protects America for the safety and 
security of our medicines and drugs, but it is also important 
that we have someone who has practiced in medicine and knows 
that sometimes we have not kept up with the ability to bring 
things into the market that could save lives. So, I think that 
he is the perfect person for this position.
    His credentials are impeccable. He served as director of 
the National Cancer Institute. He is a nationally recognized 
urologic surgeon, medical educator, and cancer advocate. As you 
mentioned, Senator Kennedy, he's a cancer survivor. He's a 
cancer survivor three times, so he really does have the patient 
viewpoint, which is, I think, so important in someone who is 
doing research and who would seek this position.
    Prior to his nomination and service as director of NCI, he 
spent 25 years at M.D. Anderson Cancer Center in Houston, one 
of the leading cancer research and treatment centers in 
America--and, in fact, in the world. He was executive vice 
president and chief academic officer there. He led a faculty of 
nearly 1,000 cancer researchers and clinicians.
    At the time of his selection to be National Cancer 
Institute director, he was president-elect of the American 
Cancer Society. He has made significant contributions to the 
scientific literature through more than 2,000 articles, books, 
and book chapters. Dr. von Eschenbach received the National 
Healthcare Humanitarian Award from the Patient Advocate 
Foundation in 2005. In 2004, Friends of Cancer Research 
presented him its Cancer Leadership Award. And George 
Washington University presented him its Distinguished Cancer 
Public Service Award.
    Dr. von Eschenbach is a native of Philadelphia. He earned a 
bachelor of science degree from St. Joseph's University, and 
his medical degree from Georgetown University School of 
Medicine in 1967. He completed residencies in general surgery 
and urology at Pennsylvania Hospital in Philadelphia. He also 
served in the U.S. Navy as a lieutenant commander in the 
Medical Corps.
    Mr. Chairman and members, I know this man, and I know that 
if you're looking at qualifications, his are impeccable. If 
you're looking at experience and how he has served in every job 
he has held, he is without blemish. I think it is important 
that we have Senate confirmation of the person holding this 
very important job in our country, and I hope you will give him 
the vote for confirmation in the Senate.
    Thank you, Mr. Chairman.
    The Chairman. Thank you very much. We appreciate your being 
here and the words that you've shared with us.
    I would mention that Mr. Paul DeCamp, the nominee for the 
position of Wage and Hour Administrator at the Department of 
Labor, is currently serving at the Department of Labor in the 
position of senior policy advisor to the Assistant Secretary of 
Labor for Employment Standards. Mr. DeCamp is a graduate of 
Harvard College and Columbia University Law School, and he was 
both a Harlan Fiske Stone Scholar and editor of the Columbia 
Law Review. Following his graduation from law school, he served 
as clerk to Judge Alan E. Norris of the U.S. Court of Appeals 
of the Sixth Circuit. Following this clerkship and prior to 
entering his current position at the Department of Labor, Mr. 
DeCamp was engaged in private legal practice, which 
concentrated on labor and employment matters with emphasis on 
wage and hour issues.
    On behalf of the committee, I welcome both of you. We'll 
begin with Dr. von Eschenbach's testimony.

STATEMENT OF ANDREW VON ESCHENBACH, NOMINEE TO BE COMMISSIONER 
   OF FOOD AND DRUGS, DEPARTMENT OF HEALTH AND HUMAN SERVICES

    Dr. von Eschenbach. Thank you very much, Mr. Chairman, 
Senator Kennedy and members of the committee.
    I am honored to be here this morning to seek your support 
for my nomination to be the Commissioner for Food and Drugs, 
and to lead the Food and Drug Administration.
    In the 11 months since President Bush appointed me as 
Acting Commissioner, I've become acutely aware of the Agency's 
need for strong and permanent leadership with a commissioner 
that is not only the choice of the President, but also 
confirmed by the U.S. Senate.
    I appreciate this opportunity to earn your trust and 
support by sharing my vision for the future of this vitally 
important public health Agency, by helping you to get to know 
me better as a person, and by highlighting the experience and 
dedication that I bring to this important role.
    To know me, it is important for me to first introduce a few 
special people who are here with me today. First and foremost 
is my first date in the sixth grade, Madelyn, who, 39 years 
ago, I finally got to agree to become my wife and then the 
mother of our four children. And she is now Nonna to our five 
grandchildren and the one who's on the way. You should know 
that I am blessed by her support, and the support of our 
family, as I embark on this very important challenge.
    I also want to introduce a few key members of FDA's senior 
leadership who are behind me: Mr. Patrick Ronan, Chief of 
Staff; Dr. Janet Woodcock, the Deputy Commissioner for 
Operations; Dr. Scott Gottlieb, Deputy Commissioner for Medical 
and Scientific Affairs; and Mr. David Boyer, Assistant 
Commissioner for Legislation. They are representing the center 
directors and the office directors who lead the FDA, as well as 
the Agency's over-12,000 incredibly talented and highly trained 
professionals and staff who epitomize the true meaning of the 
word ``public servant.'' It is important to know that if I am 
confirmed, their support and guidance will be my greatest asset 
in leading the FDA.
    My fellow Texan and my friend Senator Hutchison graciously 
outlined my career as a physician. And as I come before you 
today reflecting on that career, I am struck by the fact that 
so much has changed from my early years in training as a 
urologic surgeon, to a career at the University of Texas, M.D. 
Anderson Cancer Center as an oncologist, researcher, and 
educator, to, 4\1/2\ years ago, becoming the director of the 
National Cancer Institute, and now as the President's nominee 
to lead the FDA.
    I am struck by how much has changed in my life, but, in 
fact, struck by the fact that one critical element of my life 
has not changed. When I began my career in medicine, 40 years 
ago, my singular aspiration was to accept the trust that others 
placed in me and to use my skills to save their lives and 
improve their health. Today, as I seek the Senate's 
confirmation to lead the FDA, I remain as committed as ever to 
that very simple, but profoundly important, ideal and purpose.
    It is emphatically apparent to me that, as Commissioner of 
FDA, my role, and the FDA's role, has always been, and will 
always be, no matter how much we change over time, to cherish 
the trust of patients and the public, and that our every single 
action, decision, or activity must be directed to preserving 
their lives and protecting their health.
    This year, the FDA celebrates its 100th birthday, and a 
proud tradition of service, and protecting and promoting public 
health. As the FDA regulates almost 25 percent of all the 
products that Americans consume, its talented and dedicated 
employees continue to set the gold standard that is emulated 
around the world, but has not been equaled. As a Nation, we are 
blessed that, because of our Food and Drug Administration, we 
go to bed each night not worrying about the safety of the food 
we eat or the effectiveness of the medicines we gave our 
grandchildren.
    This standard of achievement must not change. But the world 
around us is changing, and the FDA of today is faced with new 
challenges, and the FDA of tomorrow will encounter incredible 
opportunities.
    During my career as a researcher, I have witnessed 
exponential progress in science and technology that is 
revolutionizing our very concepts of health and of disease. 
But, as a physician, I am also painfully aware that, as we sit 
here today, we struggle--struggle to make available safe and 
effective new treatments for life-threatening conditions like 
cancer, Parkinson's, Alzheimer's, HIV/AIDS, to prepare against 
the risk of pandemic flu, and to deal with emerging threats to 
our food safety.
    Today, we are faced with unprecedented challenges and 
unprecedented opportunities across the continuum of discovery, 
development, and delivery of interventions and products that 
represent the fruits of a revolution in science and technology, 
but, more importantly, the solution to many problems that 
threaten our health and well-being. And central to addressing 
these challenges and seizing these opportunities is the FDA.
    While the Agency's first century was truly remarkable, the 
FDA of the 21st century must incorporate modern management 
tools and processes to meet the challenge of today while 
creating scientific tools and technologies to address the ever-
evolving, increasingly complex regulatory issues of the future.
    To accomplish this goal, the Agency needs strong permanent 
leadership and efficient strategic management. I am here asking 
for your support of my nomination, because I believe I can 
provide both.
    Let me briefly outline for you the strategic focus for 
leading this Agency into the 21st century.
    FDA is positioned as the critically important bridge 
between scientific discovery and development of products, and 
the delivery of those solutions to patients and the public. We 
can, and must, find ways to integrate new information 
technologies to streamline our regulatory processes, to make 
them more efficient, rigorous, and transparent, in order to 
assure the public we serve of the safety and efficacy of those 
products.
    The FDA of the 21st century must be prepared to respond to 
new opportunities and challenges presented by science and 
technology. And, through initiatives like the Critical Path to 
Personalized Medicine, we are working to approve the tools that 
we use to more effectively evaluate new products and processes. 
For example, the use of biomarkers, we will be able to predict, 
earlier and more accurately, both the safety and the efficacy 
of drugs, biologics, and devices. This is the pathway that will 
take us into an era of personalized medicine, where healthcare 
is tailored to each individual patient, where the safety of 
medical products is enhanced by our improved understanding of 
how they interact with different patients and under different 
conditions.
    By enhancing both our internal and external collaborations, 
we can create synergies and enhanced efficiencies to allow us 
to better communicate and carry out FDA's critical public 
health mission. Moving forward, it will not be enough just to 
do the right thing; we must be committed to doing it in the 
right way.
    Above all, I am committed to maintaining the longstanding 
traditions and values of an Agency whose processes and 
decisions are guided by sound science and vigorous analysis of 
evidence, and are based on the best interests of the patients 
and the public we serve.
    Much work remains to fully equip FDA to face the challenges 
and seize the opportunities ahead, but I am confident that we 
are on the right path. And, if confirmed, I believe I can 
provide the leadership and the management that will guide this 
important public health agency proudly and effectively into its 
second century of service.
    As a physician, one other thing in my life has not changed. 
I continue to speak with patients and offer advice and 
consultation. A few weeks ago, I spoke with a young mother who 
happened to be celebrating her daughter's birthday when I 
returned her call. She shared with me that she had had a tumor 
for which she had already been treated with surgery and with 
chemotherapy, but the tumor was growing and threatening her 
life and her hope of being there for her daughter's next 
birthday. The question she wanted to ask of me was, ``Is there 
anything else?''
    Senators and members of the committee, millions of people 
are asking, ``Is there anything else?'' Anything else for 
cancer, Alzheimer's, AIDS, diabetes, avian flu, anything else 
to protect our food supply, improve nutrition, alleviate 
obesity, keep our animals healthy and our cosmetics safe? The 
fact is, there cannot be anything else without the FDA--a 
modern, efficient, and effective FDA.
    I know the FDA is capable of fulfilling its mission to 
assure hope that one day there will, indeed, be something else. 
FDA is the Agency that can assure Americans hope. Through 
strong management and leadership, we have the ability to 
translate innovations into safe and effective new interventions 
that protect and promote human health. In this task, the Agency 
cannot, and will not, fail.
    It would be the fulfillment of my aspiration to have your 
trust, and the trust of the American people, to have the 
privilege to lead the FDA, to save lives, and to assure the 
health of our Nation and the world. If confirmed, I look 
forward to working closely with this committee on the many 
important issues that we'll address together.
    I thank you for the opportunity of coming before you today, 
and I'm happy to answer any questions the committee may have.
    [The prepared statement of Dr. von Eschenbach follows:]
           Prepared Statement of Andrew von Eschenbach, M.D.
    Mr. Chairman, Senator Kennedy, and members of the committee, I am 
Dr. Andrew von Eschenbach, and I am honored to be here this morning to 
seek your support for my confirmation to be Commissioner for Food and 
Drugs, to lead the Food and Drug Administration. In the 11 months since 
President Bush appointed me as Acting Commissioner, I have become 
acutely aware of the Agency's need for strong and permanent leadership 
with a Commissioner that is not only the choice of the President but 
also confirmed by the U.S. Senate. I appreciate this opportunity to 
earn your trust and support by sharing my vision for the future of this 
vitally important public health agency, by helping you to get to know 
me better as a person, and by highlighting the experience and 
dedication I bring to this role.
    To know me, it is important for me to introduce a few special 
people who are here with me today. First and foremost is my first date 
in the 6th grade, Madelyn, who 39 years ago finally agreed to be my 
wife and mother of our four children--Nonna to our five grandchildren 
and one on the way--you should know that I am blessed by her support 
and the support of our family as I embark upon this challenge.
    I want to introduce a few key members of FDA's senior leadership:

     Mr. Patrick Ronan, Chief of Staff;
     Dr. Janet Woodcock, Deputy Commissioner for Operations;
     Dr. Scott Gottlieb, Deputy Commissioner for Medical and 
Scientific Affairs; and
     Mr. David Boyer, Assistant Commissioner for Legislation.

    They are representing the Center Directors and Office Directors who 
lead the FDA as well as the Agency's workforce of over 12,000 
incredibly talented and highly trained professionals and staff who 
epitomize the true meaning of the word public servant. It is important 
for everyone to know that if confirmed, their support and guidance will 
be my greatest asset in leading the FDA.
    My fellow Texan and my friend Senator Hutchison graciously outlined 
my career as a physician, and as I come before you today, reflecting on 
that career, I am struck by the fact that so much has changed--from my 
early years training as a urologic surgeon, to a career at the 
University of Texas M.D. Anderson Cancer Center as an oncologist, 
researcher and educator, to 4\1/2\ years ago becoming the Director of 
the National Cancer Institute, and now as the President's nominee to 
lead the FDA. I am struck by how much has changed in my life, but in 
fact one critical element in my life has not changed.
    When I began my career in medicine 40 years ago, my singular 
aspiration was to accept the trust that others placed in me to use my 
skills to save their lives and improve their health.
    Today, as I seek the Senate's confirmation to lead the FDA, I 
remain as committed as ever to that very simple, but profoundly 
important ideal and purpose. It is emphatically apparent to me that as 
Commissioner of FDA, my role and the FDA's role has always been and 
will always be--no matter how much we change over time--to cherish the 
trust of patients and the public and that our every single action, 
decision or activity must be directed to preserving their lives and 
protecting their health.
    This year the FDA celebrates its 100th birthday and a proud 
tradition of service in protecting and promoting public health.
    As the FDA regulates almost 25 percent of all the products 
Americans consume, its talented and dedicated employees continue to set 
the Gold Standard that is emulated around the world but never equaled. 
As a Nation we are blessed that because of our Food and Drug 
Administration we go to bed each night not worrying about the safety of 
the food we eat or the effectiveness of the medicines we gave our 
grandchildren. This standard of achievement must not change. But the 
world around us is changing and the FDA of today is faced with new 
challenges and the FDA of tomorrow will encounter incredible 
opportunities.
    During my career as a researcher I have witnessed exponential 
progress in science and technology that is revolutionizing our very 
concepts of health and disease. But, as a physician, I am also 
painfully aware that as we sit here today, we struggle to make 
available safe and effective new treatments for life threatening 
conditions like cancer, Parkinson's, Alzheimer's and HIV/AIDS, to 
prepare against the risk of pandemic flu and to deal with emerging 
threats to food safety.
    Today we are faced with unprecedented challenges and unprecedented 
opportunities across a continuum of discovery, development and delivery 
of interventions and products that represents the fruits of a 
revolution in science and technology, but more importantly the solution 
to the many problems that threaten our health and well being. And 
central to addressing these challenges and seizing the opportunities is 
the FDA.
    While the Agency's first century was truly remarkable, the FDA of 
the 21st Century must incorporate modern management tools and processes 
to meet the challenges of today, while creating the scientific tools 
and technologies to address the ever-evolving, increasingly complex 
regulatory issues of the future.
    To accomplish this vital goal, the Agency needs strong, permanent 
leadership, and efficient, strategic management--I am here asking for 
your support of my nomination, because I believe I can provide both.
    Let me briefly outline for you my strategic focus for leading this 
Agency into the 21st Century.
    FDA is positioned as the critically important bridge between 
scientific discovery and development of products AND the delivery of 
these solutions to patients and the public. We can, and must, find ways 
to integrate new modern information technologies to streamline our 
regulatory processes to make them more efficient, rigorous and 
transparent, in order to ensure the public we serve of the safety and 
efficacy of those products.
    The FDA of the 21st Century must be prepared to respond to the new 
opportunities and challenges of science and technology. Through 
initiatives like Critical Path and Personalized Medicine, we are 
working to improve the tools we use, to more effectively evaluate new 
products and processes. For example, through the use of biomarkers, we 
will be able to predict, earlier and more accurately, both the safety, 
as well as efficacy, of drugs, biologics and devices.
    This is the pathway that will take us into the era of personalized 
medicine, where health care is tailored to each individual patient, and 
where the safety of medical products is enhanced by our improved 
understanding of how they interact with different patients, different 
drugs, and under different conditions.
    By enhancing both our internal and external collaboration, we can 
create synergies and enhanced efficiencies to allow us to better 
communicate and carry out FDA's critical public health mission. Moving 
forward, it won't be enough just to do the right thing--we must be 
committed to doing it in the right way.
    Above all, I am committed to maintaining the long-standing 
traditions and values of an Agency whose processes and decisions are 
guided by sound science and vigorous analysis of evidence and based on 
the best interests of the patients and public we serve.
    Much work remains to fully equip FDA to face the challenges and 
seize the opportunities ahead, but I am confident that we are on the 
right path. And if confirmed, I believe I can provide the leadership 
and management that will guide this important public health agency 
proudly and effectively into its second century of service.
    As a physician, one other thing in my life has not changed--I 
continue to speak with patients and offer advice and consultation. A 
few weeks ago I spoke with a young mother who happened to be 
celebrating her daughter's birthday when I returned her call.
    She shared with me that she had a tumor for which she had already 
been treated with surgery and chemotherapy but the tumor was growing 
and threatening her life and her hope of being there for her daughter's 
next birthday. The question she wanted to ask me was, ``IS THERE 
ANYTHING ELSE.'' Senators and members of the committee, millions of 
people are asking if there is anything else. Anything else for cancer, 
Alzheimer, AIDS, diabetes, Avian flu--anything else to protect our food 
supply, improve nutrition, alleviate obesity, and keep our animals 
healthy and cosmetics safe. The fact is that there can not be anything 
else without this FDA--a modern, efficient and effective FDA.
    I know the FDA is capable of fulfilling its mission to assure hope 
that one day there will indeed be something else. FDA is the Agency 
that can assure Americans hope.
    Through strong management and leadership, we have the ability to 
translate innovations into safe and effective new interventions that 
protect and promote human health. In this task, the Agency cannot, and 
will not fail.
    It would be the fulfillment of my aspiration to have your trust and 
the trust of the American people to have the privilege to lead the 
FDA--to save lives and assure the health of our Nation and the world. 
If confirmed, I look forward to working closely with this committee on 
the many important issues that we'll address together.
    Again, thank you for the opportunity to come before you today. I'm 
happy to answer any questions the committee may have.

    The Chairman. Thank you, Doctor.
    The committee will now hear the testimony of Mr. DeCamp.

 STATEMENT OF PAUL DeCAMP, NOMINEE TO BE THE ADMINISTRATOR OF 
        THE WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR

    Mr. DeCamp. Mr. Chairman, Senator Kennedy, distinguished 
members of the committee, thank you for the opportunity to 
appear before you today to discuss my nomination to be the 
Administrator of the Department of Labor's Wage and Hour 
Division. I am humbled and honored to have been nominated by 
the President for this position.
    The Wage and Hour Division enforces some of our Nation's 
most important and broadly applicable laws, including the Fair 
Labor Standards Act, the Family and Medical Leave Act, the 
Migrant and Seasonal Agricultural Worker Protection Act, the 
Davis-Bacon Act, and the Service Contract Act, as well as 
dozens of other statutes. At its core, every law that the Wage 
and Hour Division enforces is about protecting workers. These 
laws apply to approximately 130 million employees, and they 
benefit the countless millions more who are the family members.
    I believe that my background has given me an inherent 
empathy for all working Americans. I grew up in a small town in 
southeastern Massachusetts. People in my town tended to work in 
trades, textiles, jewelry fabrication, and other predominantly 
blue-collar occupations. I attended public schools from 
kindergarten through high school. My father, who was not a 
college graduate, spent most of his working life as a night 
watchman, relying on every cent of his shift premium and his 
overtime pay just to make ends meet. My mother lost her job, 
due to company downsizing, after 15 years of service.
    I have personally worked in a number of jobs. I have had 
the experience of punching time clocks, working for minimum 
wage and overtime, and pulling double shifts. I have washed 
dishes, bussed tables, mopped floors, stocked shelves, de-iced 
freezers, flipped burgers, gotten splashed by fryolator grease, 
run a cash register, and more. I spent years working side by 
side with people who needed these jobs to support their 
families. Most recently, my wife is currently on leave under 
the Family and Medical Leave Act. Our second child, William 
Charles DeCamp, was born a week ago today.
    I respect working men and women, as well as their families. 
I respect the right of youth to work in a safe environment. I 
understand and empathize with people who are economically 
vulnerable. I appreciate how what may seem like small amounts 
of money by Washington, DC., standards--$20 here or $100 
there--can, for a great many families, make all the difference 
between paying the rent, or not; making the car payment, or 
not; being able to afford food and clothing, or not.
    I would consider it a genuine honor and privilege to serve 
as Administrator so that I can protect workers like my parents, 
the people I grew up with, and the many millions of Americans 
like them throughout the Nation who depend on the Federal wage 
and hour laws to ensure that they get a fair day's pay for a 
fair day's work.
    In my career as an attorney, I have gained useful insights 
into how wage and hour issues play out in the workplace, 
including how employers formulate workplace policies, how 
violations occur, and how disputes develop. I believe that most 
employers intend to comply with the law, and that many wage and 
hour violations result from an employer's good-faith 
misunderstanding or lack of knowledge of what the law requires. 
At the same time, I appreciate the importance of obeying the 
law and securing any appropriate remedies for workers whose 
rights have been violated, even inadvertently.
    In my view, the primary goal for the Wage and Hour Division 
is to achieve maximum compliance with the law. If I am 
confirmed, I would pursue that goal in a number of ways.
    First, the Wage and Hour Division must promptly process and 
investigate complaints it receives alleging violations of law. 
That activity accounts for most of the Agency's enforcement 
work, and I would continue to emphasize that aspect of its 
operations.
    Second, I would continue, and increase, directed 
enforcement efforts that focus on protecting the rights of the 
Nation's most vulnerable workers, such as children, employees 
in low-wage industries, migrant workers, and undocumented 
individuals. I would work closely with field personnel to 
identify specific areas, whether types of claims, specific 
industries, geographic regions, or particular employers, where 
the Agency believes that violations are going unreported or 
under-reported. In such instances, it may be appropriate to 
supplement the Agency's complaint-based enforcement activities 
with directed investigations, and that work may differ from 
region to region.
    Third, I would make it a priority to review and to update 
the child labor regulations. Those regulations have not been 
substantially revised in approximately three decades. I believe 
those regulations should reflect current information regarding 
the risks posed to minors in employment. These measures would 
be in addition to the actions necessary to respond to broader 
challenges that may arise, such as protecting workers in the 
Gulf Coast region in the aftermath of Hurricane Katrina, 
addressing the needs of day laborers, and safeguarding 
reforestation workers.
    I believe in our wage and hour laws and the essential 
purposes they serve. I know how important these laws are to the 
individuals and families whom the laws protect. If I am 
confirmed, I will do my best to enforce those laws justly, 
fairly, and vigorously.
    Mr. Chairman, this concludes my prepared remarks. I will be 
happy to answer any questions you or the members of the 
committee may have.
    [The prepared statement of Mr. DeCamp follows:]
                   Prepared Statement of Paul DeCamp
    Mr. Chairman, Senator Kennedy, distinguished members of the 
committee, thank you for the opportunity to appear before you today to 
discuss my nomination to be the Administrator of the Department of 
Labor's Wage and Hour Division. I am humbled and honored to have been 
nominated by the President for this position.
    The Wage and Hour Division enforces some of our Nation's most 
important and broadly-applicable laws, including the Fair Labor 
Standards Act, the Family and Medical Leave Act, the Migrant and 
Seasonal Agricultural Worker Protection Act, the Davis-Bacon Act, and 
the Service Contract Act, as well as dozens of other statutes. At its 
core, every law that the Wage and Hour Division enforces is about 
protecting workers. These laws apply to approximately 130 million 
employees, and they benefit the countless millions more who are their 
family members.
    I believe that my background has given me an inherent empathy for 
all working Americans. I grew up in a small town in southeastern 
Massachusetts. People in my town tended to work in trades, textiles, 
jewelry fabrication, and other predominantly blue-collar occupations. I 
attended public schools from kindergarten through high school. My 
father, who is not a college graduate, spent most of his working life 
as a night watchman, relying on every cent of his shift premium and his 
overtime pay just to make ends meet. My mother lost her job due to 
company downsizing after 15 years of service.
    I have personally worked in a number of jobs. I have had the 
experience of punching time clocks, working for minimum wage and 
overtime, and pulling double shifts. I have washed dishes, bussed 
tables, mopped floors, stocked shelves, de-iced freezers, flipped 
burgers, gotten splashed by fryolator grease, run a cash register, and 
more. I spent years working side-by-side with people who needed these 
jobs to support their families.
    Most recently, my wife is currently on leave under the Family and 
Medical Leave Act. Our second child, William Charles DeCamp, was born a 
week ago today.
    I respect working men and women as well as their families. I 
respect the right of youth to work in a safe environment. I understand 
and empathize with people who are economically vulnerable. I appreciate 
how what may seem like small amounts of money by Washington, DC. 
standards--$20 here or a $100 there--can for a great many families make 
all the difference between paying the rent or not, making the car 
payment or not, being able to afford food and clothing or not. I would 
consider it a genuine honor and privilege to serve as Administrator so 
that I can protect workers like my parents, the people I grew up with, 
and the many millions of workers like them throughout the Nation who 
depend on the Federal wage and hour laws to ensure that they get a fair 
day's pay for a fair day's work.
    In my career as an attorney, I have gained useful insights into how 
wage and hour issues play out in the workplace, including how employers 
formulate workplace policies, how violations occur, and how disputes 
develop. I believe that most employers intend to comply with the law 
and that many wage and hour violations result from an employer's good 
faith misunderstanding, or lack of knowledge, of what the law requires. 
At the same time, I appreciate the importance of obeying the law and 
securing any appropriate remedies for workers whose rights have been 
violated, even inadvertently.
    In my view, the primary goal for the Wage and Hour Division is to 
achieve maximum compliance with the law. If I am confirmed, I would 
pursue that goal in a number of ways.
    First, the Wage and Hour Division must promptly process and 
investigate complaints it receives alleging violations of law. That 
activity accounts for most of the Agency's enforcement work, and I 
would continue to emphasize that aspect of its operations.
    Second, I would continue and increase directed enforcement efforts 
that focus on protecting the rights of the Nation's most vulnerable 
workers, such as children, employees in low-wage industries, migrant 
workers, and undocumented individuals. I would work closely with field 
personnel to identify specific areas--whether types of claims, specific 
industries, geographic regions, or particular employers--where the 
Agency believes that violations are going unreported or underreported. 
In such instances, it may be appropriate to supplement the Agency's 
complaint-based enforcement activities with directed investigations, 
and that work may differ from region to region.
    Third, I would make it a priority to review and to update the child 
labor regulations. Those regulations have not been substantially 
revised in approximately three decades. I believe those regulations 
should reflect current information regarding the risks posed to minors 
in employment.
    These measures would be in addition to the actions necessary to 
respond to broader challenges that may arise, such as protecting 
workers in the Gulf Coast region in the aftermath of Hurricane Katrina, 
addressing the needs of day laborers, and safeguarding reforestation 
workers.
    I believe in our wage and hour laws and the essential purposes they 
serve. I know how important these laws are to the individuals and 
families whom the laws protect. If I am confirmed, I will do my best to 
enforce those laws justly, fairly, and vigorously.
    Mr. Chairman, this concludes my prepared remarks. I will be happy 
to answer any questions you or the members of the committee may have.

    The Chairman. Thank you very much.
    I appreciate the testimony of both of you. I'll begin with 
a question for Dr. von Eschenbach.
    The most important part of your job will be making 
decisions. And I appreciate, in your testimony, where you 
briefly explained how you go about making a decision, and what 
it would be based on.
    Now, in light of your testimony, I'd like to explore how 
you made the decision that you just made on Plan B. Yesterday, 
you announced that remaining issues could likely be worked out 
within a few weeks. Your predecessor said the Plan B 
application raised complex legal and regulatory questions, and 
he directed the FDA to issue an advance notice of proposed 
rulemaking. He received tens of thousands of comments in 
response to the notice. Yesterday, in your letter to the 
sponsor, you indicated that the comments suggested there was no 
need for rulemaking. If the FDA's authority was, indeed, 
unclear, as the Agency suggested in its notice, is it clear 
now? How did the comments inform your decision? And what new 
information did they add to the discussion? And, finally, why 
did you make the announcement yesterday, the day before the 
confirmation hearing?
    Dr. von Eschenbach. Thank you, Mr. Chairman. I will attempt 
to answer each of those points. And perhaps, with your 
permission, it might be helpful to do so if I just frame the 
issue as I encountered it, and some of the background that's 
associated with it.
    When I arrived at the FDA, approximately 11 months ago, 
this was, of course, a process that had already been underway. 
It began in April 2003, when the manufacturer of this 
particular product applied for a switch from it being available 
by prescription to being available without prescription.
    This particular drug is a contraceptive, an oral 
contraceptive, that is used for emergency purposes, not for 
routine purposes, and it acts by preventing conception. It had 
been used by prescription, across all age groups of women. Now 
it was being requested to be applied to all age groups of women 
without the need for a prescription. And, under those 
circumstances, the issue that the FDA was addressing was 
whether it could be used safely, and whether it could be used 
appropriately, without the need for medical supervision.
    The decision that was ultimately arrived at by the Center 
director in reviewing and coming to a decision was that there 
was a subset of women, young girls in their teenage years, in 
whom it was not clear that this could, in fact, be used without 
the need for medical supervision. And, on that basis, the 
application was denied. And the company submitted an amended 
application in which they bifurcated the ability to dispense 
this drug by providing it for over-the-counter, or without 
prescription, if you will, for women who were older than 16, 
and by prescription for those who were 16 and younger. This 
created, for the Agency, a new question with regard to the 
regulatory framework, a question independent of the review of 
the application, per se, but having to do with the issue of 
being able to appropriately provide access to a drug that would 
be both by prescription and nonprescription, when the drug was 
in the exact same formulation, in the exact same dose, in the 
exact same packaging, and how that could be managed 
appropriately and still protect and preserve public health.
    On that basis, my predecessor believed that we needed to 
move to a process of an advance notice for a proposed 
rulemaking in which that process would allow that question to 
be open to a wide range of opinions that would inform the 
Agency with regard to whether it would or would not need to go 
forward with separate rulemaking to address that issue of 
something being nonprescription and prescription at the same 
time. That is the process as it existed at the time that I came 
to the FDA.
    My commitment, at that point, in carrying through on that 
process, was to, first and foremost, address the issue of the 
process, the mechanism that had been put in place for the 
advanced notice for proposed rulemaking. The public commentary 
came to a close in November. There were approximately 47,000 
comments to the record. They were able to be, then, processed 
and categorized in a way that addressed the various questions 
that were posed to the Agency. Those responses, and that input, 
was analyzed with an internal process. I engaged in the 
analysis of that, and the examination of the evidence. And it 
was the conclusion of career staff, and I concurred in that 
conclusion, that the overwhelming evidence that came out of 
that process indicated we did not need to move forward with a 
special process of rulemaking, that we could accommodate the 
bifurcation of this application within our current regulatory 
framework.
    Based on that decision, and the fact that I could remove 
the need for rulemaking, I turned my attention back to the 
application itself, and, as you indicated, I informed the 
company, yesterday, that we were prepared to engage with them 
in a discussion of going forward with consideration of their 
application if we could arrive at an agreement in which we 
could move forward and allow the drug to be available by 
nonprescription for women who are 18 years of age and older, 
and with prescription for those who are less than 18 years of 
age, and with a risk-management plan that would assure, and be 
certain, that young girls who are in need of medical 
supervision if they are going to use this particular emergency 
intervention safely and appropriately, I was willing to move 
forward with a final decision on their application. And so, I 
made a decision to not go forward with rulemaking, and I made a 
decision to engage with the company to work through an adequate 
risk-management plan that would then lead to a final decision 
on their application.
    And the reason it was done yesterday is that this has been 
a process that has been unfolding and has been underway, and, 
by virtue of the legal prescriptions and requirements, I could 
not disclose or make public any of these discussions until I 
first notified the company of my decision, and that occurred 
yesterday morning.
    The Chairman. My time has expired.
    Senator Kennedy.
    Senator Kennedy. The unfolding underway is, I think, the 
understatement. Let me just go through--because I think we're 
going to have questions in this area, and I think you've given 
us an overview on it. Just very quickly, as you remember, 
Doctor, you had--December 16, 2003, FDA Science Advisory voted 
24 to 3 to support approval of Plan B for over-the-counter use. 
And, on February 22, 2004, FDA was required by law to issue a 
decision, failed to meet the deadline. July 21, 2004, response 
FDA, belated rejection of its initial application. The 
manufacturer modified the application to address the FDA's 
concerns. Then, in January 2005, FDA failed to meet the 
statutory deadline for acting on the revised application. Then, 
July 2005, Secretary Leavitt committed to taking action on the 
application by September 1, but the only action the FDA took 
was to say it needed more time to study the application. Then, 
on November 15, 2005, GAO issued a report stating,

          ``In the decade from 1994 to 2004, only one application for a 
        drug to go OTC, over-the-counter, that was rejected after the 
        Advisory Committee voted for approval, and that case was Plan 
        B.''

    So then, yesterday, the administration issued not a 
decision, but a framework.
    Now, you have that background, plus the background that 
says that the changing of the date of the individual women, the 
Agency reviews the data and says that it can be approved if the 
company files an amendment for women 16 and up. Then the 
company does so, and the Agency says, ``Actually, we need to 
make the application for 17 and up.'' And then, a year later, 
it says, ``No, it has to be 18 and up.''
    So, there's a number of issues and questions. First, the 
question to you is, When can the American people, at least, 
expect the FDA to decide what the science says about Plan B? 
Will it be next week or next month or next year? We'll have to 
wait until the future on that issue. And then, second, nearly 
3\1/2\ years--this is the broader issue--and that is, 3\1/2\ 
years after the application, FDA hasn't made a decision, one 
way or another, and moved the goal posts. And what's your 
reaction to those that say that this kind of a process really 
makes it basically unacceptable, in terms of approving, you 
know, new drugs? What message does that say?
    Granted, these are all prior to the time--you know, that 
you're familiar with this issue, so we--put it in that context. 
What's it say about the process? And then, when do we--are we 
going to get the actions?
    Dr. von Eschenbach. Senator, if I can just address that, 
and I'll attempt to do it succinctly, but I need to 
compartmentalize this very complex issue into some parts.
    With regard to the initial application and the difference 
of opinion that occurred with regard to the scientific review 
and the Advisory Committee recommendation, I completely concur 
with the decision that was made at that time by the director of 
the Center for Drug Evaluation and Research. In looking at that 
data, although in--overall, across all age groups, the data 
indicated that this drug could be used properly and safely in a 
nonprescription form, that data did not apply equally to all of 
the subsets of women within that study. And, in fact, the 
amount of data and information that was available for young 
girls, who were 12, 13, 14, 15 years of age, was really 
inadequate in which to draw a decision. And, because of the 
concern about not being able to understand how to use this 
emergency contraceptive properly, and because of the concern 
that without medical supervision in abuse that would, in fact, 
create safety issues or concerns, as compared to older, adult 
women who are more mature and able to make decisions, he did 
not move forward with the approval of that application. And I 
concur with that decision.
    That resulted, then, in the reapplication by the company 
with regard to this bifurcation of prescription versus 
nonprescription. And that opened up a different set of 
questions.
    Senator Kennedy. I don't want to interrupt, but I will, 
just on this point, quickly, because my time is up. The GAO 
report says that there are no age-related marketing 
restrictions for safety reasons for any of the prescriptions of 
OTC that FDA has approved. I don't know whether you're familiar 
with that finding that they had in there. It was just related 
to your comment.
    Dr. von Eschenbach. I----
    Senator Kennedy. I'm----
    Dr. von Eschenbach. I apologize. I'll----
    Senator Kennedy. No, that's okay.
    Dr. von Eschenbach [continuing]. Be more succinct.
    Senator Kennedy. Do you want to just continue----
    Dr. von Eschenbach. Well, I--to that point, what I hope to 
rapidly communicate is the fact that there are issues related 
to age within this group, and what the advance notice for 
proposed rulemaking commentary provided was additional 
information that made it possible to make a decision now that 
couldn't be made when that first came before the FDA, when the 
company amended their application.
    Senator Kennedy. Thank you.
    My time's up, Mr. Chairman.
    The Chairman. Senator Isakson.
    Senator Isakson. Dr. von Eschenbach, I don't often have the 
occasion to make a decision on someone having had experience in 
working with them, but, in your case, I do. And I thought I 
would open my questions, really, with a statement for you to 
respond to.
    About, I guess it was 9 months ago, or very shortly after 
you became Acting Commissioner, an incident came up--three 
incidents came up with regard to Tysabri. And the decision was 
made to pull that drug off the market. For the edification of 
the people here, Tysabri is a breakthrough drug for multiple 
sclerosis that had had remarkable success, and was actually 
bettering the lives of many people who felt like their life was 
about gone.
    Because of a doctor in Atlanta, and because of friends of 
mine who suffer from MS, I had a working knowledge of the 
benefits, and had seen, firsthand, those benefits. And when the 
FDA pulled the drug off, because of three particular incidents 
of death, it concerned me greatly, and it concerned them 
greatly, because, for them, the only way to stay alive was 
Tysabri.
    I brought this to your attention. And if my recollection is 
clear, in less than 4 months, maybe 5 months, you and the 
Agency worked through all the research you had to do, and 
Tysabri is now back on the market, with particular protocols 
for the physicians and the patients.
    My understanding is that that was a record time for the FDA 
to respond in such an incident. So, I want to, first of all, 
say thank you, on behalf of thousands of MS patients in the 
United States, for your quick response. And, second, have you 
addressed that particular process?
    Dr. von Eschenbach. Thank you very much, Senator.
    And I think your question points out the principle that 
guided that decision, as well as the one we have just been 
discussing, and that is to find that correct balance between 
protecting and promoting public health.
    In the case of Tysabri, the deaths that occurred were 
totally unexpected, and had not been anticipated as to be 
associated with that particular drug. And in order to protect 
the public health, the drug was voluntarily withdrawn until we 
could get additional information and until we could put in 
place processes that would then allow us to reintroduce that 
drug to provide that lifesaving intervention for those 
unfortunate patients with multiple sclerosis, while, at the 
same time, having safeguards in place that could then assure 
their protection, as well. Once we arrived at that point, and 
working judiciously because of the severe problem that MS 
presents, we were able to arrive at a place where we believe 
now, it's back on the market with restraints and constraints 
that protect health, while also providing lifesaving 
intervention. And that principle and that process will guide 
all of the decisions that we make at FDA.
    Senator Isakson. Well, again, I want to thank you on behalf 
of those people that suffer with MS that are benefiting from 
the prescription of the Tysabri, and thank you for your swift 
action as Acting Commissioner.
    Just so Mr. DeCamp doesn't go to sleep when everybody's 
talking about Plan B and asking you questions, I probably ought 
to ask Mr. DeCamp a question. Are you an attorney, sir?
    Mr. DeCamp. Yes, I am, Senator.
    Senator Isakson. I did not get to read everything. What was 
your most recent private-sector responsibility as attorney? 
What type of an attorney were you?
    Mr. DeCamp. I worked as ``of counsel'' with Gibson, Dunn & 
Crutcher, focusing on labor and employment law and appellate 
matters, with an emphasis on wage and hour work.
    Senator Isakson. Very good. Are you familiar with the 
Senate version of the immigration reform bill that passed the 
Senate?
    Mr. DeCamp. I have not reviewed the legislation yet. I've 
read what's in the papers about it.
    Senator Isakson. OK. Well, at some point in time--I'm not 
going to put you on the spot, then, but I would like, if I can, 
Mr. Chairman, to ask you to--I'll send you a formal request, 
but I think the issues over the application of Davis-Bacon and 
the Senate immigration bill that passed raises significant 
questions in terms of a reach of its application beyond its 
original intent, and I'd like to know--from your standpoint as 
a labor lawyer, and from your professional opinion--what you 
think of that. So, I'll submit that to you in writing, rather 
than catch you having not read it and then try and get you to 
make a decision. But I would like to have your input on that.
    Mr. DeCamp. Yes, Senator.

    [Editors Note: The information previously referred to was 
not available at time of print.]

    Senator Isakson. That's all I have, Mr. Chairman.
    The Chairman. Thank you. As you can tell, I'm following the 
past practice of hearing from those that are here at the sound 
of the gavel, then by arrival following that. So, Senator 
Mikulski, you'd be next.
    Senator Mikulski. Mr. Chairman, did you say in how we 
arrived, or by seniority?
    The Chairman. It's by how you arrived at the sound of the 
gavel and then after.
    Senator Mikulski. I think my colleagues at the other----
    The Chairman. I----
    Senator Mikulski. First of all, I'd love to have my time 
now, but--
    [Laughter.]
    The Chairman [continuing]. I thought----
    Senator Mikulski [continuing]. But I don't want to----
    The Chairman [continuing]. I thought the four of you----
    Senator Mikulski [continuing]. Go in front of my 
colleagues.
    The Chairman [continuing]. Were here at the sound of the 
gavel.
    Senator Murray. We always cede to our Senator Mikulski.
    [Laughter.]
    Senator Mikulski. Well, then, thank you very much, Mr. 
Chairman.
    And my question goes to the fact that I sit here as the 
very proud and enthusiastic Senator representing FDA. FDA is in 
my State. And there is over 10,000 very, very earnest and 
dedicated employees, and, over the years, who have fought for 
working on a bipartisan basis, the right facilities for these 
employees, working with Senator Hatch to make sure that 
employees that were working in 39 different spots, some 
converted hotel/motel rooms, could be in--consolidated at a 
realigned military base--and we've done that on a bipartisan 
basis--worked to create, on a bipartisan basis, the Office of 
Woman's Health with Senator Snowe, and also to be able to 
support the employees. But, Dr. Eschenbach, as I spoke to you 
yesterday and before, FDA's in crisis. There is a crisis of 
morale, there is now a crisis of confidence in the reliability 
of FDA decisions, there is a crisis about are there the 
scientists operating under a gag rule, putting politics above 
science, and there is a crisis ensuring the reliability and the 
safety of our drugs.
    My questions today to you are, while your--you have a 
compelling personal narrative and a compelling background of 
professionalism and competence, but we need plans, and we need 
commitments. If one looks at where we are now--let's just take 
the issue of morale. There are--the Union of Concerned 
Scientists have surveyed FDA and said the scientists are 
hemorrhaging, they're leaving your agency, because they don't 
know if they have a future where they can put their talents 
together, there are over 100 whistleblower cases pending from 
your agency, 100 scientific whistleblower cases. What do you 
intend to do about the morale? And, No. 2, do I have your 
commitment that you will not politicize the scientific 
decisions at FDA? And what would be your plans for doing so?
    Dr. von Eschenbach. Thank you very much, Senator.
    And I would like to address this issue of morale by first 
thanking you and Senator Hatch, as well as other Members of the 
Congress, for the tremendous support of the White Oak 
consolidation for FDA, because, although that--views possess 
important----
    Senator Mikulski. I only have a very few minutes, let's get 
to the answers. You can thank me later.
    [Laughter.]
    Dr. von Eschenbach. Well, the issue there is, it's a morale 
improvement to bring the Agency together for greater 
integration and sharing, which is one of my strategies. Second, 
within that integration and sharing, to create the climate for 
vigorous scientific debate in which, when there is a difference 
of opinion, we have in place guidances and processes for 
refutation, including an ombudsman process, so that we can 
surface that difference of opinion and not have that become an 
issue in which people fear that they will be penalized for 
voicing that opinion appropriately within the context of that 
vigorous scientific debate.
    Attention to our workforce is my No. 1 priority. It is the 
most precious asset that FDA has. And improving and enhancing 
retention and recruitment opportunities, career-development 
opportunities, will also address morale.
    Senator Mikulski. Let's come back to the concern about 
being stifled and under a gag rule for presenting views. Would 
you consider establishing, kind of, a back-channel, dissent 
channel, where employees who have concern that perhaps mid-
level people, or even political employees at FDA, would be 
unduly exercising improper influence, and that you would have a 
dissent channel that would come directly to you, or so that you 
would be aware of what they say and what their concerns would 
be, so that they could be properly addressed?
    Dr. von Eschenbach. Yes, Senator, I would. And that is 
parallel with the experience that I had, as Senator Hutchison 
alluded to, in being the chief academic officer at a very 
large, complex academic institution where that kind of 
scientific debate and difference of opinion is part and parcel 
of what we do. And to allow a mechanism for adjudication of 
differences, to allow, where there are grievances and concerns 
about the process, to have a pathway forward to the senior 
leadership and to, in fact, I----
    Senator Mikulski. So, what I'm suggesting----
    Dr. von Eschenbach [continuing]. Would be there.
    Senator Mikulski [continuing]. Is not in lieu of the normal 
personnel adjudication, but it's often too slow and too 
frustrating.
    Let me, then, get to drug safety. Your predecessor did not 
see the need for an independent drug-safety board, yet Senator 
Grassley, myself, Senator Dodd, others, feel that they should. 
You're familiar with the cases, the antidepressants around 
children, there was--Andrew Mosholder raised flashing yellow 
lights, they were ignored--the Vioxx issue, the Ketek issue, 
the defibrillator issue. So, my question to you is, What do 
you--and when I talked to Dr. Crawford, he said he was going to 
have a board, but it wasn't going to report directly to him, 
because it dealt with personnel and budget, and he didn't think 
that was his job. I was a little surprised at that. How do you 
intend to ensure--what would you see, the way of ensuring drug 
safety, and also the safety of medical devices that are so 
important and are part of our innovation economy? What 
mechanisms would you see? And do you see the need for new 
legislation? Or do you believe you can do this with the 
administrative authority that you have?
    Dr. von Eschenbach. I believe I can accomplish this with 
the administrative authority I currently have, to put in place 
a system that would include the incorporation of principles in 
critical path that have tools, scientific tools, to be able to 
determine safety of these new products and interventions before 
they are ever introduced into patients, to have processes 
internally within our review mechanisms, based on the modern 
information technology where we can----
    Senator Mikulski. Well, what do you see? Do you see a drug 
safety board within FDA, or do you see one outside of FDA?
    Dr. von Eschenbach. I see using the current mechanisms that 
are already present within FDA, including the fact that we have 
a drug safety board, that includes other members outside of the 
FDA, within the Federal Government, who can engage in these 
confidential discussions and really provide some additional 
oversight. And then, once the drug is approved, we need to 
continue that safety----
    Senator Mikulski. Well, that's the post-marketing issue, 
but there's been a GAO report on postmarketing that talks about 
the Office of New Drugs and the Office of Drug Safety. And the 
GAO found it woefully lacking. You see, our concern is that 
what is now at FDA hasn't been working. Now, this is not a 
hearing to fingerpoint, it is the hearing to pinpoint that. And 
I really don't know if FDA is capable of having a board within 
itself. I really don't know. All I'm interested in is that we 
be the gold standard for not only our own country; it's what 
you and I talked about on the phone.
    Dr. von Eschenbach. Yes.
    Senator Mikulski. All over the world, there are people that 
are going to take drugs that were invented in America, and 
they've got to know that it's okay.
    Dr. von Eschenbach. Well, what I'd like to assure you of, 
Senator, is, this is my highest priority, and it will not be 
one thing, but it will be a number of things that I am 
committed to do to bring the Agency on a modern basis of 
management and infrastructure that'll enable us to address the 
issue of safety in multiple ways and in multiple parts and 
components. The integration, I talked to earlier. And so, this 
will be a systemic--or a systematic approach to safety that's 
going to be comprehensive, and I'm absolutely committed to it, 
as you are.
    Senator Mikulski. Is my time up?
    The Chairman. Thank you.
    Senator Hatch.
    Senator Hatch. Well, thank you, Mr. Chairman.
    Mr. DeCamp, you're--I'm not going to ask you any 
questions--you're certainly highly qualified, and--I've looked 
at your resume and your background, and you certainly have all 
that it takes to do this job, and more, in my opinion.
    Dr. von Eschenbach, you're one of my favorite people. 
There's no question that you have the qualifications to be FDA 
head. It was well over a decade ago when we passed the FDA 
Revitalization Act to create the White Oak campus, and I am so 
grateful to Senator Mikulski and others on this committee and 
throughout the Congress for working with us to get that finally 
up and running. But let me just ask you this. When is the 
completion of the campus expected? And how much money is it 
going to cost?
    Dr. von Eschenbach. I cannot give you at this moment, 
Senator, the final cost. And I'm anticipating that opening--
completion will be occurring around 2011-2012.
    Senator Hatch. See, if we had done that right off the bat, 
it would have been completed by now. And, of course, we 
wouldn't have these 39 different locations, with supervisors 
traveling in between and losing all that time and efficiency.
    Dr. von Eschenbach. I would comment, Senator, that GSA has 
been extraordinarily cooperative and is working extremely hard 
in--to keep that on a very accelerated----
    Senator Hatch. I don't blame----
    Dr. von Eschenbach [continuing]. Timeline.
    Senator Hatch [continuing]. GSA. I blame us, up here. I 
think we didn't put the funds up, when we should have done 
that. I agree with Senator Kennedy, this is one of the most 
important agencies in any government anywhere. The health of 
our people depends a great deal on what you do.
    Ten years ago, the Dietary Supplemental, Health, and 
Education Act authorized the FDA to develop GMPs, or good 
manufacturing practice standards, specific to dietary 
supplements. And I recognize that the law did not require you 
to do so, but it did allow this process to begin. And we were 
greatly heartened that FDA began to develop dietary supplement 
GMPs. Now, that's the good news.
    The bad news is that somewhere over 10 years ago, DSHEA 
authorized the FDA to develop GMPs for dietary supplements, and 
we have not yet seen them published. Now, it's my understanding 
that the HHS-approved GMP regs were forwarded to OMB for final 
clearance during the Clinton administration. And shortly after 
President Bush was elected, my office received a call from a 
senior HHS official stating that HHS is going to make certain 
that GMP regulations were exempted from the general freeze on 
pending regulations so that the new administration could review 
them and allow them to proceed forward. Over the past 4 years, 
we've had numerous reports that the regulations were going 
forward, but they still have not been published.
    Accordingly, I'd like to know the following about the 
status of these regulations. Have they been cleared in final 
form by the FDA? Have they been cleared in final form by HHS? 
What specific issues remain outstanding so that these 
regulations may be finalized, if they haven't? And when will 
the regulations be published? What date certain can be--can we 
be assured that the regulations will have been finalized? Can 
you tell me a little bit about that?
    Dr. von Eschenbach. The regulation has cleared the FDA, 
Senator, and is at OMB for their analysis and review. FDA is 
committed to working very closely with OMB about any issues or 
questions they raise so that we can facilitate this coming to 
its final conclusion and closure, because, like you, we are 
very committed to the important role that dietary supplements 
can play in promoting health and well-being of Americans, and 
want to assure their safety and the quality of their 
manufacturing and their labeling so that Americans can use them 
safely and appropriately.
    Senator Hatch. Well, the responsible people in that 
industry want to have this done, and they want to be able to 
have the benefits that come from having GMPs guiding them. And 
I think it's critical that we do that, because we've had an 
explosion in dietary supplement development and manufacture 
since the DSHEA was enacted, and it's just really critical that 
we do that.
    Let me just ask one other question, and that is--I wouldn't 
mind hearing you talk about your goals as FDA Commissioner. And 
I'd like to know about what you've been thinking your 
priorities will be as FDA Commissioner. I think that would be 
helpful to us all.
    Dr. von Eschenbach. Well, thank you, Senator.
    I think I can most easily describe them as falling into two 
parts. One, and most important issue at present, is to put the 
FDA on a modern management infrastructure where I would make 
certain that we were carrying out our processes and activities 
in the most efficient and effective way, that we were utilizing 
our resources with great stewardship, and maximizing their 
impact. And, at the same time, the other issue is to continue 
to advance initiatives like the Critical Path for Personalized 
Medicine, to bring new modern scientific tools and technologies 
into the regulatory process so that we can address many of the 
complex issues that are emerging out of these new 
opportunities.
    Senator Hatch. Well, thank you.
    Mr. Chairman, I appreciate this time. I appreciate you and 
Senator Kennedy holding this hearing, and I hope that we can 
push this nominee through. We need an absolute head at the FDA, 
and it would mean a lot to, I think, the country, to everybody 
concerned. And I would appreciate any efforts that all of us 
here on this committee can make.
    The Chairman. Thank you. And as a former chairman, I always 
appreciate the careful work that you do in the hearings, as 
well as prior and after. Thank you.
    Senator Murray.
    Senator Murray. Thank you, Mr. Chairman.
    Mr. DeCamp, I do have questions and concerns. I hope that I 
can get to them. I'm not going to ignore you entirely.
    But, Dr. von Eschenbach, let me start by just saying that I 
echo the concerns of several of my colleagues that have talked 
about the deep crisis that's in the FDA because of the lack of 
decisionmaking. We've worked very hard, on this committee, to 
put in place predictability for consumers, so they know, when 
they purchase a drug, that it is, based on science, safe and 
effective; that the scientists themselves who work at FDA know 
that, when their work is done in a scientific manner, that it 
will be accepted that way; certainly, for the manufacturers, 
who spend millions of dollars getting to the point where 
they've brought a drug to you, know that predictability is 
going to be based on science.
    So, Plan B is, sort of--you're hearing a lot about, and 
will hear a lot about, because it's symbolic of people's crisis 
of confidence in the FDA. And how you handle that, and your 
leadership on that, is truly key to whether or not many of us 
feel that your nomination should go forward.
    Yesterday, you did send out a letter, and I want to ask you 
about that. I want to--well, let me just ask you. The science 
is critical. Is Plan B safe and effective for women who are 18-
years old? Is----
    Dr. von Eschenbach. Plan----
    Senator Murray [continuing]. Is Plan B safe and effective 
for women who are 18-years old?
    Dr. von Eschenbach [continuing]. Plan B can be used safely 
and effectively----
    Senator Murray. For women who are 18, correct? Is it safe 
and effective for women who are 17?
    Dr. von Eschenbach. Plan B can be used, but with medical 
supervision.
    Senator Murray. Well----
    Dr. von Eschenbach. I believe it could be used appropri-
ately----
    Senator Murray. I have a letter from your predecessor from 
August 2005, who says, ``The FDA found it safe over-the-counter 
for women ages 17 and older.'' Do you disagree with that?
    Dr. von Eschenbach. Senator, what I'm trying to communicate 
to you is, I believe the drug can be used safely and 
effectively. I believe that there need to be processes in place 
that reflect the differences----
    Senator Murray. Well----
    Dr. von Eschenbach [continuing]. In age----
    Senator Murray [continuing]. Let me----
    Dr. von Eschenbach [continuing]. So that that can happen.
    Senator Murray. OK. Last year, FDA found that it was safe 
and effective for women who are 17 and older. Yesterday, all of 
a sudden, you send out a letter changing the age from 17 to 18. 
What new scientific or medical data about safety and 
effectiveness can you share to justify that change?
    Dr. von Eschenbach. That change--that decision is based 
primarily around our ability to manage this particular drug 
being both prescription and nonprescription at----
    Senator Murray. So, there's----
    Dr. von Eschenbach [continuing]. The same time.
    Senator Murray [continuing]. No medical or scientific data.
    Dr. von Eschenbach. There's no difference in the drug, 
medically or scientifically. It's the ability to make sure that 
it's used safely and appropriately when it's both by 
prescription and not by prescription.
    Senator Murray. Well, did--is it safe and effective for 
women--safe and effective--just asking those questions--science 
based, for women who are 17 and under?
    Dr. von Eschenbach. It is safe and effective, if used 
appropriately.
    Senator Murray. But you are holding this drug to a higher 
standard, and I would like to know where in the FDA's charter 
it says that FDA should approve drugs based on behavior.
    Dr. von Eschenbach. I'm sorry, Senator, I'm not making the 
decision essentially holding it to a higher standard or based 
on behavior, I'm holding it to a principle that, in order for 
the drug to be approved as the application currently exists, I 
must assure the safety and the protection of the women who will 
be using it.
    Senator Murray. Do you have data that shows it cannot be 
used safety and effectively for women who are 17?
    Dr. von Eschenbach. Well, the point of the data that was 
analyzed, and the decision that was made by the Center 
director, which I support, was the fact that the data was 
inadequate to be----
    Senator Murray. Well, I actually----
    Dr. von Eschenbach [continuing]. Absolutely sure.
    Senator Murray. But the letter that we have says it is--
scientific data does show that it, from a year ago, from your 
agency--that it's safe for 17.
    Dr. von Eschenbach. Senator Murray, I've looked at the 
data, and I've reviewed the decision.
    Senator Murray. So, you've changed the FDA's decision from 
a year ago.
    Dr. von Eschenbach. I've made the decision, and I am of the 
opinion that, as had been judged by the Center director, the 
data was insufficient to be able to assure the safe and 
effective use of this drug----
    Senator Murray. You can understand----
    Dr. von Eschenbach [continuing]. By young women.
    Senator Murray [continuing]. I mean, a year ago, it's safe 
for women who are 17, by your own data, and now, all of a 
sudden, it's 18. I'm pointing this out, because we need to show 
scientific data. This is why this is so startling to all of us.
    But let me ask you another question, because, as you know, 
our time's short. I was really surprised yesterday to see that 
you want to put the burden of enforcement on the manufacturer, 
and you said that if the manufacturer doesn't meet these 
standards, the FDA will deny the over-the-counter application 
for all ages. So, if a pharmacist ignores a warning label, or 
the manufacturer's instruction, who is to blame? The pharmacist 
or the manufacturer?
    Dr. von Eschenbach. Well, the application is to provide the 
drug across the continuum, prescription and nonprescription. 
And, in order to do that, it is my opinion that we must have a 
proper risk-management plan, which the company did, in fact, 
submit with its application. And as long as that risk-
management plan assures that we are going to protect the women 
and young girls who are going to have----
    Senator Murray. The manufacturers----
    Dr. von Eschenbach [continuing]. Access to this drug.
    Senator Murray [continuing]. Do. I guess that's the 
question that I am going for, and the concern that I have, that 
you're basically, in your letter yesterday, telling the 
manufacturer, if they can't prove themselves--that they can 
control the pharmacists across the country, that all women will 
be denied the use of Plan B. And, as we know, Plan B is only 
effective within a short amount of time, so basically you're 
saying to women who are 25 and 35 and 45 that they will be 
denied the use of an effective drug. So, based on a 
manufacturer, it's a question I raise, because it sort of goes 
to the whole issue of the crisis of confidence we have in the 
FDA in making decisions not on behavior, but on science. And 
that's my concern.
    And the second concern is--as you know, we've been down 
this road before--right before a nominee is to be confirmed, we 
are told that a decision is imminent. You talked about meeting 
the manufacturer within the next 7 days. But that's not a 
decision. That's looking for more information. It is exactly 
where we were 1 year ago today. And I want to know from you, 
What is a date certain that you will make a decision, yes or 
no?
    Dr. von Eschenbach. Well, Senator, I hope you'll understand 
that I view it as yesterday, having made an important decision 
to not go forward with rulemaking.
    Senator Murray. To change----
    Dr. von Eschenbach. I invite----
    Senator Murray [continuing]. The age to 18, to ask the 
manufacturer and then to--what?
    Dr. von Eschenbach. And to then invite the manufacturer to 
come in immediately so that we could address the elements of 
the risk-management plan. If we can then provide that risk-
management plan to assure the safe, appropriate use of this 
medication, this high dose hormone, both for these young girls, 
who may not use it appropriately, because the data was 
inadequate to assure the FDA that that was the case, then we 
would go forward with----
    Senator Murray. Is it not----
    Dr. von Eschenbach [continuing]. The approval.
    Senator Murray [continuing]. The case that you can meet 
them--with the manufacturer and decide to have a 90-day--
another--send out opinions and ask people--opinions back again?
    Dr. von Eschenbach. It----
    Senator Murray. You could do that, correct?
    Dr. von Eschenbach. It is my intent, Senator, to have the 
FDA meet with the manufacturer of this drug to address the 
elements of the risk-management plan so that we could move 
forward in a way that would provide this drug with greater 
access----
    Senator Murray. But you can't give us a date certain.
    Dr. von Eschenbach. That date certain depends upon the 
company and the discussions and negotiations. So, it is not a 
date I can guarantee; it's a date that, right now, quite 
frankly, is dependent upon the company coming in and us having 
these conversations.
    Senator Murray. The uncertainty is what is causing everyone 
deep concern. You understand that. And leadership is making 
decisions. You understand that.
    Dr. von Eschenbach. I hope that the facts that I outlined 
in the letter, which you alluded to, create for the company a 
very clear, very specific set of issues that they can 
immediately address, and, if they do so, then this application 
will move forward.
    Senator Murray. Mr. Chairman, my time is expired.
    The Chairman. Senator Reed.
    Senator Reed. Thank you very much, Mr. Chairman.
    And, Doctor, I just want to see if I understand, sort of, 
the logic of the decision. You're creating a break--18 and 
under, and 18 and above. Is that because there's a different 
dosage that's required, or a physical evaluation or a--someone 
under 18-years old?
    Dr. von Eschenbach. No, Senator, it's precisely because the 
drug is exactly the same, regardless of which age group, but 
the issue of being able to use it safely and appropriately is 
what has created this question about the bifurcation and where 
you draw that line. I believe 18 is appropriate. It's 
consistent with the data. It's consistent with other processes 
and principles that we use for individuals to be able to make 
decisions as adult, whether it happens to be alcohol or tobacco 
or other things that we consume. So, it's a cut point, and we 
have to have some cut point.
    Senator Reed. Well--you know, I'm following up on Senator 
Murray's questioning--last year, there was data, or at least 
analysis, suggesting 17 was the appropriate age. But what 
concerns me--and I ask these questions, honestly, to try and 
understand--it seems like you're saying that certain women 
might not be capable of administering their drug themselves 
without supervision. And that seems--18 is sort of an arbitrary 
construct, if that's the underlying notion. There are some men 
and women, who are 16 and 17, who are probably more capable of 
understanding directions on a drug, and following those 
directions. And I think that's accurate.
    Dr. von Eschenbach. Well, that's a very important point, 
Senator. And one of the other issues is, in the way in which 
this drug would be administered, it would not be available in 
convenience stores or supermarkets or places where people would 
have access without the opportunity to purchase it from a 
licensed pharmacist where that opportunity for guidance in how 
to properly use this can be provided by a professional.
    Senator Reed. But that would apply--I ask the question--
that would apply to any age group, is that the----
    Dr. von Eschenbach. That's correct.
    Senator Reed. So, if a 30-year-old person walked in, and 
the pharmacist thought that they would have difficulties 
understanding the packaging, labeling, and the directions, he 
would, professionally, have the obligation to try to explain 
it, to ensure they knew that.
    Dr. von Eschenbach. The opportunity to do that. And I 
believe that would enhance public health.
    Senator Reed. And if a 17-year-old walked in, he would, 
similarly--or she would, similarly--have the professional 
obligation to do that.
    It just seems to me that this line you're drawing is 
arbitrary, and it's being drawn for reasons unrelated to the 
actual dispensing of this medicine.
    Dr. von Eschenbach. Well, the application from the company 
created the bifurcation. The issue that I'm addressing is where 

that bifurcation should be. And 18 is a date, given all the 
com-
mentary----
    Senator Reed. What was their original line of bifurcation?
    Dr. von Eschenbach. Sixteen.
    Senator Reed. Sixteen. And how did we go from--you, 
yourself, have said, ``If you make it 18, we can talk.''
    Dr. von Eschenbach. If we make it 18, we have extended that 
period of time in which young girls, who are in the midst of 
their reproductive development, where they--the data has not 
been adequate to assure that they will use this drug properly 
and appropriately as an emergency contraceptive, provides us, I 
think, a greater safeguard in protecting and promoting the 
health of these young girls. And I believe that, at the same 
time, we've provided a pathway where older women can have 
access to this drug in a way that could prevent unwanted 
pregnancies, that oftentimes, unfortunately, result in 
abortions. And I believe this, then, creates a dynamic in which 
we've protected and promoted public health.
    Senator Reed. Who first initiated, or suggested, a 
bifurcation? Was it the manufacturer or FDA?
    Dr. von Eschenbach. Well, as I understand the process, when 
the decision was made, based on the initial application, to not 
go forward because of these concerns, the company resubmitted 
an amended application with the bifurcation.
    Senator Reed. But their initial application had no 
bifurcation.
    Dr. von Eschenbach. Had no bifurcation. It was----
    Senator Reed. So, it was----
    Dr. von Eschenbach [continuing]. Without prescription for 
anyone and everyone.
    Senator Reed. But the FDA has gradually, or not so 
gradually, suggested that it be bifurcation. And I think the 
question, which I continue to pose is--I don't know, it doesn't 
seem to be a logical, appropriate break, based upon the 
behavior of people and the suitability that is variable at 
ages.
    Dr. von Eschenbach. Well, I think that--Senator, as you 
pointed out, the initial application was to make this available 
without prescription for anyone and everyone--12-, 13-, 14-
year-olds, as well as older women--and the data did not support 
the safety----
    Senator Reed. A final question. And I think you've--in your 
discussions with Senator Murray, you've talked about this--but 
the data last year seemed, based on that letter, to be 
supportive of 17 and above. And she's asked, and I----
    Dr. von Eschenbach. Yeah.
    Senator Reed. Is there new data? Is there new analysis? Or 
have you made a decision that you don't like the conclusion of 
your predecessor?
    Dr. von Eschenbach. The issue last year was, the company's 
application was 16. There was a question about the data not 
aligning with 16, and suggestion that it should be 17. In 
looking at the data, but also taking advantage of the benefit 
of what came out of the discussion and the commentary for 
advance notice for proposed rulemaking, even though we're not 
going forward with that process, I believe that the more 
appropriate age bifurcation or cutoff would be 18.
    Senator Reed. Thank you.
    The Chairman. Senator Clinton.
    Senator Clinton. Thank you, Mr. Chairman. And thanks, to 
our two witnesses, who are here.
    I'd like to take a moment also to thank someone else, Dr. 
Susan Wood, who is here. I think Dr. Wood is here. If she would 
just, maybe, stand or raise her hand. Dr. Wood was the former 
director of the Women's Health Office at the FDA who resigned 
as a matter of principle over the failure to make a decision 
and the politicization of this process last year. And I think 
her principled stand is something that clearly speaks volumes 
about what we really believe is at work here, Dr. von 
Eschenbach.
    And I want to make very clear, I agree 100 percent with 
Senator Hutchison's description of you, of your qualifications, 
of your experience. They are impeccable. You are caught, 
unfortunately, in a situation that gives great pause to many of 
us, because of what it means for the direction of the FDA. The 
FDA is, and should be, the gold standard for drug safety and 
efficacy. And, unfortunately, like so much else of this 
Government in the last 5\1/2\ years, it has been turned into a 
political football. And you're on the field.
    So, we are directing these questions to you, because, 
unfortunately, given the way things run around here, there are 
very few opportunities for us to take stands on principle and 
to point out to the public what is at stake, because, 
unfortunately, this is not just about Plan B, although one 
would think, having listened to the previous Senators question 
you, that that's all you would do at the FDA. You know, the FDA 
is a very important agency for the sake of all of us, and I'm 
sure there are people in the audience, or maybe people watching 
on C-SPAN, who would say, ``Well, that has nothing to do with 
me. I'm a 55-year-old man. I don't have any, you know, 
daughters. Why do I care about Plan B?''
    I think the reason one should care is because once we start 
politicizing the FDA, there is no stopping. And, from my 
perspective, it is essential that we draw a line. And we're 
drawing the line right here. You know, somebody could come, in 
the future, and say, ``They disapprove of smoking, so a new 
drug to treat lung cancer, directly related to smokers 
shouldn't be approved, because, by George, those people ought 
to just live with the consequences.'' Somebody could say, ``You 
know, people need to start controlling their eating habits, so 
drugs and interventions, medical devices to deal with obesity, 
we shouldn't approve those. You know, it's immoral that people 
get obese, so let's make them have to learn the lesson.'' This 
is a slippery, dangerous slope we're on, Doctor, and we are 
looking to you to get a decision made.
    And I have to ask you--you have great concern for the 
integrity of the FDA, and I applaud that--I want to ask you, 
under the circumstances of what many of us believe is at stake 
with respect to this decision, would you accept a recess 
appointment before a decision is made on Plan B?
    Dr. von Eschenbach. Senator, let me say, I want, and look 
forward to, the Senate's confirmation of me as your choice to 
be the Commissioner of the FDA. And I would hope that you would 
judge me on my record. I believe that I--the decision I made 
yesterday, and the principles upon which that decision was 
made, are exactly consistent with the principles that I alluded 
to with regard to the decision that was made about Tysabri, the 
decision that was made with regard to approving human papilloma 
virus vaccine, and all the other decisions. It has been based 
on my assessment of what the facts and the data and the science 
informed me, and informed the Agency, in my judgment. No one 
told me what I should, or could, do. No one told me what 
decision I must, or must not, make. This was my assessment and 
my commitment, and I hope you'll judge me on that record.
    Senator Clinton. Well, Doctor, last year, as my colleague 
Senator Murray pointed out, we were in the same position with 
the prior nominee to head the FDA. I want to thank the 
Chairman, who worked very closely with us to try to get some 
assurance that a decision would be made.
    And I ask unanimous consent to put into the record a copy 
of the letter that Secretary Leavitt sent to Chairman Enzi.
    The Chairman. Without objection.
    [The information previously referred to follows:]

        The Secretary of Health and Human Services,
                                      Washington, DC 20201,
                                                     July 13, 2005.
Hon. Michael Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, DC 20510.

    Dear Chairman Enzi: Per your request, this letter is to follow up 
on concerns that the Food and Drug Administration (FDA) has not acted 
on the application of Barr Laboratories to shift the product known as 
``Plan B'' to over-the-counter for women 16 years of age and older, and 
prescription-only for younger age groups.
    As you know, this decision rests solely with the FDA and must be 
made according to the scientific evidence and FDA's authority. 
Accordingly, I am not a part of this decisionmaking process.
    However, I have spoken to the FDA, and, based on the feedback I 
have received, the FDA will act on this application by September 1, 
2005.
    I hope this is responsive to your request.
            Sincerely,
                                        Michael O. Leavitt.
                                 ______
                                 

    Senator Clinton. And, in the final paragraphs, he said,

          ``As you know, this decision rests solely with the FDA and 
        must be made according to the scientific evidence and FDA's 
        authority. Accordingly, I am not a part of this decisionmaking 
        process. However, I have spoken to the FDA, and, based on the 
        feedback I have received, the FDA will act on this application 
        by September 1, 2005.''

    And we know what happened. It did not. It, once again, 
failed to act, refused to act.
    The GAO, in reviewing the history of this application, 
concluded it had been politicized, that people like Dr. Wood 
had every reason, on principle, to say this was not the FDA she 
had joined, this was not the FDA that she had pledged her 
loyalty to, and so, she left, as so many others are now 
leaving.
    In the letter that you sent, July 31, 2006, to Duramed 
Research--and, again, I ask unanimous consent it be admitted 
into the record.
    The Chairman. Without objection.
    [The information previously referred to follows:]

           Department of Health and Human Services,
                             Public Health Service,
                      Food and Drug Administration,
                                       Rockville, MD 20857,
                                                     July 31, 2006.
NDA 21-045/S-001,
Duramed Research, Inc.,
Attention: Joseph A. Carrado, M.Sc., R.Ph.,
Senior Director, Regulatory Affairs,
Bala Cynwyd, PA 19004.

    Dear Mr. Carrado: Please refer to your supplemental new drug 
application (sNDA) dated April 16, 2003, received April 22, 2003, 
submitted under section 505(b) of the Federal Food, Drug, and Cosmetic 
Act for Plan B (levonorgestrel) Tablets, 0.75 mg.
    In our August 26, 2005, letter to you we stated that the Agency was 
unable to reach a decision on the approvability of your application at 
that time because of unresolved difficult and novel issues raised by 
your sNDA. On the same day, the Agency issued an Advanced Notice of 
Proposed Rulemaking (ANPRM) seeking input from the public on certain 
issues regarding Rx to OTC switches, which related to the regulatory 
issues raised by your application. The comment period on the ANPRM 
closed on November 1, 2005, and the Agency received approximately 
47,000 comments. FDA then hired a contractor to summarize and 
categorize the comments, and we received the contractor's final reports 
on May 19, 2006. FDA has reviewed the comments and, while they have 
provided the Agency with valuable insights regarding how the Agency 
might enforce an age-based restriction like the one proposed by your 
amended sNDA, we concur with the overwhelming majority of the comments 
(from individuals both for and against the approval of your sNDA) that 
it is not necessary to engage in rulemaking to resolve the novel 
regulatory issues raised by your application.
    We are now proceeding with further evaluation of your sNDA. We 
would like to meet with you as soon as practicable, and preferably 
within 7 days, to discuss the status of your sNDA, including any 
necessary amendments. For example, your sNDA seeks approval for OTC use 
for women ages 16 and older. As we informed you in our August 26, 2005 
letter, the Center for Drug Evaluation and Research concluded the 
available scientific data are insufficient to support the safe use of 
Plan B as an OTC product for everyone in that age group. Moreover, 
because of enforcement considerations, we believe that the appropriate 
age for OTC access is 18. Should you desire to proceed with your sNDA, 
you would need to amend it to seek approval for OTC status for women 
ages 18 and older. An addition, you would need to amend your sNDA with 
respect to packaging.
    We would also like to discuss the details of the CARESM Program 
that you submitted with your sNDA. That program regards your proposed 
marketing, education, distribution, and monitoring for the OTC version 
of Plan B. Specifically, we would like to learn more about your 
proposal to restrict distribution of Plan B to certain pharmacies, 
i.e., the OTC version of Plan B would not be available at gas 
stations, convenience stores, etc., but only to those pharmacies 
agreeing to (1) keep the OTC version of the drug behind the pharmacy 
counter and (2) dispense the drug only upon the production of a valid 
photo identification card establishing the age of the consumer. In 
particular, we would like to learn more about your plan to routinely 
monitor these pharmacies to make sure they comply with the restricted 
distribution plan. In addition, we are very interested in learning how 
you plan on enforcing the restrictions if a pharmacy fails to comply 
with them, e.g., whether the restrictions will be incorporated into the 
terms of a formal contract and, if so, what the terms of that contract 
(particularly those terms related to a breach) look like. If after our 
discussions we conclude that the CARESM Program isn't sufficiently 
rigorous to prevent the OTC version of Plan B from being used by young 
girls who can't safely use the product without the supervision of a 
practitioner licensed by law to administer the drug, Plan B will 
remain Rx-only for women of all ages.
            Sincerely,
                               Andrew von Eschenbach, M.D.,
                             Acting Commissioner of Food and Drugs.
                                 ______
                                 

    Senator Clinton. You asked the company to explain how the 
company will enforce the restrictions if a pharmacy fails to 
comply with them. In other words, whether the restrictions will 
be incorporated into the terms of a formal contract. Is this 
unprecedented, Dr. von Eschenbach, that a company that submits 
an application to the FDA which is then going to rule on that 
as to whether or not it's available by prescription or over-
the-counter, is going to be held responsible, in perpetuity, 
for what pharmacists and retail outlets do?
    Dr. von Eschenbach. Senator, there is precedent in a number 
of cases in which risk-management plans are a part of the 
application, and are----
    Senator Clinton. But the risk----
    Dr. von Eschenbach [continuing]. Considered a part of----
    Senator Clinton [continuing]. Management plans don't----
    Dr. von Eschenbach [continuing]. The approval.
    Senator Clinton [continuing]. Include having the company 
police it. They have warning labels, they have agreements with 
the pharmacy office. But you know, that would be as though--
when we have law enforcement that goes and says to a liquor 
store or to a retail outlet that sells alcohol or cigarettes, 
and doesn't follow the law, that it's the maker of the product 
that is going to be held responsible. Is that what you're 
intending?
    Dr. von Eschenbach. What we're intending is to have a risk-
management plan in place where there will be opportunities 
within that plan to be assured that, as this drug is being 
provided, it's being provided in accordance with the principles 
that we laid out in the plan. That is an issue that the company 
could oversee and take responsibility for. It could be a matter 
of sampling, from time to time, what happens when a young girl 
goes into a pharmacy to request this particular medication.
    Senator Clinton. Well, I would assume, then, that the 
requirements would be, in your words, ``sufficiently 
rigorous,'' but not unprecedented, not beyond what has been 
expected of any other company. Is that correct?
    Dr. von Eschenbach. Yes. ``Sufficiently rigorous'' is, I 
think, an important way of describing that, but not that it is 
any way, shape, or form different than issues and ways that we 
would deal with any other drugs that require risk management.
    Senator Clinton. Thank you, Mr. Chairman.
    The Chairman. Thank you.
    Senator Dodd.
    Senator Dodd. Thank you, Mr. Chairman.
    Let me, first of all, thank both of our witnesses. I 
regret, in a way, we have both of you here simultaneously. I 
realize the constraints on the chair and the committee, but 
it's--I have a series of questions for both of you here, and, 
with the limited amount of time we get--both very important 
subject matters, obviously, as you've heard. Most of the 
questions going to you, Doctor, but there are a lot of 
questions we have, Mr. DeCamp, for you. As the author of the 
Family and Medical Leave Act, I'm very interested, and I hope 
we'll have a chance, Mr. Chairman, to get back and come here.
    But I want to followup on the issues that have been raised 
here with you, Doctor, and a number of other areas, and 
underscore the points that have been made by others already, 
raised by Senator Mikulski, and you've heard reiterated by my 
other colleagues, Senator Murray, Senator Reed, Senator 
Clinton, and that is the concern about the FDA. I've sat on 
this committee for a quarter of a century, and there's no other 
agency that has as much direct significance in the lives of the 
people we represent than the Food and Drug Administration.
    Dr. von Eschenbach. Yes, sir.
    Senator Dodd. And I think all of us who have been here over 
a number of years have taken great pride in the fact that--
Republican and Democratic administrations, by and large--that 
Good Housekeeping seal of approval, FDA-approved, really, 
really has meant something. In fact, it's a standard, a gold 
standard, not just here, but around the world, in many, many 
ways. So, it is with a deep great of--a deep sense of concern 
that we raise these issues about what is apparently a rising 
level of concern within the scientific community about what's 
happening at FDA.
    I was absolutely startled to read, here, that we talked 
about 420 FDA scientists reported--out of 997, when a survey 
was done--reported that they knew of cases in which the 
Department of Health and Human Services, or FDA, political 
appointees have inappropriately injected themselves into FDA 
determinations or actions--Vioxx, the SSRIs, Ketek. FDA has 
been accused of suppressing internal safety concerns, ignoring 
repeated warnings of safety concerns from FDA's own scientists.
    In late 2004, FDA officials reportedly tried to prevent Dr. 
David Graham, from the Office of Drug Safety, from presenting 
his findings, demonstrating substantial cardiovascular risk 
from Vioxx. Dr. Graham claims he was told to change his 
findings and recommendations, because the FDA did not intend to 
make any additional labeling changes to the drug. Then-Acting 
Commissioner Dr. Lester Crawford did not intervene in this 
incident. The FDA denies suppressing the findings.
    In 2003, another scientist in the Office of Drug Safety, 
Dr. Andrew Mosholder, reviewed data from more than 24 pediatric 
clinical trials for antidepressants. He found increased 
incidence of suicidal thoughts among children and adolescents 
taking the drug. FDA officials prevented the scientist from 
presenting his findings in the January 2004 Advisory Committee 
meeting on the drugs. It was not until the fall of 2004, more 
than a year after the initial study was completed, that the FDA 
issued a black-box label warning against pediatric use of most 
antidepressants.
    And there's just case after case after case of these kinds 
of stories, and it's of great, great concern to us here. And, 
again, I underscore the points that have been made by those who 
presented you and introduced you. You've got an incredible 
record--a stunning record, really. I can't think of anyone who 
could bring a better set of personal credentials and background 
to this job. We're just pleading with you here. I know the 
temptations in others. Don't go along with this stuff. We 
really are counting on you, if you're confirmed, to restore the 
confidence of this Agency. It is absolutely critical.
    Now, I know that the Plan B issues are going to be raised 
again. I want to jump into a couple of quick areas, if I can. 
And Senator Clinton rightly points out, a lot of people out 
there are concerned about some other issues.
    I've spent a lot of time on the pediatric drug issues. And 
I've written the legislation with Senator DeWine and others 
dealing with the Pharmaceuticals for Children Act and the 
Pediatric Research Equity Act. And I'm concerned about whether 
or not more authority is needed in some of these areas. I 
wonder if you would continue, first of all, to support the 
efforts to expand pediatric testing, which is something we care 
very deeply about; what steps the Agency could take to improve 
in this area; and to ensure that pediatric studies are 
answering the right questions and providing useful results. And 
is there any additional authority that you feel that Congress 
should provide to be helpful in this area? I wonder if, as 
well, would you take a look at whether or not we could be more 
effective, in terms of the delineation--differentiations on 
labels when a product is not approved for use in children 
because it has been shown, through studies, to be ineffective 
or unsafe, versus when it is not approved for children because 
it's just not been studied in that population.
    I want to quickly jump, as well, to the issue of pediatric 
medical devices. Again, Senator Kennedy and others over the 
years have paid a lot of attention to these issues. The obvious 
problem here, with devices that were never suited to be used on 
infants and children, is the need to expand and to develop that 
area. And I'm very interested in whether or not the FDA would 
support or approve areas in which we could improve the 
production of medical devices for children. There's a 5- to 10-
year lag behind those for adults in producing the technology 
that's necessary.
    Let me ask you those questions first. And if you care to 
respond to my first point, the point that's been raised by 
others here, as well, I think you need a clearer statement on 
what you're going to do, if confirmed, on putting a stop to 
what clearly is a growing problem. When you listen to 
scientists who complain about the politicalization of your 
agency, or the agency you're heading right now, what are you 
really going to do? What message can you give us here today 
that would raise the level of confidence that the FDA is not 
going to be contaminated by this kind of thinking?
    Dr. von Eschenbach. Thank you, Senator.
    And I am completely committed to the principle that you 
just espoused. The FDA has, and must continue to be, based on 
that sound scientific platform and infrastructure. And I will 
work to be sure that we continuously have processes, and 
continue to improve those processes--whether it's the 
appointment of advisory committees on the openness and 
transparency and those issues, and management conflict, whether 
it's providing opportunities with regard to creation of 
ombudsmen and pathways so that open scientific controversy can 
be discussed appropriately, or making certain that when we come 
to closure and conclusion after all that process has been 
adequately exercised--that the public and those of you who hold 
the public trust can see and understand how those decisions 
were made and the basis upon which they were made. That is my 
commitment, and I will find every way possible to implement 
that.
    As it relates to the very important area of pediatrics, I 
completely share with you the commitment that we need to 
continue to expand the opportunities to bring these lifesaving 
interventions into the pediatric population. We'll continue to 
work to find ways to enhance the ability to do the clinical 
trials and clinical studies that are necessary for the adaption 
of many of the things we're discovering in adults to be able to 
be applied to patients. I think continuing the opportunities to 
create devices that are, if you will, appropriate, 
miniaturized, if you will, for pediatric populations, ought to 
be given a very important priority. And I'll continue to seek 
mechanisms to enhance the ability to further the development of 
these interventions.
    Senator Dodd. Would you give a quick reaction here? Senator 
Grassley and I have introduced some legislation dealing with an 
independent office within the FDA on drug safety legislation. 
Senator Kennedy and the Chairman are also working on some 
legislation. We've had a number of incidences here, where the 
same department within the FDA that approves drugs, are also 
charged with the responsibility of going back and reviewing, 
after problems have arisen. Obviously, the inherent conflict of 
asking the same people who have approved a product being out in 
the marketplace, then asking the same people to make a judgment 
about whether or not there's a need for label changes or taking 
it off the market. It seems to me rather obvious, but I'd like 
you to comment on the wisdom of having some independent office 
within the FDA that could make those determinations, dealing 
with a variety of issues that have been raised with Vioxx and 
other such products.
    Dr. von Eschenbach. I would want to be sure that we had 
processes that were able to look at the issues of safety in an 
independent and appropriate way, but I would not want to 
separate, in a way, the issues that are related to 
understanding the efficacy or effectiveness of a drug and those 
issues that are associated with its safety, because as we move 
into the molecular era, and as we're seeing more and more of 
these opportunities that are coming from the Critical Path 
initiatives, for example, it is impossible, from a molecular 
perspective and a genetic perspective, to separate those. They 
are, in fact, part and parcel of each other. And so, I would 
like to see integration and coordination continue in a way that 
what we learn about the mechanism of a drug informs us as to 
whether it's going to be effective against a particular disease 
and whether it's going to be safe for that particular 
individual in that particular circumstance. And I think they're 
interwoven, and I want to keep that science and that knowledge 
base interwoven.
    Senator Dodd. Well, I understand that, but, just quickly, 
on the issue of the independence, once a product is out in the 
marketplace, and issues have been raised about it, as was with 
Vioxx and others, do you believe that the same office within 
the FDA ought to be making the determination as to whether or 
not some changes, either in labeling or the usage, or even 
calling for that product to be withdrawn, should be done by the 
same office?
    Dr. von Eschenbach. I don't see, at this point, a need to 
change the mechanism that's currently in place, and separate 
those even more so, but to use the Office of Drug Safety and 
the consultation that's incorporated in that, that even comes 
from outside of the Agency, to really address that specifically 
and effectively.
    Senator Dodd. Mr. Chairman, I have----
    The Chairman. The Senator's time has expired.
    Senator Dodd [continuing]. A load of other questions, and 
I'm going to ask unanimous consent that additional questions 
can be submitted to the nominee, if that's okay.
    The Chairman. Absolutely.
    In the initial remarks, I did say that we'd have a period 
of 10 days to get questions, and would ask for quick answers 
from both people. So, there will be that opportunity with both 
people. The record will remain open.
    Senator Clinton. So, Mr. Chairman, just to clarify, because 
I, unfortunately, am going to have to leave, also, we will be 
able to submit questions, and then we will be able to get 
answers to those questions, before any vote in the committee is 
scheduled?
    The Chairman. Absolutely.
    Senator Clinton. Thank you.
    The Chairman. Senator Harkin.
    Senator Harkin. Thank you, Mr. Chairman.
    Well, Dr. von Eschenbach, I just want to take a couple of 
minutes on Plan B. I think Senator Clinton is exactly right, we 
all know what's going on here. It is a disregard of science for 
ideological concerns. How much have we seen that in this 
administration? Need I mention anything more than the stem cell 
debate and vote that was held here, in which science has been 
trumped by ideological concerns? That's what's going on here. 
And you know it as well as I do.
    You know, here we are, in 2000, the American Medical 
Association said that this should be available over-the-counter 
without a prescription. In 2003, your Advisory Committee, 23 to 
4, that it should be sold over-the-counter; 27 to nothing, they 
voted that the drug could be safely sold as an over-the-counter 
medication. Your own Advisory Committee, FDA. We know that.
    Then I started--I asked about how many countries here. 
Forty-five countries now allow Plan B without a prescription--
everything from Albania to Uruguay, Canada, Iceland, India, 
Israel, Morocco, Portugal, Sweden, Switzerland, Togo, Tunisia, 
United Kingdom, Uruguay--all these countries are permitting 
Plan B to be sold without a prescription to any young woman.
    Now, you say you don't have enough data. You don't have 
enough data about young girls who are 13 or 14 or 12 or 
whatever. You don't have enough data. But it almost seems to 
me--and excuse me for saying this, because I have great respect 
for you--but, in saying that, you're saying that somehow our 
young women are stupider than the girls in these countries, 
that they're more illiterate, they can't even read a label. But 
the young women in Togo can, or in New Zealand, or Portugal, or 
Mauritania, or Mali, or Mauritius, or Benin. They can do it, 
but our young women can't.
    How do you respond to that?
    Dr. von Eschenbach. Senator, I hope that you will accept 
the fact that I made this decision not on a political ideology, 
but on a medical ideology, that the data----
    Senator Harkin. Medical?
    Dr. von Eschenbach [continuing]. That you're alluding is 
not there to suggest that 12-, 13-year-old girls can understand 
how to use this drug without medical supervision. And without 
that data being present, my ideology, and what I hope to always 
express, as the Commissioner of the FDA, is to protect and 
promote their health and welfare. And the decision was based on 
the fact that they should not have access to this drug without 
medical supervision. That's the ideology that is----
    Senator Harkin. Are you saying this of yourself? They 
should not have it without medical supervision. Is that what 
you're saying----
    Dr. von Eschenbach. I----
    Senator Harkin [continuing]. Of yourself?
    Dr. von Eschenbach. I believe that the application, as it 
had been reviewed, the decisions that were made by the Center 
director affirmed and supported that position, and I also 
affirm and support that decision. So, that as we're going to 
have to go forward with this application, as I'm prepared to 
do, it has to have a risk-management plan. And it is common 
with other risk-management plans to ask the company to be part 
of that agreement and to help police enforcement, so we're not 
doing anything different.
    Senator Harkin. Well, Dr. von Eschenbach, with all due 
respect, I think you're going way far afield here on this one. 
I think you're going way far afield on this. I don't know all 
the data, myself, but I just think the FDA is getting into an 
area that's not as from--and I've been on this committee a long 
time--in an area that I've not seen it tread before.
    Dr. von Eschenbach. Well, I appreciate that, Senator, and I 
think this particular application, with this high-dose hormone 
being available to young girls----
    Senator Harkin. But all of these----
    Dr. von Eschenbach [continuing]. Is a unique circumstance.
    Senator Harkin. Forty-five other countries--United Kingdom, 
Canada, our neighbor to the north? Give me a break. Australia? 
I'm just talking about, sort of, the English-speaking 
countries. Now we can go to--we can go now to Islamic 
countries, we can go to India, Israel----
    Dr. von Eschenbach. Well----
    Senator Harkin [continuing]. Iceland. I mean, give me a 
break.
    Dr. von Eschenbach. Can I point out, in many of those cases 
that you just alluded to, Senator, I think that what they are, 
in fact, doing is providing it, as we would describe it, as 
behind-the-counter. It is being provided, but it's being 
provided in the context of it being behind-the-counter, which 
is in line with----
    Senator Harkin. I don't know' em all, but I know, in 
France, it's done with school nurses. A young girl can go----
    Dr. von Eschenbach [continuing]. With----
    Senator Harkin [continuing]. To the school nurse and get 
it.
    Dr. von Eschenbach. With medical supervision, yeah.
    Senator Harkin. That's fine. Would you be in favor of that 
here? School nurses? I don't know. I shouldn't--you probably 
shouldn't answer----
    Dr. von Eschenbach. It----
    Senator Harkin. You probably shouldn't answer that 
question.
    [Laughter.]
    Senator Harkin. I don't want to get into that.
    Can I move to something----
    Dr. von Eschenbach. Sure.
    Senator Harkin. I just think this Plan B is going to be 
real trouble. It has to--and this, kind of, leads into my next 
question, in terms of scientific integrity at FDA.
    The Union of Concerned Scientists recently sent a survey to 
5,918 scientists at FDA. A thousand responded. The survey asked 
a series of questions about political interference with 
scientific findings. Here are some troubling findings in the 
survey: 20 percent said they ``have been asked explicitly by 
FDA decisionmakers to provide incomplete, inaccurate, or 
misleading information to the public, regulated industry, 
media, or elected officials.'' In addition, 40 percent said 
they could not publicly express, ``concerns about public health 
without fear of retaliation.''
    As a scientist, do you believe there is ever any reason for 
political appointees to change, edit, emphasize, de-emphasize, 
or otherwise alter scientific findings? Want me to repeat that? 
As a scientist----
    Dr. von Eschenbach. Yes.
    Senator Harkin [continuing]. Do you believe there is ever 
any reason for a political appointee to change or edit, de-
emphasize, emphasize, or otherwise alter scientific findings?
    Dr. von Eschenbach. No one should ever alter scientific 
findings.
    Senator Harkin. As the head of the National Cancer 
Institute, did you ever ask any scientist under your 
jurisdiction to edit, change, emphasize, or de-emphasize, or 
otherwise alter any scientific findings?
    Dr. von Eschenbach. Not the scientific data or the 
findings, no, sir.
    Senator Harkin. OK. And how will you ensure that politics 
does not substitute for sound science? I just read you the 
survey that was taken. I mean, this is going on right now at 
FDA.
    Dr. von Eschenbach. There is a very important set of issues 
that you are addressing and alluding to that I intend to be 
personally responsible for and address. I think the survey--and 
there are other surveys that I have looked at--indicate the 
fact that we are in the process of being able to continue to 
improve our mechanisms and our processes with regard to 
openness and transparency. We've created guidances very 
recently with regard to our ability to manage our advisory 
committees. And this is a continuous quality improvement.
    There is another issue, Senator, on the other side of it, 
and that is, when we talk about scientific deliberation and 
discussion and debate, no one should ever alter the data or the 
scientific facts, but there are differences of opinion that 
arise with regard to the interpretation----
    Senator Harkin. Interpreting. I understand that.
    Dr. von Eschenbach [continuing]. Of those facts.
    Senator Harkin. Sure.
    Dr. von Eschenbach. And that is an area in which, once 
consensus is arrived, if they don't happen to be one 
individual's point of view, that does not necessarily mean that 
that individual was right and the consensus was wrong. And 
because they protest or assume that somehow or other their 
point of view wasn't the accepted one, doesn't mean theirs was 
the right one.
    Senator Harkin. You're right. Scientific certainty is not 
an absolute.
    Dr. von Eschenbach. The data informs the decisions, but the 
decisions are made with judgment.
    Senator Harkin. I'm running out of time. I just want to ask 
him about salt. And you're thinking, ``Boy, this guy's going 
far afield.''
    The FDA still regulates as GRAS, generally recognized as 
safe, salt.
    Dr. von Eschenbach. Uh-huh.
    Senator Harkin. The Dietary Guidelines for Americans urging 
them to reduce their intake of salt. Everyone says high blood 
pressure, Americans have got to reduce their intake of salt. 
However, FDA's continued treatment of salt is not consistent 
with HHS and USDA recommendations. Do you anticipate in any way 
revisiting the issue of the GRAS, the generally recognized as 
safe, status of salt, or taking any additional steps to 
decrease salt consumption in America?
    Dr. von Eschenbach. Yes, Senator, we are. And the Agency is 
intending to really solicit much more information with regard 
to even holding a future public hearing. We do collaborate and 
cooperate with the other components of the Department, in terms 
of establishing a healthy diet for Americans. And so, we'll 
continue to stay engaged and committed to addressing this 
question.
    Senator Harkin. Last, Mr. Chairman--please go after this: 
Liquid Zoo. These are the flavored cigarettes that are going 
out to kids. FDA has got to get stronger on this. You've got to 
start regulating Liquid Zoo, strawberry-flavored cigarettes 
that hook kids onto smoking right now. And, again, we've passed 
legislation before. There's overwhelming support. And FDA ought 
to have regulatory authority over stuff like this.
    Dr. von Eschenbach. Thank you, Senator.
    Senator Harkin. Thank you.
    Thank you, Mr. Chairman.
    The Chairman. Thank you.
    Mr. DeCamp, I don't want you to feel neglected.
    [Laughter.]
    You've moved from a private practice to being a government 
advisory. Now you will be moving from being an advisor to being 
an administrator. The committee is aware of your significant 
career in employment law. You've represented many clients in 
employment-related litigation, and written a number of articles 
on Fair Labor Standards Act. Through these experiences, have 
you formed a philosophy on the appropriate approach for this 
enforcement agency? What do you believe the Wage and Hours 
Division's priority should be? What could the Agency do to 
better protect American workers?
    Mr. DeCamp. Ultimately, I think the most important thing 
that Wage and Hour does is to protect workers. There are 
obviously a lot of statutes that the Agency is responsible for 
administering, and it is the job of the administrator and the 
Agency to enforce those statutes correctly under the law, but 
vigorously and fairly and completely. And I think that that is 
the most important thing that the Agency does.
    In terms of being more specific about that, one of the 
things that the Agency needs to do, and an activity that I 
would focus on, is increasing our responsiveness to complaints 
that come in. The Agency has worked hard over the past several 
years to decrease the amount of time that it takes, for 
example, from when a complaint is received by an aggrieved 
worker to actually getting that complaint resolved. And so, 
continuing along that road, and trying to be better service 
oriented to the people who are bringing complaints, that's the 
first area.
    The second area would be to continue the Agency's targeted 
enforcement activities with regard to low-wage workers, workers 
who are economically vulnerable, workers who, for various 
reasons, perhaps because of immigration status or other 
concerns, are perhaps under-reporting claims and are more 
likely to have their rights violated, without aggressive 
enforcement on the part of the Agency. So, helping those who 
are less likely to be able to help themselves.
    Third, working on updating the child labor regulations, 
which have not been significantly revised in about 30 years. I 
think it's essential; in part, because there is no private 
enforcement, no private-sector enforcement of the child labor 
regulations. The Department of Labor is, in effect, the only 
show in town on that issue. And so, the Department needs to, in 
my view, really focus on making sure that the regulations 
continue to reflect what is known about the risks to youth and 
employment, and to protect the youth, based on current 
information, including a report that was submitted by NIOSH in 
2002.
    The Chairman. Good. Changing subjects pretty drastically 
here, Senator Kennedy and I, and others, traveled to New 
Orleans and the Gulf Coast immediately following Hurricane 
Katrina, and we saw the catastrophic damage that occurred. Work 
is being done in that area that requires a lot of labor 
resources, time to rebuild and a lot of hard work, but there 
have been reports of labor abuses, such as the failure to pay 
overtime. And there are allegations that the Department of 
Labor is not doing enough to enforce the laws in the region.
    I know that the Wage and Hour Division has sent a task 
force to the region to investigate the allegations of 
noncompliance. As head of the Wage and Hour Division, can you 
tell me what kind of priority you'd place on that work?
    Mr. DeCamp. If confirmed, I would definitely want to 
emphasize that work. This is a region, in the Gulf Coast, where 
the infrastructure was largely decimated, where even our own 
workers, even the Agency's own workers, were personally 
affected by the hurricane. For example, one of our district 
directors had no hot water in her own home for approximately 6 
months following the hurricane. So, it was very disrupting to 
the lives of the Agency's workers, let alone the many other 
workers who were in that region.
    One of the steps that the Agency has taken is--in addition 
to trying to get our own workers back up and running and on 
their feet in the region--we've been bringing in workers on 
detail, bringing in investigators on detail, from other parts 
of the country to supplement the workers who are already there 
on the ground in the Gulf Coast.
    In addition, as part of the 2007 budget request, the 
Agency, the Department, has sought additional funding for 
additional investigators; specifically, has sought an addition 
of $6 million for an additional 39 investigators, which, if 
granted--if that money is appropriated, certainly some portion 
of that would, perhaps, be available for assignment either on 
detail or permanent assignment into the Gulf Coast region.
    The Chairman. Before my time runs out, I also have to bring 
up a pet project that I've been working on. Most of Wyoming's 
firefighting is done by volunteers. And you may not be aware 
that approximately 75 percent of all firefighting service in 
the United States is provided by volunteers. For some time now, 
the International Association of Fire Chiefs representing these 
volunteers has been seeking clarity from the Department of 
Labor's Wage and Hour Division about their status under the 
Fair Labor Standards Act. They need to know when a nominal fee 
rises to the level that would classify a volunteer as an 
employee. The request for guidance was made in July 2003, and 
they're still waiting for an answer, despite a number of 
meetings and my own request that the Department respond. As 
head of the Wage and Hour Division, would you work to promptly 
respond to this request for clarity? Do you think that 3 years 
is a reasonable amount of time to wait?
    Mr. DeCamp. If confirmed, I would certainly work to get 
that issue resolved as expeditiously as possible. I'm familiar 
with the issue. It's a question of section 3(e)(4)(A) under the 
Fair Labor Standards Act. It's an important issue. It's one 
that arises in a variety of contexts. And, if confirmed, I 
would work to get resolution on that issue promptly.
    The Chairman. Thank you. I appreciate the brevity of your 
answers, too.
    Senator Kennedy.
    Senator Kennedy. Thank you, Mr. Chairman.
    I ask consent that the testimony of Mr. Samuel, legislative 
director, AFL-CIO, be included in the record.
    The Chairman. Without objection.

    [Editors Note: The information previously referred to was 
not available at time of print.]

    Senator Kennedy. And, as I understand, other members will 
be able to ask questions of the panel, and in a timely way.
    The Chairman. Absolutely. Yes, we'll leave the record open, 
so----
    Senator Kennedy. We'll have a short period of time, Mr. 
DeCamp. I'd like to keep--there's a lot of areas I'd like to 
cover. One is this--today marks the 10th anniversary of the 
last time this Congress voted for an increase in the minimum 
wage. We have a proposal that's coming over from the House of 
Representatives attached to the estate tax. Do you have a view 
about the increase in the minimum wage? Do you support that 
proposal? What is----
    Mr. DeCamp. My view is that, if confirmed, the most 
important thing that an administrator can do is to enforce the 
law, as written. And I certainly appreciate and understand the 
importance of minimum wage, in particular, to employees who are 
economically vulnerable.
    Senator Kennedy. But you don't have a position on the 
increase in the minimum wage.
    Mr. DeCamp. With respect, Senator, I've been----
    Senator Kennedy. OK.
    Mr. DeCamp [continuing]. Nominated for an enforcement 
position, and not for an economic----
    Senator Kennedy. Well, there's----
    Mr. DeCamp [continuing]. Policy position.
    Senator Kennedy. Those are going to be--that's, under the 
Fair Labor Standards Act, enforcement of it. So, they also will 
be decreasing the number of businesses subject to the 
requirement, and then pre-empting the States on the Federal 
standard on the tipped employee. So, it's, sort of, one step 
forward and two steps back.
    I noted in your response that you gave us, in answering 
questions, on April 24, you talked about the fact that now 
you're working with the Secretary and other senior Department 
officials, and one of the areas you're going in is the Gulf 
Coast region, also day laborers, also independent contractors. 
The GAO has just issued, and were releasing today, a report 
about independent contractors, and it is critical of the 
Department of Labor. You've had some responsibility over there. 
Why should we think you're going to do a better job in defining 
the rights and the protections of workers, when the GAO finds 
that the Labor Department has failed, in terms of getting 
information out and defining the definition of who is an 
independent contractor and who isn't, and who, therefore, will 
get protection for the range of different protections of the 
Fair Labor Standards Act?
    Mr. DeCamp. Senator, I've not seen the report, obviously, 
but what I would note is that the issue of independent 
contractor versus employee is a very difficult, challenging 
question under Federal law. It's one of the tougher questions 
under employment law. There is no easy, bright-line test for 
it, and it involves a multitude of factors. I can say, from 
personal experience, I have been classified as an independent 
contractor in the past, and I know that--the burdens that go 
along with that, including having to pay double taxes and not 
getting overtime and not getting any regulation of hours. My 
involvement in--with regard to independent contractors at the 
Department, so far--was really tied to the notion of day 
laborers and the Gulf Coast, and finding ways----
    Senator Kennedy. OK.
    Mr. DeCamp [continuing]. To try to protect----
    Senator Kennedy. All right. Well, let's get to those, 
although I'll refer you to the GAO, particularly on pages 31 
and 32. Let's get to Gulf Coast. You mentioned--this is the 
report by the National Immigration Law Center. The Chairman 
mentioned--very quickly, we're all caught on the time, but this 
is an extensive report about the absolute disastrous 
circumstances for workers, and worker protections, down there. 
It talks about a whole range--personnel wage theft, rampant 
wage theft, many different types of wage theft--page after page 
after page. This was an area that you say you had some 
responsibility of. This is about a fierce indictment, in terms 
of what is happening down--even with all the complex 
circumstances down there. It's illustration after illustration 
after illustration, story after story after story. And they 
said that the Labor Department was missing in action, as AWOL. 
This was an area of responsibility that you had, that you just 
admit to it now, you say, in here--why are we going to think 
that these workers are going to get protected?--and you say, 
``Well, we get the 39 detailees.'' Detailees, as you well know, 
only work 2 weeks in a particular assignment, they don't stay--
they don't go on down there and stay. It's 2 weeks. That's what 
they--it is in the Department of Labor. Why should we think 
that you're going to do a better job?
    Mr. DeCamp. With regard to detailees, it's not just sending 
somebody down for 2 weeks and then they're gone. It would be 
rotating detailees in----
    Senator Kennedy. All right.
    Mr. DeCamp [continuing]. To try to increase the----
    Senator Kennedy. But your reaction to this report, you 
said, in your statement, ``with Gulf Coast region'' and you 
also indicate independent contractors--we have a GAO report 
that says the Labor Department has failed, in terms of meeting 
its responsibility of contractors. You indicated the Gulf 
region. We have the report here that is a fierce indictment of 
the Department of Labor by the National Immigration Law Center, 
chapter and verse, on this issue. And, on the day laborers, 
what have you done in terms of bringing cases against employers 
that are exploiting undocumented workers? How many suits has 
the Labor Department brought against employers for undocumented 
workers in this last year since you've been in?
    Mr. DeCamp. I don't know about the number of lawsuits with 
regard to undocumented workers.
    Senator Kennedy. You know how--what has been recovered or 
what the penalties have been? Does----
    Mr. DeCamp. In the----
    Senator Kennedy [continuing]. Three sound about right?
    Mr. DeCamp. In the Gulf Coast, there have been 
approximately 300 hurricane-related cases that the Department 
has been investigating, including bringing over a hundred of 
them to conclusion and recovering in excess of $1.3 million in 
back wages. There are, in addition, about 200 cases or so that 
are still in process. The Department has pursued remedies under 
the Service Contract Act, including withholding, including 
debarment. And those statutes--they do confer certain 
procedural rights on employers, and so, those cases are working 
their way through the system, but the Department is pursuing 
those. And, if confirmed, I would vigorously enforce those 
statutes and try to assign additional resources to the region 
to make sure that the workers are being protected.
    Senator Kennedy. Well, my time--and on the day laborers, 
these are individuals, more often than not, undocumented. We've 
got a big issue on the immigration. But one of them is 
effective enforcement. And this is an area where the 
Department--we hear much from a lot of our speakers around 
here, ``We've got to have law enforcement.'' And here, we have 
the Labor Department's--I believe it's been three cases, 
penalties somewhere around $300,000, nationwide. Does all of 
that ring a bell or----
    Mr. DeCamp. I'm familiar with the Department's efforts to 
try to protect day laborers, but those issues are very complex, 
and one of the hardest parts about the issue is to reach the 
day laborers to make sure that they understand their rights. 
They're, in many instances, because of their immigration 
status, reluctant to approach the Department, for fear of 
deportment of other kinds of adverse consequences from law 
enforcement. And so, part of the issue--and this has played out 
in the Gulf Coast, as well--is trying to gain the trust of 
these workers so that they will come to the Department or work 
through intermediaries, such as community groups and advocacy 
groups, to let us know where the rights are being violated so 
that we can protect them. That's an area where continued work 
is necessary.
    Senator Kennedy. Let me just, finally--and I thank the 
chair--how many contractors have you sought to debar under the 
Davis-Bacon and Service Contract Acts?
    Mr. DeCamp. My understanding is that several are in 
process, where the remedy is being considered. And I believe 
it's at least two or three. If confirmed, I would be----
    Senator Kennedy. Two or three?
    Mr. DeCamp. That's my understanding. There may be more. If 
confirmed, I would certainly make sure that the field personnel 
understand that they should use that, and any other available 
remedies, including withholding and other appropriate remedies, 
to make sure that their rights are being enforced vigorously.
    Senator Kennedy. Thank you, Mr. DeCamp, thank you. I 
apologize for interrupting you. And there's a whole series of 
areas in here. I'll submit these additional questions in 
writing, and some followup questions. I appreciate--thank the 
chair.
    The Chairman. Certainly.
    Senator Murray.
    Senator Murray. Thank you, Mr. Chairman. And I just have 
one more line of questioning for Dr. von Eschenbach. I hope to 
have time to ask Mr. DeCamp a question, as well.
    The only other case I know of, where FDA puts the burden on 
the manufacturer, is Accutane. Because it can cause serious 
birth defects. Unlike Plan B, which has no side effects, 
Accutane has very serious side effects. And we know that the 
requirements for women taking Accutane is, they have to be on 
two contraceptives. Do you have any concerns about girls who 
are 17 or 18 being able to understand the instructions with 
Accutane, which is to be on two forms of contraceptives while 
taking it?
    Dr. von Eschenbach. It's my understanding, Senator, that 
within that risk-management plan for Accutane it is intended to 
be able to guide and direct them to the appropriate and proper 
use of Accutane.
    Senator Murray. So, you understand that those women can 
understand the directions that go with taking it, because it 
has very serious side effects. So, I don't understand why 
you're concerned about women who are 17 or 18 being able to 
understand instructions for Plan B----
    Dr. von Eschenbach. Well, the 18-year-old----
    Senator Murray [continuing]. Which has no side effects.
    Dr. von Eschenbach [continuing]. The 18-year-old 
bifurcation was derived from the comments that came out of the 
process for advance notice for proposed rulemaking with regard 
to guiding enforceability of a bifurcation in the application. 
And, at the same time, it----
    Senator Murray. Are you talking about Plan B?
    Dr. von Eschenbach. Right. So, the concern I have with 
regard to the 18-year-old bifurcation----
    Senator Murray. Came from the questions, so the public 
opinion influenced you on that?
    Dr. von Eschenbach. The indication of how we could, in 
fact, provide enforceability of it being both prescription and 
nonprescription at the same time. And the issue with regard to 
its safety is around the issue of misuse or inappropriate use 
in the context of the----
    Senator Murray. But you don't have concerns about Accutane, 
which has serious side effects----
    Dr. von Eschenbach. Well----
    Senator Murray [continuing]. For a woman to be able to 
understand those instructions?
    Dr. von Eschenbach. I agree with you, Senator. I do have 
concerns about Accutane, as well. And there is a risk-
management plan in place that was, in fact, intended to address 
those concerns, as well.
    Senator Murray. Well, I think it leads us all to the 
question of how the decisions are made. We've been down this 
road, and I will let it go, at this point. But, to me, it seems 
very important, Mr. Chairman, that we have a decision on Plan 
B, so we can put all of these questions behind us and have 
someone at the head of FDA that we all can count on.
    But I do want to ask Mr. DeCamp a question. And I listened 
to your opening remarks, and you talked about your career and 
all the washing dishes and mopping floors, which I assume was 
in high school, since you didn't include those in your 
qualifications statement to the committee.
    Mr. DeCamp. High school and college.
    Senator Murray. High school and college. Well, given your 
working-class background, I was surprised, then, that your 
professional career has really been defending employers against 
workers in a wide range of employment matters. And, in 
particular, you chose to work for Wal-Mart in appealing the 
certification of a nationwide class of 1.6 million women who 
were alleging systematic gender discrimination in pay and 
promotions. So, listening to you talk about your working-class 
background, I was surprised, and would like to hear from you 
why you chose to defend a company with a history of 
questionable employment practices against a group of--very 
large--low-wage women, and their pay.
    Mr. DeCamp. The focus of my career, in law practice, was on 
the law. It was on protecting the rights of clients of the law 
firms where I worked. And it has never been anti-worker, it's 
never been pro-employer. It's been defending clients. 
Specifically, one of the insights that I've had from working 
with employers----
    Senator Murray. Do you think that the 1.6 million had a 
case?
    Mr. DeCamp. My firm's involvement in that case had nothing 
to do with whether, individually, they had been the victims of 
sex discrimination in pay and promotions, which was the 
underlying claim; my firm's involvement was limited to the 
question of whether the procedural remedy of class 
certification was appropriate in that instance. In my view and 
the view of the client at the time, the view was that the 
District Court had erred, had incorrectly construed the law----
    Senator Murray. Do you think there's ever a case where 
women have been discriminated on by gender?
    Mr. DeCamp. Oh, absolutely. Of course. And----
    Senator Murray. Can you tell me when that was?
    Mr. DeCamp. There have been lots of meritorious claims 
where women have prevailed in claims against all kinds of 
employers for sex discrimination. I have no----
    Senator Murray. That you think were legitimate?
    Mr. DeCamp. Absolutely. Absolutely. The issue in the Dukes 
case was the procedural class certification that of whether the 
case should--in other words, proceed as a nationwide class 
action of 1.6 million people, versus store-by-store class 
actions or some other smaller aggregation. There were 
evidentiary problems in the case that made a nationwide class 
action improper, but that says nothing about whether 
individually or in smaller groups the women had perfectly----
    Senator Murray. So, you think it would have been better for 
the women, one by one, to come forward and go after Wal-Mart.
    Mr. DeCamp. One by one, or on a store-by-store basis, which 
would be----
    Senator Murray. You think that's fair?
    Mr. DeCamp. I think it's----
    Senator Murray. Wal-Mart against one woman, who gets 
minimum wage?
    Mr. DeCamp. It's not--under the law, class certification 
has certain requirements. And, in our view, the law of class 
certification was not satisfied with regard to what the 
District Court did in that case. It is entirely possible--and 
in the briefs, the client argued--that smaller class actions 
could well have been appropriate in that case, but not a case 
that, in essence, tries to take stores where there were 
statistics indicating gender disparities, and lump them in with 
stores where they were indicating--where the evidence showed 
that there were no disparities. The problem was that you had 
a----
    Senator Murray. Well, have you ever defended a worker in a 
lawsuit against an employer?
    Mr. DeCamp. I have not. My firm represented employers with 
regard to employment disputes. That's the nature of private 
bar. It tends to be that law firms will represent either 
employees or employers, but not both, because of the issue 
conflicts that are presented. One of the insights that I got 
from working in private practice was that whether you're 
talking about employers or employees, you're talking about 
people, and most of them, whether it's employers or employees, 
are good, and tend to do the right thing; some do not, some get 
it wrong, whether it's employees or employers. If confirmed, I 
would very vigorously go after employers and enforce the laws 
with regard to employers who have broken the law. I believe, 
absolutely, that--whether it's Wal-Mart or any other business 
in the country--that they have to follow the law, they have to 
respect the rights of workers that are set forth in Federal 
statutes. And I take that obligation absolutely seriously.
    Senator Murray. Well, I see my time is out, Mr. Chairman. I 
do have a number of questions for both of the nominees, and my 
understanding is that we have 10 days to submit the questions. 
How long will they have to respond to them?
    The Chairman. I'm hoping that they will respond rapidly so 
that we can continue on with the process. We'll be gone during 
August.
    Senator Murray. Right. So, I assume it'll be September 
before we have a chance, in this committee, to--if you are 
going to bring it up for a vote.
    And my question is--because there's a lot of rumor about a 
recess appointment for the FDA Director. And since we have time 
to submit questions, they will have time to respond, I assume 
that there won't be a recess appointment while we are still 
having the opportunity to look at the questions and responses.
    The Chairman. That's not a decision that I can make, nor is 
it one that anybody's talked to me about.
    Senator Murray. Thank you, Mr. Chairman.
    The Chairman. I want to thank Dr. von Eschenbach and Mr. 
DeCamp for their testimony, their responsiveness, their vast 
range of knowledge, and, probably most of all, their 
willingness to serve, realizing that they would have to go 
through a hearing like this.
    [Laughter.]
    I also want to thank my colleagues for their interest and 
attendance, and the way that they've addressed questions, and 
their thoroughness. I do look forward to working with both of 
you, and to working with my colleagues to move these 
nominations to the Senate floor.
    Both rounds of questions have been completed. I will 
reiterate, again, that the members of this committee will be 
submitting additional questions in writing to both of you. I 
would note to my colleagues that if they intend to propound any 
written questions, that these questions have to be submitted 
within 10 days following the adjournment of today's hearing, 
and we would ask that the nominees provide their responses as 
quickly as possible so there would be no inordinate delay in 
completing the confirmation process.
    Again, thank you very much for your participation today.
    We had said that we would go into an executive session. We 
do not have a quorum for an executive session, so the executive 
session is postponed, and that date and time will be announced 
shortly, and will probably be with a vote tomorrow.
    So, at this point, the hearing is adjourned.

                          ADDITIONAL MATERIAL

   Response to Questions of Senator Enzi by Andrew C. von Eschenbach
    Question 1. Our regulatory system is data and science driven. In 
the past, the FDA has not accepted post-hoc subgroup analysis without 
further data collection on the subgroups. For example, in withdrawing 
the lung cancer drug Iressa from the market, the Agency pointed out 
that suggestions of efficacy in a subgroup were not enough. In 
considering action on the Plan B emergency contraceptive, what data did 
you use to pick 18 as the age cutoff for nonprescription access? The 
2004 Plan B application used 16 as an age cutoff, while the label 
comprehension study used 17 as a breakpoint in age groups. If the 
switch to 18 was not data-driven, what authority was the decision to 
use 18 based upon?
    Answer 1. The Center for Drug Evaluation and Research (CDER) at FDA 
determined that the data submitted by the sponsor (Duramed or Barr) in 
its 2004 application supported OTC use for women 17 and older. In 
considering the difficulty of enforcing an age-based restriction on the 
availability of this oral hormonal contraceptive, however, I have 
concluded that 18 (rather than 17) is the more appropriate cutoff to 
best promote and protect the public health. The State-regulated 
pharmacies that will be dispensing Plan B under Barr's voluntary 
Convenient Access, Responsible Education (CARE) program (as well as 
society as a whole) are more familiar with 18 as a cutoff age. I 
understand that in all 50 States, 18 is the age of majority (i.e., the 
legal delineation between minor and adult), and retail outlets, 
including pharmacies, are familiar with using 18 as the age of 
restriction for the sale of certain products. With regard to drug 
products, for example, the legal age to purchase FDA approved non-
prescription nicotine replacement therapy products is 18. Moreover, I 
understand that as a matter of State law, many products routinely sold 
by pharmacies, e.g., tobacco products and nonprescription cough-cold 
products like pseudoephedrine are restricted to consumers 18 and older. 
The approach builds on well-established State and private sector 
infrastructures to restrict certain products to consumers 18 and older. 
This approach should, therefore, help ensure safe and effective use of 
Plan B.

    Question 2. Restrictions on distribution and use, although somewhat 
rare, are not unheard of for prescription drugs. Are there 
nonprescription drugs that have restrictions on distribution or use? In 
the case of prescription drugs with restrictions on distribution and 
use, who is responsible for enforcing those restrictions? What role 
does the manufacturer of the product typically play in enforcing those 
restrictions?
    Answer 2. The FDA-approved labeling for nonprescription nicotine 
replacement therapy products states that they are for use by consumers 
18 years of age and older. In addition, some States have restricted 
nonprescription cough-cold medications like pseudoephedrine to 
consumers 18 and older. In this case, the company proposed to market 
prescription Plan B and nonprescription Plan B in the same box. 
Therefore, certain marketing restrictions are appropriate to ensure 
that Plan B is made available to one population on a prescription basis 
and another population on a nonprescription basis. Both FDA and 
manufacturers are involved in ensuring that restrictions on 
distribution and use are followed. Manufacturers typically submit, as 
part of their application, a plan to address any marketing 
restrictions, which often includes, as here, education and monitoring.

    Question 3. The Critical Path Initiative is an important 
collaboration between the Agency, industry and academia to develop new 
tools to evaluate medical products. The Opportunities List was released 
in March of this year, identifying 76 project areas for research. How 
many of these projects are moving forward? Have you seen the sort of 
response you had hoped to these proposals? When do you expect to see 
some results from these projects?
    Answer 3. Within current resources we have been able to initiate 
projects in all six priority areas discussed in the Opportunities 
Report and List. For example, we have been able to initiate several 
collaborations described in Opportunity #2, to ensure that micro-array 
technology can be used for biomarker identification in product 
development. A collaboration involving the NIH and others to validate 
FDG-PET as a response measure in nonHodgkins lymphoma is already 
writing the clinical protocol (see Opportunity #26). We are actively 
working on concept papers toward developing consensus on more 
innovative clinical trial designs (see Opportunity #34-37). In the next 
few weeks, we will publish a followup report describing specific 
Critical Path projects we are undertaking in calendar year 2006. 
(Timeframe for results varies across the projects, and often depends on 
the resource commitment not only of FDA but of our collaborating 
partners.)
    Based on the many inquiries we have received regarding potential 
partnerships with FDA on Critical Path projects, we believe the 
Initiative is already having an effect on how industry, academia, and 
others think about product development sciences. We hope stakeholders 
will use the List and Report to begin planning their activities in the 
national effort to modernize the Critical Path sciences. Since the List 
and Report have been out for only a few months, and the timeframe for 
planning research and development activities is longer, it is too soon 
to assess whether this is occurring on a broad scale.

    Question 4. Some of my colleagues have proposed a separate drug 
safety office on the theory that scientists who make a decision 
supporting marketing of a drug would be reluctant to change that 
decision in light of new data. FDA scientists have integrity, talent 
and dedication, and I find it hard to believe they would or even could 
ignore what the data is telling them. Isn't science an inherently self-
correcting enterprise? Please comment on how the drug review and post-
market evaluation processes incorporate science into decisionmaking.
    Answer 4. The decisionmaking processes at FDA incorporates science 
at all levels. FDA medical reviewers and scientists make regulatory 
judgments based on scientific data during both the drug review and 
post-market evaluation processes. The Agency makes these decisions in 
an open, transparent, and collaborative environment that offers several 
mechanisms for resolving differing scientific opinions. We weigh the 
scientific data regarding the inherent benefits of a product against 
its risks, and based upon the judgment of our medical reviewers, 
experts, and management about what that data tell us, we ultimately 
make a regulatory decision about that product. Over time, as the 
science underpinning our decisions changes and as we get new 
information regarding the basis and standards for our decisions, we 
move to re-visit our processes and respond to the new scientific 
information as appropriate and as necessary.
    With respect to a separate drug safety office, the nature of our 
knowledge of a drug's safety profile and the expertise required for the 
ongoing assessment of a drug's risk-benefit balance demand that these 
two activities be housed in a single center. Our knowledge of a drug's 
safety profile proceeds along a continuum, which begins with in vitro 
and animal studies (before the drug is ever administered to humans), 
continues to grow through rigorous clinical trials, and is further 
refined after a drug is marketed. It is the review and synthesis of 
this cumulative knowledge base that leads to the most accurate 
assessment of the drug's safety profile. In CDER, Office of New Drug 
(OND) staff is the most knowledgeable about the pre-marketing safety 
data, while Office of Surveillance and Epidemiology (OSE) staff 
specializes in the post-marketing safety issues. Staff from the OSE and 
OND work closely in the analysis of appropriate regulatory actions, 
together they take into consideration both risk and benefit information 
from pre- and post-approval sources. If pre-approval and post-approval 
functions were split, there would be a loss of continuity in the review 
of risks and benefits.
    Additionally, separating these two activities into two centers 
would be very costly, because of the duplication of the wide range of 
expertise involved. Medical officers in OND whose areas of expertise 
include the affected patient population(s), medical conditions, and 
treatments, know the results of animal and clinical studies that 
supported approval of the product; in addition, they review studies 
with products that are used in the same patient populations, and 
products, some still in the investigational phase, from drugs in the 
same or related classes. This expert knowledge of the patients' medical 
conditions, availability of alternative therapies, and safety profiles 
from IND and NDA submissions is a crucial component in the review of 
newly identified risks and how they may impact benefits. OSE personnel 
provide expertise in the areas of epidemiological studies of large 
populations, evaluation of data from AERS (that is, spontaneous adverse 
event reporting) and large external data sets purchased for adverse 
event tracking and evaluation in specific populations, medication error 
prevention, and risk management techniques.
    If the responsibilities were split into two centers, the safety 
center would have to duplicate the expertise of OND staff, with expert 
knowledge of patient populations, medical conditions, alternative 
therapies, and safety profiles from investigational new drug 
applications and studies in marketing applications to support approval 
to enable the safety center to make appropriate risk-benefit decisions 
and the drug approval center would have to duplicate the expertise of 
the OSE staff. Cross-center consultation would be much more difficult, 
and therefore, less efficient, than within center collaboration.
    OND routinely meets with OSE staff to discuss the current or 
anticipated safety of marketed products. In addition, CDER has recently 
instituted safety meetings that are held periodically (monthly or bi-
monthly) to discuss new safety issues and the status of reviews and 
analysis of previously identified safety signals. Also, prior to 
approval of applications to market new molecular entities (NMEs), or 
nonNMEs, OND and OSE staff have pre-approval safety conferences. The 
OSE staff is also consulted by OND in many pre-approval activities that 
increase CDER's ability to understand and adequately monitor risk and 
benefit for marketed products such as medication error prevention and 
risk management plan review.
    For the reasons mentioned previously--resources, communication, 
collaboration, leadership, and shared responsibilities--I do not 
believe that two separate and independent centers would improve FDA's 
ability to fulfill its mission to protect the public health.

    Question 5. The Agency recently announced an overhaul of its 
advisory committee process. As you know, Senator Kennedy and I consider 
this an important issue, and we have proposed reforms to the process in 
our drug safety legislation. I don't want to work at cross-purposes 
with the FDA, so could you please tell me more about what you have 
planned? Do you believe that FDA can sufficiently improve the 
transparency and credibility of its processes with respect to advisory 
committee participation solely by administrative means?
    Answer 5. In a speech given July 24, 2006, Deputy Commissioner Dr. 
Gottlieb discussed efforts to revise guidelines detailing the kind of 
industry ties that are permitted for those who serve on our advisory 
committees (see http://www.fda.gov/oc/speeches/2006/
conference0724.html).
    More specifically, we plan to revise the guidance documents used to 
determine how potential conflicts are evaluated, how waivers are 
granted, and how information regarding conflicts and waivers is 
disclosed. The goal is to make the process more transparent and clarify 
more of the case-by-case qualitative judgments we make when we evaluate 
each potential conflict. We do not plan to re-write existing rules, but 
instead, we intend to provide additional guidance and clarity regarding 
implementation of the existing statutory and regulatory framework 
regarding conflicts of interest. The revision process is currently 
underway and is a high FDA priority. We will make public the revised 
guidances as soon as they are completed.
    We believe that these administrative changes will substantially 
improve the transparency of the process of managing our advisory 
committees, evaluating potential conflicts, and granting waivers where 
appropriate.

    Question 6. The Nutrition Labeling and Education Act (NLEA) was 
enacted in 1990 to assist consumers in understanding the nutritional 
characteristics and ingredients in food and beverage items. I believe 
consumers need more and better information to make informed choices 
when purchasing foods and beverages for themselves and their families. 
It is my understanding that FDA is planning to re-evaluate the 
Nutrition Facts Panel (NFP) on food labels. Have you given any thought 
to requiring the disclosure of artificial sweeteners on the front of 
the package and listing the amounts in the Nutrition Facts Panel or 
additional labeling to help consumers distinguish between natural and 
artificial sweeteners?
    Answer 6. FDA intends to issue an Advance Notice of Proposed Rule 
Making (ANPRM) to re-evaluate the Daily Values used in the Nutrition 
Facts panel based on recent recommendations from the Institute of 
Medicine Dietary Reference Intake and other scientific reports (e.g., 
2005 Dietary Guidelines). This re-evaluation will be a comprehensive 
effort that will include a review of the Reference Daily Intakes 
(RDIs), which apply to vitamins and minerals, as well as the Daily 
Reference Values (DRVs), which apply to macronutrients. Sugars will 
also be addressed in the ANPRM.
    Generally speaking, the Nutrition Facts panel (NFP) on conventional 
food labels contains nutrients of the type that have reference values; 
the only items in the NFP that do not currently have reference values 
are sugars and trans fat. Artificial sweeteners are not nutrients and 
thus do not have reference values. When used in foods, artificial 
sweeteners are required to be listed by common or usual name in the 
ingredients list. Thus, consumers can currently determine when 
artificial sweeteners have been used to sweeten a food product. In 
addition to the listing in the ingredient list, a manufacturer can 
provide statements elsewhere on the package about the type of sweetener 
used in the product as long as the information is truthful and not 
misleading.

    Question 7. In August 2002, a number of organizations sent a 
citizen petition to FDA, asking that FDA revoke its approval of the 
abortion drug RU-486. The petition argues that FDA violated drug law 
and its own regulations and standards in approving RU-486 for medical 
abortion. FDA gave an interim response in June 2003. However, your 
agency has yet to give a final response. I would like to know when you 
intend to act on this petition, as we are now approaching the 4-year 
mark.
    Please also tell me about what conclusions FDA, CDC and NIAID drew 
from the recent workshop on RU-486 and Clostridial infections. What are 
the next steps? It has been suggested that these unusual infections are 
not connected to the drug, but are instead an ``emerging risk of 
pregnancy.'' What is FDA doing to make that determination?
    Answer 7. In August 2002, three organizations (Concerned Women for 
America, Christian Medical Association and American Association of Pro 
Life OB-GYNs filed a citizens' petition requesting the FDA commissioner 
to stay the approval of Mifeprex ``in light of legal violations and 
important safety concerns'' and pending an audit (proposed by the 
petitioners) ``of all records from the French and American clinical 
trials.'' FDA is still considering the numerous and complex issues 
raised in the citizen petition submitted in August 2002 as well as the 
supplement to the petition submitted in October 2003. Some of the 
concerns raised in the petition have been addressed through recent 
labeling changes and Dear Health Care Practitioner and Dear Emergency 
Room Director letters sent by the sponsor.
    On May 11, 2006, in Atlanta, Georgia, Centers for Disease Control 
and Prevention (CDC), Food and Drug Administration (FDA), and National 
Institutes of Health (NIH) jointly convened a public workshop entitled, 
``Emerging Clostridial Disease.'' The goal of the public workshop was 
to identify research needs and priorities to enable rapid progress in 
understanding the virulence, pathogenesis, host factors and non-
antimicrobial risk factors contributing to reports of morbidity and 
mortality associated with Clostridium difficile (C. difficile) and 
Clostridium sordellii (C. sordellii). The workshop resulted in a draft 
research agenda with recommendations for detecting cases and conducting 
surveillance of diseases and organisms.
    As part of the meeting, it was anticipated that the three 
sponsoring agencies would publish proceedings of the workshop in a 
peer-reviewed medical journal. This is a time-consuming but important 
process that requires the focused participation of a number of 
individuals, and is being worked on at this time.
    As part of the workshop, FDA expected to establish realistic time-
lines for obtaining more knowledge on the pathophysiology and etiology 
of C. sordellii and determining whether regulatory action affecting the 
appropriate use and availability of these drug products is warranted. 
During the workshop, however, it became clear that understanding how 
and under what circumstances C. sordellii leads to clinical illness 
will be a daunting task. Research in this area is scant, and while the 
published cases of women who had recently undergone medical abortions 
are striking in their rapid, virulent course, they remain rare and 
unpredictable. Most importantly, it was clear from the workshop 
presentations that C. sordellii causes rapid and serious clinical 
illness in other settings as well, including among pregnant women who 
have recently undergone spontaneous abortion or term delivery. While 
there has been some speculation that certain immune-altering properties 
of mifepristone are the root cause of the cases reported in association 
with medical abortion, this is based primarily on in vitro data, and 
data to link in vitro properties of the drug to a single dose of the 
drug in humans are sparse. This point was made especially strongly at 
the inter-agency workshop by some of the most knowledgeable researchers 
in the field. It is also well known that pregnancy itself alters immune 
function from very early in gestation. The cases of infection in 
pregnant women who have not undergone medical abortion, as well as 
those who have, support the idea that pregnancy itself may be a 
plausible risk factor for C. sordellii illness.
    At this time, FDA awaits the completion of CDC's study of maternal 
deaths in California as one set of data that may contribute to 
understanding the relative roles of pregnancy, mifepristone, other 
drugs, and other procedures to the occurrence of Clostridium illness. 
Nonetheless, it is unlikely that results from the study will 
definitively point to a specific cause of the infections and illnesses. 
Therefore, we have been and will continue to monitor adverse events 
associated with mifepristone, and will continue evaluating whether the 
labeling for Mifeprex, including the Medication Guide that is required 
to be given to patients, will need to be updated to ensure that 
available safety information is clearly communicated to both healthcare 
providers and patients.
    We offer the following Website as a source for further details on 
the workshop: http://www.fda.gov/cder/meeting/clostridia_disease.htm.

    Question 8. During the last reauthorization of the drug user fee 
law, FDA was instructed to come up with a 5-year strategic plan for 
information technology. In addition, there are numerous efforts across 
the Department of Health and Human Services to move toward 
interoperable platforms and electronic health records. However, we are 
still hearing that the IT infrastructure at FDA may be inadequate to 
meet the Agency's mission. What is the status of the strategic plan? 
Are you meeting the milestones set out under the plan? What resources 
are still needed?
    Answer 8. FDA met all the goals of the PDUFA III 5-year IT 
strategic plan. We established an IT shared services organization, 
developed service level agreements, and implemented a consolidated call 
center, to improve efficiency and effectiveness and provide a one-stop 
shop for some IT services.
    Although the PDUFA III legislation mandated publication of only a 
2003-2007 IT strategic plan, FDA honored the spirit of the legislation 
through a process of continual improvement. We implemented a data 
center consolidation effort to reduce the number of FDA data centers 
from six to the current three and eventually to two, reducing the staff 
and facilities needed to operate our infrastructure. We are in the 
process of a hardware consolidation project, to allow us to move as 
little hardware as possible under the data center consolidation, and to 
retire the oldest hardware to save on maintenance costs. We are also 
using some new software and processes to better manage our IT 
resources.
    FDA also invested in selected portions of its hardware 
infrastructure to accommodate the highest priority initiatives. The 
completed FDA Electronic Submissions Gateway allows for the secure 
submission of regulatory documents over the Internet. HHSMail, one of 
many departmentwide efforts in which FDA participates, is on track to 
provide robust e-mail capability in fiscal year 2007.

    Question 9. There has been a lot of focus lately on the number of 
generic drug applications pending at the Agency. The number that gets 
mentioned a lot is 800 pending applications. My understanding is that 
about a quarter of these are known as Paragraph III certifications, 
which means that FDA couldn't do anything to speed the product to 
market, since the patent hasn't expired yet. Is this correct? If so, 
that reduces the number, but still leaves a large number of 
applications in the queue. Can you tell me what FDA is doing to shrink 
the backlog? A number of blockbuster medications are going to lose 
patent exclusivity over the next couple of years. How will FDA be able 
to speed generic versions of those drugs to market, if it doesn't first 
take care of the backlog?
    Answer 9. It is correct that approximately one fourth of the 
applications in the backlog are paragraph III applications. We should 
also point out that the backlog, as traditionally defined, includes 
ANDAs cycling through our Office of Generic Drugs (OGD) during second 
and subsequent review cycles. In some cases, the applicant does not 
respond to these deficiencies in a timely manner due to their own 
resource limitation and priorities, which contributes to the backlog.
    FDA has taken significant steps to improve our resources. Total 
spending on the Generic Drug Program is $64.6 million, which is more 
than a 66 percent increase from the comparable fiscal year 2001 amount. 
FDA has increased its generic drugs full-time equivalent (FTE) 
positions from 134 in fiscal year 2001 to 201 in fiscal year 2006.
    Last year, FDA added 12 new FTE positions to OGD's staff. These 
individuals, now fully trained, have recently reached the point in 
their learning curve where they are now full contributors to the 
efforts of OGD. In addition, OGD has taken actions to streamline the 
ANDA review process. These actions include adding a third chemistry 
review division and a fifth team in OGD's Division of Bioequivalence. 
Also, a number of new review practices have been implemented to improve 
interactions with generic drug companies. We have begun utilizing 
nonreviewer Project Management staff to take certain actions not 
requiring scientific expertise, thus alleviating the burden of these 
activities on the review staff. OGD has instituted other efficiencies 
to application review.
    Other efficiencies we have implemented include:

     Reviewing Drug Master Files (DMFs) prior to the time the 
related ANDAs are assigned since the DMF evaluation is often the 
limiting factor in completing the ANDA review.
     Utilizing telephone conversations with ANDA sponsors, when 
appropriate, to resolve deficiencies more efficiently and 
expeditiously.
     Assigning applications to reviewers with related expertise 
or experience with a particular drug class.
     Utilizing a new format for the chemistry review called 
question-based review. It is based on the structure of the 
International Conference on Harmonization Common Technical Document for 
the chemistry review.
     Utilizing a team review approach for ``clusters'' of 
applications for the same product.

    Because of these efforts, OGD has been able to issue final 
approvals on most applications when the last applicable patents or 
exclusivities blocking approval expire. If there are no products 
eligible for 180-day exclusivity, OGD has usually been able to approve 
two or more applications for the same product. Recent examples of 
approvals when the patents expired include pravastatin (Provachol); 
sertraline (Zoloft); and simvastatin (Zocor). On July 19, 2006, 
multiple applications for meloxicam (Mobic), a product with no patent 
or exclusivity protection blocking approval, were approved. Using OGD's 
``cluster'' team approach, these applications were approved in just 
over 9 months. These approvals will result in generic products 
available for patients potentially saving millions of dollars in 
medication costs.

    Question 10. In the fiscal year 2007 Budget proposal, there was a 
``strategic redeployment'' of funds within the Agency to address 
priority needs. These funds largely came from the Center for Food 
Safety and Nutrition, a very important part of FDA. I was relieved to 
see that most of these cuts are likely to be restored during the 
appropriations process. I am a strong supporter of wringing 
efficiencies out of the budget, but I am concerned that food safety is 
not considered a high enough priority. This concern was echoed this 
July during a HELP Committee hearing on food uniformity. Could you 
comment on the proposed redeployment and how the Agency will continue 
to support its mission in those areas? Can FDA expand its efforts with 
the resources available?
    Answer 10. The strategic redeployment associated with the 
President's fiscal year 2007 budget will allow the Agency to fund six 
critical high priority initiatives: pandemic preparedness, food 
defense, drug safety, critical path to personalized medicine, human 
tissues and budget authority to ensure we meet the devices and animal 
drug user fee triggers. Food safety is another high priority initiative 
for FDA. The Agency will continue to meet its food safety obligations 
by employing a risk-based approach, which relies on the Agency's 
strategic planning process to focus resources on high-risk public 
health challenges while maintaining our century-old commitment to 
principles that have made FDA the world's ``gold standard'' for 
regulating food and ensuring food safety.

    Question 11. I've heard some people argue that the Prescription 
Drug User Fee Act was a bad idea because the fees co-opt the FDA and 
force the Agency to make hasty or unwise decisions to approve drugs. Do 
you agree with this perspective? Please explain to the committee: (1) 
the importance of PDUFA and the way you will ensure, as Commissioner, 
that (2) there will continue to be no compromise of FDA's standards in 
reviewing products covered by user fees.
    Answer 11. FDA has established and continues to operate under 
stringent criteria for scientific and regulatory review of drug 
products and biologics, no matter the source of funding.
    PDUFA authorized FDA to collect fees from companies that produce 
certain human drug and biological products. Previously, taxpayers alone 
paid for product reviews through budgets provided by Congress. In 
PDUFA, industry provides funding in exchange for FDA agreement to meet 
drug-review performance goals, which emphasize timeliness.
    PDUFA funds allowed FDA to accomplish a number of important goals. 
FDA hired more review and support staff to speed review. The number of 
full-time equivalent (FTE) staff devoted to the new drug review process 
has nearly doubled, growing from 1,277 FTE in 1992 to 2,503 FTE in 
2004. FDA upgraded its data systems and gave industry guidance to help 
minimize unnecessary trials and generally improve drug development. FDA 
gave industry guidance on how to improve the quality of applications, 
with the goal to reduce misunderstandings and the need for sponsors to 
rework and resubmit applications. Finally, FDA improved procedures and 
standards to make review more rigorous, consistent, and predictable.
    Since PDUFA's inception, FDA has met or exceeded all PDUFA NDA and 
BLA review goals. Between 1993 and 2003 the median approval time for 
priority NDAs and BLAs decreased by over half--from 13.2 months in 1993 
to 6.4 months in 2003. Over this same time period the median approval 
time for standard NDAs and BLAs decreased by over one third, from 22.1 
months in 1993 to 13.8 months in 2003.
    Additional PDUFA goals specifically focused on preserving an 
appropriate balance between drug efficacy and drug safety by funding 
safety-related activities for the first 2 years of product marketing 
for most drugs, and the first 3 years for potentially dangerous drugs. 
PDUFA fees also enabled FDA to issue guidance for FDA and industry on 
how best to assess, manage, and monitor drug risk. Additional details 
can be found on our Website: http://www.fda.gov/oc/pdufa/default.htm.

    Question 12. Public health officials, physicians and scientists 
alike are increasingly concerned about the likelihood of a flu 
pandemic. Though not of terrorist origin, a flu pandemic would be a 
biomedical catastrophe that could seriously compromise homeland 
security, through its impact both within and outside this country. 
Vaccines will be the key part of our response to a flu pandemic. 
However, scientific, legal, and economic considerations have led to a 
shrinking domestic vaccine industry. What more can FDA do to prepare 
for a flu pandemic? How could Congress and FDA best work together to 
rebuild our vaccine capacity?
    Answer 12. FDA has worked to streamline the vaccine approval and 
licensing process to encourage new vaccine development and make 
vaccines available sooner. In March 2006, the Agency published two 
draft guidance documents to aid manufacturers in developing vaccines 
for both seasonal and pandemic influenza. The guidances recommend 
specific approaches that vaccine developers can follow to provide 
evidence of the safety and effectiveness of new vaccines. Additionally, 
the guidances provide information on flexible, regulatory pathways for 
getting vaccines to market. One of these pathways is the accelerated 
approval process that can substantially reduce the time for the 
development of a new vaccine. Because these guidances assist 
manufacturers in the development and evaluation of new vaccines for 
seasonal and pandemic influenza, they will help address the increased 
demand for vaccine.
    Having additional manufacturers will enhance the capacity to 
produce more doses of influenza vaccine every year, and contribute to 
the Nation's pandemic preparedness as well as provide better protection 
against failures of single manufacturers. To this end, FDA contacted 
major manufacturers of influenza vaccine throughout the world to 
stimulate interest in producing vaccine for the U.S. market. This 
outreach resulted in one additional vaccine product approval for the 
2005-2006 season, helping to prevent a significant shortage. We 
continue to work with additional manufacturers to encourage them to 
enter the U.S. market, a potentially important step in helping increase 
and diversify the supply of flu vaccine in future flu seasons. For 
example, ID Biomedical of Canada recently submitted a U.S. license 
application for its flu vaccine.
    FDA is also undertaking efforts to facilitate development of 
influenza vaccines using new technologies, including cell-based, and 
other novel types such as DNA and synthetic peptide. The Agency will 
continue to work with Congress to address the critical need for a 
dependable supply of influenza vaccine.

    Question 13. I have heard a lot this year from all sides regarding 
the use of carbon monoxide (CO) in ``case ready'' meat. It seems to me 
this debate hinges on whether CO is a food additive or a color 
fixative. Could you please explain to me the statutory and regulatory 
differences between a food additive and a color fixative, and how FDA 
made the determination that CO is a color fixative?
    Answer 13. One of the issues that has been raised on the use of 
carbon monoxide (CO) in ``case ready'' meat is whether CO should be 
considered a color additive under the statute for this use. This 
distinction is important because, under the statute, the use of a color 
additive is unlawful unless it is subject to pre-market review and 
approval and is listed in the Code of Federal Regulations; there is no 
generally recognized as safe (GRAS) exception from this requirement in 
the case of a color additive as there is for food additives.
    The Federal Food, Drug, and Cosmetic Act defines a color additive, 
in part, as a substance that when added to food ``. . . is capable . . 
. of imparting color thereto.'' During its review of the GRAS 
notifications for the use of CO in modified atmosphere packaging for 
meat, the Agency concluded that the CO did not ``impart'' color, but 
rather maintained the red color of the meat. As a color ``fixative'' 
rather than a color additive, this use of CO may be GRAS, which exempts 
the CO from the requirement for approval and listing by FDA.
    FDA has received a petition stating that the Agency should have 
classified this use of CO as a color additive; the Agency is currently 
reviewing the petition and will respond as soon as possible.

    Question 14. On June 8, 2006, FDA released a final Compliance 
Policy Guide regarding unapproved prescription drugs. Many of the drugs 
that fall under this category have been marketed for many years and 
used in thousands, if not millions, of patients without significant 
safety issues. However, some of these drugs do have safety issues, and 
I am concerned about how FDA's enforcement resources are being 
prioritized. Please describe for me how FDA is prioritizing the 
regulation and enforcement of these drugs.
    Answer 14. FDA takes seriously the threat posed by drugs that have 
not been subject to FDA's rigorous scientific review before being 
provided to patients. Because many of these unapproved drugs have been 
around for a long time, some people presume that these drugs are safe 
and effective. But, unapproved drugs may not be safe and effective, and 
their manufacturing quality and labeling also may not meet modern 
standards necessary to protect public health.
    The final Compliance Policy Guide (CPG) entitled, ``Marketed 
Unapproved Drugs,'' issued by the FDA on June 8, 2006, outlines a risk-
based enforcement approach that is flexible, but firm, and includes the 
identification of illegally marketed drugs, the prioritization of those 
drugs based on their potential to harm the public health, and 
subsequent regulatory followup.
    The guidance articulates FDA's expectation that manufacturers of 
products requiring FDA approval submit new drug applications to FDA to 
show that their products are safe and effective. The guidance also 
outlines the Agency's enforcement policies. As described in the CPG, 
the highest priorities for enforcement action will continue to include 
drugs with potential safety risks, drugs that lack evidence of 
effectiveness, and health fraud drugs. This CPG is available online at: 
http://www.fda.gov/cder/guidance/6911fnl.htm.
    FDA has been focused on addressing the threat of unapproved drugs 
problem as one part of our broader drug safety initiative, announced 
last year, to ensure that patients, consumers, and health-care 
providers have the most up-to-date drug safety information.

    Question 15. FDA regulations permit any interested party to submit 
a citizen petition to the Agency requesting, among other things, the 
FDA to issue, amend or revoke a regulation or to take or refrain from 
taking a particular action. I understand that FDA has been reviewing 
its citizen petition process. However, I am concerned that FDA still 
frequently fails to meet the requirement to respond to citizen 
petitions within 180 days. What is FDA doing to be more responsive to 
citizen petitions? If the use of citizen petitions was limited, as some 
have proposed, wouldn't that also limit the mechanisms through which 
the public can comment on a pending FDA action?
    Answer 15. The Center for Drug Evaluation and Research (CDER) is 
responsible for responding to citizen petitions relating to certain 
drug products, including generic drugs. Within CDER, the Office of 
Regulatory Policy (ORP) has primary responsibility for drafting 
responses to citizen petitions, except for petitions relating to over-
the-counter drug monographs or ``suitability'' petitions (see 21 CFR 
314.93). Recently, CDER has seen a significant increase in petitions. 
For example, ORP saw a 50 percent increase in petitions received in 
calendar year 2004 over calendar year 2003, and in calendar year 2005 
ORP received 65 petitions, nearly the calendar year 2004 total of 70. 
For calendar year 2006, we anticipate a greater increase because ORP 
received 53 petitions as of July 31. This increase includes not only 
citizen petitions relating to Abbreviated New Drug Applications (ANDAs) 
or generic drug applications, which involve the Office of Generic Drugs 
(OGD), but also an increasing number of petitions raising drug safety 
issues handled by other parts of CDER.
    In response to the increase in petitions and an increasing backlog 
of pending petitions, ORP initiated an extensive review of processes 
for responding to petitions. As a result, CDER instituted a number of 
changes, including:

     ORP has been increasing its early interactions with other 
offices to better coordinate responses.
     All parties involved in responding to petitions have 
attempted to increase communications to avoid misunderstandings, wasted 
efforts, or unnecessary delays.
     ORP and the OGD regularly discuss priorities and 
anticipated timetables, so responses can be coordinated with ANDA 
approval actions.

    In addition, OGD has made organizational changes to improve the 
petition response process. OGD has dedicated a group of highly skilled 
scientists to address complex scientific issues related to review of 
ANDAs and citizen petitions. This change is expected to increase the 
consistency, quality and speed of OGD's input on petition responses.
    Although much of the focus on the citizen petition process has been 
on challenges to the approval of generic drugs submitted to the Agency 
in citizen petitions, the Agency also receives scientific and legal 
challenges in correspondence sent directly to OGD and to other offices 
in the Agency, and in submissions to applications. As with citizen 
petitions, if the issues raised relate to the approval requirements for 
an ANDA, the Agency must address the issues raised in the submission to 
determine whether the pending application meets the statutory and 
regulatory requirements for approval.

    Question 16. In December of last year, the FDA announced the 
results of an operation that examined prescription drugs entering our 
borders via personal importation. According to the FDA press release, 
of the parcels that FDA examined that claimed to be Canadian, 85 
percent actually came from 27 countries around the globe. You stated in 
the press release that these results make clear there are Internet 
sites that claim to be Canadian that are in fact peddling drugs of 
dubious origin, safety and efficacy. This seems to coincide with recent 
public statements made by so-called Canadian Internet pharmacies which 
have stated they are filling 50 percent of their prescriptions from 
foreign countries. Can you describe the analysis FDA conducted last 
year of drugs entering our borders and whether you still have concerns 
regarding importation, even if limited only to drugs imported from 
Canada?
    Answer 16. FDA remains concerned about drug importation by American 
consumers. There is no evidence that drugs purchased by consumers 
directly from foreign sources are safe and effective or that these 
drugs have been produced under FDA's current good manufacturing 
practice standards. American consumers often seek out Canadian 
suppliers because they believe them to be reliable. However, we have 
found that many ``Canadian'' sources falsely purport to be Canadian 
and/or many of the drugs purchased are not even of Canadian origin. An 
FDA effort last year (referred to as ``Operation Bait and Switch'') 
confirmed these findings.
    Operation Bait and Switch was designed to examine mail parcels 
imported into the United States containing pharmaceuticals that claim 
to have originated from Canada, and to provide an overall assessment of 
the quality, identity and potency of these pharmaceutical products.
    FDA evaluated the admissibility of the parcel contents coming from 
India, Israel, Costa Rica, and Vanuatu (an island in the South 
Pacific), photographed the parcels and contents, captured the Canadian 
link information (i.e., Website, firm name, province), collected 
samples for analysis, and entered the parcel/product data elements 
(i.e., firm name, product, web address) into FDA's import database.
    Analysis showed that about 43 percent of the parcels were ordered 
from ``Canadian'' Internet pharmacies and were represented as being of 
Canadian origin. However, only 15 percent of these parcels examined 
actually originated in Canada. The remaining 85 percent were 
manufactured in 27 different countries. FDA selected products that met 
the following criteria (based on the ``Orange Book'' approval status of 
each product) and then performed assay and identification testing:

    1. The active ingredient of the drug or drug combination itself was 
unapproved for sale in the United States; or
    2. The dosage strength of the drug was unapproved for sale in the 
United States; or
    3. The drug was approved for sale in the United States, but the 
manufacturer was not an approved manufacturer of the drug.

    In addition to assay and identification testing, frequently 
counterfeited products were analyzed for authenticity. Techniques used 
included visual analysis (macroscopic and microscopic) and chemical 
analysis (impurity/inactive ingredient profiling). Results of the 
sample analyses showed sub-potent, super-potent, and counterfeit drugs.
    Further, even for drugs obtained from a Canadian source, we still 
cannot be certain that the drugs are identical to those approved by the 
FDA; they could in fact be counterfeit. Also, since Canadian drugs are 
not subject to FDA scrutiny and have moved about in a foreign 
distribution system, they could have been stored under improper 
temperatures, or subject to tampering or other interventions that could 
cause them to be unsafe.

    Question 17. With the recent expiration of patents on a handful of 
blockbuster drugs and more coming in the next year, there has been 
greater attention focused on the issue of authorized generics. Some 
studies have shown that there are consumer benefits to authorized 
generics, because they increase competition and can drive down the 
price of drugs. Others have suggested that authorized generics in fact 
create disincentives to entering the market. This issue has gained 
attention from Congress and the Federal Trade Commission has asked for 
public comments on a proposed study.
    As you know, the FDA has in the past denied citizen petitions 
requesting that FDA prohibit the marketing and distribution of 
authorized generics until after the 180-day exclusivity period. This 
decision by FDA has subsequently been upheld by the courts. Can you 
describe FDA's basis for its decision?
    Answer 17. As you know, under the 1984 Hatch-Waxman amendments to 
the Federal Food, Drug, and Cosmetic Act, the first generic drug 
applicant to submit an abbreviated new drug application (ANDA) that 
challenges the validity or applicability of a patent claiming the brand 
name drug is eligible to receive 180 days of marketing exclusivity, 
during which it may be the sole manufacturer to obtain approval of an 
ANDA for a generic version of the brand name drug.
    Citizen petitions filed by two generic drug companies sought, in 
essence, to extend this marketing exclusivity to also prevent 
competition during the 180-day exclusivity period from ``authorized 
generics'' (lower-priced versions of the innovator drug itself, 
marketed by or for that innovator company and marketed pursuant to the 
innovator's approved NDA). Innovator companies are increasingly 
engaging in this type of competition.
    The Agency denied the two petitions because it concluded that, 
although it must refuse to approve any other ANDA for the same generic 
drug during the 180-day exclusivity period, FDA does not have the 
statutory authority to prohibit the marketing of authorized generics, 
because these drugs are marketed subject to the innovator 
manufacturer's approved new drug application (NDA), not pursuant to an 
ANDA. The Courts of Appeals for the District of Columbia Circuit and 
the Fourth Circuit have upheld the Agency's decision.

    Question 18. When it comes to drugs, I have heard the argument that 
children are not mini-adults. In other words, we cannot assume that 
because a medicine behaves one way in the body of an adult, it will 
have a similar effect in a child. I understand that conducting trials 
in children raises a number of ethical issues and scientific 
complexities and the costs for conducting pediatric research is likely 
to climb in the next decade as requirements expand and there is greater 
difficulty in recruiting. However, I do believe we have some success 
stories to tell in this area. Next year, we will reauthorize both the 
Best Pharmaceuticals for Children Act and the Pediatric Research Equity 
Act. Please summarize the status of FDA's activities under these two 
laws.
    Answer 18. As of August 1, 2006, under the exclusivity provisions 
of the Best Pharmaceuticals for Children Act (BPCA) and the Food and 
Drug Administration Modernization Act (FDAMA), FDA has issued 323 
Written Requests and made 135 exclusivity determinations for studies 
submitted in response to the Written Requests. Pediatric studies 
conducted under those provisions have resulted in 114 labeling changes. 
Summaries of study reviews have been posted for 64 drugs. The number of 
exclusivity determinations differs from the number of summaries posted 
because the authority to post the reviews was granted under BPCA, and 
the 135 exclusivity determinations are cumulative since the passage of 
FDAMA. In general about 25 percent of the products that were being used 
in children that were studied under these incentive programs have 
gained new dosing or safety information in addition to data on efficacy 
in a new age group as a result of these pediatric studies. Important 
new information has been developed on antivirals for HIV in the 
neonatal population; drugs for the treatment of cancers in children; 
drugs for the relief of pain resulting from cancer and its treatment, 
as well as from the severe nausea that occurs with chemotherapy; and 
drugs for asthma, a disease that is becoming more prevalent in the 
United States and which can result in sudden acute attacks and possibly 
death in children.
    Following enactment of BPCA, the Office of Pediatric Therapeutics 
(OPT) was established within the Office of the Commissioner. OPT has 
five mandated areas of responsibility: pediatric ethics and 
coordination of Subpart D referrals for public review by the Pediatric 
Ethics subcommittee (PES), safety reviews and reporting to the 
Pediatric Advisory Committee (PAC), agency-wide scientific coordination 
of pediatric issues, external communications with pediatric 
stakeholders and international colleagues, and program management of 
the PAC. One year post-exclusivity adverse event reports have been 
presented on 54 drugs at 9 meetings of the PAC, all coordinated by OPT. 
In addition, there have been 3 Subpart D referrals, 6 meetings of the 
PES and numerous consultations on the ethical conduct of studies in 
children. The ethicist in the Office of Pediatric Therapeutics, a newly 
created position mandated by BPCA, has provided over 80 consults on 
trial design issues and related questions. In addition there were 10 
pediatric scientific issues brought to the PAC for discussion between 
2002-2005.
    FDA has also seen significant improvements in labeling for 
pediatric populations due to studies conducted under the Pediatric 
Research Equity Act (PREA). Preliminary numbers indicate that, for 
applications that were submitted to CDER since April 1, 1999, 286 
applicants have fulfilled their pediatric studies requirements under 
PREA. CDER has granted 570 waivers of pediatric studies and 429 
deferrals of pediatric studies pursuant to PREA provisions. We are now 
in the process of compiling labeling changes that resulted from PREA 
studies and expect to be able to publicly post these labeling changes 
to the pediatric Website by the end of this year. The Center for 
Biologics Evaluation and Research (CBER) had 16 approved Biologics 
License Applications (BLA) and Biologics License Supplements (BLS) 
submissions received from April 1, 1999 through August 21, 2006 which 
included the complete required pediatric studies. Since April 1, 1999, 
CBER has granted 24 deferrals and 5 waivers.

    Question 19. This past January, voluntary principles on direct-to-
consumer (DTC) advertising went into effect. In addition, FDA has 
stated that ads are doing a better job weaving together discussions of 
risks and benefits. I believe responsible direct to consumer 
advertising should inform and educate patients about treatable 
conditions and available therapies. I think things are getting better, 
but I am still concerned that all too often, product sponsors do not 
use DTC advertising to help raise disease awareness, facilitate more 
informed and more meaningful discussions between physicians and 
patients, or educate patients about various treatment options and the 
risks associated with those options.
    Do you generally believe in the merits of DTC advertising and in 
its role in educating and empowering patients? Are you encouraged by 
the direction these ads seem to be heading in recent months? How can we 
ensure consumers get the best of DTC advertising?
    Answer 19. We believe direct-to-consumer (DTC) advertisements can 
play an important role in advancing the public health by encouraging 
consumers to seek treatment for diseases that may be under-treated and 
diseases for which consumers may not be aware treatment options exist. 
We continue to monitor the impact of consumer-directed promotion on the 
public health.
    Following the implementation of ``PhRMA's Guiding Principles on 
Direct to Consumer Advertisements about Prescription Medicines'' in 
January 2006, FDA reviewers of DTC ads are encouraged by improvements 
in some consumer-directed advertisements. Some companies are making an 
effort to more fully integrate risk messages into ads and to work to 
achieve a tone that does not minimize the serious nature of 
prescription drugs. We believe the principles issued by the 
Pharmaceutical Research and Manufacturers of America (PhRMA) are a 
positive development, and we are pleased that PhRMA is taking steps to 
address several of the problems associated with DTC advertising. We 
agree with the concepts in PhRMA's principles that: DTC promotion 
should truthfully and accurately convey the benefit and risk 
information about products; PhRMA's member companies should fully 
comply with the applicable laws and regulations; DTC ads should respect 
the seriousness of the advertised medical condition and the importance 
of the relationship between the patient and healthcare provider; and 
companies should be encouraged to promote disease and health awareness 
as part of their DTC advertising. In our opinion, however, it is too 
soon to tell whether there has been a real and lasting shift in the DTC 
environment.
    The Agency believes that consumers can receive the best information 
from DTC advertising when companies comply with FDA's regulations and 
promotion is accurate, nonmisleading, and presents a fair balance of 
information about the benefits and the risks of the product. It is very 
important that companies present information in clear, understandable 
and nontechnical language. Efforts by pharmaceutical companies to 
promote disease and health awareness are very important, particularly 
for conditions that are under-diagnosed and under-treated in the 
population.

    Question 20a. In recent weeks, I have been contacted by Rebecca 
Painter, a capable and respected physician from my home town of 
Gillette, and by numerous Wyoming patients regarding mercury in dental 
amalgam. My conversations with her have raised a number of questions.
    FDA allows devices on the market either by the manufacturer 
demonstrating safety and efficacy (a ``pre-market approval'' 
application, or PMA) or by a truncated method (a ``pre-market 
notification,'' also known as a 510(k)). For dental amalgam, FDA used 
the latter system. Can you explain the basis for FDA's decision to 
allow marketing of dental amalgam under the 510(k) process? What was 
the ``predicate device'' used for dental amalgam?
    Answer 20a. The medical device provisions of the Food, Drug, and 
Cosmetic Act have two systems to allow for marketing of medical 
devices, the pre-market approval system and the pre-market notification 
system. PMA devices are almost always devices classified into Class 
III; they often involve new concepts and many are not of a type 
marketed prior to the 1976 Medical Device Amendments. A 510(k) is a 
pre-marketing submission made to FDA to demonstrate that the device to 
be marketed is as safe and effective, that is, substantially equivalent 
(SE), to a legally marketed device that is not subject to pre-market 
approval (PMA). Applicants must compare their 510(k) device to one or 
more similar devices currently on the U.S. market and make and support 
their substantial equivalency claims. A legally marketed device is a 
device that was legally marketed prior to May 28, 1976 (pre-amendments 
device), or a device which has been reclassified from Class III to 
Class II or I, a device which has been found to be substantially 
equivalent to such a device through the 510(k) process, or one 
established through the ``de novo'' process, which allows down 
classification of devices automatically classified into class III. The 
legally marketed device(s) to which equivalence is drawn is known as 
the ``predicate'' device(s). Dental amalgam devices are pre-amendments 
devices, that is, they were on the market prior to 1976 when the 
medical device amendments were instituted. In addition the Dental 
Products classification panel that met between 1976 and 1978 classified 
dental amalgam devices. Dental Mercury was classified as class I and 
amalgam alloy was classified as class II.

    Question 20b. A Zogby poll in 2006 indicated that less than one in 
four Americans can identify mercury as the main component of dental 
amalgam. This may be due in part to its nickname, ``silver fillings.'' 
What does FDA do to help consumers understand the composition of dental 
amalgam so they can make an informed choice?
    Answer 20b. In our February 20, 2002 proposed reclassification of 
dental amalgam devices we proposed ingredient labeling, such that all 
components would be listed on the device. This would be very different 
from other medical devices, in that ingredient labeling is not required 
by law or regulation. Although the reclassification has not been 
finalized, there is a Consumer Update on our FDA/CDRH Website http://
www.fda.gov/cdrh/consumer/amalgams.html.

    Question 20c. Most people would probably want to reduce their 
mercury exposure, and there are a number of ways to work toward this. 
Manufacturers of many mercury-containing products are voluntarily 
reformulating their products to use a nonmercury-based preservative. 
FDA has taken action regarding some products containing mercury. For 
example, in 1998, it banned mercury in wound disinfectants, such as 
Mercurochrome. Finally, other countries are also acting. Health Canada 
has recommended against pregnant women and children receiving fillings 
with mercury-containing dental amalgam. Does FDA have any plans to make 
a similar recommendation? If not, why not?
    Answer 20c. FDA has based its regulation of dental amalgam products 
on scientific reviews of the literature in 1993, 1997 and other peer-
reviewed literature. None of these reviews of the literature have found 
studies showing that adverse health effects occur as a result of dental 
amalgam restoration use, except potentially in individuals with 
allergic reactions to mercury. We have also compared estimated mercury 
exposures from dental amalgam restorations to health-based comparison 
values established by EPA and ATSDR which explicitly consider sensitive 
populations such as women and children. These comparisons also do not 
indicate that adverse health effects are likely as a result of dental 
amalgam restoration use. We continue to look at the literature to 
determine if there is additional information that would cause us to 
change our view. We will again in September 2006, during a joint CDER 
Neurology panel and CDRH Dental panel meeting, look at the peer-
reviewed scientific literature relevant to consideration of health 
effects for dental amalgam restoration use. Any new information that 
has been published since 1997 will be discussed at this meeting.

    Question 20d. In September, FDA will host a joint committee meeting 
to, quoting from your announcement, ``review and discuss peer-reviewed 
scientific literature on dental amalgam and potential mercury toxicity, 
specifically as it relates to neurotoxic effects.'' I believe this is 
the first time FDA has held such a hearing, and I commend you for your 
leadership on this issue. The general function of this joint committee 
is listed as ``to provide advice and recommendations to the agency . . 
.'', but the agenda simply lists review and discussion of scientific 
literature. Will the joint committee be specifically charged with 
making recommendations? If they make recommendations, will you carry 
out those recommendations?
    Answer 20d. We do have a panel meeting scheduled in September 2006 
to discuss this topic. However, this is not the first time that FDA has 
held such a meeting. In 1993-1994, the Dental Products panel also 
discussed the regulation of dental amalgam, and we received 
classification recommendations from that panel. The September panel 
will be asked to answer specific questions concerning any possible 
adverse health effects of dental amalgam. The proceedings and 
recommendations of the panel will be considered by FDA in our 
regulation of dental amalgam devices.

    Question 21. In October 2005, FDA proposed an additional rule to 
prohibit certain high-risk material from all animal feeds and pet 
foods. What is the status of this regulation?
    Answer 21. FDA has considered approximately 800 public comments 
submitted in response to the October 2005 proposed rule. FDA has 
completed its analysis of these comments, and significant progress has 
been made in drafting the final rule. A number of comments dealt with 
the economic costs and potential environmental consequences of the 
proposal and noted that FDA had not adequately considered these 
impacts. The new information has caused FDA to reconsider the 
underlying assumptions on which the economic and environmental impacts 
were based in the proposed rule. As a result, we are currently 
completing a detailed re-analysis of the economic and environmental 
impacts of the proposal in light of the comments and other new 
information that has become available. Though this re-analysis has 
caused some delay, FDA plans to develop and issue a final rule as 
expeditiously as possible.

    Question 22. Among the Agency's priorities last year was writing 
and issuing a draft regulation clarifying the Agency's policies on the 
conditions that apply when a drug company wants to make its promising 
investigational drugs available to dying and seriously ill patients. 
These programs are sometimes called compassionate use or expanded 
access programs. There is also a pending Citizen Petition on reform of 
these programs. Patients dying from terminal diseases think this 
regulation should be among the FDA's highest priorities. What is the 
status of this regulation and when will the draft regulation be 
published in the Federal Register?
    Answer 22. Publication of rules on expanded access to 
investigational drugs (Expanded Access to Investigational Drugs and 
Treatment Use and Charging for Investigational Drugs) remains a very 
high FDA priority. As is our longstanding policy, we are unable to 
comment publicly on the specific clearance status of rules. Moreover, 
it is quite difficult to predict publication dates due to multiple 
steps in the review process. It is also too early for us to accurately 
revise the publication date estimate for these rules that will appear 
in the next Semi-annual Regulatory Agenda to be published this fall. As 
noted, FDA continues to treat these important rules with the highest 
priority, and remains committed to their publication at the earliest 
possible time. I also want to stress that even as we work on these 
clarifying rules, there are expanded access programs in place to 
provide access to needed drugs for persons with serious and life-
threatening diseases.

    Question 23. Some electronic products are regulated by both FDA and 
OSHA. Please tell me about how you work with OSHA to establish uniform 
standards for these products, eliminate duplication of regulatory 
efforts, and maximize resources used to assure compliance.
    Answer 23. FDA and OSHA avoid duplication of regulatory efforts 
because they regulate different aspects of the same products. FDA 
regulates the manufacturers of electronic products. Under authority of 
Sections 531-542 of the Federal Food, Drug, and Cosmetic Act, FDA 
promulgates and administers radiation safety performance standards for 
electronic products that generate ionizing, nonionizing, sonic, or 
particulate radiation. The FDA standards recognize that some electronic 
products may emit hazardous radiations that are necessary for their 
intended functions, and require controls, indicators, and warnings 
appropriate to the level of the hazard. OSHA regulates employers and 
evaluates their control measures in place to protect workers using or 
near the products. For example, for laser products, the FDA enforces 
the laser product radiation safety performance standard at 21 CFR Part 
1040, and OSHA uses the ANSI Z136 series (American National Standards 
for the Safe Use of Lasers) of user standards as the basis for its 
determinations.
    FDA and OSHA also work together to write Federal guidance and 
voluntary radiation safety consensus standards for electronic products. 
Current projects include:

     An Interagency Steering Committee on Radiation Standards 
(ISCORS) work group drafting ``Guidance for Security Screening of 
Humans Utilizing Ionizing Radiation'';
     An American National Standards Institute (ANSI) work group 
updating N43.17 Radiation Safety of Personnel Security Screening 
Systems; and
     An ANSI work group drafting N43.16 Radiation Safety for X 
and Gamma Radiation Security Inspection Systems.

    Question 24. In December 1999, FDA published regulations 
implementing provisions of the Prescription Drug Marketing Act (PDMA) 
regarding the wholesale distribution of drugs that set forth 
requirements regarding pedigrees. The FDA has stayed that regulation a 
number of times. Earlier this year, FDA announced that the stay would 
be lifted, and the regulation would go into effect on December 1, 2006. 
Given what we have heard about counterfeiting and diversion of 
pharmaceuticals, I am very pleased that the Agency is moving forward on 
this. However, I am concerned that simply lifting the stay may not 
really solve the problem. This regulation does not fully take into 
account new technologies, such as RF-ID, and was written in a pre-9/11 
world. Can you tell me more about how FDA will implement this 
regulation in a modern, effective way?
    Answer 24. In February 2004, FDA delayed the effective date of 
certain provisions of regulations that implement the PDMA's pedigree 
requirements (21 C.F.R. Sec. Sec. 203.3 (u) and 203.50) for the 
distribution of drugs until December 1, 2006, in part, because we were 
informed by stakeholders in the U.S. drug supply chain that the 
industry would voluntarily implement electronic track and trace 
technology by 2007. If widely adopted, this technology could create a 
de facto electronic pedigree that would document the sale of a drug 
product from the place of manufacture through the U.S. drug supply 
chain to the final dispenser. Although, progress has been made, it 
appears that the use of electronic track and trace technology, 
including RFID, will not be widely adopted by 2007. The issue of 
developing technologies was explored at FDA's public workshop in 
February 2006.
    Following the public workshop, FDA announced in June 2006 that it 
did not intend to further delay the effective date of 
Sec. Sec. 203.3(u) and 203.50 beyond December 1, 2006, and that the 
stayed regulations will go into effect on that date. At the same time, 
FDA issued a draft Compliance Policy Guide to clarify for FDA personnel 
and the regulated industry how the Agency intends to prioritize its 
enforcement efforts during the next year regarding the pedigree 
requirements. Given the absence of widespread implementation of 
electronic pedigree technology to date and the continuing threat to 
public health as described in the FDA Counterfeit Drug Task Force 
Report: 2006 Update, the Agency determined that lifting the stay is the 
best method of protecting the public health and meeting the mandates of 
the PDMA. The Agency is hopeful that the implementation of these 
regulations may spur the development and adoption of electronic track 
and trace technologies.
    Furthermore, FDA has received a number of questions from 
stakeholders about complying with the regulations and is working on a 
document to address these questions. We believe that this document may 
address your implementation concerns as well.
  Response to Questions of Senator Kennedy by Andrew C. von Eschenbach
    Question 1a. Could you please describe the ``enforcement 
considerations'' referred to in your July 31 letter that warrant 
allowing Plan B over-the-counter status only for women 18 and older, 
and not 16 and older, or 17 and older?
    Answer 1. In considering the difficulty of enforcing an age-based 
restriction on the availability of this oral hormonal contraceptive, I 
have concluded that 18 (rather than 17) is the more appropriate cutoff 
to best promote and protect the public health. The state-regulated 
pharmacies that will be dispensing Plan B under Barr's voluntary 
Convenient Access, Responsible Education (CARE) program are accustomed 
to the age 18 as a cutoff age for access to restricted products. I 
understand that in all 50 states, 18 is the age of majority (i.e., the 
legal delineation between minor and adult), and retail outlets, 
including pharmacies, are familiar with using 18 as the age of 
restriction for the sale of certain products. With regard to drug 
products, for example, the legal age to purchase FDA approved non-
prescription nicotine replacement therapy products is 18. Moreover, I 
understand that as a matter of State law, many products routinely sold 
by pharmacies, e.g., tobacco products and nonprescription cough-cold 
products like pseudoephedrine are restricted to consumers 18 and older. 
The approach builds on well-established State and private sector 
infrastructures to restrict certain products to consumers 18 and older.

    Question 1b. Could you also please point to those portions of the 
summary of the comments on the Advanced Notice of Proposed Rulemaking 
in which this age limit is discussed?
    Answer 1b. The Advanced Notice of Proposed Rulemaking (ANPRM) which 
published on September 1, 2005 included a section titled ``Agency 
Request for Information.'' Question 2 of the ANPRM asked for comments 
on limiting sales of an over-the-counter (OTC) product to a particular 
subpopulation. This question generated comments which addressed various 
age subpopulations.
    The issue outline developed to assist in categorizing and 
summarizing the ANPRM comments broke Question 2 down into several 
areas. The two main issue areas were identified as: (1) ``If FDA 
Limited Sale of OTC Product to Sub-population, Would FDA be Able to 
Enforce Limitation as a Matter of Law?'' and (2) ``Would FDA be Able to 
Enforce Limitation to Sub-population as a Practical Matter?'' These two 
questions were further divided into sub-issue areas to categorize 
comments that provided legal or policy arguments and the actions FDA 
could or could not take to enforce a specific limitation to a 
particular subpopulation. Included in the comments to the ANPRM were 
comments that discussed age limits.

    Question 2. Your July 31 Plan B letter also indicates that to get 
Plan B approved OTC for women 18 and over, the manufacturer needs a 
plan that is ``sufficiently rigorous'' and that will ``prevent'' 
younger women from getting the drug without a prescription.
    I don't believe restrictions on distribution for other drugs are 
expected to ``prevent'' safety concerns presented by the drug. Rather, 
I think the idea has been to reduce and minimize risks. Moreover, the 
limitations are supposed to be commensurate with the specific safety 
concerns presented by the drug.
    Please compare what you are looking for with what is required for 
other drugs with restrictions on distribution and use. In addition, 
what are the specific safety concerns presented by Plan B, and compare 
them to the safety concerns with other drugs with restrictions on 
distribution and use.
    Answer 2. On August 24, 2006, FDA approved Plan B over-the-counter 
for those ages 18 and older. This approval was based upon the sponsor's 
submission of a proposed educational program (Convenient Access 
Responsible Education Program, CARESM with the following elements: (1) 
labeling, packaging, Website, and informational 24-hour toll-free 
number, (2) education initiatives for healthcare providers, 
pharmacists, and consumers, (3) distribution plans, and (4) monitoring 
efforts to assess whether the Rx/OTC age distinction is understood and 
adhered to. We concluded that the CARESM program is sufficiently 
rigorous to prevent young women from obtaining Plan B over-the-counter 
without the supervision of a practitioner licensed by law to prescribe 
the drug. We believe that the limitations described in the CARE program 
are commensurate with the specific concerns presented by Plan B, and 
are no more rigorous or burdensome than have been proposed by other 
sponsors for other drugs approved by FDA with restricted distribution.

    Question 3. I am very concerned by the Union of Concerned 
Scientists survey of FDA scientists. About 150 FDA scientists said 
their superiors asked them to inappropriately exclude or alter 
technical information or their conclusions. About 170 FDA scientists 
said FDA decisionmakers asked them to provide incomplete, inaccurate, 
or misleading information to the public, industry, the press, or 
government officials. About 360 scientists don't believe they can 
express concerns about public health even within the Agency without 
fear of retaliation.
    You spoke at the hearing about your commitment to make decisions 
based on science. Please describe the specific steps you would take, if 
confirmed as Commissioner, to see that scientific judgments at FDA are 
not clouded by politics. Do you have a plan to ensure that FDA 
leadership and management value and respect Agency scientists, and will 
not suppress their views? What will you do to identify and reprimand 
managers who compel certain answers or suppress scientific dissent?
    Answer 3. I am committed to ensuring FDA makes decisions based on 
sound science and will make myself personally available to staff who 
want to appeal decisions made by FDA management. I believe that the 
need to appeal to me will be rare, however, because I will ensure that 
there are strong policies and procedures in place for resolving issues 
involving dissenting opinions. Efforts toward that end will include 
promulgating new policies and procedures as necessary, and 
strengthening, by process improvement and best practices measures, many 
of those that are already in place.
    For example, we are working to ensure a rigorous ombudsman program 
through which staff are welcome to promulgate dissenting opinions. 
Staff may also invoke standard written procedures for facilitating and 
resolving differing professional opinions. In addition, Under the 
Secretary's leadership, FDA established a Drug Safety Oversight Board 
whose charter includes responsibility for deliberating on any 
dissenting opinions raised during evaluation of drug applications and 
surveillance of marketed products. Through these and other traditional 
management techniques, I believe we will successfully address any 
dissenting opinions, and I am committed to evaluating our processes and 
refining them as necessary to ensure that there is a healthy, open, 
unsuppressed scientific debate of issues at FDA.

    Question 4. Representative Henry Waxman issued a report in June 
about the 50 percent decline in the number of enforcement actions since 
2000. In one example, Agency headquarters declined to bring a criminal 
prosecution when the error of a medical gas company killed 4 nursing 
home patients in Ohio, and injured 6 others. In another example, FDA 
headquarters rejected taking action when errors by a blood bank 
resulted in 1 death and other patients receiving the wrong products.
    Have you reviewed Mr. Waxman's report yourself? Do you believe the 
decline in enforcement actions is defensible? What is your reaction to 
each of the examples cited above? Can you assure this committee and the 
American public that you will vigorously enforce FDA's laws and 
regulations?
    Answer 4. I have reviewed Mr. Waxman's report with serious concern, 
but I believe FDA enforcement cannot be properly judged merely by 
counting the number of actions taken by the Agency. Because FDA has 
increasingly used an enforcement strategy based on efficient risk 
management principles that focuses on combating the greatest public 
health risks and maximizing deterrent effect against potential 
violators, FDA's focus is on those firms and those violations that 
present the highest risk to consumers and public health. The Agency has 
taken prompt, targeted and aggressive action against firms that are in 
violation of law; thus the number may have decreased, but the impact 
factor has increased, with positive deterrent effects on industry.
    Notably, over the past few years FDA has won a string of legal 
actions against firms in violation of the law. These include 
settlements and penalties against a broad spectrum of violators. 
Criminal fines and equitable monetary payments including restitution 
and disgorgement resulting from FDA's enforcement actions alone since 
fiscal year 2000 have amounted to more than $2.5 billion--a figure that 
exceeds the Agency's annual budget. Recent years have also seen record 
individual FDA enforcement actions, including a case against a major 
pharmaceutical company in 2002 that resulted in a $500 million civil 
fine, the largest in agency history. In 2005, FDA enforcement efforts 
against another pharmaceutical company resulted in the largest seizure 
in FDA history--a seizure of nearly $600 million worth of goods.
    The deterrent effect of these and other targeted actions can be 
seen in a number of ways including a small but steady decline since 
fiscal year 2000 in the rate of serious violations encountered in FDA 
inspections of regulated firms. The Agency is constantly working to 
improve its enforcement efforts by improving its management of 
enforcement activities and by bringing state-of-the-art science and 
risk-based management principles to our enforcement work.
    Please allow me to address the specific incidents referenced in 
your question. In the medical gas case, FDA did not expend its 
enforcement resources on exacting punishment, but instead focused on 
trying to prevent further medical gas mix-up tragedies. FDA undertook a 
number of creative and meaningful steps including issuance of a 
guidance document, information sheet, and educational video for 
hospitals and other health care facilities on how to prevent medical 
gas mix-ups, creation of a widely-circulated poster (with the slogan, 
``if it won't connect, don't connect'') combating a common cause of 
medical gas mix-ups, and work with industry to set standards for 
medical gas fittings that make it significantly more difficult for 
someone to accidentally connect the wrong medical gas to a gas supply 
system. In other words, although it did not pursue this particular 
single prosecution, FDA did proactively launch a number of measures 
that have resulted in a very positive public health outcome: since the 
Ohio incident to which you refer, there have been no more deaths from 
mix-ups of large cryogenic containers of medical gases.
    In the blood bank incident, it is important to note that the 
Centers for Medicare and Medicaid Services (CMS) and FDA regularly 
collaborate when there are blood-related fatalities. This occurred in 
the referenced incident, where problems were identified on both the 
manufacturing and transfusion ends of the process. In this case, CMS 
did an inspection and took action against both the manufacturing and 
transfusion operations by limiting CLIA accreditation and suspending 
Medicare participation until corrections were made. In addition, a 
$10,000 Civil Money Penalty was imposed for errors that led to the 
fatality and $3,050 was imposed for two errors, one in 2001 and one in 
early 2004, that resulted in the wrong units being transfused without 
adverse health consequences. Here, when FDA considered issuing a 
warning letter, the establishment had already implemented corrective 
action that would have been sought in such a letter. You should note 
that prior to the incident to which you refer, the facility had been 
subject to routine inspections by FDA.
    Finally, in reference to the last part of your question, I welcome 
this opportunity to assure the committee and the American people that I 
will vigorously enforce FDA's laws and regulations. As I stated in my 
prepared testimony to the committee, I cherish the trust of patients 
and the public and want to convey that I am committed to using FDA's 
laws and regulations to make sure that each action, decision or 
activity taken by the Agency is directed to preserving their lives and 
protecting their health.

    Question 5. As you know, Chairman Enzi and I are working on a drug 
safety bill, and of course there are a number of important 
reauthorizations for us to complete next year, including the drug and 
device user fee programs and the pediatric drug provisions. Are you 
committed to working with this committee to get these bills done and 
implemented promptly and appropriately?
    Answer 5. I am committed to working closely with Congress to 
reauthorize these critically important programs.

    Question 6. I am very concerned about the effect of the tight 
budget on the FDA. This year's budget directed funds away from 
important programs, especially in the food center. I fear it will only 
be worse next year.
    At the same time, FDA's product review programs are relying 
increasingly on user fees because appropriations have not kept pace 
with FDA's needs. I think appropriated funds are the first choice to 
fund the Agency, yet to address a real and critical funding shortfall, 
it seems FDA must turn increasingly to user fees.
    As Commissioner, what will you yourself do to assure that FDA's 
appropriations are sufficient to meet its needs and accomplish its 
public health goals? What will you do specifically at each level, at 
the Department, at OMB, and at Congress? If cuts in appropriations are 
made, how will you meet the Agency's public health goals in each 
product area: foods and dietary supplements, drugs, biologics, medical 
devices, electronic products?
    Answer 6. When I was appointed Acting Commissioner in September 
2005, one of my first priorities was to develop a fiscal year 2007 
budget proposal for FDA that meets the Agency's needs and advance the 
proposed budget through the Administration and congressional approval 
processes. These efforts resulted in proposed increases in the 
President's fiscal year 2007 budget to address a number of high 
priority public health concerns. The proposed increases include 
pandemic preparedness, food defense, critical path, drug safety, tissue 
safety, funding to meet user fee triggers, pay increases for cost of 
living, and increases to support our essential infrastructure needs. In 
the months since the President released the fiscal year 2007 budget, I 
have been working personally and directly with the members of the House 
and Senate Appropriations Committees and others in Congress to secure 
these important funding increases.

    Question 7. In 1996, after 2 years of assessment and consultation 
with scientists and governments both within Canada and abroad, Health 
Canada released a position statement on dental amalgam ``The Safety of 
Dental Amalgam'' to all Canadian dentists and doctors. (http://www.hc-
sc.gc.ca/english/media/releases/1996/96_63e.htm)
    Health Canada stated that current evidence does not indicate that 
dental amalgam is causing illness in the general population. It also 
stated that a ban is not justified, and neither is the removal of 
existing sound amalgam fillings.
    Health Canada recommended that dental amalgam not be used in people 
allergic to mercury, those with impaired kidney function, or in contact 
with existing metal devices, such as braces. Health Canada also 
recommended that, whenever possible, amalgam fillings should not be 
placed in or removed from the teeth of pregnant women and that 
alternatives should be considered for use in the primary teeth of 
children. Health Canada also made a number of recommendations to 
dentists about technique and handling of dental amalgam. Health Canada 
emphasized that dentists should be providing their patients with 
sufficient information to make an informed choice regarding the 
material used to fill their teeth.
    Do you agree with the Health Canada statement? Do you agree with 
the recommendations from Health Canada? If so, please explain how the 
Agency intends to communicate these recommendations to both dentists 
and patients.
    Answer 7. In our 2002 proposed reclassification of dental amalgam, 
the Agency recommended that dental amalgam devices have ingredient 
labeling. This same document also discusses appropriate handling of 
dental amalgam. FDA has looked at the literature on the potential 
toxicity of dental amalgam systematically over the years along with our 
colleagues from the Centers for Disease Control and National Institute 
for Dental and Craniofacial Research. All of our reviews have indicated 
that FDA's position on labeling is supported in the literature. That 
is, no warnings are recommended on amalgam devices against use in 
pregnant women or children. FDA continues to regularly review any new 
data on these topics that might alter our view.

    Question 8. When clearing or approving a device, FDA must consider 
risks vs. benefits. Please discuss the risks of dental amalgam, which 
contains mercury, as compared to its benefits, especially considering 
the availability of cavity-filling alternatives, such as resin.
    Answer 8. Dentists today have numerous materials from which to 
select when restoring teeth, including amalgam, composite (resin), 
glass ionomer cement, gold foil, cast metals, ceramics, and 
metalceramics. Specific clinical situations, however, dictate a much 
narrower range of appropriate restoration options.
    The clinical decision as to which restorative material to place is 
complex, involving factors relating to the tooth, the patient, the 
clinician, and the properties of the restorative materials. Individual 
restorative materials ideally are applied in a defined set of clinical 
circumstances, and it is not possible to freely substitute one material 
for another and expect long-term success.
    For much of the last century it was believed that dental caries 
could be treated away with restorations (Anusavice, 1989). Clearly, 
this is not the case. The long-term consequences of the insertion of 
the first restoration in any tooth always must be a consideration in 
the treatment decision (Lutz et al., 1987). Dental restorations have a 
limited clinical durability. As restorations need replacement, an 
increasing amount of tooth structure is lost and the patient may enter 
into a repetitive restorative cycle with larger restorations, weaker 
teeth, and more complex therapy (Elderton and Davies, 1984). Indeed, it 
has been estimated that as many as two-thirds of restorations placed 
each year are replacements for existing restorations (Maryniuk and 
Kaplan, 1986). As the cavity size expands, the range of restorative 
materials to effectively employ becomes limited, and the option of 
appropriately placing a more economical direct restorative material 
that conserves tooth structure is lost.
    There are potential risks and benefits from any restorative 
material. For dental amalgam:

                            potential risks
     Exposure to minute amounts of elemental mercury
     A small proportion of individuals may manifest allergic 
reactions to amalgam.
                                benefits
     Dental amalgam is durable.
     It is least technique sensitive of all restorative 
materials.
     It is applicable to a broad range of clinical situations.
     It is long lasting.
     It often can be repaired.
     Many restorations are replacements. Most of these will 
require amalgam or other metallic materials, because composite 
materials often lack sufficient strength or durability to be considered 
adequate substitutes.

    Question 9. I understand dental amalgam is the largest source of 
mercury in wastewater and, in some communities, the largest source of 
mercury in the air (due to cremation). Please discuss the Agency's 
obligations under the National Environmental Policy Act, section 746 of 
the Federal Food, Drug, and Cosmetic Act, and the Agency's implementing 
regulations to consider the environmental impact of the use of dental 
amalgam.
    Answer 9. As with other FDA classification regulations, the Agency 
included an environmental impact section in the classification rule. 
This section noted that FDA had determined under 21 CFR 25.34(b) that 
its classification of the devices is of a type of action that does not 
individually or cumulatively have a significant effect on the 
environment and therefore, under the National Environmental Policy Act, 
neither an environmental assessment nor an environmental impact 
statement was required. FDA is evaluating all comments on the proposed 
rule and in this context will consider the treatment of this issue 
under NEPA.

    Question 10. I understand that the FDA clears dental amalgam 
capsule using a pre-market notification under section 510(k) of the 
Federal Food, Drug, and Cosmetic Act, as ``substantially equivalent'' 
to a non-mercury powder alloy. Please explain the Agency's 
determination that dental amalgam capsule is substantially equivalent 
to a non-mercury powder alloy. In particular, it would seem that dental 
amalgam would ``raise different questions of safety and effectiveness'' 
than a nonmercury product.
    Answer 10. All three dental amalgam devices (dental mercury, 
amalgam alloy and encapsulated amalgam) are pre-amendments devices, 
i.e., they were legally on the market prior to enactment of the 1976 
Medical Device Amendments. Similar products to be marketed for the 
first time after 1976 require the submission of a pre-market 
notification (510(k)) and a substantial equivalence determination to 
these three pre-amendments devices (containing mercury) before they can 
be marketed. Dental mercury (class I) and amalgam alloy (class II) when 
sold separately are intended to be mixed together to form the dental 
amalgam device. Encapsulated amalgam is a device that contains dental 
mercury and amalgam alloy separated via a septum in the capsule. It is 
therefore a combination of the class I and class II devices. When two 
regulated devices are sold together they are generally regulated at the 
higher class, in this case, class II. We have not cleared the dental 
amalgam devices as substantially equivalent to non-mercury powder 
alloy.

    Question 11. I understand that FDA is holding an advisory committee 
meeting in September on the neuro-toxicity of dental amalgam. I believe 
such a meeting would be required to be ``balanced,'' yet there are 
allegations that FDA has chosen as members only those who favor FDA 
policies on dental amalgam. Please explain.
    Answer 11. The assembled advisory panel consists of CDRH's Dental 
Products Panel and CDER's Peripheral and Central Nervous System Drugs 
Advisory Committee. The combined expertise of these two panels will 
facilitate and enhance a discussion of the peer reviewed literature on 
dental amalgam and any adverse health effects. We believe that the 
panel consists of scientists who clearly will be able to discuss with 
intellectual honesty the material presented to them from the 
literature. We feel that the expansion of the panels' expertise to 
include neurologists and toxicologists will only benefit and balance 
this process.

    Question 12. Do you support legislation amending the Federal Food, 
Drug, and Cosmetic Act to give FDA the authority to review and approve 
genetically engineered crops before they are marketed to the public? 
Currently, FDA requests that industry voluntarily submit information on 
such products, but it has not required companies to do so. Moreover, it 
appears that FDA would have to start from scratch having no information 
and be required to prove that such a product was unsafe if a company 
refused to comply voluntarily. Why is a voluntary system sufficient to 
protect the public health and address the environmental concerns?
    Answer 12. We believe that our current system is the appropriate 
approach to the oversight of bioengineered foods. As noted in a 2004 
report on genetically-engineered foods from the National Academy of 
Sciences (Safety of Genetically Engineered Foods Approaches to 
Assessing Unintended Health Effects), a policy to assess products based 
exclusively on their method of development is scientifically 
unjustified. We believe our current authority under the Federal Food, 
Drug, and Cosmetic Act (the act) is sufficient to oversee the safety of 
bioengineered foods. Under the act, we have authority to require pre-
market review and approval of a substance introduced into food unless 
its use is generally recognized as safe (GRAS). We also have broad 
authority to take action against a food if it bears or contains any 
poisonous or deleterious substance that may render it injurious to 
health, such as increased levels of a naturally-occurring toxicant. Our 
consultation process provides us and developers of bioengineered crops 
with a tool to ensure that safety questions are resolved prior to 
marketing. We believe that our post-market legal authorities, in tandem 
with market and trade forces, provide significant incentives for 
developers of bioengineered crops to consult with FDA.
    We believe that bioengineered foods intended for commercialization 
in the United States have been the subject of a consultation prior to 
marketing. Our current approach is working well, and we do not believe 
that there is need or scientific justification for a pre-market 
approval program specific to bioengineered foods.

    Question 13. I have been concerned by reports that the FDA is not 
considering genetically engineered animals to be regulated as new 
animal drugs, despite the fact that Congress clearly intended them to 
be regulated as new animal drugs, drugs that may not be reviewed under 
the special review provisions in the Minor Use and Minor Species Animal 
Health Act of 2003. Please explain.
    Answer 13. FDA continues to meet internally and to work with other 
Federal Agencies to determine the most appropriate system for 
regulation of genetically engineered animals. At the same time, 
industry has submitted, and the Agency is reviewing, applications for 
genetic constructs inserted into transgenic animals to be approved as 
new animal drugs. None of these applications have received FDA approval 
yet.

    Question 14. Do you believe that it would promote the public health 
if partially hydrogenated vegetable oils were eliminated from packaged 
and restaurant foods? If so, what steps will you take as Commissioner 
to eliminate partially hydrogenated vegetable oils from these foods?
    Answer 14. I agree that there is compelling evidence of a public 
health concern associated with consumption of partially hydrogenated 
vegetable oils (trans fats), and FDA is taking steps to foster the 
development of healthier food products that are lower in trans fats.
    Most significantly, as you are aware, the FDA's trans fat labeling 
rule became effective just this past January. This rule requires the 
amount of trans fat in grams to be declared on the Nutrition Facts 
panel of all foods under FDA jurisdiction. The rule does not apply to 
foods served in restaurants unless a claim is made, in which case 
certain nutrition information must be provided. We believe that this 
action will have a significant positive impact in reducing the levels 
of trans fats in packaged foods and in preventing coronary heart 
disease and death. We will be closely monitoring the effectiveness of 
this rule.
    FDA has also updated its Website and undertaken other educational 
and outreach efforts to increase consumer understanding of the 
Nutrition Facts panel and to inform consumers of how to use the label 
to choose products low in trans fat, saturated fat, and cholesterol.
    Finally, FDA has received a citizen petition requesting that FDA 
undertake several other regulatory actions and educational activities 
to further limit the use of trans fats in processed foods and to 
encourage manufacturers and restaurants to switch to more healthful 
oils. The Agency is currently reviewing this petition.

    Question 15. How do you intend to implement the 2004 
recommendations of the Institute of Medicine with respect to sugars and 
added sugars in foods?
    Answer 15. The Nutrition Facts panel (NFP) of food labels provides 
consumers with information on total carbohydrates and total sugars in a 
product. The ingredient list provides consumers with information on 
what is in the product, including ingredients that are sources of added 
sugars. The Agency intends to issue an Advance Notice of Proposed 
Rulemaking (ANPRM) on updating the NFP based on several reports issued 
by the Institute of Medicine (IOM). Included in this ANPRM are 
questions regarding how information on carbohydrates should be 
presented in the NFP.

    Question 16. Please explain why the Agency continues to allow foods 
with qualified health claims to be distributed in interstate commerce, 
in violation of the Federal Food, Drug, and Cosmetic Act. The FDA's own 
research demonstrates that consumers are misled by them. The claim for 
green tea is particularly dubious:

          One weak and limited study does not show that drinking green 
        tea reduces the risk of prostate cancer, but another weak and 
        limited study suggests that drinking green tea may reduce this 
        risk. Based on these studies, FDA concludes that it is highly 
        unlikely that green tea reduces the risk of prostate cancer.''

    Answer 16. Although the Federal Food, Drug, and Cosmetic Act 
directs FDA to authorize only health claims supported by ``significant 
scientific agreement'' to appear in the labeling of conventional foods, 
the U.S. Court of Appeals for the DC. Circuit held unambiguously in 
Pearson v. Shalala and Whitaker v. Thompson that the First Amendment 
does not permit FDA to prohibit health claims that the Agency 
determines to be potentially misleading unless the Agency also 
reasonably determines that a disclaimer would not eliminate the 
potential deception. FDA would risk judicial sanctions if it were to 
ignore the DC. Circuit's rulings or subsequent rulings by lower courts 
directing FDA to permit certain qualified health claims. Further, 
although FDA's consumer research raises significant concerns about 
consumer understanding of some disclaimers used in current qualified 
health claims, the Agency's research is ongoing, and at this point, we 
feel it would be imprudent to change current policy based on incomplete 
data.
    The FDA has progressed through a series of steps to implement the 
Pearson and Whitaker decisions. In December 2002, the FDA announced a 
major new initiative, the ``Consumer Health Information for Better 
Nutrition Initiative.'' As part of the Initiative, FDA conducted 
consumer studies on ways to communicate different levels of scientific 
support for claims about the relationship between a food substance and 
reduced risk of a disease. FDA is continuing to conduct consumer study 
research for appropriate qualifying language for health claims such 
that consumers are not misled.

    Question 17. During your tenure at the National Cancer Institute, 
you may have worked in close collaboration with companies from the 
pharmaceutical, biotechnology, or medical device industries. Could you 
please identify any matters from which you are recused because of such 
collaborations?
    Answer 17. In order to assure the fruits of biomedical research 
would be translated into life saving and health enhancing interventions 
for patients and the public, I have focused my efforts on a 
comprehensive strategy, from discovery to development to delivery. This 
continuum spans the academic, private, and public sectors, and requires 
cooperation and at times close collaboration among them. I have always 
respected and maintained the legal and ethical boundaries of these 
delicate relationships. My work at NCI did not create any interests 
that would constitute a real or apparent conflict of interest under the 
government ethics rules. I will seek and abide by the advice of agency 
ethics counsel in the Office of the General Counsel with respect to any 
potential conflict of interest or recusal.

    Question 18. The FDA recently announced that it will be redrawing 
its guidelines for staffing outside advisory committees, to make 
greater efforts to exclude scientists with conflicts of interest who 
currently get waivers to serve on these committees, and to make the 
process more open to outside participation, with increased 
transparency. Could you please give us the specifics in each of these 
areas: Which conflicts of interest will be eligible for waivers? Will 
any conflicts be grounds for automatic exclusion under the new 
guidelines? How will the Agency encourage greater public participation 
in the staffing of these committees? How will its waiver and recusal 
decisions become more transparent?
    Answer 18. In a speech given July 24, 2006, Deputy Commissioner Dr. 
Gottlieb discussed efforts to revise guidelines detailing the kind of 
industry ties that are permitted for those who serve on our advisory 
committees (see http://www.fda.gov/oc/speeches/2006/
conference0724.html). More specifically, we plan to revise the guidance 
documents used to determine how potential conflicts are evaluated, how 
waivers are granted, and how information regarding conflicts and 
waivers is disclosed. The goal is to make the process more transparent 
and clarify more of the case-by-case qualitative judgments we make when 
we evaluate each potential conflict. We do not plan to re-write 
existing rules, but instead to provide additional guidance and clarity 
regarding implementation of the existing statutory and regulatory 
framework regarding conflicts of interest. The revision process is 
currently underway and is a high FDA priority. We will make public the 
revised guidances as soon as they are completed.
    We believe that these administrative changes will substantially 
improve the transparency of the process of managing our advisory 
committees, evaluating potential conflicts, and granting waivers where 
appropriate.

    Question 19. The public should be given a real opportunity to 
nominate members of its advisory committees. How do you intend to make 
that happen?
    Answer 19. Our process has always welcomed nominations for our 
advisory committees from any interested party. FDA generally notifies 
the public about vacancies on committees through Federal Register 
notices on an annual basis. Many professional societies use these 
notices to share news of potential vacancies among interested 
professionals. We are committed to welcoming and carefully reviewing 
nominations that we receive from the public for advisory committees.

    Question 20. Consumers need to rely on food labeling to make 
healthy choices and decrease the risk of obesity. Yet reports from 
consumer groups and State officials indicate there are numerous 
examples of mislabeled products, and the FDA has brought an 
insufficient number of enforcement actions to address the problem. Why 
doesn't FDA take action when competitors and consumer groups bring 
misbranded products to its attention? If FDA lacks sufficient funding 
to do its job, what will you do to get it the resources it needs?
    Answer 20. As part of FDA's Nutrition Labeling and Education Act 
(NLEA) Compliance Program (the Compliance Program), FDA investigators 
routinely review selected food labels during regularly scheduled food 
manufacturer inspections performed under the Agency's food safety 
compliance programs. The Compliance Program includes guidance for FDA 
investigators to review labels and collect samples for nutrition 
analysis of domestic and imported food products.
    Between October 1, 2004, and December 6, 2005, FDA conducted 
approximately 28,000 field examinations of domestic and imported food 
labels. FDA also collected 543 samples for nutrient analysis and/or 
label review. As a result of FDA's label reviews and nutrient analysis, 
FDA issued 56 Warning Letters addressing misbranding violations 
involving a variety of food products.
    FDA is updating the Compliance Program to provide increased 
emphasis on ingredient labeling in conjunction with our efforts to 
implement the Food Allergen Labeling and Consumer Protection Act, which 
became effective on January 1, 2006.

    Question 21. I would like you to comment further about salt.
    In a 2004 Commentary in The American Journal of Public Health, 
Claude Lenfant, then director of the National Heart, Lung, and Blood 
Institute, and two colleagues noted that diets high in salt, or sodium, 
increase blood pressure and increase the risk of heart attacks and 
strokes. They estimated that halving the sodium content of the American 
diet could save 150,000 lives per year. The January 2005 Dietary 
Guidelines for Americans, the Institute of Medicine of the National 
Academy of Sciences, the World Health Organization, the American 
Medical Association, and other authoritative health agencies have 
called for reducing sodium levels in the American diet. A 1979 advisory 
committee report to the FDA concluded that salt could not be considered 
``generally recognized as safe'' and recommended that the FDA limit the 
salt content of packaged foods.
    How many FTEs has the FDA devoted over the past 10 years to this 
enormous public health problem? As Commissioner, what will you do to 
lower salt levels in packaged foods, restaurant food, and the American 
diet generally?
    Answer 21. I believe this is an important issue for public health 
and that FDA has a central role to play in efforts to lower salt levels 
in the American diet. I will continue to work with FDA's Center for 
Food Safety and Applied Nutrition (CFSAN) on this issue, emphasizing 
the need for effective, feasible measures that will reduce salt 
consumption.
    Our current reporting system does not allow us to distinguish the 
FTEs devoted specifically to salt over the past 10 years; however, we 
are presently working diligently on issues related to reducing salt in 
the American diet. I believe you are aware that FDA received a citizen 
petition in late 2005 that proposed, among other things, to require 
reductions in the salt content of processed foods, including processed 
foods intended for restaurant use. In preparation for an informed and 
comprehensive response to this citizen petition, FDA is planning as a 
first step to announce the availability of the citizen petition for 
comment in an upcoming Federal Register notice. This announcement will 
likely be followed by a public meeting intended to solicit comments 
from stakeholders and the public in general. FDA feels this additional 
information is important given the complexity of the regulatory 
response proposed in the citizen petition and the complexity of issues 
surrounding the use of salt in foods in general.
    I should also note that FDA has been active in its efforts to 
reduce salt in foods through providing information for consumers. For 
example, FDA requires disclosure of the sodium content on food 
packaging, has an authorized health claim relating to reductions in the 
risk of high blood pressure for foods low in sodium, and has qualifying 
levels of sodium that a food may contain for foods to be labeled 
``healthy.''

    Question 22a. In 2002, Congress gave the FDA new authorities to 
protect the Nation's food supply against the threat of intentional 
contamination and other food safety emergencies.
    However, due to inadequate staffing, FDA has turned much of its 
border inspection responsibilities over to Customs and Border 
Protection (CBP). FDA also lacks mandatory authority to recall 
contaminated food that it regulates.
    How many ports of entry are used for FDA inspected products?
    Answer 22a. According to U.S. Customs and Border Protection (CBP), 
there are 317 official ports of entry in the United States (U.S.). FDA 
staff provides coverage on a routine basis at the 90 ports of entry 
through which the greatest volume of FDA-regulated products pass. These 
ports include all major sea/air ports and the highest volume land 
border ports.

    Question 22b. How many FDA inspectors check ports of entry?
    Answer 22b. FDA staff provides coverage on a routine basis at the 
90 ports of entry through which the greatest volume of FDA regulated 
products passed. In fiscal year 2005, 424 ORA employees conducted Field 
Exams on imported, FDA-regulated commodities offered for entry into the 
United States.

    Question 22c. How many ports of entry are now covered by CBP 
employees instead of trained FDA inspectors?
    Answer 22c. First, it is important to note that FDA has not turned 
much of its border inspection responsibilities over to Customs and 
Border Protection (CBP), as you suggest. Staff from FDA's Office of 
Regulatory Affairs (ORA) currently provides coverage at the 90 ports of 
entry. FDA has not requested CBP to provide coverage at any ports of 
entry in lieu of FDA coverage at those same ports of entry. FDA's 
import data system, Operational and Administrative System for Import 
Support (OASIS), receives electronic data from CBP's Automated 
Commercial System for FDA-regulated merchandise entered through all 317 
ports of entry. If, upon review of this data, FDA decides to sample or 
examine product, FDA and CBP regulations require that the product be 
held under bond until sampled/examined and released by FDA. Pursuant to 
the Public Health Security and Bioterrorism Preparedness and Response 
Act of 2002 (BT Act), FDA and CBP signed a Memorandum of Understanding 
(MOU) that has allowed ORA to commission approximately 9,500 CBP 
Officers in ports and other remote locations to conduct, on FDA's 
behalf, investigations and examinations of imported foods at ports 
where FDA may not currently have staff or to augment FDA staff at ports 
that do have an FDA presence. FDA has not yet had a need to utilize 
this MOU.

    Question 22d. What sort of food safety training do these CBP 
inspectors have?
    Answer 22d. FDA senior import personnel provided training to 
selected CBP officers following the enactment of the BT Act. The CBP 
officers were trained in how to conduct food import field examinations. 
They were also taught how to sample, package and ship products to FDA 
laboratories for analysis. Upon return to their respective ports, it 
was the responsibility of these selected CBP officers to train other 
commissioned officers (CBP) within their port's jurisdiction via the 
``train the trainer'' model. Additional guidance for commissioned CBP 
officers, should there be an occasion where they would have to act on 
FDA's behalf, would come via mission specific assignments from FDA's 
Prior Notice Center.

    Question 22e. Do you think the FDA needs mandatory recall 
authority, such as it has for infant formula and medical devices, to 
quickly remove contaminated food from the market?
    Answer 22e. FDA, through its authority under the Federal Food, 
Drug, and Cosmetic Act, can remove a violative product from the market 
by using its seizure authority. It is also important to note that the 
BT Act granted substantial new powers to FDA to administratively detain 
foods for which there is credible evidence or information that the food 
presents a serious adverse health consequence or death to humans or 
animals. This authority is coupled with additional authority, under 
certain circumstances, to detain imported foods at ports of entry for a 
period of time sufficient to enable their inspection. Since enactment 
of this important legislation, FDA has been busy implementing these and 
other authorities provided under the BT Act.

    Question 23a. Increasingly, imported foods are the source of food-
borne illness. For example, in 2003 a hepatitis A outbreak associated 
with green onions imported from Mexico sickened over 550 people. Since 
1994 the volume of food imports regulated by the Agency has grown 
fivefold. Meanwhile FDA inspects fewer than 2 percent of these 
shipments with an increasingly diminishing budget.
    With dwindling resources how would you improve FDA's oversight of 
imported food?
    Answer 23a. To manage the increasing volume of imported food 
shipments, FDA is using risk management criteria to achieve the 
greatest protection possible when it comes to safeguarding imported 
food. Currently, a significant effort is underway to broaden, develop 
and apply appropriate knowledge-based risks to the examination of 
imported food.
    In addition, the Bioterrorism Act [BT Act] provided a significant 
new tool that enhances FDA's ability to electronically review FDA-
regulated imported shipments. As you know, that law requires that FDA 
receive prior notification before food is imported or offered for 
import into the United States. Advance notice of imported food 
shipments, called ``Prior Notice,'' allows FDA, with the support of the 
CBP, to target food import inspections more effectively and to help 
protect the Nation's food supply against terrorist acts and other 
public health emergencies. With the Prior Notice requirement, specific 
information mandated by the BT Act must be submitted to FDA before the 
imported food arrives in the United States. This allows the electronic 
system to review and screen the shipments for potential serious threats 
to health (intentional, alleged or otherwise) before the food arrives. 
It also allows FDA staff to review Prior Notice submissions for those 
products flagged by the systems as presenting the most significant 
risk. FDA worked very closely with CBP in developing the targeting 
criteria. FDA's experience with the prior notice system has been that 
it permits FDA to further refine our risk-based targeting criteria and 
allows us to allocate resources for inspections more effectively.
    The fiscal year 2007 President's budget request includes almost $20 
million in increases for food defense efforts, including $3.2 million 
to support the Field's risk-based domestic and imports food safety 
operations. The request supports continuing efforts to target 
potentially high-risk imported foods through Prior Notice Import 
Security Reviews, which utilize information from intelligence data, 
records of FDA inspections, Prior Notice submissions, and other 
sources. Also included in the request is $12.7 million for the Food 
Emergency Response Network, $1.5 million for Crisis Management, and 
$2.5 million for Bio-surveillance activities.

    Question 23b. What percentage of food shipments should FDA be 
inspecting and on what basis do you make that determination?
    Answer 23b. In fiscal year 2005, nearly 8.7 million line entries of 
imported food were offered for entry into the United States, on which 
FDA conducted approximately 85,000 food import field examinations 
(exams). FDA believes that the best approach to improving the safety 
and security of imported food is to devote resources to expanding and 
refining the targeting criteria and to conduct more intensive reviews 
on potentially high risk entries, rather than to simply increase the 
percentage of food import lines that receive a field exam. A food 
import field exam is a visual and physical examination of a food 
product to determine whether it complies with FDA requirements for 
admissibility. During food import field exams, FDA personnel check 
attributes such as damage during storage or transit, inadequate 
refrigeration, rodent or insect activity, presence of lead in 
dinnerware, appearance of decomposition, and compliance with labeling 
requirements. Food import field exams have always been just one part of 
FDA's import strategy. FDA does not rely solely on the physical 
examination of a product through a food import field exam to reduce the 
potential risks posed by imported foods.
    While we do not physically inspect every shipment, it is important 
to note that every shipment containing FDA-regulated products entered 
through CBP's automated system is electronically reviewed by FDA's 
system. FDA's import data system, OASIS, determines if the shipment 
meets identified criteria for physical examination or sampling and 
analysis or warrants other review by FDA personnel. This electronic 
screening method allows FDA to concentrate its enforcement resources on 
high-risk shipments while allowing low-risk shipments to proceed.
    In addition, FDA receives and its data systems review approximately 
35,000 Prior Notice submissions containing specific information about 
incoming food shipments every day.

    Question 24. In August 1977 the FDA published a proposed rule to 
withdraw approval of the subtherapeutic use of penicillin in livestock. 
Almost 30 years later, in May 2004, the Director of the Center for 
Veterinary Medicine wrote to the three manufacturers of penicillin for 
animal use--Alphamra, Pennfield Oil, and Phibro Animal Health--to 
remind them that the 1977 proposal is still pending and to express its 
concerns about their products' ``possible role in the emergence and 
dissemination of antimicrobial resistance.'' So far as I know, the 
companies have not responded.
    Please explain what steps you will take as Commissioner to complete 
the work on this 1977 proposal. Do you believe the FDA needs additional 
legal authority to complete what the FDA proposed in August 1977, and 
to address antibiotic resistance more generally?
    Answer 24. FDA's Center for Veterinary Medicine (CVM) has a working 
group tasked with reviewing the scientific basis for the 1977 Notice of 
Opportunity for a Hearing (NOOH) for penicillin products and, in light 
of the review of the penicillin new animal drug applications (NADAs), 
to make a recommendation regarding actions that may need to be taken. 
The group has completed its review of NADAs providing for the use of 
penicillin for nontherapeutic uses and is currently finalizing its 
recommendations regarding the safety of these penicillin products. CVM 
intends to solicit public input once the working group has completed 
its work.
    Using its existing legal authorities, FDA has developed a 
regulatory strategy for managing the potential risks associated with 
the use of antimicrobial drugs in food-producing animals. This 
innovative approach includes the use of risk assessment to quantify the 
human health impact from antimicrobial use in animals, in conjunction 
with robust monitoring through the National Antimicrobial Resistance 
Monitoring System (NARMS), research, and risk management. FDA does not 
believe that any additional legal authority is required, but the Agency 
will continue to work with Congress and various stakeholders to address 
safe use of antimicrobials in food animals and ensure that significant 
human antimicrobial therapies are not compromised or lost.

    Question 25. It has been nearly 2 years since the manufacturer of 
one of the progestin-only oral contraceptives informed me that FDA was 
discussing with it a change to the drug's labeling to indicate that 
some women experience reductions in breast milk production when on the 
progestin-only pill.
    This matter was brought to my attention by a constituent, who 
experienced this problem when nursing each of her first two children. 
Her first child did not thrive before she discovered the problem, and 
she had to switch him to formula because she had stopped producing 
milk. His lack of weight gain fortunately reversed once he was on 
formula. She noticed this problem more quickly with her second child, 
stopped using the pill, and was able to continue nursing the child.
    The drug is currently promoted, and so I assume labeled, as having 
no negative side effects on breast feeding. Although I understand that 
clinical trials of the drug showed this to be the case for the women in 
the trials, these trials did not include that many women, and they 
clearly do not rule out the possibility that some women do experience 
negative side effects on breast feeding.
    I believe that reduction in breast milk production in a nursing 
mother is a serious, if rare, side effect of these drugs that nursing 
mothers should be warned about. Do you agree? If you do not agree, 
please explain. If you do agree, please explain why it has taken so 
long to address this serious problem and when you anticipate that the 
drug's labeling will properly warn women about this drug risk.
    Answer 25. We agree that a statement concerning the risk of a 
reduction in breast milk production should be included in labeling of 
progestin-only nonemergency oral contraceptive products. Accordingly, 
we are in the process of ensuring that the labeling for progestin-only 
nonemergency oral contraceptives is revised to indicate that there have 
been rare post-marketing safety reports of decreased milk production in 
lactating women. To this end, the following statement (underlined text) 
has been added to the labeling for Nor-QD (norethindrone 0.35 mg 
tablets), a progestin-only oral contraceptive, under the section 
PRECAUTIONS, Nursing Mothers.

          ``No adverse effects have been found on breastfeeding 
        performance or on the health, growth, or development of the 
        infant. However, isolated post-marketing cases of decreased 
        milk production have been reported. Small amounts of progestin 
        pass into the breast milk, resulting in steroid levels in 
        infant plasma of 1-6 percent of the levels of maternal 
        plasma.''

    We are in the process of ensuring that similar language is included 
in the approved labeling for other progestin-only non-emergency oral 
contraceptives.

    Question 26. Earlier this year, the FDA issued a final rule to 
improve how prescription drugs are labeled. In the preamble of that 
final rule, the Agency made the extraordinary and unprecedented claim 
that its regulation of prescription drugs preempted many different 
kinds of State product liability claims against the manufacturers of 
prescription drugs. The Agency made this statement despite the fact 
that it had said in the preamble to the proposed regulation that it did 
not intend the regulation to have preemptive effect and despite a 
statement in the 1962 drug amendments that Congress only rarely 
intended FDA's regulation of prescription drugs to preempt any State 
law, let alone product liability actions. Moreover, the Agency did so 
by completely overstating and mischaracterizing the Agency's authority 
over drugs postapproval. Do you agree with this claim, and if so, why?
    Answer 26. I do agree with the statements FDA made in the preamble 
to the final rule on prescription drug labeling with regard to 
preemption. I do not agree that FDA overstated and mischaracterized the 
Agency's authority over approved drugs, nor that the Agency made any 
extraordinary or unprecedented claims.
    By way of explanation, FDA issued a proposed Physician Labeling 
Rule in 2000. FDA received numerous comments in response to the 
proposal regarding the product liability implications of revising the 
drug labeling, in particular regarding the truncated description of the 
risks in the new highlights section. The Administrative Procedure Act 
requires the Agency, when issuing a final rule, to address the comments 
it receives in response to proposed rules. The discussion in the 
preamble to the final rule regarding Federal preemption that you are 
referring to was written in response to comments received, and merely 
restates the Agency's longstanding position as articulated in amicus 
briefs filed in court by DOJ in cases regarding Federal preemption and 
drug labeling. These product liability cases involved State law 
challenges to FDA approved labeling. DOJ argued on behalf of FDA that 
such law suits are preempted by the act when State requirements cause 
drug products to be misbranded under Federal law. The 2006 preamble 
merely set out well settled principles of preemption law and FDA's 
current understanding of the way in which a State tort judgment can 
interfere with FDA's implementation of Federal law.
    In the context of drug labeling, Congress has authorized FDA to 
apply its scientific expertise to determine, in the first instance, 
what labeling, including warnings, are appropriate and necessary for a 
particular drug. See Henley v. FDA, 77 F.3d 616, 621 (2d Cir. 1996); 
Public Citizen Health Research Group v. Commissioner, 740 F.2d 21, 28 
(D.C. Cir. 1984). Therefore, FDA's determinations about the scientific 
evidence surrounding a drug product, and determinations about whether 
particular labeling is false or misleading are paramount. In addition, 
even in the absence of an express preemption provision, implied 
conflict preemption principles still function to preempt State law. See 
Geier v. American Honda Co., 529 US 861 (2000). This type of preemption 
arises when there is conflict between Federal and State law, and the 
preemptive effect can occur with any Federal regulation. Under the 
Supremacy Clause (U.S. Const. art. VI, cl.2), a State may not force a 
drug manufacturer to choose between compliance with Federal law and 
State law. See Geier, at 873. In addition, companies could be held 
liable under State product liability law where State requirements 
neither conflict with Federal requirements nor frustrate Federal 
purposes.
    FDA's regulation of prescription drugs is designed to ensure each 
drug's optimal use through requiring scientifically substantiated 
warnings. Under the Federal Food, Drug & Cosmetic Act, FDA is the 
public health agency charged with ensuring that drugs and devices are 
safe and effective, and that the labeling of drugs and devices 
adequately inform users of the risks and benefits of the product. FDA 
employs scientists and other experts who review the information 
submitted by the manufacturer on a product's risks and carefully 
titrate the warnings, etc. that should be placed on the labeling. FDA 
continuously works to evaluate the latest available scientific 
information to monitor the safety of products and to incorporate 
information into the product's labeling when appropriate. The public 
health risks associated with overwarning are as great as--if not 
greater than--the health risks associated with underwarning. 
Overwarning can cause patients not to take beneficial drugs and doctors 
not to prescribe them.
    Under-utilization of a drug based on dissemination of 
scientifically unsubstantiated warnings, so as to deprive patients of 
beneficial, possibly lifesaving treatment, could well frustrate the 
purposes of Federal regulation as much as over-utilization resulting 
from failure to disclose a drug's scientifically demonstrable adverse 
effects. Further, allowing unsubstantiated warnings may also diminish 
the impact of valid warnings by creating an unnecessary distraction and 
making even valid warnings less credible.
   Response to Questions of Senator Gregg by Andrew C. von Eschenbach
    Question 1. As you know, earlier this month, the Senate passed 
Senator Vitter's drug importation amendment to the DHS appropriations 
bill. This amendment prevents Customs and Border Protection from using 
funds to stop the personal importation of FDA-approved drugs from 
Canada. I opposed this approach to dealing with the importation of 
prescription drugs.
    Do you believe the Vitter amendment provides for safe importation 
of drugs? Should the Vitter amendment be included in the Homeland 
Security Appropriations Conference Report?
    Answer 1. I agree with you that this is not the right approach to 
deal with the importation of prescription drugs. The Administration 
strongly opposes a provision to the Homeland Security Appropriations 
Bill allowing the personal importation of prescription drugs, and I 
agree. This provision would prevent the U.S. Customs and Border 
Protection (CBP) from assisting Food and Drug Administration (FDA) 
efforts to prevent the importation of misbranded and potentially unsafe 
drugs. It would also prevent CBP from helping FDA enforce section 
801(d)(1) of the Federal Food, Drug, and Cosmetic Act (the act), which 
prohibits anyone other than the original manufacturer from importing 
into the United States a prescription drug that was originally 
manufactured in the United States and then sent abroad. Congress 
enacted section 801(d)(1) in 1987 to help safeguard the safety and 
integrity of the domestic drug supply.
    The December 2004 HHS Task Force Report on Drug Importation 
identified significant safety risks associated with drugs imported by 
individuals. FDA has found that many drugs ordered at Websites from 
apparently Canadian pharmacies, in fact, originate from countries 
around the world. If this provision is enacted into law, FDA's 
resources would not be sufficient to examine these drugs at the border 
to ensure that they are FDA-approved and not counterfeit. The 
Administration recommends that the amendment be deleted because it 
could threaten the health and safety of Americans.
                             generic drugs
    Question 2. Not only has PDUFA ensured the timely review of new 
drug applications, but it now funds almost half of the Agency's drug 
review activities. It is this success that prompted me to co-author 
legislation that extended the user fee model to the FDA's review of 
medical devices and animal drugs. I understand that there is a backlog 
of about 200 generic drug Abbreviated New Drug Applications at the 
Office of Generic drugs and this backlog can be expected to grow given 
the relatively large number of blockbuster drugs that are coming off 
patent in the next few years.
    Would a steady stream of income through a user fee program for 
generic drugs enable the Agency to increase their resources to reduce 
the backlog?
    Answer 2. As you may know, the Prescription Drug User Fee Act does 
not apply to generic drugs approved under the ANDA process, section 
505(j) of the Federal Food, Drug and Cosmetic Act. We have heard public 
discussion of a generic drug user fee program, but at this time, the 
Administration has no position on such proposals.

    Question 3. Both FDA and the generic drug industry recognize that 
the citizen petition process has been used to cause delay to the 
introduction of generic drugs.
    Do you believe the current structure is balanced? Does FDA need to 
act to ensure generic drugs are not delayed on their way to market?
    Answer 3. FDA regulations permit any interested person to file a 
citizen petition requesting FDA ``to issue, amend, or revoke a 
regulation or order, or to take or refrain from taking any other form 
of administrative action'' (Title 21, Code of Federal Regulations 10.25 
and 10.30). Citizen petitions may be submitted at any time requesting 
that FDA impose new criteria for approval of ANDAs.
    It is incumbent upon FDA to consider and address the merits of 
petitions. The data and information submitted with these petitions may 
require detailed analysis and precise scientific documentation, often 
involving multiple disciplines within CDER. Because the same issues 
sometimes are raised in a subsequent court challenge to an ANDA 
approval and because petitioners sometimes submit nonscientific 
petitions that raise purely legal questions related to ANDA approvals, 
a thorough legal review is also necessary. Although it is not required 
that a citizen petition response be issued before approval of a related 
ANDA, it is important that FDA comprehensively assess the scientific 
issues prior to approval of the ANDA. It is very rare that petitions 
present new issues that CDER has not fully considered, but the Agency 
must nevertheless assure itself of that fact by reviewing the citizen 
petitions.
    CDER has made considerable efforts in the last year-and-a-half to 
improve the process for responding to citizen petitions. As part of 
this process, OGD constituted a group of highly qualified and skilled 
scientists dedicated to assessing the citizen petitions related to 
generic drugs and formulating FDA's responses to them. Other 
improvements include: increased prospective management of the petition 
response process; development of clear timelines for completing 
actions; and improved communication among the CDER components involved 
in responding to citizen petitions.
                               bioshield
    Question 4. There appears to be some differences of approach by 
CBER and CDER regarding the pathway to licensure for biodefense 
countermeasures. CBER appears to put more weight on the risk of a 
terrorist event and the need to ensure safety and efficacy while CDER 
appears to discount the risk of a bio-terrorist attack to a greater 
degree in ensuring safety and efficacy.
    How would you attempt to reconcile these apparent inconsistencies 
between the centers?
    Answer 4. FDA remains strongly committed to facilitating the 
development and availability of safe and effective medical 
countermeasures to protect the public against a broad range of 
terrorist threat agents. To this end, our Medical Centers (CBER, CDER, 
and CDRH) are working closely with sponsors who are interested in 
developing new products to diagnose, treat, and prevent illnesses 
caused by chemical, biological, radiological, and nuclear (CBRN) 
agents.
    The legal standards for product approval, clearance, and licensure 
under the Federal Food, Drug, and Cosmetic Act and the Public Health 
Service Act apply equally to countermeasures and to other products. 
Similarly, the legal standard for issuance of an Emergency Use 
Authorization (EUA) applies to all types of countermeasures. These 
legal requirements establish the framework for our scientific review of 
product submissions.
    As we develop new counterterrorism policies, we look for 
opportunities for a comprehensive (cross-Center) approach. For example, 
the Animal Efficacy Rule (Animal Rule) was jointly promulgated by CBER 
and CDER to help expedite the regulatory pathway for new 
countermeasures. Under the Animal Rule, animal efficacy data may be 
used when efficacy studies in humans are not ethical and field trials 
are not feasible. More recently, FDA published a Draft Guidance on 
Emergency Use Authorization of Medical Products (Draft Guidance). The 
Draft Guidance was developed by an agency-wide working group and 
presents Agency recommendations on EUA submissions that are applicable 
to the full range of countermeasures (biologics, drugs, and devices).

    Question 5. Under the animal efficacy rule used for approval of 
biodefense countermeasures, there is little guidance provided by the 
FDA to developers of these products about what the ultimate indication 
for the product will be. This is particularly true for therapeutics.
    What is your view of the best way for FDA to provide enough 
guidance to these critical development efforts to ensure they are 
successful in obtaining the appropriate clinical data that will be 
required for licensure?
    Answer 5. FDA has an important role in the Nation's effort to 
identify, prepare for, and respond to chemical, biological, 
radiological, and nuclear (CBRN) threats and incidents. To this end, we 
have a broad strategy for working closely with industry and with our 
Federal, State, and local partners to facilitate the development and 
availability of new medical countermeasures.
    We encourage early interactions with sponsors interested in 
developing a new countermeasure or a new counterterrorism-related 
indication for a previously approved product. Based on feedback from 
industry, we believe that these interactions offer sponsors valuable 
technical assistance and expertise and can help to expedite the 
development and successful approval of new countermeasures. Sponsors 
interested in developing a new countermeasure come to the Agency with a 
proposed indication for their product and the Agency then advises them 
with regard to the necessary data needed to achieve the desired 
indication.
                      drug development and access
    Question 6. In light of recent concerns over drug safety, how will 
the Agency best ensure safety without limiting patient access to 
lifesaving drugs?
    Answer 6. All drugs have risks, and FDA reviewers balance these 
risks against identified benefits for each product. When a new drug 
application (NDA) is being reviewed, it is imperative that the drug's 
risks as well as its benefits be understood as thoroughly as possible. 
FDA has new industry guidance and internal initiatives for optimizing 
safety data collection during large phase III trials. In addition, new 
initiatives, such as the standardization of study variable names, the 
development of computer-based review tools to speed the identification 
of safety risks in NDA databases, the development of a safety template 
for use by FDA reviewers, and the Critical Path Program all promise to 
maximize the understanding of a drug's safety profile at the time of 
the NDA review.
    This deeper understanding of a drug's risk profile allows FDA 
reviewers to make better informed benefit-risk evaluations. Decisions 
regarding drug approval always factor in the severity of the underlying 
disease, and the benefits and risks of potential alternative 
treatments. FDA understands that the American public will accept a 
higher risk of serious side effects when the drug effectively treats a 
life-threatening disease with few or no treatment alternatives (e.g., 
some types of cancer, AIDS).
    In contrast, when there are many available beneficial and well 
tolerated drug alternatives for a disease or condition, FDA is more 
cautious about approval of new drugs with significant toxicity. For 
example, with the many well tolerated drugs available to lower 
cholesterol or blood pressure, a new drug for these purposes that was 
more toxic than the available drugs might ordinarily not be approved 
(or could be withdrawn) unless it could treat a resistant population 
(whose elevated risk of complications and/or death would make the extra 
risk of the drug acceptable).
    At times, the judgment of whether the need for more safety data 
outweighs the need for a new effective treatment is controversial. In 
these cases, discussion at an FDA advisory committee meeting allows 
academia, the practice community and the public to share their 
knowledge and perspective on the benefit-risk balance and therapeutic 
need. This external advice helps guide FDA in its final decisionmaking.
    In all cases, FDA works to ensure that a drug's risks have been 
well studied and that drug labeling reflects those risks and benefits. 
Effective communication between the Office of New Drugs and the Office 
of Surveillance and Epidemiology prior to drug approval and afterwards 
sets the foundation for shared monitoring of the new drug's identified 
and potential risks as it is introduced into the market.

    Question 7. The cost and time of new product development has been a 
concern for patients as well as sponsors. What is the Agency 
considering doing to address these concerns in regards to trial size, 
duration, and patient accrual?
    Answer 7. FDA is actively considering under the Critical Path 
initiative a variety of study designs, methods of analysis and uses of 
data from other studies to improve decisionmaking and the rate of 
success of studies. We continuously evaluate new clinical trial designs 
that hold the promise of more efficient drug development as well as 
nontraditional statistical approaches that may lead to more efficient 
drug development. For example, the appropriate use and applicability of 
historical controls in which the effect of a new treatment in a group 
of patients is compared to well-documented experience from other 
studies is considered in detail in the International Conference on 
Harmonization (ICH) guidance E-10 (Choice of Control Group and Related 
Issues in Clinical Trials.), and in certain circumstances such trials 
designs are employed to expedite drug development.
    Under certain circumstances, we also have the authority to base a 
finding of substantial evidence of effectiveness on the results of a 
single adequate and well controlled clinical study rather than the more 
traditional two-study standard. This standard can help speed important 
new therapies to market by reducing the number of trials that must be 
performed to gain marketing approval. Also, under the law and 
regulations, we can approve drugs on the basis of their effects on a 
marker that is reasonably likely to predict a clinical benefit, 
provided that we are able to obtain evidence after approval to 
establish that the drug had clinical benefit. This approach is reserved 
for serious or life-threatening conditions for which there are 
inadequate available treatments. Although there are difficulties with 
this approach and it must be used responsibly and with caution, where 
appropriate, it can drastically reduce the time to market for important 
new drugs.

    Question 8. While the Director of NCI, you were instrumental in 
creating a joint task force with FDA to optimize the development and 
review process for new cancer drugs. Do you see the potential for other 
FDA-NIH partnerships that could be applied to other indications?
    Answer 8. In 2003, Secretary Thompson, Dr. McClellan, and I 
announced a collaboration to streamline cancer drug development--the 
Interagency Oncology Task Force (IOTF). Under the agreement between the 
Food and Drug Administration (FDA) and the National Cancer Institute 
(NCI), an institute within the National Institutes of Health (NIH), the 
two agencies would share knowledge and resources to facilitate the 
development of new cancer drugs and speed their delivery to patients. 
Although FDA and NCI have distinctly separate missions, they share a 
common goal in the fight against cancer. NCI's mission is one of basic 
and clinical research to foster discovery and development of new 
medical products. FDA's mission is to assure the safety, efficacy, and 
quality of manufacturing of new medical products prior to marketing. 
This interagency collaboration takes full advantage of their combined 
knowledge bases.
    FDA and NIH recently announced the first major program from this 
collaboration entitled the Research and Regulatory Review Fellowship 
Program. The program is designed to train a cadre of researchers to 
bridge the processes from scientific discovery through clinical 
development and regulatory review of new oncology products. This 
program is a critical first step in establishing a knowledge base that 
is built, not just on ideas from biomedical research, but on reliable 
insights into the pathway to marketed products for use in patients.
    Staffs from both agencies continue to work jointly in other major 
areas under the IOTF umbrella. This effort will be crucial in fostering 
the new age of medical products to conquer cancer. Some of these 
products will include nanotechnology, clinical beneficial surrogate 
markers and chemoprevention.
    I hope that this interagency prototype will serve as a model for 
other NIH and FDA collaborative efforts for other areas of research and 
drug development.
                    plan b (``morning after pill'')
    Question 9. FDA announced its intention to work with Duramed, the 
manufacturer of Plan B, to resolve the remaining policy concerns 
regarding the application for over-the-counter (OTC) status. Is there 
precedent for approving a drug for OTC use for a subset of the 
population solely based on age, but requiring a prescription for 
another set of the population? How will FDA enforce restrictions on OTC 
use of Plan B for women only over the age of 18? What requirements 
would be made for marketing Plan B for OTC use vs. prescription-only?
    Answer 9. There are currently no other products approved for OTC 
use for one population based solely on age and by prescription for 
another population based solely on age, although non-prescription 
nicotine replacement therapy products are approved only for consumers 
18 and older.
    Duramed has agreed to conduct a ``Point-of-Purchase Monitoring 
Program'' to track how Plan B is being sold at the time of purchase. 
Using the data collected, the sponsor agrees to document and analyze 
the level of comprehension of the Plan B prescription age requirement 
and how it is handled at the point of purchase. The program will be 
conducted twice in the first year and annually thereafter. The sponsor 
also agreed to report repeat violators to the relevant State Boards of 
Pharmacy. Finally, the sponsor committed to report to FDA on the 
results of these activities on a 6-month interval beginning 30 calendar 
days after the 6-month interval commencing on the date of the approval 
of the amended sNDA. Monitoring of the program's effectiveness will 
allow FDA to assess whether further modifications will be necessary to 
prevent inappropriate use of Plan B. Additional details of the other 
commitments made by the sponsor to support the OTC marketing of Plan B 
may be found on FDA's Website at http://www.fda.gov/cder/drug/infopage/
planB/default.htm.
                    ipledge risk management program
    Question 10. A bipartisan letter on the iPLEDGE program was co-
authored by me and my colleague Senator Durbin and sent to you 
recently. Senators Roberts, Hatch and Dodd--colleagues on this 
committee--joined Senators Bennett, Wyden, and Feingold on this letter. 
Hundreds of dermatologists and their isotretinoin (Accutane) patients 
have contacted us to share their frustrations and concerns with the 
iPLEDGE program. It is essential that stakeholders like prescribers and 
patients be involved at every step of the process to ensure continued 
access to this valuable medication.
    Can you tell me what specific steps FDA is taking to guarantee that 
stakeholders are involved in a meaningful way in the process of 
developing iPLEDGE program features, and reviewing and updating the 
iPLEDGE program? There is a paucity of data on the incidence of severe 
nodular cystic acne in the United States. What data did FDA use in its 
review and approval of the iPLEDGE program?
    Answer 10. iPLEDGE is intended to ensure that isotretinoin is 
prescribed and dispensed under conditions of safe use. Thus all 
patients, whether being treated for severe recalcitrant nodular acne or 
for recognized off-label uses (for example, neuroblastoma), need to be 
registered and activated in iPLEDGE to ensure that the risk of fetal 
exposure to isotretinoin is minimized. The data that FDA considered and 
presented in February 2004 to a joint meeting of the Drug Safety and 
Risk Management and Dermatologic and Ophthalmic Drugs Advisory 
Committees addressed the ability of the existing RiskMaps for 
isotretinoin products to prevent pregnancy. The existing programs 
included the System to Manage Accutane Related Teratogenicity 
(S.M.A.R.T.) and similar programs from generic drug manufacturers. 
After reviewing this data, the joint committees advised and FDA 
concurred that the programs in place at that time could be improved by 
having a single RiskMap for isotretinoin and more stringent controls to 
include mandatory registration of all participants and to link negative 
pregnancy testing to prescription dispensing for female patients who 
can become pregnant. The Agency approved the labeling supplement for 
the iPLEDGE program on August 12, 2005. The specific data presented 
that led to these conclusions can be found on the Website for that 
Advisory Committee meeting.
    FDA has taken several steps to guarantee stakeholder input into 
decisions made about how to manage the risks of using isotretinoin. 
First, stakeholders had input into the decisions regarding the design 
of iPLEDGE. Input from outside interested parties was solicited and 
heard at the February 2004 joint Advisory Committee at which FDA 
presented its assessment of previous programs to reduce the risk of 
fetal exposure to isotretinoin.
    Second, once the decision was made to modify the risk management 
plan for isotretinoin, we sought stakeholder input into how best to 
implement it. Covance, the sponsor's vendor, convened a Scientific 
Advisory Board in March 2005 to obtain stakeholder input on iPLEDGE. 
The Scientific Advisory Board meets regularly to provide stakeholder 
input on iPLEDGE issues and future updates. Additionally, both Covance 
and the FDA have participated in professional meetings of various 
stakeholder groups such as the American Academy of Dermatology, the 
National Association of Chain Drug Stores, and the Health Distributors 
Management Association.

    Question 11. I brought to FDA's attention a young woman from New 
Hampshire who was prevented from filling her prescription of 
isotretinoin due to systemic problems in the iPLEDGE program. FDA was 
instrumental in ensuring that the young women's prescription was filled 
even though the iPLEDGE system denied her access to the drug.
    What is FDA doing to improve the operation of this program and 
ensure that its risk management goals are met?
    Answer 11. FDA has worked closely with isotretinoin sponsors and 
their vendor, Covance Inc., to maintain a critical balance between 
access to the drug by patients who need it and ensuring its safe use. 
In response to concerns raised by dermatologists and pharmacists in 
recent weeks, FDA has ensured that rapid and significant progress has 
been made by the sponsors and Covance to address operational aspects of 
the program. Specific measures taken include an increase in iPLEDGE 
call center staffing to handle the expected increases in call volume 
and user questions, as well as an enhanced system to process requests 
for new passwords by users who have forgotten or lost their original 
passwords.

    Question 12. The drug company sponsors of the iPLEDGE program 
(known collectively as the Isotretinoin Products Manufacturing Group, 
or IPMG) stopped providing free isotretinoin to indigent patients with 
the launch of the iPLEDGE program. Promoting access to this medication 
for all patients qualified to take it is an important issue. Is the 
Agency taking action to promote the renewal of the free medication 
program? If not, why not?
    Answer 12. Provision of free medication for indigent patients was 
not prohibited as a result of the iPLEDGE program launch. Decisions to 
provide free medication for indigent patients lie solely with the 
sponsors and are not under FDA purview.
                            medical devices
    Question 13. During the SARS epidemic, the Administration urged the 
device industry to develop a rapid SARS diagnostic test and several 
companies agreed to pursue development of a test. However, those 
companies were never able to obtain SARS biological samples in order to 
develop tests. The problem still exists today for pandemic influenza 
and may hamper development of point of care diagnostic pandemic 
influenza tests. The device industry has proposed that a process be 
established for emerging biohazards and threats--similar to that used 
during the West Nile Virus outbreak--that would establish regular 
meetings between FDA and CDC and interested industry stakeholders and 
require the adoption of processes for sharing samples needed to develop 
tests for emerging infectious diseases. Would you be willing to work 
toward such a process?
    Answer 13. The Agency will work with all stakeholders and 
interested parties to assist in sharing information and samples that 
will advance this field.

    Question 14. A second barrier that may hinder the development of 
potentially lifesaving medical product countermeasures is FDA's 
requirement that original samples be used for the review or approval of 
a medical product countermeasure. I understand, however, that in the 
case of the West Nile virus, detection medical devices received 
approval conditioned on a requirement to provide post-clearance data. 
Given that this uncertainty surrounding product approval will be an 
ongoing problem with emerging infectious diseases, is it appropriate 
for FDA to develop an approval process using virus isolates conditioned 
upon a requirement to provide post-clearance data to ensure that safe 
and efficacious products are developed and reviewed or approved?
    Answer 14. FDA is willing to work with sponsors to determine the 
least burdensome methods of generating data to support pre-market 
review and satisfy the legal requirements for clearance or approval of 
diagnostic devices for emerging infectious diseases.
    When prospective clinical samples are difficult to obtain, in some 
cases FDA is able to accept information obtained with spiked samples to 
support analytical claims and with banked samples to support clinical 
claims. Post-market studies are not used to replace the pre-market 
review process for establishing the safety and effectiveness or 
substantial equivalence of new devices. These studies, however, can be 
very helpful in gathering data to refine use of a new test. For PMA 
products, post-market studies can be ordered as a condition of product 
approval.
    In cases in which there is insufficient data to establish the 
safety and effectiveness or substantial equivalence of a new diagnostic 
device, FDA can work with sponsors to ensure availability of tests with 
appropriate patient safety controls using Investigational Device 
Exemption (IDE) submissions, or in cases of actual potential emergency 
can use the Emergency Use Authorization (EUA), if statutory criteria 
are met, to ensure availability of critically important cutting edge 
diagnostics for public health use.
                           black box warnings
    Question 15. In its Drug Safety report released earlier this year, 
the GAO found that ``there is a lack of criteria for determining what 
safety action to take and when to take them,'' and cited the imposition 
of ``black box warnings'' as an example. If confirmed, what action 
would you take to address concerns raised by GAO?
    Answer 15. FDA's Center for Drug Evaluation and Research (CDER) has 
already embarked on many improvement efforts to address the points made 
by the GAO report entitled, ``Drug Safety: Improvement Needed in FDA's 
Post-market Decision-Making and Oversight Process.'' FDA continues to 
build upon these efforts. For instance, the Agency asked the Institutes 
of Medicine (IOM) to perform a study on drug safety, aiming to evaluate 
the drug safety system in the United States and to assess what 
additional steps could be taken to provide more certainty about drug 
side effects. This study is nearing completion. I will ensure that the 
recommendations are carefully considered as we work to improve Agency 
actions on drug safety issues.
    Additionally, in January, the Agency published two documents on the 
presentation of risk information in professional labeling for 
prescription drug products to assist drug manufacturers in 
communicating drug safety information through labeling:

     Final guidance to industry, ``Adverse Reactions Section of 
Labeling for Human Prescription Drug and Biological Products--Content 
and Format'' to aid in the selection, characterization, organization, 
and updating of information in the Adverse Reactions section; and
     Draft guidance to industry, ``Warnings and Precautions, 
Contraindications, and Boxed Warning Sections of Labeling for Human 
Prescription Drug and Biological Products--Content and Format'' to seek 
comment on proposals on when and what information should be included in 
these sections. This document may be accessed online at: http://
www.fda.gov/cder/guidance/5538dft.pdf.

    In addition, FDA implemented changes in how drug safety is assessed 
in CDER. As an example, CDER's Office of Surveillance and Epidemiology 
(OSE) and Office of New Drugs (OND) have initiated routine, periodic 
safety meetings to discuss ongoing post-marketing safety issues and to 
ensure effective communication and efficient prioritization of work. 
This effort is one response to work that OND and OSE have been doing 
using internal process improvement teams in place to clarify roles and 
responsibilities and standardize processes for staff working on post-
marketing safety issues.
    Finally, CDER has established a clear pilot program to provide a 
new mechanism to ensure that the opinions of scientific reviewers are 
incorporated into the decisionmaking process, in CDER's Manual of 
Policies and Procedures (MAPP) 4151.2, Documenting Differing 
Professional Opinions and Dispute Resolution--Pilot Program. This 
document is available online at: http://www.fda.gov/cder/mapp/
4151.2.pdf.
                    evaluating 21st century science
    Question 16. The FDA created the Critical Path Initiative to 
identify opportunities in modernizing new product development. What are 
your priorities for making the March 2006 C-Path Opportunities Report a 
reality?
    Answer 16. The critical path initiative is a high priority for the 
Agency. In fact, we have made this initiative a top priority in the 
fiscal year 2007 budget. We have been able to initiate projects in all 
six priority areas discussed in the Opportunities Report and List. In 
the next month, we will publish a followup report describing specific 
Critical Path projects we are undertaking in calendar year 2006.
    More important, our over-arching priority is to reach beyond 
specific opportunities and build public and private collaborations to 
work together to encourage continued development of the Critical Path 
sciences. As Secretary Leavitt noted when we released the List and 
Report, ``The power of public-private partnerships is vital to 
accomplish the tasks set forth in the Critical Path Opportunities 
List.'' For additional information about the critical path initiative, 
please see the FDA web page entitled, ``The Critical Path to New 
Medical Products,'' http://www.fda.gov/oc/initiatives/criticalpath/.

    Question 17. Recent discoveries such as the completion of the human 
genome project have the potential to lead to advanced techniques and 
products that could revolutionize treatments for patients. How is FDA 
preparing to keep up with the associated new regulatory challenges?
    Answer 17. Completion of the human genome project has provided a 
unique opportunity to identify sources of inter-individual variability 
in drug response (both efficacy and toxicity) and identification of 
biomarkers for biologic product quality. This unique approach will help 
individualize therapy with the intent of maximizing effectiveness and 
minimizing risk. FDA scientists have developed a multifront strategy to 
meet the regulatory challenges of the post-genome era. One example is 
FDA's ``Guidance for Industry: Pharmacogenomic Data Submissions'' 
intended to facilitate scientific progress in the field of 
pharmacogenomics and facilitate the use of pharmacogenomic data in 
regulatory decisionmaking. Another strategy is continuing education of 
regulatory scientists at FDA through hands-on training, workshops, and 
off-site visits to leading genomics-oriented companies. FDA is 
currently accepting Voluntary Genomics data submissions (VGDS) not 
associated with regulatory applications for product development in 
order to facilitate application of the technology and provide hands on 
learning and discussions between FDA regulatory scientists and 
industry. In addition, we have formed a Genomics and Proteomics working 
group to coordinate all genomics activities across the FDA.
    Some initiatives underway to aid in the development of partnerships 
with stakeholders to standardize the acquisition, quality, storage and 
exchange of data include: unique outreach to regulated industry to 
encourage submissions using joint interpretations of data from new 
technologies promising for the regulatory process; and, where 
appropriate, research partnerships to evaluate the utility of emerging 
technologies in evaluating safety and efficacy of regulated products. 
The stakeholders include scientists from every aspect of the scientific 
enterprise including: regulatory scientists from other government 
agencies, academicians engaged in discovery research, scientists from 
applications industries, as well as scientists in regulated industry. 
Examples of partnerships include: an intra-Agency consortia (primarily 
between NCTR and CDER) to receive and secure regulatory data, 
development of technical standards for application of genomics 
technology in medical research, data organization, integrity 
characteristics and analysis; characterization of quality control 
parameters for effective comparison of results across commercial 
analytical products; CRADAs for co-exploration of emerging technology 
to predict health and disease; and CRADA for the characterization of 
cell substrates used for the production of vaccines, blood and blood 
components and cell and gene therapy products.
    In addition, in order to provide effective regulatory review of 
biological products, the Center for Biologics Evaluation and Research 
(CBER) conducts mission-related research programs. This research 
greatly expands our knowledge of fundamental biological processes and 
provides a strong scientific base for regulatory review. For example, 
CBER is conducting research to find genes that control development of 
inhibitors against factor VIII in hemophilia patients as part of 
understanding the safety and efficacy of hemophilia therapy. This 
research utilizes the benefits derived from the human genome project, 
in which the variable sites in the human genome have been cataloged and 
methods for analysis of a large number of polymorphic sites in the 
genome were made possible.

    Question 18. As you know, the FDA Modernization Act sought to 
provide the Agency with new tools to address the rapidly changing 
technologies associated with medical devices. With the rapid 
advancement of science, including genomics and proteomics, soon it may 
be possible to prevent disease before it starts, treat those at risk 
preemptively, and develop personalized treatments for those who do fall 
ill. What new tools will FDA need to transform FDA's current approval 
process to evaluate 21st century science?
    Answer 18. As previously stated, the FDA of the 21st Century must 
incorporate modern management tools and processes to meet the 
challenges of today, while creating the scientific tools and 
technologies to address the ever-evolving, increasingly complex issues 
of the future. To accomplish this task, FDA will require 21st Century 
IT infrastructure and personnel expertise to manage and interpret the 
data from modem technology. Additionally, we will continue working 
diligently to assure proper development of guidance, proper 
modifications of regulations (when appropriate) and proper staffing to 
assure rapid review of new technology.
    The Critical Path Initiative is FDA's effort to stimulate and 
facilitate a national effort to modernize the scientific process 
through which a potential human drug, biological product, or medical 
device is transformed from a discovery or ``proof of concept'' into a 
medical product. Through this Initiative, FDA took the lead in the 
development of a Critical Path Opportunities List and Report to 
describe and provide examples of how new scientific discoveries--in 
fields such as genomics and proteomics, imaging, and bioinformatics--
could be applied to improve the accuracy of the tests we use to predict 
the safety and efficacy of investigational medical products. Additional 
information about the critical path initiative, including the List and 
Report, may be accessed at http://www.fda.gov/oc/initiatives/
criticalpath/.

    Question 19. FDA is working on adaptive clinical trial techniques, 
which will result in a clearer indication of who can benefit from the 
drug and a narrower indication. Will this type of drug development 
produce drugs with which we will have greater confidence in safety?
    Answer 19. There are many aspects to the adaptive trial approach. 
One approach may be to better target those study subjects that may be 
at higher (or lowered) risk for certain adverse events. Another way may 
be to better differentiate patient subpopulations with improved 
benefit/risk profiles.
    With the use of prospectively adaptive study designs, researchers 
may be able to select a promising dose regimen that may help minimize 
safety concerns or increase chances of success for late phase drug 
development. These types of designs may allow the sponsor to drop doses 
early on in the process that may be cause for safety concerns or lack 
of effect. This approach is more likely to produce a final tested 
regimen that will be both safe and effective. FDA is very interested in 
discussing adaptive trial design strategies with drug developers in an 
effort to foster innovation and increase drug development efficiency.
   Response to Questions of Senator Burr by Andrew C. von Eschenbach
    Question 1. Can you please update the committee on the efforts the 
Agency is taking, in advance of the September 30th effective date of 
the Combat Meth Act, to implement that statute and its provisions 
addressing pseudoephedrine-based meth diversion?
    Answer 1. While the primary responsibility for implementation of 
the Combat Meth Act is with the Department of Justice (DOJ), FDA has 
acted to ensure regulated industry understands its obligations with 
respect to FDA-regulated products. Immediately after enactment, we 
provided manufacturer and drug information to the Drug Enforcement 
Administration (DEA) needed for DEA's rulemaking on manufacturer 
production and import quotas, part of the Combat Meth Act.
    Also, the Office of Non-Prescription Products (ONP) is interacting 
with manufacturers to help them interpret the Combat Meth Act 
provisions for packaging of both NDA and OTC monograph products. For 
example, OTC products that are marketed under the OTC Drug Review may 
be reformulated following the stipulations for active ingredients, 
manufacturing, and labeling that are set out in the regulations 
associated with the OTC monographs. These reformulations do not require 
approval by the FDA prior to marketing. Accordingly, an immediate 
release tablet containing pseudoephedrine as a decongestant in 
combination with an antihistamine could be reformulated under the 
monograph to contain an alternative decongestant, phenylephrine, in 
combination with the same antihistamine. This reformulation would not 
require prior approval, supporting a rapid transition from products 
containing pseudoephedrine to products using other antihistamines. In 
addition, a new salt of phenylephrine was recently added to the 
monograph to allow manufacturers more flexibility in formulating 
products.
    In addition, OTC products that are marketed under New Drug 
Applications (NDAs) require FDA review and approval prior marketing of 
a reformulated product. Such supplementary applications are reviewed 
under the specific timelines and procedures associated with the 
Prescription Drug User Fee Act (PDUFA) and other pertinent regulations. 
ONP interacts with applicants to insure that only essential testing is 
required to demonstrate that the reformulations will be safe and 
effective. For instance, applicants would, in general, not be required 
to conduct clinical trials to demonstrate the safety and effectiveness 
of a product reformulated to include phenylephrine in place of 
pseudoephedrine. Applicants would instead be able to demonstrate the 
bioequivalence of the new product in humans compared to reference 
standards, a lesser demand on applicant resources.

    Question 2. As you know, the Senate Appropriations Committee Report 
on the fiscal year 2007 FDA Appropriations Bill (like the House 
Appropriations Committee Report) includes an ``Expedited Filing'' 
provision that directs the Commissioner to encourage, expedite, and 
support the filing, review, and final action on any new drug 
application, or supplement to a new drug application, seeking approval 
of a combination of active ingredients previously approved as safe and 
effective, that would replace or provide a therapeutic alternative to a 
currently-marketed drug product that contains an active ingredient that 
currently is the subject of diversion and/or abuse outside regulated 
channels of commerce. In the context of this Appropriations provision, 
would you please delineate for the committee the steps that the Agency 
has taken to enhance access to new prescription combinations of safe 
and effective marketed drugs that could provide alternative therapies 
to replace pseudoephedrine-containing products and address major public 
health and safety concerns arising from meth production?
    Answer 2. Products which require New Drug Applications (NDA) or a 
supplement to an NDA (SNDA) may qualify for a priority review. We will 
meet with applicants to determine if such applications qualify to be 
considered under priority review. The ability to actually develop such 
a formulation and provide data to demonstrate that it is abuse 
resistant (and not simply defeatable by another mechanism) is complex. 
We interact with such applicants to ensure that only essential testing 
is required to demonstrate that the reformulations will be safe and 
effective. For instance, clinical trials are not required in any 
instance in which a demonstration of bioequivalence in humans can be 
appropriately applied. This may help shorten the time necessary to 
provide data for the NDA or SNDA. We also will respond to submissions 
and meeting requests quickly so that access is not delayed based upon 
the ability of a company to get feedback or to interact with the 
Agency.
  Response to Questions of Senator DeWine by Andrew C. von Eschenbach
    Question 1. What kind of restrictions will be in place to ensure 
that Plan B does not end up in the hands of children under 18?
    Answer 1. Duramed has agreed to conduct a ``Point-of-Purchase 
Monitoring Program'' to track how Plan B is being sold at the time of 
purchase. Using the data collected, the sponsor agrees to document and 
analyze the level of comprehension of the Plan B prescription age 
requirement and how it is handled at the point of purchase. The program 
will be conducted twice in the first year and annually thereafter. The 
sponsor also agreed to report repeat violators to the relevant State 
Boards of Pharmacy. Finally, the sponsor committed to report to FDA on 
the results of these activities on a 6-month interval beginning 30 
calendar days after the 6-month interval commencing on the date of the 
approval of the amended sNDA. Monitoring of the program's effectiveness 
will allow FDA to assess whether further modifications will be 
necessary to prevent inappropriate use of Plan B. For details of the 
other commitments made by the sponsor to support the OTC marketing of 
Plan B, see the attached approval letter, labeling, and the CARE 
program.

    Question 2. What penalty, if any, will there be for manufacturers 
or distributors who distribute Plan B to children under 18?
    Answer 2. The sponsor committed to report to FDA on the results of 
its point-of-purchase monitoring program on a 6-month interval 
beginning 30 calendar days after the 6-month interval commencing on the 
date of the approval of the amended sNDA. In addition, the sponsor 
agreed to report repeat violators to the relevant State Boards of 
Pharmacy. Monitoring of the program's effectiveness will allow FDA to 
assess whether further modifications will be necessary to prevent 
inappropriate use of Plan B.

    Question 3. What penalty, if any, will there be for pharmacies or 
pharmacists who distribute Plan B to children under 18?
    Answer 3. The same penalties that would apply to any pharmacy or 
pharmacists who dispense a prescription product without a valid 
prescription would apply.

    Question 4. The Best Pharmaceuticals for Children Act (BPCA), 
passed in 2002, has resulted in more than 100 changes to drug labels 
reflecting pediatric information. BPCA is due to be reauthorized next 
year, what proposals would you make for strengthening this important 
legislation to produce an even greater number of drugs labeled for 
children?
    Answer 4. I believe that BPCA has been an important tool in 
obtaining needed pediatric information to treat pediatric patients. We 
have been reviewing possible improvements that could make the program 
even more effective. Our review is not yet complete. If we determine 
new legislative proposals are necessary, we look forward to working 
with you to enhance the program.

    Question 5. BPCA encourages pediatric drug studies by providing an 
additional 6 months of patent protection to a drug if sponsors respond 
satisfactorily to a written request by FDA. Several proposals in 
Congress have been made to limit the patent extension or to ``tier'' 
the length of the extension based on the sales of the drug. What would 
be the effect of such proposals on the number of pediatric drug studies 
conducted? Does FDA have the capacity to administer a system where 
exclusivity extensions are ``tiered?''
    Answer 5. We understand that there are a number of proposals being 
discussed by external groups to change the way the pediatric 
exclusivity period is implemented. We have not yet evaluated these 
proposals in detail. As we approach reauthorization next year, our 
primary concern will be to ensure that (1) the program remains 
effective in getting drug products labeled for pediatric use, and (2) 
FDA is not given additional burdens or responsibilities that we are 
unable to handle within our public health mission and level of funding.

    Question 6. The European Union recently adopted legislation to 
encourage testing and development of drugs for children. Did the 
European Union consult FDA in the development of this legislation? How 
does the EU model differ from the United States' approach to pediatric 
drug development and testing? In particular, how does the EU approach 
to studying generic drugs for children differ from the United States?
    Answer 6. The EU regulation for pediatric product development, 
which will be implemented later this year, combines the incentive 
aspects of BPCA and the requirement aspects of PREA into one 
regulation. Prior to finalizing the amendments the European Medicines 
Agency (EMEA) consulted with FDA on numerous occasions concerning U.S. 
pediatric initiatives.
    FDA does not yet have a detailed analysis on all of the differences 
between the U.S. and EU approach to studying innovator and generic 
drugs for children, but can provide some general information on the 
overall EU pediatrics program. The EU model provides a mechanism to 
obtain pediatric information on products with marketing protection (on-
patent products), products with no marketing protection (off-patent 
products), and orphan products. There also is a post-marketing mandate 
that obligates sponsors to monitor efficacy and adverse drug reactions 
of all products approved for pediatric indications within 2 years of 
approval.
    The EU model has many similarities to the U.S. approach. Both 
include an incentive for conduct of pediatric studies, both require 
that sponsors conduct certain studies, and both provide a mechanism for 
waivers and deferrals. Some key provisions are:

     The EU approach requires that all products seeking a 
marketing approval (``authorization''), with or without a pediatric 
indication, will go through a Pediatric Committee which will work to 
develop the Pediatric Investigational Plan (PIP). The incentive cannot 
be awarded unless the studies are consistent with the PIP.
     Under the EU system, the Pediatric Committee will be 
primarily responsible for the scientific assessment and development of 
the PIP and for administering the system of waivers and deferrals. In 
the United States, the BPCA process and the PREA process operate with 
less centralization. Written Requests issued by the FDA under BPCA, are 
drafted by the review divisions and reviewed by a central review team 
called the Pediatric Implementation Team (PDIT). The review divisions 
also determine the studies required for and the availability of waivers 
and deferrals under PREA.
     Under the EU system, products not covered by a patent or a 
supplementary protection certificate may qualify for a new type of 
authorization called a ``Pediatric Use Marketing Authorisation'' or 
PUMA. This provides 10 years of data protection, use of the existing 
brand name (brand name recognitions) and a symbol on the label 
indicating the product has been studied for this indication in 
pediatrics.
     All EU products which have participated in the pediatric 
process will be identified on their labels with a symbol that will 
indicate the product has been studied in the pediatric population.
     Under the EU system, orphan products can obtain an 
additional 2 years of marketing exclusivity for studies conducted in 
the pediatric population. In the United States, these products would be 
eligible for 6 months marketing exclusivity.

    Question 7. The Pediatric Research Equity Act (PREA) is also due to 
be reauthorized next year. PREA has been successful in making pediatric 
studies a routine component of a new drug application or supplement. 
Does FDA track the number, types of studies and labeling changes 
resulting from PREA?
    Answer 7. PREA was passed into law on December 3, 2003 and is 
retroactive to April 1, 1999. Preliminary numbers indicate that for 
applications submitted to the Agency since April 1, 1999, 286 
applicants have fulfilled their pediatric studies requirements under 
PREA for CDER. CDER has granted 570 waivers of pediatric studies and 
429 deferrals of pediatric studies pursuant to PREA provisions. We do 
not have a specific combined tracking system for the numbers and types 
of studies from each division. We are now in the process of compiling 
labeling changes that resulted from PREA studies and expect to be able 
to publicly post these labeling changes to our pediatric Website by the 
end of this year. Studies that have been deferred upon approval of the 
drug are listed in the Post-Marketing Study Commitments Database that 
can be located on the CDER Website. The Center for Biologics Evaluation 
and Research (CBER) had 16 approved Biologics License Applications 
(BLA) and Biologics License Supplements (BLS) submissions received from 
April 1, 1999 through August 21, 2006 which included the complete 
required pediatric studies. Since April 1, 1999, CBER has granted 24 
deferrals and 5 waivers.

    Question 8. FDA does not have explicit authority to distinguish on 
a label whether a product has been studied in children and found not to 
be effective or if it has not been studied in children. Is explicit 
legislative authority necessary and, if granted, how would it improve 
the speed of labeling changes? Are there other resources or authorities 
FDA needs to reduce the time it takes for pediatric information to be 
included on a drug label?
    Answer 8. Increasingly, product labeling is being used to convey 
the current state of knowledge about the safety and efficacy of a drug 
in the pediatric population. We already have begun to implement an 
effort to ensure that label changes are made for all drugs for which 
studies are submitted under BPCA. These labeling changes aim to ensure 
that products studied under BPCA have labeling that includes more 
information than the statement ``safety and efficacy had not been 
established in the pediatric population.'' Thus, where a study is 
inconclusive about safety or effectiveness, the labeling may describe 
the results of the study without stating that the drug should or should 
not be used in certain pediatric populations. Similarly, if FDA has 
information that establishes that a drug does not work in pediatric 
populations or if clinical trials reveal a safety concern, FDA would 
place that information in the labeling, even if the drug is not 
approved for use in the pediatric population.
    Section 5 of the BPCA provides a process for timely labeling 
changes for drugs granted exclusivity, including a provision for 
referral to the Pediatric Advisory Committee. Although this process 
does not apply to labeling changes for studies performed under BPCA 
where exclusivity was not granted, nor for studies conducted outside of 
the scope of BPCA, we have moved forward to ensure sufficient 
information will be included in the label. The changes made in BPCA 
have been of great assistance in ensuring more prompt agreements once 
the supplement has been reviewed and acted on by FDA.
    There is also legislative authority granted by PREA that allows us 
to require sponsors to include information in their label indicating 
that pediatric studies were waived because they believe the drug would 
not be effective in pediatric patients or because there are safety 
concerns for pediatric patients.
    FDA acknowledges that we use various terminologies in labeling to 
describe the results of studies, some of which may not convey, as 
clearly as one might hope, if data were collected in pediatric 
patients. FDA is working to improve the clarity of pediatric 
information included in labeling and will continue to do so.

    Question 9. Cutting-edge research and revolutionary technologies 
have led to the development of countless innovative medical devices, 
allowing patients to live longer, healthier lives. However, as science 
and medicine move forward, children are at risk of being left behind. 
Too few critical medical devices are designed specifically with 
children's needs in mind. What efforts are being made by FDA to 
increase the access of children to appropriate medical devices?
    Answer 9. Although cutting-edge research and revolutionary 
technologies have led to the development of new innovative devices, 
pediatric device development faces additional challenges that may cause 
it to lag behind adult device development. The type of applicants 
(small companies) and obstacles to the development of pediatric 
devices, including the difficulties in conducting device clinical 
trials involving children, make this issue extremely challenging. FDA 
believes that communication between the Agency, industry, patients, and 
clinicians is essential for fostering pediatric device innovation. To 
this end, CDRH has been focusing on increasing interactions among these 
parties during product development and pre-market review. Examples 
include:

     CDRH is working to develop more device-specific guidances 
that would, when appropriate, include advice for manufacturers on 
issues such as the type of modifications, testing, and/or labeling 
changes needed for the device to be used in pediatric populations.
     CDRH is holding workshops to discuss the development of 
critical pediatric devices. In 2005, CDRH held an advisory panel 
meeting to discuss clinical trial designs for, and ethical issues 
related to, the evaluation of devices to treat pediatric obesity. In 
2006, FDA sponsored a workshop for manufacturers of pediatric left 
ventricular assist devices intended for infants and children from 2 kg 
to 25 kg with congenital or acquired cardiovascular disease. Finally, 
in collaboration with NIH, CDRH held a public workshop to identify new 
approaches to evaluating fetal intrapartum monitoring devices, 
including the possible development of a large validated test database.
     As part of FDA's Critical Path Initiative, CDRH is 
collaborating with the Juvenile Diabetes Research Foundation to 
accelerate development of an artificial pancreas for children with 
diabetes by creating new clinical protocols and improved outcome 
measures for evaluating the performance of continuous glucose sensors 
and a closed loop artificial pancreas.

    Question 10. Is FDA currently tracking the number of devices 
approved for children each year along with the need for such devices? 
If not, why not?
    Answer 10. FDA does not have a data system capable of tracking all 
studies, submissions, or approvals for pediatric devices, but as 
discussed below, we have made important strides in this area. Some 
medical devices are specifically designed for use on infants and 
children, such as infant incubators and infant radiant warmers, and 
each has a unique classification regulation associated with it. For 
these devices, we are able to identify the number of applications that 
have been cleared or approved. Under a provision in the Medical Device 
User Fee and Modernization Act of 2002, device submissions solely for 
pediatric use are exempt from user fees in order to encourage their 
development. FDA's user fee database allows us to identify those 
applications that seek to take advantage of this incentive. Most 
medical devices, however, are indicated for general use, which often 
includes pediatric use with the only difference being the size of the 
device available. Since these devices can be used in both the pediatric 
and adult populations, these are not specifically tracked as pediatric 
devices.
    CDRH believes there are potential advantages in being able to track 
pediatric device submissions and approvals, and we are modifying our 
tracking systems to accomplish this. For instance, in addition to 
tracking the number of marketing clearances/approvals for pediatric 
devices, tracking the number of submissions of Investigational Device 
Exemption (IDE) applications would allow us to report how many studies 
of pediatric devices are currently ongoing. CDRH is currently making 
these database changes, so that we will be able to track the number of 
PMAs, HDEs, and IDEs for pediatric indications in the near future.
    In addition, FDA believes there may be value in tracking pediatric 
subpopulations (neonates, infants, children adolescents) for both 
marketing and investigational applications. We are examining whether 
and how our current database can accommodate such tracking, as well as 
determining the resources necessary to making such changes

    Question 11. Does FDA agree with the findings and recommendations 
in the Institute of Medicine's July 2005 report, ``Safe Medical Devices 
for Children,'' on adverse event reporting, monitoring of post-market 
study commitments, strengthening post-market studies and 
responsibilities for medical device safety? What actions have FDA taken 
to implement IOM's recommendations?
    Answer 11. The FDA agrees that post-market surveillance of 
pediatric devices needs to be improved, and has taken a number of steps 
in this area. With regard to reporting of adverse events, FDA has been 
working to improve its capabilities to receive adverse event 
information for all devices electronically. Rapid development and 
implementation of these systems would enable the Agency to quickly 
identify and address post-market problems and elevate the quality of 
information and data received by using automatic error-checking 
routines. Currently, CDRH receives over 200,000 reports each year. 
These reports are manually entered into the FDA database at a cost of 
over $2.5M annually. Electronic Medical Device Reporting (eMDR) will 
allow electronic data entry and processing of all post-market medical 
device adverse event information. Cost-benefit analyses show that eMDR 
can save a significant portion of the data-entry cost, with potential 
for increased savings longterm. In addition, reports will be available 
for review and action immediately after submission. FDA's MedSun 
Program is also well-positioned to strengthen device-related 
surveillance and safety activities.
    The IOM also recommended that the FDA improve the procedures for 
monitoring the status of post-market study commitments. Beginning in 
early 2005, the Center instituted a new electronic tracking system and 
draft guidance entitled ``Procedures for Handling Post-Approval Studies 
Imposed by PMA Order.'' FDA intends to post the status of these studies 
on the Agency's Website. These changes will enable FDA--and the 
public--to better monitor the progress of the trials and the submission 
of required status reports.
    FDA has also strengthened its post-market studies and 
responsibilities for medical device safety in several ways. The Center 
has expanded use of its epidemiologists and pediatricians during the 
pre-market review process. The epidemiologists have also helped to: 
develop a comprehensive plan for monitoring devices postmarket; 
determine the need for post-approval studies; lead the design of the 
post-approval study protocols; and work interactively with the sponsors 
to finalize the post-approval study protocols at the time of device 
approval. After device approval, epidemiologists continue to closely 
monitor the progress of the studies and critique interim and final 
reports. The Center is also planning periodic presentations to Advisory 
Panels on the status of post-approval studies.

    Question 12. As you know, FDA is one of the key Federal agencies 
that must be in constant readiness for the next public health threat--
the risks that have yet to blossom into full blown challenges. Drug-
resistant infections like MRSA (methicillin-resistant Staphylococcus 
aureus) are epidemic. CDC says 60,000 to 80,000 Americans die every 
single year from hospital-acquired infections like MRSA. What is FDA 
doing about this infectious disease threat?
    Answer 12. FDA provides regulatory guidance to sponsors to 
facilitate the development of drugs to treat infections caused by 
resistant pathogens such as methicillin-resistant Staphylococcus aureus 
(MRSA). Drugs for the treatment of MRSA infections are often eligible 
for Fast Track designation and/or priority review because MRSA 
infections may be serious and life-threatening and products that treat 
MRSA infections may address an unmet medical need.
    There have been several drugs that have garnered approval of 
clinical indications that include MRSA as one of the listed bacterial 
pathogens within the indication. These include:

    (a) Pfizer's product Zyvox (linezolid) for the following 
indications: nosocomial pneumonia and complicated skin and skin 
structure infections, including diabetic foot infections; both 
indications include MRSA as one of the listed bacterial pathogens.
    (b) Wyeth's product TygacilTM (tigecycline) for complicated skin 
and skin structure infections includes MRSA among the listed bacterial 
pathogens.
    (c) Cubist's product Cubicin (daptomycin) for complicated skin and 
skin structure infections and the recently-approved indication of 
Staphylococcus aureus bloodstream infections, both indications include 
the bacterial pathogen MRSA.

    FDA conducted priority reviews for these products, committing 
resources to make these products available more quickly, while still 
ensuring their safety and effectiveness.

    Question 13. Pseudoephedrine (PSE) is a safe and effective 
decongestant in many over-the-counter (OTC) medicines for treatment of 
the common cold and hay fever. However, PSE also is a precursor 
chemical being diverted to illicit manufacture of methamphetamine. 
Addressing this critical public health and safety problem necessitates 
transitioning consumers relying on PSE-containing OTC products to 
therapeutically-equivalent replacements that cannot be used in meth 
production.
    During 2005, the Congress took action, reflected in the Conference 
Report on the Combat Meth Act, to facilitate FDA approval of such 
reformulated OTC products. Some longstanding OTC medicines that 
currently contain PSE and are marketed under the applicable FDA 
monograph potentially can be reformulated to include an alternate 
active ingredient in accordance with the steps Congress took in the 
Combat Meth Act.
    In approaching the September 30th effective date of the Combat Meth 
Act, Congress understands there is a similar opportunity to facilitate 
development of new prescription products that could be approved by FDA 
as safe and effective therapeutic alternatives to fill the need 
currently met by PSE that could provide similar therapeutic benefits 
and be equally convenient--but without the diversion or abuse risks 
associated with PSE.
    Can you please update the committee on the efforts the Agency is 
taking, in advance of the September 30th effective date of the Combat 
Meth Act, to implement that statute and its provisions addressing 
pseudoephedrine-based meth diversion?
    Answer 13. While the primary responsibility for implementation of 
the Combat Meth Act is with the Department of Justice (DOJ), FDA has 
acted to ensure regulated industry understands its obligations with 
respect to FDA-regulated products. Immediately after enactment, we 
provided manufacturer and drug information to the Drug Enforcement 
Administration (DEA) needed for DEA's rulemaking on manufacturer 
production and import quotas, part of the Combat Meth Act.
    Also, the Office of Non-Prescription Products (ONP) is interacting 
with manufacturers to help them interpret the Combat Meth Act 
provisions for packaging of both NDA and OTC monograph products. For 
example, OTC products that are marketed under the OTC Drug Review may 
be reformulated following the stipulations for active ingredients, 
manufacturing, and labeling that are set out in the regulations 
associated with the OTC monographs. These reformulations do not require 
approval by the FDA prior to marketing. Accordingly, an immediate 
release tablet containing pseudoephedrine as a decongestant in 
combination with an antihistamine could be reformulated under the 
monograph to contain an alternative decongestant, phenylephrine, in 
combination with the same antihistamine. This reformulation would not 
require prior approval, supporting a rapid transition from products 
containing pseudoephedrine to products using other antihistamines. In 
addition, a new salt of phenylephrine was recently added to the 
monograph to allow manufacturers more flexibility in formulating 
products.
    In addition, OTC products that are marketed under New Drug 
Applications (NDAs) require FDA review and approval prior marketing of 
a reformulated product. Such supplementary applications are reviewed 
under the specific timelines and procedures associated with the 
Prescription Drug User Fee Act (PDUFA) and other pertinent regulations. 
ONP interacts with applicants to insure that only essential testing is 
required to demonstrate that the reformulations will be safe and 
effective. For instance, applicants would, in general, not be required 
to conduct clinical trials to demonstrate the safety and effectiveness 
of a product reformulated to include phenylephrine in place of 
pseudoephedrine. Applicants would instead be able to demonstrate the 
bioequivalence of the new product in humans compared to reference 
standards, a lesser demand on applicant resources.

    Question 14. As you know, the Senate Appropriations Committee 
Report on the fiscal year 2007 FDA Appropriations Bill (like the House 
Appropriations Committee Report) includes an ``Expedited Filing'' 
provision that directs the Commissioner to encourage, expedite, and 
support the filing, review, and final action on any new drug 
application, or supplement to a new drug application, seeking approval 
of a combination of active ingredients previously-approved as safe and 
effective, that would replace or provide a therapeutic alternative to a 
currently-marketed drug product that contains an active ingredient that 
currently is the subject of diversion and/or abuse outside regulated 
channels of commerce. In the context of this Appropriations provision, 
would you please delineate for the committee the steps that the Agency 
has taken to enhance access to new prescription combinations of safe 
and effective marketed drugs that could provide alternative therapies 
to replace pseudoephedrine-containing products and address major public 
health and safety concerns arising from meth production?
    Answer 14. Products which require New Drug Applications (NDA) or a 
supplement to an NDA (SNDA) may qualify for a priority review. We will 
meet with applicants to determine if such applications qualify to be 
considered under priority review. The ability to actually develop such 
a formulation and provide data to demonstrate that it is abuse 
resistant (and not simply defeatable by another mechanism) is complex. 
We interact with such applicants to ensure that only essential testing 
is required to demonstrate that the reformulations will be safe and 
effective. For instance, clinical trials are not required in any 
instance in which a demonstration of bioequivalence in humans can be 
appropriately applied. This may help shorten the time necessary to 
provide data for the NDA or SNDA. We also will respond to submissions 
and meeting requests quickly so that access is not delayed based upon 
the ability of a company to get feedback or to interact with the 
Agency.

    Question 15. While both drugs and medical devices are used to 
diagnose and treat human illness, there are also significant 
differences between the two categories of FDA-regulated products that 
Congress recognized in drafting their respective statutory frameworks. 
Will you continue to treat medical device issues on their own merits 
and tailor medical device policies so as to recognize their unique 
features and unique role in medical practice?
    Answer 15. FDA recognizes that there are important inherent 
differences between drugs and devices and these differences require 
unique regulatory approaches.
    Whereas small changes in a drug compound can often have profound 
effects on its mechanism of action and therefore the product's safety 
and effectiveness, minor changes in devices can often be made without 
greatly altering the function of the device. CDRH's 510(k) pre-market 
notification regulations for lower risk devices allow many products 
which are ``substantially equivalent'' to existing, legally marketed 
devices, to reach the marketplace in an efficient manner, for example, 
based on pre-clinical bench and/or animal data alone. Every year CDRH 
clears thousands of new devices through this less-burdensome mechanism. 
FDA has also succeeded in applying the appropriate level of regulatory 
controls to assure the safety and effectiveness of combination products 
where there is a merging of devices and drugs.
    How devices are used also requires us to tailor device-specific 
policies. For example, most drugs are administered orally or 
intravenously and a placebo is often indistinguishable to the patient 
and/or clinician in a clinical trial. However, devices often require 
surgical implantation or cause a physical reaction to the body which a 
patient and physician would be well aware of. In addition, device use 
(and hence safety and effectiveness) can often be affected by the 
experience and skill level of the user. These and other issues make 
device trial design and data interpretation especially challenging.
    We also recognize the financial burden on sponsors when clinical 
trials require expensive operations or where the nature of the device 
requires particularly long follow-up. FDA's regulations and policies 
allow us to take these issues into consideration by providing ample 
latitude in defining what constitutes ``valid scientific evidence.''
    In summary, our current device classification system allows us to 
apply different policies and regulations to products depending on their 
associated risk and/or equivalence to other similar products in a least 
burdensome way, thus enabling FDA to address the unique issues 
associated with medical devices.

    Question 16. The FDA's Critical Path Initiative has potential to 
improve the development process for medical technologies and bring 
better devices to market faster. Yet most of FDA's projects under the 
Critical Path initiative are focused on drugs--very few are dedicated 
to medical technology development. Given that the device development 
process for drugs and devices are vastly different, will you work to 
ensure the Agency dedicates more projects to device issues?
    Answer 16. I am committed to ensuring the Agency's Critical Path 
Initiative encompasses devices and work is underway in this area. For 
example, FDA has established partnerships with the Juvenile Diabetes 
Research Foundation to work toward development of an artificial 
pancreas, with the Critical Path Institute to use genomics for better 
dosing decisions for anti-coagulants, and with the University of Utah 
on virtual models to evaluate coronary and peripheral vascular stents. 
The Agency is actively looking for other collaborative work 
partnerships to ensure devices are appropriately represented in the 
Critical Path program.
    Also, we would note that it could be misleading to see these as 
narrow categories of projects. The List is divided into six priority 
areas, rather than into product types, because these priorities--and 
many of these projects--apply across product areas and will require 
collaboration among experts in the development of drugs, devices, and 
biologics in order to succeed. For example, work to improve clinical 
trial design or to develop a robust clinical bioinformatics 
infrastructure will improve development of all medical products. 
Similarly, the full potential of genomic biomarkers to usher in an era 
of personalized medicine cannot be achieved without new approaches, not 
only to development of the drug or biologic therapy, but also to 
development of the partner in vitro diagnostic device needed to 
identify the presence or absence of the biomarker in an individual.
  Response to Questions of Senator Ensign by Andrew C. von Eschenbach
    Question 1. Plan B contains the same ingredient used in 
prescription birth control pills, only in the case of Plan B, each pill 
contains a higher dose and the product has a different dosing regimen. 
Given this, why should we allow the stronger drug, Plan B, to be made 
over the counter when birth control is not?
    Answer 1. Although the dose of the progestin in Plan B (0.75 mg 
levonorgestrel per tablet or 1.5 mg per treatment) is higher than that 
in individual prescription birth control pills, Plan B is to be used 
only as emergency or back up contraception while birth control pills 
that contain both estrogen and progestin (0.1 to 0.15 mg 
levonorgestrel) are generally taken for 21 of every 28 days in a cyclic 
pattern.
    A major consideration for requiring that combination oral 
contraceptives be prescription-only products is the risks associated 
with oral contraceptive products that contain an estrogen. Women who 
take traditional oral contraceptives, in contrast to women who use Plan 
B for emergency or back up contraception, are at an increased risk of 
developing serious and sometimes fatal venous or arterial blood clots. 
This increased risk is attributed primarily to the estrogen component 
of oral contraceptives when taken on a cyclic, chronic basis. A similar 
increased risk for serious blood clots has not been reported for users 
of Plan B.

    Question 2. From a broad perspective, what changes in FDA 
regulation and policy do you believe are necessary in order to 
modernize and improve the drug development, manufacturing, and review 
process?
    Answer 2. On March 16, 2004, in the document ``Innovation/
Stagnation: Challenge and Opportunity on the Critical Path to New 
Medical Products,'' FDA released a report addressing the recent 
slowdown in innovative medical therapies submitted to the FDA for 
approval. The report described the urgent need to modernize the medical 
product development process--the Critical Path--to make product 
development more predictable and efficient. A key insight is that FDA, 
industry, and academia are stakeholders in helping to coordinate, 
develop and disseminate solutions to these scientific hurdles. FDA has 
demonstrated a commitment to designating topics for joint development 
and investment while preparing internally for these changes.
    Efforts are in progress to require clinical study data be provided 
in electronic format and require the use of standard data structure, 
terminology and code sets. The goals of this initiative will be to 
improve the efficiency of evaluation of the safety and efficacy of 
investigational treatments, enhance communication between the Agency 
and applicants, facilitate development of a more efficient review 
environment (e.g., access to data, orientation, redundancy, training, 
analysis tools), improve efficiency for clinical research, facilitate 
design and conduct of clinical trials, and enhance communication 
between researchers and study sponsors.
    FDA leadership is developing a series of concept papers and 
guidance documents in areas such as advanced clinical trial designs, 
building greater efficiency in late stage clinical research, predictive 
toxicology models, use of biomarkers in drug development, and adverse 
event data mining. Collectively, these documents will help articulate 
the pathway toward improvement of the drug development process.
    The regulatory groundwork for pharmacogenomics in the Critical Path 
is well underway. A final guidance on voluntary submissions of 
pharmacogenomic data has been issued and a concept paper on how to co-
develop a drug or biological therapy along with a device test in a 
scientifically robust and efficient way has been created. The CDRH/CDER 
Draft Guidance for Industry and FDA Staff: Pharmacogenetic Tests and 
Genetic Tests for Heritable Markers was issued on February 9, 2006. 
This draft guidance document is intended to facilitate progress in the 
field of pharmacogenomics and genetics by helping to shorten 
development and review timelines, facilitate rapid transfer of new 
technology from the research bench to the clinical diagnostic 
laboratory, and encourage informed use of pharmacoge-
nomic and genetic diagnostic devices. As part of the cGMP Initiative of 
the 21st Century, CDER continues to make significant changes to our 
regulatory policies and the drug review process.
    FDA will now be using a quality systems approach to improve the 
predictability, consistency, integration, and overall effectiveness of 
our entire regulatory operation. This quality systems model, now 
incorporated into the FDA Staff Manual Guide, Quality Systems Framework 
for Internal Activities, defines the essential quality elements to 
consider as part of any system that controls an internal FDA regulatory 
activity.
    The Agency has released a draft guidance (Quality Systems Approach 
to Pharmaceutical Current Good Manufacturing Practice Regulations) 
describing how industry can implement quality management systems and 
risk management principles into the manufacture of pharmaceuticals.
    CDER has developed and is implementing a new risk-based 
pharmaceutical quality assessment system to replace its current CMC 
review process. This new system should reduce the need to submit 
manufacturing supplements and increase first-cycle approval of new drug 
applications, thereby making drug products available to patients in a 
timelier manner. The system should also encourage manufacturers to 
implement new technologies, such as process analytical technology, and 
facilitate continuous manufacturing improvements.
    FDA has revised its regulatory procedures for determining when to 
issue warning letters in response to noncompliance with CGMP 
requirements. All proposals to issue warning letters to human and 
animal drug and medicated feed manufacturers are reviewed by, among 
others, the centers with product jurisdiction. The Centers' continued 
role in the process will ensure that adverse findings will be based on 
the best science available. We are enhancing communication and 
coordination between the field and Centers with the goal of identifying 
possible program inconsistencies that can be resolved before a warning 
letter is issued.
    At this time we believe that most of the necessary changes can be 
implemented without changing the regulations, however, as we move 
forward, we may find that regulatory changes may help in the 
implementation process. Currently, there is only one change in the 
regulations that we are working on to facilitate modernization of drug 
regulatory process; that is the regulation that covers how to report 
manufacturing changes and other changes to an approved marketing 
application (i.e., 21 CFR 314.70). The current regulation is more 
prescriptive and not flexible enough to allow manufacturers to 
efficiently implement innovative technologies into their pharmaceutical 
manufacturing plants.

    Question 3. Do you believe that there are areas in which the FDA 
can improve the transparency of some of its regulatory decisions, 
particularly in how it addresses post-market drug safety issues? If so, 
what types of improvements should be made?
    Answer 3. In the last 2 years, FDA has made a concerted effort to 
be more transparent about post-market drug safety issues by providing 
to health care professionals and the public timely information about 
new and emerging important drug risks. Since 2005, FDA has posted 
important new drug risk information on its Internet site, at: http://
www.fda.gov/cder/drug/DrugSafety/Druglndex.htm. This site contains 
information sheets for healthcare professionals and for patients.
    Healthcare Professional Sheets provide a brief description of the 
specific safety issue and recommendations or considerations (such as 
special monitoring or limiting use to specific patients) for the 
practitioner who is prescribing the drug. These sheets also summarize 
the data or other information that was the basis of the alert.
    Patient Information Sheets provide a brief summary of the essential 
information about a specific drug in plain language. When there is an 
emerging safety concern for the drug, this concern will be summarized 
on the patient information sheet, along with the other information 
about the drug.
    These information sheets are widely disseminated through the FDA 
MedWatch list serve program, which reaches more than 65,000 contacts. 
FDA is continuously evaluating this new program to identify ways to 
improve it.
    In 2005 and 2006, the FDA began a series of other efforts to 
improve internal processes for identifying and resolving new safety 
concerns about specific drugs, such as establishing regular meetings to 
review the status of post-marketing drug safety concerns and 
establishing a system for tracking emerging concerns. For more 
information about the many advances FDA is making in this area, please 
visit: http://www.fda.gov/cder/drugSafety.htm.

    Question 4. There is some debate about having the FDA collect data 
related to cost, cost-effectiveness, value, and other reimbursement 
considerations in order to address concerns with the Centers for 
Medicare and Medicaid Services coverage process. As you know, these are 
responsibilities that are outside of the current scope of FDA review.
    Answer 4. I concur that these are the prerogatives of CMS, and I 
look forward to our close collaborations in support of our respective 
missions. Please see the answers to questions 5 and 6 for specific 
information on how FDA and CMS work together.

    Question 5. Do you believe that FDA and CMS have distinct 
regulatory missions and that any harmonization of their 
responsibilities should be approached carefully?
    Answer 5. Yes, FDA and CMS have distinct regulatory missions. 
However, the agencies share similar broad goals for enhancing the 
effectiveness of the health care system and work together productively 
and appropriately to further our respective missions. An excellent 
example of FDA-CMS collaboration is our recent effort to use certain 
CMS data to enhance FDA's computerized Adverse Event Reporting System.

    Question 6. How can the FDA and CMS work together to speed access 
of safe and effective medical technologies for Medicare beneficiaries 
without delaying access to those same technologies by the rest of the 
American public?
    Answer 6. By working together, FDA and CMS can enhance the speed in 
which Medicare beneficiaries, as well as the American public, gain 
access to safe and effective medical technologies. For example, 
industry is encouraged to work with both FDA and CMS simultaneously 
when seeking approval for marketing and Medicare national coverage. 
Working with both agencies at the same time can reduce the time it 
takes for specific medical technologies to be made available to the 
American public and to reduce the time it takes for a Medicare coverage 
decision.

    Question 7. Given that the Medicare program and the Veterans 
Administration reimburse for compounded medicines, that virtually every 
hospital compounds medicines, and that our Armed Forces use compounded 
medications and require their pharmacists to be versed in compounding, 
would you agree that this demonstrates pharmacy compounding is a 
unique, legal and very valuable healthcare practice?
    Answer 7. FDA has long recognized the important benefits of 
traditional pharmacy compounding. FDA regards traditional pharmacy 
compounding as the combining, mixing, or altering of ingredients by a 
pharmacist in response to a physician's prescription to create a 
medication tailored to the specialized medical needs of an individual 
patient. Traditional compounding enables a physician to prescribe, and 
a pharmacist to prepare, medication tailored to the needs of an 
individual patient, such as medication for a patient who is allergic to 
an ingredient in a commercially available drug, or diluted dosages for 
children.
    Because of the benefits of traditional compounding, FDA exercises 
its enforcement discretion toward some kinds of compounding. FDA's 
willingness to exercise enforcement discretion does not change the fact 
that, under the Federal Food, Drug, and Cosmetic Act, compounded drugs 
are ``new drugs'' that require FDA approval before they may be 
marketed. When a pharmacist compounds a drug, by definition, he or she 
creates a new drug under Federal law because the compounded product is 
not ``generally recognized among experts . . . as safe and effective.'' 
The fact that these drugs are produced in a pharmacy does not exempt 
them from the new drug definition.
    Traditional pharmacy compounding serves an important public health 
function by meeting the specialized medical needs of individual 
patients for whom commercially available approved drugs are inadequate 
or inappropriate. FDA has directed its enforcement actions toward 
establishments that manufacture, under the guise of compounding, large 
quantities of unapproved new drugs that are commercial copies of 
approved drugs, or whose compounding practices pose a significant or 
immediate threat to the public health or to the integrity of the drug 
approval processes of the FDA.
    FDA's current enforcement policy with respect to pharmacy 
compounding is articulated in Compliance Policy Guide (CPG), section 
460.200 [``Pharmacy Compound-
ing''] (May 2002), which is available on FDA's Internet site at: 
www.fda.gov/cder/pharmcomp/default.htm. The CPG lists factors that the 
Agency considers in deciding whether to exercise its enforcement 
discretion with respect to pharmacy compounding. The factors in the CPG 
are not intended to be exhaustive and other factors may also be 
appropriate for FDA's consideration.
    FDA has seen abuses, such as large-scale drug manufacturing under 
the guise of pharmacy compounding, compounding drugs that are 
essentially copies of commercially available FDA-approved products or 
that were withdrawn or removed from the market for safety reasons, and 
compounding products containing active ingredients that are not 
components of FDA-approved drugs. In some cases, FDA has reason to be 
concerned about the quality of the drugs being compounded and the 
potential risks to patients who may take them. Some compounding 
pharmacies may lack sufficient controls to ensure product quality or to 
compound difficult products such as sterile or modified release drugs. 
Additionally, compounding that is done on a large scale and is not done 
properly can expose large numbers of patients to health risks 
associated with unsafe or ineffective medications.

    Question 8. The Washington Post recently reported that more than 
one-fifth of all prescriptions for approved drugs are used for off-
label use, which means for uses that, like compounded medicines, are 
not subject to FDA approval requirements for safety and efficacy. Would 
you agree that it is important to protect the right of physicians to 
prescribe such treatments for their patients?
    Answer 8. Once a drug is approved for marketing, a physician may 
prescribe it for uses or in treatment regimens or patient populations 
that are not listed in the FDA-approved labeling. FDA does not 
generally interfere with the practice of medicine, such as the decision 
by a physician to prescribe a legally marketed medication for their 
patient for an indication not listed on the drug's label. Physicians 
under their own responsibility may exercise judgment for the use of an 
approved drug for unlabeled indications when they are satisfied there 
is medical and scientific support that such use may benefit their 
patients.

    Question 9. Are all compounded medications new drugs, and does 
every new compounded prescription need to go through a drug approval 
process?
    Answer 9. All compounded prescription drugs are ``new drugs'' 
within the meaning of the Federal Food, Drug, and Cosmetic Act (FDCA). 
When a pharmacist compounds a prescription drug, by definition, he or 
she creates a new drug under Federal law because the compounded product 
is not ``generally recognized among experts . . . as safe and 
effective.'' The fact that these drugs are produced in a pharmacy does 
not exempt them from the new drug definition.
    Under the FDCA, a ``new drug'' (including a compounded new drug) 
may not be legally introduced, or delivered for introduction into 
interstate commerce in the United States unless it has been pre-
approved by FDA as safe and effective for its intended uses. 
Traditional compounding typically is used to prepare medications that 
are not commercially available; it involves providing a service in 
response to a physician's prescription to accommodate the specialized 
medical needs of a particular patient. In virtually every instance, the 
drugs that pharmacists compound have not been so approved. FDA, as a 
matter of policy, historically has not brought enforcement actions 
against traditional forms of pharmacy compounding.
    FDA has directed its enforcement actions toward establishments that 
manufacture, under the guise of compounding, large quantities of 
unapproved new drugs that are commercial copies of approved drugs, or 
whose compounding practices pose a significant or immediate threat to 
the public health or to the integrity of the drug approval processes of 
the FDA.

    Question 10. According to a recent Institute of Medicine Study, at 
least 1.5 million Americans are sickened, injured, or killed each year 
by errors in prescribing, dispensing, and taking medications. Does the 
FDA receive reports that suggest that medication errors occur and that 
such errors may contribute to adverse health outcomes? Could e-
prescribing help solve these problems? What do you plan to do to 
advance the Agency's drive to reduce medication errors?
    Answer 10. The Food and Drug Administration has been receiving 
reports of medication errors since January 1992. Although there is no 
requirement to submit reports of medication errors to FDA, we receive 
over 5,000 reports yearly, primarily from health care professionals and 
consumers.
    Medication errors occur due to numerous contributing factors at any 
point in the medication use process (e.g., procurement, prescribing, 
preparing/dispensing, administering and monitoring). Patient outcomes 
may vary from ``no harm'' to ``death,'' depending on the drugs involved 
and the nature of the event.
    The Agency's approach to medication error prevention includes the 
review of proposed brand names along with labels, labeling and 
packaging for drugs and biologics to minimize the potential for errors. 
After approval we evaluate, monitor, and take appropriate action based 
on reports of medication errors. We educate and provide feedback to 
health professionals and share information with outside organizations 
involved in preventing medication errors.
    E-Prescribing or Computerized Physician Order Entry (CPOE) has been 
found to improve drug safety. However, CPOE will not in itself solve 
all medication errors. CPOE will have a greater impact on errors that 
result from misinterpretations of prescriber handwriting or 
misinterpretations of incomplete or ambiguous drug orders, and it 
affords a number of checks for health care providers about a patient's 
drug allergies, possible drug interactions, higher-than-recommended 
doses, and drug-laboratory problems.
    In 2004, the Food and Drug Administration (FDA) issued a new rule 
to require certain human drug and biological product labels to have bar 
codes. The bar code for human drug products and biological products 
(other than blood, blood components, and devices regulated by the 
Center for Biologics Evaluation and Research) must contain the National 
Drug Code (NDC) number in a linear bar code. The rule will help reduce 
the number of medication errors in hospitals and other health care 
settings by allowing health care professionals to use bar code scanning 
equipment to verify that the right drug (in the right dose and right 
route of administration) is being given to the right patient at the 
right time. The rule also requires the use of machine-readable 
information on blood and blood component container labels to help 
reduce medication errors.
    On January 18, 2006 FDA issued the physician labeling rule which is 
the first major revision to the format of prescription drug information 
(package insert) in 25 years.
    The revisions are a major public health advance in that they make 
it easier for healthcare professionals to access, read, and use 
prescribing information, and therefore, will enhance the safe and 
effective use of prescription drug products.
    Some of the most significant changes include:

     A new section called Highlights to provide immediate 
access to the most important information about risks and benefits.
     A Table of Contents for easy reference to detailed safety 
and efficacy information.
     The date of initial product approval, making it easier to 
determine how long a product has been on the market.
     A toll-free number and Internet reporting information for 
suspected adverse events to encourage more widespread reporting of 
suspected side effects.
    The new prescription information format will be integrated into 
FDA's other 
e-Health initiatives and standards-setting efforts through a variety of 
ongoing initiatives. As prescription information is updated it will be 
used to provide medication information for DailyMed, a new interagency 
online health information clearinghouse that will provide the most up-
to-date medication information free to consumers, healthcare 
professionals and healthcare information providers. In the future, this 
new information will also be provided through a Website called 
facts@fda, a comprehensive Internet resource designed to give one-stop 
access for information about all FDA-regulated products.
    FDA is committed to working with other government agencies, 
professional and patient groups and industry to continue to reduce the 
incidence of medication errors through better consumer medical 
information, improved drug labeling and naming, and through an enhanced 
electronic health information architecture to ensure that safety 
information is communicated efficiently and effectively.

    Question 11. In terms of drug safety, I am extremely concerned 
about the approval process for RU-486. At least three women in the 
United States have died using RU-486, which was approved under FDA's 
emergency ``Subpart H,'' an approval process reserved only for drugs 
that treat ``severe or life-threatening illnesses.'' Can you please 
explain the approval process for RU-486? How was this drug determined 
to be ``safe and effective,'' and why was this drug approved under an 
accelerated review process, and why is this drug still accessible?
    Answer 11. I strongly support women's health issues and ensuring 
that the medical products FDA regulates are safe and effective for 
consumers who use them. While I was not at FDA when Mifeprex was 
originally approved, I am committed to rigorous post-approval adverse 
event reporting. The Agency takes all adverse event reports seriously, 
and we are especially concerned with reports of deaths of otherwise 
healthy women potentially associated with use of a FDA-approved drug. 
We are monitoring this situation closely.
    FDA's review and approval of the Mifeprex application complied with 
the Federal Food, Drug, and Cosmetic (FD&C) Act and FDA regulations, 
including the requirements under section 505(d) of the FD&C Act that 
(1) there be adequate tests to show that the drug is safe for use under 
the conditions prescribed, recommended, or suggested in the approved 
labeling (section 505(d)(1)) and (2) there be substantial evidence that 
the drug will have the effect it purports or is recommended to have 
under the conditions of use prescribed, recommended, or suggested in 
the labeling (section 505(d)(5)). Section 505(d) defines ``substantial 
evidence'' as ``evidence consisting of adequate and well-controlled 
investigations, including clinical investigations, by experts qualified 
by scientific training and experience to evaluate the effectiveness of 
the drug involved . . . ''
    FDA's approval of the Mifeprex application on September 28, 2000, 
was based on three ``adequate and well-controlled'' studies as that 
term is defined in Title 21, Code of Federal Regulations (CFR) section 
314.126, applicable to new drug applications (NDAs) under 505(b) of the 
FD&C Act. The Mifeprex NDA contained data from three clinical trials (a 
large U.S. trial and two French trials) and safety data from a post-
marketing database of over 620,000 women in Europe who had had a 
medical termination of pregnancy (approximately 415,000 of whom had 
received the combination regimen of mifepristone together with the drug 
misoprostol). These data constituted evidence that mifepristone was 
safe and effective for its approved indication, the medical termination 
of intrauterine pregnancy through 49 days' pregnancy, in accordance 
with section 505(d) of the FD&C Act. Previously, FDA's Reproductive 
Health Drugs Advisory Committee voted 6 to 0 (with two abstentions) on 
July 19, 1996, that the benefits of mifepristone exceeded the risks of 
the product.
    The Mifeprex application was approved under FDA's Subpart H 
regulations (21 CFR part 314 Subpart H). FDA approved the Mifeprex NDA 
under Subpart H because the Agency determined that post-marketing 
distribution restrictions on the product were necessary to ensure its 
safe use. As FDA made clear in the preamble to the final rule adopting 
Subpart H, the Subpart H regulations are intended to apply to serious 
or life-threatening conditions as well as diseases. For example, the 
final rule cites depression and psychoses as ``examples of conditions 
or diseases that can be serious for certain populations or in some or 
all of their phases'' and that therefore drugs to treat them `could be 
covered by the' regulations.'' (57 FR 58942 at 58946, Dec. 11, 1992).
    Under Sec. 314.520 of FDA's regulations, if FDA concludes that a 
drug product shown to be effective can be used safely only if 
distribution or use is restricted, the Agency will require post-
marketing restrictions. As part of the Subpart H approval for Mifeprex, 
distribution of the drug was restricted in several ways, including that 
it must be provided by or under the supervision of a physician who 
meets several qualifications. Approval under this regulation does not 
imply that the review was ``accelerated'' by virtue of reliance on a 
surrogate endpoint, but rather that FDA had concluded that Mifeprex had 
been shown to be effective, but could be used safely only if 
distribution or use was restricted.
    FDA has been following and evaluating safety concerns about 
mifepristone since its approval. As a result of this ongoing monitoring 
of safety issues, FDA has approved two revisions to the Mifeprex drug 
labeling and Medication Guide, in November 2004 and in July 2005. In 
November 2004, the boxed warning was revised and strengthened to add 
new information on the risk of serious bacterial infections, sepsis, 
bleeding, and death that may occur following any termination of 
pregnancy, including use of Mifeprex. In July 2005, FDA approved a 
labeling supplement to again strengthen the boxed warning on the 
product by noting that ``atypical presentations of serious infection . 
. . can occur without fever, bacteria or significant findings on pelvic 
exam . . . '' and to advise patients to seek immediate medical 
attention if they experience prolonged heavy bleeding. Additionally, 
FDA has issued several Public Health Advisories and updated the 
Mifeprex webpage on the Agency's Website several times to reflect new 
safety information. The sponsor has issued several Dear Healthcare 
Professional letters and a Dear Emergency Room Director letter, and two 
MedWatch alerts have been issued.
    The deaths that have occurred in the United States in association 
with the use of mifepristone for termination of pregnancy continue to 
be of concern to the Agency. Most of the deaths have been caused by 
severe infection, or sepsis, primarily with a specific bacterium, 
Clostridium sordellii. These cases of severe infection occurred with 
regimens of mifepristone and misoprostol that were not in approved 
labeling, although the relationship of the infections to the use of 
mifepristone and misoprostol remains unknown. In a recent workshop, 
``Emerging Clostridial Diseases,'' held Thursday, May 11, 2006, in 
Atlanta, Georgia, cases of infection due to Clostridium sordellii were 
also identified in women with ongoing pregnancies and delivery and in 
women who had recently experienced spontaneous miscarriages. There 
appeared to be broad consensus at the workshop that additional research 
is necessary to improve our clinical understanding of Clostridial 
infections associated with pregnancy, labor and delivery, and 
termination of pregnancy. FDA is committed to continuing to work with 
other Federal agencies to develop more information on Clostridial 
diseases.

    Question 12. Biotech drugs can cost between $10,000 and $20,000 a 
year per patient. As a result, few patients can afford these new drugs, 
and even when some insurers cover their costs, they constitute an 
unsustainable and growing burden on Medicare, Medicaid, and the 
healthcare system in general. Other countries, including the European 
Union have already approved a general regulatory pathway or the 
approval of generic or follow-on biologics.
    Over the past few years, the FDA has held a number of advisory 
committee and public hearings on the issue of generic or ``follow-on'' 
biologics. I understand that the Agency may have even developed some 
draft guidance documents. Do you know if the FDA intends to release any 
guidance on this issue any time in the near future?
    Answer 12. For biologic products approved under section 505 of the 
Food, Drug, and Cosmetic (FD&C) Act, we believe there is existing 
authority to allow applications for generic or follow-on protein 
products to be approved under sections 505(b)(2) or 505(j) of the FD&C 
Act where scientifically appropriate. Numerous protein products, 
however, are licensed as biological products under section 351 of the 
Public Health Service (PHS) Act, and are not approved as drugs under 
the FD&C Act. There is no abbreviated approval pathway for protein 
products licensed under section 351 of the PHS Act analogous to 
sections 505(b)(2) or 505(j) of the FD&C Act for drugs. Such a pathway 
for the approval or licensure of follow-on protein products under the 
PHS Act would require new legislation.
    Please be assured that FDA's consideration of regulatory 
requirements for follow-on protein products is progressing. FDA has 
sought input from stakeholders and conducted an extensive public 
discussion on scientific issues relating to the development and 
approval of follow-on protein products, including two public meetings 
(September 2004 and February 2005) and a co-sponsored workshop 
(December 2005). The public meetings resulted in a large number of 
comments and concerns from interested parties that are being considered 
further as we develop policies for regulating follow-on protein 
products. FDA recognizes that guidance for industry would be helpful, 
and intends to publish guidance broadly applicable to follow-on protein 
products in a timely manner. FDA expects that this approach will 
provide useful guidance to the industry, while ensuring that we do not 
stifle innovation and the utilization of state-of-the-art technologies. 
In addition, a sponsor may contact the Agency to request advice on a 
case-specific basis regarding the development of a follow-on protein 
product for submission in an application under section 505 of the FD&C 
Act.
    I do want you to know, however, that even as guidance documents on 
follow-on protein products are being developed, the Agency has been 
moving forward with the review and approval of those follow-on protein 
products for which the sponsors have met the statutory and regulatory 
approval requirements under section 505. Most recently, we have 
approved Fortical (calcitonin salmon recombinant) Nasal Spray in August 
2005, Hylenex (hyaluronidase recombinant human) in December 2005, and 
Omnitrope (somatropin [rDNA origin]) in May 2006.

    Question 13. As you know, the prescription drug user fee program 
has been tremendously successful in strengthening the FDA's resources 
and ensuring the timely review of new treatments. Do you think that 
such a user fee program could successfully be extended to the review of 
generic drugs?
    Answer 13. As you may know, the Prescription Drug User Fee Act does 
not apply to generic drugs approved under the ANDA process, section 
505(j) of the Federal Food, Drug, and Cosmetic Act. We have heard 
public discussion of a generic drug user fee program, but at this time, 
the Administration has no position on such proposals.

    Question 14. As you know, human papillomavirus (HPV) is the cause 
of nearly all cervical cancer. In 1999, the National Cancer Institute 
reported to Congress that ``Condoms are ineffective against HPV'' and 
that ``additional research efforts by NCI on the effectiveness of 
condoms in preventing HPV transmission are not warranted.'' In 2000, 
President Clinton signed Public Law 106-554, which directs the FDA to 
re-examine condom labeling to ensure that such labels are medically 
accurate regarding the lack of effectiveness of condoms in preventing 
HPV infection. It has been 5\1/2\ years since this law was signed and 
this label change has still not occurred. Millions of Americans have 
become infected with HPV during that time. Will you ensure that FDA 
will enforce this law by the end of this year?
    Answer 14. Public Law No. 106-554 directed FDA to re-examine 
existing condom labels and determine whether the labels are medically 
accurate regarding the overall effectiveness or lack of effectiveness 
of condoms in preventing STDs, including HPV. The Agency undertook a 
rigorous review of available scientific information and re-examination 
of condom labeling, which reaffirmed that latex condoms reduce the risk 
of HIV/AIDS and many STD's. However, FDA further concluded the degree 
of risk reduction varies for different types of STD's. Specifically, 
the Agency found that condoms provide less protection for certain STDs, 
including HPV, that can be spread by contact with infected skin outside 
the area covered by the condom. FDA also found that using a condom may 
lower the risk of developing HPV-related diseases, such as genital 
warts and cervical cancer. In November 2005, we published a proposed 
rule and draft special control guidance document with recommended new 
condom labeling language to communicate this nuanced public health 
message. FDA received roughly 400 comments on the proposed rule. Almost 
all comments suggested the proposed labeling language was confusing and 
difficult for consumers to understand. As a result, the Agency intends 
to undertake additional labeling comprehension studies to help ensure 
that the final labeling recommendations issued by the Agency are 
understandable to users. We remain committed to providing the American 
people the best possible information and believe ensuring the 
labeling's understandability to users is a critical component in 
providing this information.
   Response to Questions of Senator Hatch by Andrew C. von Eschenbach
    Question 1. Please provide a copy of the guidance, or if it was not 
finalized, the last draft, governing follow-on approvals of human 
growth hormone and insulin or any other biological products.
    Answer 1. The Agency has reconsidered issuing at this time the 
draft guidance documents on human growth hormone and insulin you 
reference for a number of reasons. After re-assessing these ``product-
specific'' draft documents, FDA has decided that it would be more 
appropriate to initially publish guidances that are more broadly 
applicable to follow-on protein products in general. FDA expects that 
this approach will provide useful guidance to the industry, while 
ensuring that we do not stifle innovation and the utilization of state-
of-the-art technologies. In addition, a sponsor may contact the Agency 
to request advice on a case-specific basis regarding the development of 
a follow-on protein product for submission in an application under 
section 505 of the FD&C Act.
    With regard to your request for the Agency's preliminary draft 
guidance documents on human growth hormone and insulin, I note that 
these internal draft documents were never finalized and were not 
cleared by Center for Drug Evaluation and Research (CDER) management, 
thus they do not necessarily reflect CDER's current thinking on these 
topics. For this reason, we would not disseminate these deliberative 
documents outside FDA.
    I do want you to know, however, that even as guidance documents on 
follow-on protein products are being developed, the Agency has been 
moving forward with the review and approval of those follow-on protein 
products for which the sponsors have met the statutory and regulatory 
approval requirements under section 505. Most recently, we have 
approved Fortical (calcitonin salmon recombinant) Nasal Spray in August 
2005, Hylenex (hyaluronidase recombinant human) in December 2005, and 
Omnitrope (somatropin [rDNA origin]) in May 2006.

    Question 2. Dr. von Eschenbach, along with Senator Harkin, I have 
been imploring the Administration to issue the Good Manufacturing 
Practice guidelines for dietary supplements that were authorized in 
1994. I believe the cGMPs for supplements were finalized during the 
Clinton administration, but never published. Despite our entreaties, 
correspondence, and language in two Senate Appropriations Committee 
reports, these guidelines have not been published.
    Could you please tell me, specifically, what issues are remaining 
that preclude issuing this rule?
    If you cannot tell me the issues, could you please tell me whom in 
the Administration I should contact to further my discussion?
    Answer 2. FDA is committed to publishing this final rule. I can 
assure you that there has been significant work done on the final rule 
since the comment period for the proposed rule ended in August 2003.
    Since we are still in the rulemaking process, I can not tell you 
what specific issues are being discussed, but I can tell you that the 
issues have been complex, legally and substantively, and in some cases, 
novel. The final rule is currently under review by the Office of 
Management and Budget.
    We have expended significant internal resources on reviewing and 
preparing responses to the comments received. We also have worked 
extremely hard to draft the final rule in order to assure quality 
products for the consumer while minimizing the economic impact to the 
dietary supplement industry. I can assure you that full attention is 
being given to the completion of the rule as soon as possible.

    Question 3. Has the FDA considered, or will you consider, issuing 
this rule in a way that allows for public comment, given that the rule 
has been several years in development? It seems that the proposed rule 
and the final could differ substantially given the time lag and it 
seems only fair to allow those who must abide by these regulations to 
be able to comment on its latest iteration.
    Answer 3. In the past, we have had rules issued in which there has 
been a similar period of time between the end of the comment period and 
publication of the final rule. We are confident that the final rule 
will address all of the issues raised by comments. If we determine 
there is any need for additional public comment, we will consider the 
appropriate means to address that need.

    Question 4. The HELP Committee has before it S. 3128, the National 
Uniformity for Food Act, which establishes a national food labeling 
standard. The bill contains a provision which allows States to petition 
FDA for an exemption from national uniformity in order to address a 
local problem. There is also a provision whereby States may petition 
for a State standard that differs from requirement imposed throughout 
the rest of the country.
    Could you please tell the committee the resources FDA expects it 
would take to implement these two provisions? In particular, I would be 
interested to learn how many FTEs would be needed and at what cost? 
Further, in each of the two cases, I would be interested to learn how 
long the Agency estimates it would take to act on a petition it 
receives? If the answer is qualified according to how complicated the 
petition might be, I would appreciate your providing me with a time 
range for action. Finally, if this bill is enacted, would your action 
on petitions be contingent on an appropriation?
    Answer 4. FDA does not have cost estimates of the impact of S. 
3128.

    Question 5. Will you commit to having an open dialogue with the 
Congress and with the dietary supplement industry on issues relating to 
the science and regulation of dietary supplements? Do you believe the 
Dietary Supplement Health and Education Act is adequate to deal with 
any problems which may arise connected with dietary supplements?
    Answer 5. I look forward to open communication with Congress and 
the dietary supplement industry on issues relating to the science and 
regulation of dietary supplements.
    With regard to your second question, the Dietary Supplement Health 
and Education Act of 1994, or DSHEA, provides FDA the authority to act 
against dietary supplements that carry unsubstantiated claims or claim 
to treat a disease, that are unsafe, or that are otherwise adulterated 
or misbranded.
    DSHEA created a regulatory framework that is primarily postmarket 
in nature. FDA's responsibilities under this framework include 
implementing DSHEA's requirements for dietary supplement safety, 
labeling, and product quality, as well as taking action against 
adulterated and misbranded products. Since the enactment of DSHEA, FDA 
has promulgated a number of implementing regulations and begun other 
regulatory actions. The challenge to FDA is to strike the right balance 
between preserving consumers' access to products and information and 
ensuring the safety and proper labeling of these products. Under DSHEA, 
the primary responsibility for producing and marketing dietary 
supplements that are safe, accurately labeled, and appropriately 
promoted rests with the manufacturer. Although the law requires a firm 
to possess substantiation that claims made for its products are 
truthful and not misleading, there is no current requirement for the 
firm to submit that information to FDA or publicly disclose it. Nor do 
dietary supplement firms have to submit safety data on their products, 
except in the case of supplements that contain certain new dietary 
ingredients. The burden of proving a product is unsafe rests with FDA.
    On August 17, 2006, the U.S. Court of Appeals for the Tenth Circuit 
in Denver upheld FDA's final rule declaring all dietary supplements 
containing ephedrine alkaloids adulterated, and therefore illegal for 
marketing in the United States, reversing a decision by the U.S. 
District Court for the District of Utah. The Tenth Circuit Court of 
Appeals' ruling demonstrates the soundness of FDA's decision to ban 
dietary supplements containing ephedrine alkaloids, consistent with 
DSHEA.
    On November 4, 2004, FDA published a Regulatory Strategy for the 
Further Implementation and Enforcement of DSHEA, in which FDA detailed 
specific steps for the further implementation of DSHEA. This Regulatory 
Strategy identified three specific initiatives: (1) monitoring and 
evaluating product and ingredient safety, (2) assuring product quality 
through CGMP regulations, and (3) monitoring and evaluating product 
labeling. With this strategy, FDA intends to improve the transparency, 
predictability, and consistency both of the Agency's scientific 
evaluations of dietary supplement product and ingredient safety, and of 
its regulatory actions to protect consumers against unsafe dietary 
supplements and dietary supplements making unauthorized, false, or 
misleading claims, including unsubstantiated claims. FDA expects that 
this improved transparency will help engage stakeholders in the 
development of further measures to implement DSHEA. The Agency believes 
that its regulatory strategy will give consumers a higher level of 
assurance of product quality and safety.

    Question 6. I am aware that Mr. Jeffrey A. Hinrichs, Chief 
Operating Officer of Nutraceutical in Park City, Utah, sent a June 13, 
2006 letter to Mr. Michael M. Landa, Deputy Director for Regulatory 
Affairs (CFSAN), about the effect on public health of your pesticide 
residue testing program for ginseng. I would appreciate your view of 
the response to Mr. Hinrichs' letter, and your making the reply 
available for this record.
    Answer 6. Nutraceuticals wrote to the Deputy Director for 
Regulatory Affairs, Michael Landa, June 13, 2006, regarding the effects 
of FDA's Pesticide Residue Testing Program for Gingseng on public 
health. Nutraceuticals maintains that there is no evidence that 
pesticides like the Quintozene and Procymidone residues found on 
gingseng have ever created, or are likely to create, any public health 
concern.
    FDA's position remains that its pesticide residue monitoring 
program is fully consistent with the law. As we have consistently found 
ginseng to be contaminated with a variety of illegal pesticide 
residues, it is appropriate for FDA to continue to monitor these 
products for pesticide residues.
    In lieu of responding in writing, FDA is in the process of 
scheduling a meeting with Nutraceuticals, as the company requested, to 
discuss the issues it has raised.
        Response to Questions of Senator Sessions by Andrew C. 
                             von Eschenbach
    Question 1. What exactly is Plan B?
    Answer 1. Plan B is a drug intended to prevent pregnancy after 
unprotected sex (if a barrier contraceptive fails or if no 
contraception was used). It contains levonorgestrel (0.75 mg per 
tablet), which is a synthetic hormone (progestin) commonly used in 
birth control pills. Plan B is for emergency use, and should not be 
used in place of regular contraception.

    Question 2. How is it to be administered?
    Answer 2. The woman should take the first Plan B tablet as soon as 
possible within 72 hours of unprotected sex. She should take the second 
tablet 12 hours after taking the first tablet. Plan B is more effective 
the sooner treatment is started following unprotected sex.

    Question 3. What are the possible side effects of Plan B and how 
are they different from regular birth control pills?
    Answer 3. The most common side effect related to the use of Plan B 
is a change in the timing and/or amount of bleeding related to the 
user's next menstrual period, which may occur earlier or later than 
expected. Menstrual bleeding is sometimes heavier and sometimes lighter 
than usual after women take Plan B. After taking Plan B most women get 
their next period within 1 week of when it is expected. Other adverse 
events that have been reported in women using Plan B in clinical trials 
have included nausea, abdominal pain, fatigue, headache, dizziness, 
breast tenderness, vomiting, and diarrhea. It is not known if these 
events were directly related to the use of Plan B since these events 
are not uncommon in women who do not use Plan B.
    All of the adverse events that have been reported in users of Plan 
B have been reported in users of oral contraceptives that contain both 
estrogen and a progestin. However, users of oral contraceptives that 
contain estrogen have an increased risk of developing serious and 
sometimes fatal venous or arterial blood clots. A similar increased 
risk for serious blood clots has not been reported for users of Plan B.

    Question 4. Currently, regular birth control pills can only be 
obtained with a prescription. Why? Are there possible side effects that 
could be harmful to a woman's health?
    Answer 4. Users of oral contraceptives have an increased risk of 
developing serious and sometimes fatal venous or arterial blood clots. 
A similar increased risk for serious blood clots has not been reported 
for users of Plan B. Because of the seriousness of this risk associated 
with the use of traditional oral contraceptives, women who use oral 
contraceptives must be carefully screened by a physician to ensure that 
they do not have any of the contraindications to the use of oral 
contraceptives that would increase their risk of developing serious 
adverse events. Users of oral contraceptives also need to have regular 
periodic medical examinations because long-term use of oral 
contraceptives may increase blood pressure, alter blood lipids levels, 
and decrease carbohydrate metabolism in some women.

    Question 5. Considering the side effects of and prescription 
requirement for traditional birth control, why does the FDA consider 
Plan B safe enough to be available over-the-counter? Is Plan B a 
stronger dose of medication than traditional birth control?
    Answer 5. Although the dose of the progestin in Plan B (0.75 mg 
levonorgestrel per tablet or 1.5 mg per treatment) is higher than that 
in individual prescription birth control pills, Plan B is to be used 
only as emergency or back up contraception while birth control pills 
that contain both estrogen and progestin (0.1 to 0.15 mg 
levonorgestrel) are generally taken for 21 of every 28 days in a cyclic 
pattern. The major consideration for requiring that combination oral 
contraceptives be prescription-only products is the risks associated 
with the estrogen component of the product. The estrogen component of 
oral contraceptives is thought to be responsible for the increased risk 
of serious blood clots as mentioned earlier. A similar increased risk 
for serious blood clots has not been reported for users of Plan B. In 
addition, users of oral contraceptives may develop other adverse 
changes (e.g., increased blood pressure) that require periodic physical 
examinations to detect.

    Question 6. Have there been any cases of women who have taken it 
incorrectly and experienced harm? I have heard stories of women who 
take Plan B regularly, as a substitute for birth control pills. Is this 
harmful, and if so, how can we prevent it from happening--especially if 
Plan B becomes an over-the-counter drug?
    Answer 6. We are not aware of any cases where a woman has taken 
Plan B incorrectly and experienced harm. It is possible that some woman 
may use prescription Plan B as a substitute for oral contraceptives; 
however, there is no evidence to indicate this is a consumer practice. 
If Plan B is available for women 18 years and older without a 
prescription, we believe that regular use of Plan B as an alternative 
for birth control pills will continue to be very uncommon. The basis 
for our belief includes: (1) our understanding that a single treatment 
(two pills) of Plan B will be more costly than a month's supply of most 
oral contraceptives and (2) the labeling for non-prescription Plan B 
will include: (a) a warning against its use as a regular birth control 
method and (b) a statement that Plan B does not work as well as most 
other forms of birth control when they are used consistently and 
correctly. The distributor of Plan B will also promote its correct use 
in advertising.
                                 ______
                                 
 Additional Questions of Senator Sessions for Andrew C. von Eschenbach
    Question 1. I am very concerned about the drug RU-486. Has anyone 
actually died as a result of taking this much-discussed drug? Please 
share a complete list of drugs that have remained on the market after 
deaths have occurred in relation with them.

    Question 2. How does RU-486 work and what is the drug's level of 
effectiveness in carrying out its intended effect, which is the 
termination of pregnancy?

    Question 3. I hear that RU-486 is 10 to 14 times more lethal to the 
mother than surgical abortion during the first 49 weeks of gestation 
when RU-486 is used. Is this true? How lethal is RU-486 to women in 
comparison to a surgical abortion?

    Question 4. In my home State of Alabama, a clinic was recently 
closed after a terrible incident. A woman went into an abortion clinic 
where a staff member performed an ultrasound and determined she was 6 
weeks pregnant--in truth she was nearly full term. At that point, the 
nurse practitioner, rather than the doctor, administered the drug even 
though the woman's blood pressure was dangerously high. I must note 
that a doctor was not present during any of these medical procedures, 
including the administering of RU-486. Six days later, the woman went 
to a hospital emergency room with the baby's head protruding and 
delivered a stillborn 
6-pound, four-ounce baby. This is not an isolated story, and in fact it 
is a story with a much happier ending than those women who have 
actually died as a result of taking RU-486. I find it shocking that 
this drug is still on the market. If you are confirmed and officially 
appointed FDA Commissioner, what will you do about this? What are your 
intentions insofar as monitoring, warning, and promptly removing 
dangerous drugs?

    Question 5. As you know, Vioxx and other drugs have been pulled, 
many of which have shown to be less dangerous than RU-486. There is 
even talk of new drug safety legislation in this very committee. What, 
if any, legislative changes need to take place to empower the FDA to do 
its job in protecting the American people and ensuring that drugs are 
safe before they go on the market, as well as pulling drugs that show 
to be dangerous in a timely manner?

    Question 6. RU-486 is a drug that requires precise timing and 
cannot be taken after a woman reaches her seventh week of pregnancy. Do 
you have any confirmed reports of RU-486 being taken past the 49th day 
of pregnancy? If so, who prescribed the drugs (i.e., clinic, a 
physician's office)?

    Question 7. I understand that RU-486 was approved in September 2000 
through the seldom-used, accelerated process called Subpart H (used to 
accelerate drugs needed for ``serious or life-threatening illnesses''). 
What other drugs were approved through this process and what illnesses 
were they intended to cure? What serious or life threatening illness 
was Mifeprex (the RU-486 drug) intended to treat? Have any other drugs 
been approved to treat this or related serious or life-threatening 
illnesses since 1992? Were any of these drugs approved pursuant to 
Subpart H, which was previously reserved?

    Question 8. Aside from Mifeprex, in the past 20 years how many new 
drug applications has FDA approved based solely on data from clinical 
trials with only a treatment art (i.e., lacking a control group)? How 
many of these approvals took place after Subpart H was enacted in 1992? 
Of the approvals since 1992, how many were approved under Subpart H?

    Question 9. In the past 20 years how many new drug applications has 
FDA approved based solely on data from historically controlled trials? 
For each answer provide the name of any drugs, and a brief description 
of the trials, including the control group used.

    Question 10. Which drugs approved prior to 1992 have restrictions 
placed on their distribution and use? Which drugs approved since 1992 
have had restrictions placed on their distribution and use under 
Subpart H? Which drugs approved since 1992 have had restrictions placed 
on their distribution and use but were not approved under Subpart H? 
How many drugs approved under Subpart H have been removed from the 
market for safety or effectiveness concerns? For these questions, 
please list the applicable drug name(s) and approval date(s).

    Question 11. What procedures are in place to evaluate and assess 
the adequacy of the restrictions on the distribution and use of 
Mifeprex and the applicant's adherence to them? Which drugs with 
restrictions placed on their distribution and use under Subpart H have 
been removed from the market for noncompliance with those restrictions? 
Which drugs with restrictions placed on their distribution and use 
under Subpart H were given additional restrictions on distribution due 
to noncompliance with those restrictions? For these questions, please 
list the applicable drug name(s) and date of removal from the market or 
date of approval of additional restrictions as applicable.

    Question 12. Who owns Danco Laboratories, the producer of Mifeprex? 
Where is their business located, and what other drugs do they produce?

    Question 13. What communication has the FDA had with Danco, and 
what type of communication do you intend to have if you are confirmed?

    [Editors Note: The response to additional questions from Senator 
Sessions were not available at time of print.]

   Response to Questions of Senator Dodd by Andrew C. von Eschenbach
    Question 1. Events of the past few years have cast into doubt the 
FDA's ability to ensure that the drugs it approves are safe--especially 
once they are on the market. These concerns are bad for patients, bad 
for physicians, and bad for the drug industry. Patients have come to 
trust the words ``FDA Approved,'' and those words have also become the 
gold standard around the world. But the FDA is and has been facing a 
crisis in confidence. A recent survey of 997 FDA scientists conducted 
by the Union of Concerned Scientists and the Public Employees for 
Environmental Responsibility, found that 378 scientists disagreed or 
strongly disagreed that the FDA is acting effectively to protect public 
health. In that survey, 420 scientists reported that they knew of cases 
in which the Department of Health and Human Services or FDA political 
appointees have inappropriately injected themselves into FDA 
determinations or actions.
    Dr. von Eschenbach, during testimony before this committee earlier 
this month, you stated that drug safety is one of your top priorities. 
Should you be confirmed as Commissioner of the FDA, your most important 
task will be to restore confidence in the words ``FDA Approved,'' so 
that patients can be sure that the drugs they take to help them will 
not harm them instead.
    Please describe, in detail, the steps you would take as FDA 
Commissioner to restore public confidence in FDA.
    Answer 1. I am committed to maintaining, and improving, the long-
standing traditions and values of an Agency whose processes and 
decisions are guided by sound science and vigorous analysis of evidence 
and based on the best interests of the patients and public we serve.
    This year, FDA celebrates 100 years of successes in becoming the 
world's gold standard for assuring the drugs we give our children, the 
medical devices we use to treat disease and the food we eat is safe and 
effective. The Agency's more than 12,000 employees remain fully 
dedicated to continuously improving and becoming even better as we 
enter our second century. FDA is as committed as ever to its time-
honored tradition of encouraging vigorous debate among experts who use 
disciplined processes to arrive at consensus and conclusions.
    Much work remains to fully equip FDA to face the challenges of the 
21st Century and seize the opportunities ahead, but I am confident that 
we are on the right path. And if confirmed, I believe I can provide the 
leadership and management that will guide this important public health 
agency proudly and effectively into its second century of service.
                              transparency
    Question 2a. Dr. von Eschenbach, the manufacturer of Ketek was 
enrolling children in clinical trials for its antibiotic since June 
2005. Despite FDA knowledge of repeated instances of fraud in adult 
clinical trials sponsored by the company and warnings from Dr. Johann-
Liang and others at FDA, pediatric clinical trials in children as young 
as 6 months of Ketek continued until June 2006.
    Do you believe mistakes were made in FDA's handling of Ketek's 
approval process and post-market surveillance?
    Answer 2a. The Ketek application was carefully reviewed and 
evaluated. There were two approvable letters issued and additional 
information submitted and reviewed prior to receiving FDA approval. The 
data from Study 3014 was eliminated as a basis for approval for Ketek 
and instead, the Agency relied on the postmarketing experience of 
approximately 4 million prescriptions for patients in foreign countries 
to conclude that the drug was safe for its intended use.
    As part of the standard FDA post-marketing surveillance program, a 
1-year post-approval assessment was performed (June 2005) and no safety 
concerns regarding liver toxicity where identified at that time.
    As with any drug, Ketek labeling contains known adverse events that 
are described in the product labeling, however, after the 1-year post-
approval assessment FDA was alerted to an increased rate of liver 
toxicity through the adverse event reporting system (AERS). FDA 
promptly initiated another safety assessment which was recently 
completed and provides support for the action that FDA took on June 29, 
2006. This action provides new safety information in the Ketek product 
label, including a Warning regarding liver toxicity.

    Question 2b. Do you think it is appropriate for the FDA to continue 
to cite studies later found to be fraudulent to support a drug's 
safety?
    Answer 2b. No, it is not appropriate. As noted above, this data was 
eliminated from consideration with respect to the approval. The 
relevant information on FDA's web page for Ketek has been updated.

    Question 3. As Commissioner of the FDA, what would you do to ensure 
transparency, so that dissenting opinions are seriously considered and 
never suppressed?
    Answer 3. First, I will make myself available to staff who want to 
appeal decisions made by FDA management. I believe that the need to 
appeal to me will be rare, however, because I will ensure that there 
are strong policies and procedures in place for resolving issues 
involving dissenting opinions. Efforts toward that end will include 
promulgating new policies and procedures as necessary, and 
strengthening, by process improvement and best practices measures, many 
of those that are already in place.
    For example, we are working to ensure a rigorous ombudsman program 
through which staff are welcome to promulgate dissenting opinions. 
Staff may also invoke standard written procedures for facilitating and 
resolving differing professional opinions. In addition, at the 
direction of the Secretary, FDA's Center for Drug Evaluation and 
Research established a Drug Safety Oversight Board whose charter 
includes responsibility for deliberating on any dissenting opinions 
raised during evaluation of drug applications and surveillance of 
marketed products. Through these and other traditional management 
techniques, I believe we will successfully address any dissenting 
opinions, and I am committed to evaluating our processes and refining 
them as necessary to ensure that there is a healthy and open scientific 
debate of issues at FDA.

    Question 4. Surveys like the recent one of 997 FDA scientists 
conducted by the Union of Concerned Scientists and the Public Employees 
for Environmental Responsibility and the one conducted by the HHS 
Inspector General in 2002 paint a picture of FDA as an agency without 
the credibility of many of its own scientists, where science is being 
suppressed for reasons other than the interest of the public health.
    Are you concerned that hundreds of senior level scientists at the 
FDA are reporting that they have been asked ``for nonscientific 
reasons, to inappropriately exclude or alter technical information or 
their conclusions in a FDA scientific document?''
    What will you do to ensure a culture of openness so that management 
both listens to and addresses scientific concerns about products 
regulated by the FDA?
    Answer 4. I am committed to ensuring FDA makes decisions based on 
sound science. I will make myself personally available to staff who 
want to appeal decisions made by FDA management. I believe that the 
need to appeal to me will be rare, however, because I will ensure that 
there are strong policies and procedures in place for resolving issues 
involving dissenting opinions. Efforts toward that end will include 
promulgating new policies and procedures as necessary, and 
strengthening, by process improvement and best practices measures, many 
of those that are already in place.
    For example, we are working to ensure a rigorous ombudsman program 
through which staff are welcome to promulgate dissenting opinions. 
Staff may also invoke standard written procedures for facilitating and 
resolving differing professional opinions. In addition, at the 
direction of the Secretary, FDA established a Drug Safety Oversight 
Board whose charter includes responsibility for deliberating on any 
dissenting opinions raised during evaluation of drug applications and 
surveillance of marketed products. Through these and other traditional 
management techniques, I believe we will successfully address any 
dissenting opinions, and I am committed to evaluating our processes and 
refining them as necessary to ensure that there is an open scientific 
debate of issues at FDA.
                             fda authority
    Question 5. According to the latest figures, companies have not 
even initiated approximately 70 percent of the post-market studies that 
they had previously committed to.
    How does the FDA plan to address this problem? Does the FDA need 
additional authority and enforcement power to require companies to do 
post-market studies?
    Answer 5. FDA is in the process of undertaking a review of the 
decisionmaking process behind requests for Post-marketing Study 
Commitments (PMCs) for human drugs, including biological drugs. An 
outside contractor has been hired to evaluate how different review 
divisions decide to request PMCs, decisions surrounding what kinds of 
PMCs to request, and what are reasonable timeframes for completing 
PMCs. The study will serve to assist FDA in harmonizing procedures. 
While this study is being conducted, the Centers within FDA have 
undertaken activities to improve the response on post-marketing and 
post-approval studies for human drugs (including biological drugs) as 
well as for devices. We do not believe that we need additional 
authority in this area.
    Human drugs (including biological drugs).--Post-marketing study 
commitments (PMCs) for approved drug products are studies that a 
sponsor either is required or agrees to conduct after FDA has approved 
a product for marketing to further define the safety, efficacy, or 
optimal use of a product. In some cases, the studies can take years to 
complete, even if everything is going according to schedule. In other 
cases, there are considerable obstacles (e.g., difficulty in recruiting 
patients and investigators to participate in a clinical trial when an 
approved therapy is available) that must be addressed before the 
studies can be completed. In these cases, FDA works closely with 
sponsors to address these obstacles. It should also be noted that 
approximately 38 percent of the currently pending PMCs for new drug 
applications were established in applications approved between October 
1, 2003, and September 30, 2005, and thus, depending on the complexity 
of the study, FDA would expect that many of these studies are in the 
development phase.
    FDA takes its statutory obligations under the Food and Drug 
Administration Modernization Act of 1997 (FDAMA) to track and monitor 
the progress of PMCs very seriously. FDA recently published a final 
guidance to industry to describe in greater detail the content, format, 
and timing of PMC annual status reports submitted by the drug industry. 
Furthermore, FDA reports annually in the Federal Register on the 
performance of applicants in conducting their PMCs and maintains a 
public Web site that contains the information that FDA is required 
under FDAMA to make available to the public. These initiatives, along 
with other FDA internal procedures, are all intended to ensure that 
industry undertakes their commitments and completes them in a timely 
manner.
    Devices.--On January 1, 2005, CDRH initiated the use of the new 
Condition of Approval Tracking System. As of that date, all post-
approval studies of class III devices are entered into the system, 
along with the due dates of any agreed upon report deliverables. The 
system is monitored daily to see that sponsors are honoring their 
commitments. Procedures are in place to notify the sponsor immediately 
if deadlines are not met, and also to acknowledge the receipt of 
reports that are on time and are reviewed. To date, under the new 
system, all reports have been delivered on time.
    CDRH is also developing the Post-approval Study Web site that will 
be available to the public. This Website will list the post-approval 
studies being done, briefly describe the study, and document the status 
of studies, as reported by industry.
    FDA believes that changes to the Condition of Approval study 
program will improve communication with industry about these studies 
and increase collaboration in designing high quality studies with 
targeted end points. The results of these studies will be important to 
FDA, industry and the health care community. Acknowledgement of receipt 
of study reports and followup on overdue reports will encourage 
compliance. Finally, we believe the public Website will prompt industry 
to do the studies and report to FDA on time.
    In addition to the efforts regarding device Condition of Approval 
studies noted above, FDA continues to use its authority under section 
522 of the act to order post-market surveillance studies of class II 
and class III devices meeting the statutory requirements of that 
section, to require the collection of useful data that can show 
unforeseen adverse events or other information necessary to protect the 
public health. Should a company subject to such an order fail to meet 
the requirements of the act and implementing regulations, FDA has 
authority to take enforcement action.

    Question 6. It took 2 years for the Vioxx label to change to 
reflect the data suggesting an increased cardiovascular risk. Much of 
the delay resulted from months of negotiation with the manufacturer.
    Dr. von Eschenbach, does this seem like an unacceptable delay given 
the huge public health implications? Does the FDA need additional 
authority and enforcement power to require companies to change the drug 
label if a safety concern arises?
    What other authorities does the FDA need in order to effectively 
respond when a safety issue is identified?
    Answer 6. I do not believe new statutory authority is needed. We 
use all existing regulatory authority and enforcement powers when 
negotiating label changes with drug companies or when monitoring or 
managing drug safety issues. FDA can and does successfully carry out 
its mission under its current statutory and regulatory authority.

    Question 7. There is substantial public concern about the lack of 
resources committed to the Office of Drug Safety (ODS), as well as its 
relative lack of authority. Some have suggested that the ODS serves 
merely as a consultative body to the Office of New Drugs. Dr. von 
Eschenbach, during your testimony you said that you didn't see a need 
to change the current structure of the FDA.
    However, given the events of the past couple of years including the 
withdrawal of Vioxx and controversy surrounding Ketek, do you believe 
the role and the authority of the ODS should change?
    How will you ensure that the FDA staff responsible for monitoring 
the safety of drugs once they are on the market will have independence 
within the Agency and the resources necessary to protect the public's 
health?
    Answer 7. We continue to believe that our current organizational 
structure, which keeps the debate about the safety and efficacy of a 
product in one FDA Center, is appropriate and effective. In the past 
year, we have moved to strengthen that structure by ensuring that the 
epidemiologists and post-market safety experts have equal 
organizational representation and stature within FDA's Center for Drug 
Evaluation and Research (CDER). With the reorganization, we established 
an Office of Surveillance and Epidemiology (OSE) that is responsible 
for most of the functions formerly managed by the Office of Drug 
Safety. This new name more appropriately represents the functions 
handled by the office and alleviates some of the confusion and 
misconception that drug safety issues are handled solely by one office 
in CDER. Further, the Director of OSE now reports directly to the 
Center Director, thus putting the OSE Director on the same footing with 
the OND Director when negotiating business and management issues 
including requests for resources. We believe that this structure 
fosters a proper environment for a fair assessment of the effectiveness 
and risk of a product.

    Question 8. The administration's fiscal year 2007 budget includes 
an additional $5 million for drug safety.
    With this budget increase, how many scientists will the ODS employ? 
How does the ODS budget and staff compare to that of the Office of New 
Drugs? Given that the ODS is charged with tracking every single drug 
that is on the market, does the balance of resources seem appropriate?
    Answer 8. FDA requested $3.9M in additional funds in fiscal year 
2007 to continue to modernize its Adverse Event Reporting System (AERS) 
and create ``AERS II''--a replacement web-accessible computer system 
that will enable FDA to maintain the current level of AERS 
functionality, while providing enhancements in several areas.
    These enhancements include adding capabilities planned in the 
original AERS. With over 5 years of experience with the database, we 
have identified areas of critical new functionality, including 
generating web-accessible adverse event information. The current AERS 
system is FDA's principal post-marketing monitoring tool. It allows FDA 
to identify events that were not observed or recognized before 
approval. It allows FDA to identify adverse events that might be 
happening because patients and prescribers are not using the drug as 
anticipated.
    The AERS system alone is not adequate for a successful, state-of-
the-art drug safety program. To appropriately monitor drug safety after 
marketing, it is essential that FDA have access to a wide range of 
clinical, pharmacy, and administrative databases, including databases 
maintained by organizations such as those maintained by the Center for 
Medicare and Medicaid Services, the Department of Veterans Affairs, the 
Department of Defense, and the Indian Health Service. We also access 
databases maintained by clinical and hospital networks and insurers, 
such as health maintenance organizations, preferred provider 
organizations, and insurers, and pharmacy benefit management 
organizations.
    FDA is actively evaluating the utility and feasibility of 
conducting specific studies of high priority safety issues using such 
linked databases. Studies conducted on these types of databases will 
provide more evidence about drug use in a broader range of conditions, 
including more detailed evidence about drug safety in subgroups of 
patients.
    FDA is actively evaluating the utility and feasibility of 
conducting specific studies of high priority safety issues using such 
linked databases. Studies conducted on these types of databases will 
provide more evidence about drug use in a broader range of conditions, 
including more detailed evidence about drug safety in subgroups of 
patients.
    Earlier this year, the Center for Drug Evaluation and Research 
reorganized and established the Office of Surveillance and Epidemiology 
(OSE) that reports directly to the Center Director. This new office is 
responsible for most functions previously conducted by the ``Office of 
Drug Safety,'' and the new name more appropriately represents the 
functions handled by the office and alleviates some of the confusion 
and misconception that drug safety issues are handled solely by one 
office in CDER. Currently, the fiscal year 2006 estimated budget for 
OSE is $34.5M, while the fiscal year 2006 estimated budget for OND is 
$110.9M. FDA ensures that adequate resources are devoted to the 
functions managed by both OND and OSE.

    Question 9. I have long been committed to ensuring that medicines 
are studied in children so that pediatricians have information about 
which drugs are most effective for their patients. The steps that we 
have taken in this area--the Best Pharmaceuticals for Children Act 
(BPCA) which Senator DeWine and I authored and the Pediatric Research 
Equity Act (PREA)--have led to enormous improvements in our knowledge 
about the appropriate use of drugs for children.
    Dr. von Eschenbach, pediatric testing in children is particularly 
relevant in light of the recent questions about drug safety, and 
especially the possible adverse effects of antidepressants (SSRIs) when 
used to treat youth. Several SSRIs had been studied in children, but 
the results of those studies were inconclusive.
    If confirmed as Commissioner, would you continue to support efforts 
to expand pediatric testing? What steps could the Agency take to 
improve in this area, and to ensure that pediatric studies are 
answering the right questions and providing useful results? Is there 
additional authority that Congress can provide that would be helpful to 
the FDA?
    Answer 9. I support efforts to expand testing drugs for use in 
pediatric patients. Both PREA and BPCA have been important tools for 
FDA in obtaining needed pediatric information. The legislative 
authority granted to FDA to obtain efficacy and safety data on products 
used in pediatric patients has allowed the Agency to re-label over 100 
products with new pediatric use information and to disseminate this 
extremely valuable product information to the public. Among other 
examples, the SSRI studies in children that enabled FDA to identify 
concerns regarding suicidality associated with pediatric use of SSRIs, 
were conducted under the pediatric exclusivity incentive.
    We are considering additional steps the Agency could potentially 
take to improve pediatric testing and to ensure that pediatric studies 
are answering the right questions and providing useful results. BPCA 
and PREA have created an environment which promotes the study of 
therapies in children. Considering that over 100 products have had new 
pediatric labeling and more than 25 percent of these products had new 
information on dosing changes or pediatric safety information, in 
addition to those that were now approved for a younger population, we 
think the program is already demonstrating the utility of studying 
products that are being used in the pediatric population.

    Question 10. I have heard the concern that it is unclear whether 
the FDA has the authority to require labeling to clearly indicate when 
a product has been studied in children under BPCA or PREA and found to 
not be effective.
    In other words, does the FDA have the ability to require a 
manufacturer to clearly differentiate on a label when a product is not 
approved for use in children because it has been shown through studies 
to be ineffective or unsafe versus when it is not approved for children 
because it has just not been studied in that population?
    Answer 10. Increasingly, product labeling is being used to convey 
the current state of knowledge about the safety and efficacy of a drug 
in the pediatric population. We already have begun to implement an 
effort to ensure that label changes are made for all drugs for which 
studies are submitted under BPCA. These labeling changes aim to ensure 
that products studied under BPCA have labeling that includes more 
information than the statement ``safety and efficacy had not been 
established in the pediatric population.'' Thus, where a study is 
inconclusive about safety or effectiveness, the labeling may describe 
the results of the study without stating that the drug should or should 
not be used in certain pediatric populations. Similarly, if FDA has 
information that establishes that a drug does not work in pediatric 
populations or if clinical trials reveal a safety concern, FDA would 
place that information in the labeling, even if the drug is not 
approved for use in the pediatric population.
    Section 5 of the BPCA provides a process for timely labeling 
changes for drugs granted exclusivity, including a provision for 
referral to the Pediatric Advisory Committee. Although this process 
does not apply to labeling changes for studies performed under BPCA 
where exclusivity was not granted, nor for studies conducted outside of 
the scope of BPCA, we have moved forward to ensure sufficient 
information will be included in the label. The changes made in BPCA 
have been of great assistance in ensuring more prompt agreements once 
the supplement has been reviewed and acted on by FDA.
    There is also legislative authority granted by PREA that allows us 
to require sponsors to include information in their label indicating 
that pediatric studies were waived because they believe the drug would 
not be effective in pediatric patients or because there are safety 
concerns for pediatric patients.
    In spite of these improvements, FDA acknowledges that we use 
various terminologies in labeling to describe the results of studies 
and that some of the terminology used may not have clearly conveyed if 
data were collected in pediatric patients. FDA is working to improve 
the clarity of pediatric information included in labeling and will 
continue to do so.

    Question 11. Currently, a number of safety protections are applied 
to products studied under BPCA, but not to products studied under PREA. 
For example, adverse events related to products studied under BPCA in 
the first year after exclusivity is awarded are reported to and 
reviewed by the FDA's Pediatric Advisory Committee. No such protection 
applies to products studied under PREA. Similarly, the results of all 
studies conducted under BPCA must be made public. No such requirement 
applies to products studied under PREA.
    Do you think the legislation should be modified so that these 
requirements apply to PREA? Are there other ways in which PREA and BPCA 
could be better coordinated?
    Answer 11. I appreciate your question and believe that both PREA 
and BPCA have been important tools in obtaining needed pediatric 
information to treat pediatric patients. We have been reviewing 
possible improvements that could make the program even more effective. 
Our review is not yet complete. If we determine new legislative 
proposals are necessary, we will look forward to working with you to 
enhance the program.
                       pediatric medical devices

    Question 12. I was pleased to hear you testify that, if confirmed, 
you would enhance opportunities for pediatric medical devices. This is 
an issue of great importance to me. Like drugs, where for too long we 
assumed that children were small adults and could just take reduced 
doses of adult products, we're finding that many essential medical 
devices used extensively by pediatricians are not designed and sized 
for children's special needs. According to pediatricians, the 
development of cutting-edge medical devices suitable for children's 
smaller and growing bodies can lag 5 or 10 years behind those for 
adults. This is simply unacceptable. As technology for prolonging and 
saving lives continues to advance at a rapid pace, children are at risk 
of being left further and further behind.
    If confirmed, what steps would you take to enhance opportunities 
for new device development for children?
    Answer 12. Although cutting-edge research and revolutionary 
technologies have led to the development of new innovative devices, 
pediatric device development faces additional challenges that may cause 
it to lag behind adult device development. The type of applicants 
(small companies) and obstacles to the development of pediatric 
devices, including the difficulties in conducting device clinical 
trials involving children, make this issue extremely challenging. FDA 
believes that communication between the Agency, industry, patients, and 
clinicians is essential for fostering pediatric device innovation. To 
this end, CDRH has been focusing on increasing interactions among these 
parties during product development and pre-market review.
    CDRH is working to develop more device-specific guidances that 
would, when appropriate, include advice for manufacturers on issues 
such as the type of modifications, testing, and/or labeling changes 
needed for the device to be used in pediatric populations. CDRH is also 
holding workshops to discuss the development of critical pediatric 
devices, which include a 2005 advisory panel meeting to discuss 
clinical trial designs for, and ethical issues related to, the 
evaluation of devices to treat pediatric obesity; a 2006, FDA sponsored 
a workshop for manufacturers of pediatric left ventricular assist 
devices intended for infants and children from 2 kg to 25 kg with 
congenital or acquired cardiovascular disease, and a public workshop 
held in collaboration with NIH to identify new approaches to evaluating 
fetal intrapartum monitoring devices, including the possible 
development of a large validated test database.

    Question 13. What is the FDA doing to ensure that devices used in 
children are designed and sized for their use? Can the FDA currently 
track how many devices have been approved for children and the number 
produced for conditions that occur in children? Would the FDA find a 
mechanism for tracking pediatric device approvals useful?
    Answer 13. There are many challenges to the design and development 
of pediatric devices. Long-term or permanent implants need to ``grow'' 
with the child or at least remain functional as the child develops. The 
devices also need to have a longer life span. In general, children 
require smaller devices, often requiring re-engineering of the entire 
product to ensure its functionality remains consistent as the child 
grows.
    Increased communication between the Agency, industry, patients, and 
clinicians is essential for encouraging pediatric device innovation and 
ensuring that the devices are appropriately designed. Therefore, CDRH 
has been focusing on these interactions during product development and 
pre-market review. Examples include:
    The Center is working to develop more device-specific guidances to 
provide regulatory clarity for industry and encourages manufacturers to 
meet with review staff during device development to ensure that key 
questions specific to their device can be addressed and has issued a 
guidance regarding the type of data needed to support marketing of 
pediatric devices and the protection measures to be addressed when 
involving this population in clinical trials; CDRH has formed a 
pediatric steering committee (SC) to oversee pediatric issues 
throughout the Center. Its functions include facilitating and 
encouraging pediatric pre-market reviews and consults by experts 
throughout the Agency, CDRH is holding workshops to discuss the 
development of critical pediatric devices.
    Regarding tracking, FDA does not have a data system capable of 
tracking all studies, submissions, or approvals for pediatric devices, 
but as discussed below, we have made important strides in this area. 
Some medical devices are specifically designed for use on infants and 
children, such as infant incubators and infant radiant warmers, and 
each has a unique classification regulation associated with it. For 
these devices, we are able to identify the number of applications that 
have been cleared or approved. Under a provision in the Medical Device 
User Fee and Modernization Act of 2002, device submissions solely for 
pediatric use are exempt from user fees in order to encourage their 
development. FDA's user fee database allows us to identify those 
applications that seek to take advantage of this incentive. Most 
medical devices, however, are indicated for general use, which often 
includes pediatric use with the only difference being the size of the 
device available. Since these devices can be used in both the pediatric 
and adult populations, these are not specifically tracked as pediatric 
devices.
    CDRH believes there are potential advantages in being able to track 
pediatric device submissions and approvals, and we are modifying our 
tracking systems to accomplish this. CDRH is currently making database 
changes, so that we will be able to track the number of PMAs, HDEs, and 
IDEs for pediatric indications in the near future.
    In addition, FDA believes there may be value in tracking pediatric 
subpopulations (neonates, infants, children, adolescents) for both 
marketing and investigational applications. We are examining whether 
and how our current database can accommodate such tracking, as well as 
determining the resources necessary to making such changes.

    Question 14a. Given some of the barriers that hinder new device 
development for children, how does the FDA think incentives could be 
improved to meet the pediatric need?
    Answer 14a. FDA agrees that, although there are many devices that 
have been developed particularly for the pediatric population, there 
still remain a number of obstacles to studying and developing devices 
appropriately for use in children. The Agency has been working with 
several pediatric professional organizations to better understand this 
important issue. Representatives from academia, medical specialty 
organizations, the device industry, and several government agencies 
participated in a series of Pediatric Device Stakeholders meetings in 
the fall of 2004. It became evident during discussions at these 
meetings that finding effective solutions to improving the availability 
of pediatric devices raises complex issues. CDRH has issued a general 
guidance, ``Pre-market Assessment of Pediatric Medical Devices--
Guidance for Industry and FDA Staff '' regarding the type of data 
needed to support marketing of pediatric devices and the protection 
measures that should be addressed when this patient population is 
involved in clinical trials of such products. The Center has also been 
working to develop more device-specific guidances to provide regulatory 
clarity for industry as they work on these new devices. FDA is also 
encouraging manufacturers to meet with the Agency during the 
development phase as questions and issues arise specific to these 
devices and/or the pediatric clinical data that may be needed to 
support their marketing.

    Question 14b. Would establishing a nonprofit consortium to promote 
pediatric device development be useful?
    Answer 14b. The idea of a pediatric device consortium was raised 
and discussed at the Pediatric Device Stakeholders meetings held in the 
fall of 2004. Depending on how it is constructed, it may be an 
effective way to promote pediatric device development. During the 
Stakeholder meetings, it was also recommended that a mechanism be 
established to allow for information to be provided to the NIH 
pediatric device contact regarding those specific pediatric device 
needs that the Consortium lacks sufficient funds to support and those 
needs for which the Consortium has been unable to stimulate 
manufacturer interest. It was also recommended that the Consortium 
coordinate with FDA and the device companies to ensure that adequate 
safety and effectiveness data, as defined by FDA, is developed for 
these new technologies.

    Question 14c. Would granting the FDA Pediatric Advisory Committee 
explicit authority to monitor pediatric devices and make 
recommendations for improving their availability and safety be helpful 
in increasing children's access to medical devices that are safe and 
effective?
    Answer 14c. In response to whether granting the FDA Pediatric 
Advisory Committee (PAC) explicit authority to monitor pediatric 
devices and make recommendations for improving their availability and 
safety would be helpful in increasing children's access to safe and 
effective medical devices, CDRH believes that the panel members 
available under its own Medical Devices Advisory Committee, as well as 
the expertise of available members on other committees, including the 
FDA PAC, provide the pediatric experience needed to adequately monitor 
the safety of pediatric devices and facilitate their development.

    Question 15. In order to improve post-market surveillance of 
children's medical devices, would you agree with the recommendations 
made by the Institute of Medicine (IOM) in a July 2005 report on the 
adequacy of post-market surveillance of pediatric medical devices that 
strongly suggests establishing a publicly accessible database of post-
market studies and increasing FDA authority to require post-market 
studies?
    Answer 15. FDA agrees with the IOM recommendation to establish a 
publicly accessible database of post-market studies. To that end, FDA 
has been working on the following:

     FDA issued a draft guidance entitled, ``Procedures for 
Handling Post-approval Studies Imposed by PMA Order'' to enhance the 
efficiency and effectiveness of conveying information on post-approval 
studies (PAS) to the Agency and for the Agency's review of such 
information. This guidance will assist industry in the pre-approval 
stage as they proceed to develop PAS.
     In its draft guidance, FDA also proposed that periodic 
public presentations to FDA's Medical Device Advisory Panels on the 
status of these studies be made by the industry and FDA. FDA believes 
that this will lead to a better informed public and clinical community 
and will provide important feedback to the Panels that often recommend 
that these studies be conducted.
     An electronic tracking system was developed and 
implemented to monitor the status of all PAS.
     A web page listing the status of PAS is under development 
and expected to be available late in 2006.
               federal preemption of state drug labeling
    Question 16. On February 23, 2006, Senator Kennedy and I wrote 
Secretary Leavitt with our concerns about the final rule published on 
January 18, 2006 in the Federal Register amending 21 CFR parts 201, 
314, and 601. The rule modifies drug labeling requirements in order to 
give information to physicians in a more concise and appropriate 
manner. On March 15, 2006, I received a letter from LaJuana D. 
Caldwell, Director, FDA Executive Secretariat informing me that a 
thorough response to my letter was being prepared at FDA. To date, my 
office has received no response from the FDA and several attempts to 
obtain information about when the response would be sent have gone 
unanswered. I am deeply concerned about the preamble to the final rule 
which asserts broad and vague Federal preemption of State drug 
labeling, advertising, and product liability laws. As I stated in my 
letter, such an assertion is inconsistent with long-standing FDA 
practice and congressional intent, not to mention the fact that such a 
drastic reversal of policy should be subject to public consideration 
and public comment on whether the Agency has the legal authority to 
preempt State requirements. When will we receive a response from the 
FDA to our letter?
    Answer 16. My apologies for the delay--we are working to provide a 
substantive response to your letter as soon as possible.

    Question 17. In the December 2000 proposed rule, the Agency stated 
that the regulations would not preempt State law. However, the preamble 
of the final rule asserts that it has been the Government's 
``longstanding'' position that State actions related to drug labeling 
and advertising, and even medical malpractice, are preempted. Can you 
please provide examples of this ``longstanding'' position and provide 
all Agency statements before 2001 with respect to this issue?
    Under the Federal Food, Drug and Cosmetic Act, the FDA is charged 
with ensuring that drugs and devices are safe and effective and that 
the labeling of drugs and devices adequately informs users of the risks 
and benefits of the product. FDA scientists work continuously to 
evaluate information submitted by the sponsor and the latest available 
scientific information to monitor the safety of products and to 
incorporate information in the product's labeling when appropriate. The 
FDA considers itself to be the final arbitor of the content of drug and 
device labeling, and believes this is further substantiated by the 
courts in response to briefs filed by the Agency in support of 
preemption dating back to at least 1977.
    Answer 17. In the preamble to the final rule, FDA was stating the 
Agency's position on the State of the law as it relates to Federal 
preemption and drug labeling. The act has long given FDA the authority 
to determine when drug products are misbranded. FDA therefore, is the 
appropriate arbiter regarding what drug labeling is considered false 
and misleading. FDA was simply restating its views about this 
congressionally assigned role with regard to State failure to warn 
claims based on FDA approved labeling. This has long been FDA's 
position and DOJ has participated on behalf of FDA in preemption cases. 
Additionally, FDA has advanced this position in rulemakings, prior to 
this administration. Indeed, FDA filed briefs during the previous 
administration taking the position that the Supremacy Clause bars State 
tort liability for failure to include a warning on a drug label that is 
in conflict with or contrary to the warnings approved by the FDA. See, 
e.g., Bernhardt v. Pfizer, Inc., No. 00 Civ. 4042 (LMM), Statement of 
Interest of United States (S.D.N.Y. filed Nov. 13, 2000). Furthermore, 
FDA rules dating back to at least 1979 reflect the Agency's views that 
the ultimate decision whether to require a warning on a drug label 
rests with FDA, and that Federal law prohibits inclusion of statements 
on a label that FDA has determined not to be supported by substantial 
evidence. See, e.g., 44 Fed. Reg. 37434, 37435, 37441, 37447 (1979).
    FDA's regulation of prescription drug labeling, and Federal 
preemption over conflicting State requirements, is extremely important 
to FDA's ability to protect the public health. FDA's regulation of 
prescription drugs is designed to ensure each drug's optimal use 
through requiring scientifically substantiated warnings. Under the 
Federal Food, Drug, and Cosmetic Act, FDA is the public health agency 
charged with ensuring that drugs and devices are safe and effective, 
and that the labeling of drugs and devices adequately inform users of 
the risks and benefits of the product. FDA employs scientists and other 
experts who review the information submitted by the manufacturer on a 
product's risks and carefully titrate the warnings, etc. that should be 
placed on the labeling. FDA continuously works to evaluate the latest 
available scientific information to monitor the safety of products and 
to incorporate information into the product's labeling when 
appropriate. The public health risks associated with overwarning are as 
great as--if not greater than--the health risks associated with 
underwarning. Overwarning can cause patients not to take beneficial 
drugs and doctors not to prescribe them. Under-utilization of a drug 
based on dissemination of scientifically unsubstantiated warnings, so 
as to deprive patients of beneficial, possibly lifesaving treatment, 
could well frustrate the purposes of Federal regulation as much as 
over-utilization resulting from a failure to disclose a drug's 
scientifically demonstrable adverse effects. Further, allowing 
unsubstantiated warnings may also diminish the impact of valid warnings 
by creating an unnecessary distraction and making even valid warnings 
less credible.

    Question 18. Under Executive Order 13132, issued by President 
Reagan and reissued by President Clinton, a Federal Agency such as FDA 
must consult with State and local authorities about, and examine, the 
effects on States and localities of each regulation it issues. In the 
proposed rule, FDA indicated that the regulation would not preempt 
State law and, as such, States did not comment on it. Can you please 
describe what the FDA did to consult with State and local governments 
about this regulation?
    Answer 18. In adopting the final rule in 2006, FDA did consult with 
a number of organizations representing the interests of State and local 
governments about the potential interaction between FDA drug labeling 
requirements and State law. See 71 Fed. Reg. 3922, 3969 (2006). FDA 
contacted several representative State groups, explained that FDA was 
considering including language explaining its position on preemption in 
the preamble to the final Physician Labeling Rule, and considered all 
responses it received. Furthermore, it is worth noting that the U.S. 
Supreme Court has suggested that Federal preemption would apply even if 
the Agency explicitly stated at the time it promulgated regulations 
that the regulations were not intended to have preemptive effect, if 
the Agency subsequently changed its view on the strength of its 
interests in preemption or the effect of the regulations in question. 
Hillsborough County v. Automated Medical Laboratories, Inc., 471 U.S. 
707 (1985).
                  direct to consumer (dtc) advertising
    Question 19. Some have suggested that DTC advertising has increased 
the magnitude of drug safety problems by drastically increasing the 
population that uses a drug, even if it might not be appropriate for 
some patients. As Commissioner, would you increase FDA regulation of 
DTC advertising? What authority does the FDA have to limit or ban 
advertising, or require disclosures, when a safety problem is 
discovered? Does the FDA require additional authority in this area?
    Answer 19. The Federal Food, Drug, and Cosmetic Act (FDCA) and 
Agency regulations focus on the content of prescription drug promotion. 
The law does not prohibit advertising prescription drugs directly to 
consumers, and the First Amendment does not permit the banning of 
truthful, nonmisleading commercial speech. Monitoring DTC promotion, 
and especially broadcast ads, is a top priority. FDA works to ensure 
that information about product claims and risks is presented in a way 
consumers can understand. We also want to ensure that consumers get 
balanced, truthful, and nonmisleading information consistent with the 
First Amendment, and are committed to do this.
                 final uva/uvb monograph for sunscreen
    Question 20. The Fiscal Year 2006 Agriculture Appropriations 
Conference Report included language directing the FDA to complete the 
final sunscreen monograph, which will guide UVA and UVB labeling 
information for over-the-counter (OTC) sunscreen products, within 6 
months of passage of the agriculture appropriations bill. That bill was 
signed into law on November 10, 2005 and the deadline for the final 
monograph was May 10, 2006. It is now nearly 3 months past the deadline 
Congress set for the final sunscreen monograph--and the summer season 
is well underway--and yet the FDA cannot provide a date by which the 
final monograph will be released. The FDA began working on a monograph 
for sunscreen products in 1978 and has yet to complete it.
    Dr. von Eschenbach, please provide the committee with the following 
information: An accurate time-line detailing a plan of action for 
completing the monograph; Any perceived or acknowledged obstacles to 
completing the monograph by the end of calendar year 2006; and a 
detailed explanation as to why the monograph has not been completed.
    Answer 20. It is anticipated that a rulemaking will be issued by 
the end of calendar year 2006 to propose new testing and labeling, 
primarily for products that contain ingredients that block UVA rays. 
FDA drafted this proposed rule after asking for comments specific to 
this topic in a June 2000 Federal Register notice. As the Agency 
developed the rule, new issues emerged that needed to be addressed. For 
example, recently FDA received a citizen petition requesting that the 
Agency amend the OTC sunscreen drug monograph to consider OTC sunscreen 
drug products containing nanoparticles as not covered under the 
monograph and instead treat them as new drugs. The proposed rule is 
currently in clearance.
    The period for public posting of comments associated with the 
proposed rulemaking, once published, is 90 days and FDA will 
subsequently issue a Final Rule. The time to publication of the final 
rule is dependent on the number and content of the comments submitted 
in response to the proposed rule and the Agency's clearance process.
                            pseudoephedrine
    Question 21. Pseudoephedrine (PSE) is a safe and effective 
decongestant in many over-the-counter (OTC) medicines for treatment of 
the common cold and hay fever. However, PSE also is a precursor 
chemical being diverted to illicit manufacturing of methamphetamine. 
Addressing this critical public health and safety problem necessitates 
transitioning consumers relying on PSE-containing OTC products to 
therapeutically-equivalent replacements that cannot be used in meth 
production.
    During 2005, the Congress took action, reflected in the Conference 
Report on the Combat Meth Act, to facilitate FDA approval of such 
reformulated OTC products. Some longstanding OTC medicines that 
currently contain PSE and are marketed under the applicable FDA 
monograph potentially can be reformulated to include an alternate 
active ingredient in accordance with the steps Congress took in the 
Combat Meth Act.
    As we approach the September 30th effective date of the Combat Meth 
Act, Congress understands there is a similar opportunity to facilitate 
development of new prescription products that could be approved by FDA 
as safe and effective therapeutic alternatives to fill the need 
currently met by PSE that could provide similar therapeutic benefits 
and be equally convenient, but without the diversion or abuse risks 
associated with PSE.
    Can you please update the committee on efforts the FDA is taking, 
in advance of the September 30th effective date of the Combat Meth Act, 
to implement that statute and its provisions addressing 
pseudoephedrine-based meth diversion?
    Answer 21. While the primary responsibility for implementation of 
the Combat Meth Act is with the Department of Justice (DOJ), FDA has 
acted to ensure regulated industry understands its obligations with 
respect to FDA-regulated products. Immediately after enactment, we 
provided manufacturer and drug information to the Drug Enforcement 
Administration (DEA) needed for DEA's rulemaking on manufacturer 
production and import quotas, part of the Combat Meth Act.
    Also, the Office of Non-Prescription Products (ONP) is interacting 
with manufacturers to help them interpret the Combat Meth Act 
provisions for packaging of both NDA and OTC monograph products. For 
example, OTC products that are marketed under the OTC Drug Review may 
be reformulated following the stipulations for active ingredients, 
manufacturing, and labeling that are set out in the regulations 
associated with the OTC monographs. These reformulations do not require 
approval by the FDA prior to marketing. Accordingly, an immediate 
release tablet containing pseudoephedrine as a decongestant in 
combination with an antihistamine could be reformulated under the 
monograph to contain an alternative decongestant, phenylephrine, in 
combination with the same antihistamine. This reformulation would not 
require prior approval, supporting a rapid transition from products 
containing pseudoephedrine to products using other antihistamines. In 
addition, a new salt of phenylephrine was recently added to the 
monograph to allow manufacturers more flexibility in formulating 
products.
    In addition, OTC products that are marketed under New Drug 
Applications (NDAs) require FDA review and approval prior to marketing 
of a reformulated product. Such supplementary applications are reviewed 
under the specific timelines and procedures associated with the 
Prescription Drug User Fee Act (PDUFA) and other pertinent regulations. 
ONP interacts with applicants to insure that only essential testing is 
required to demonstrate that the reformulations will be safe and 
effective. For instance, applicants would, in general, not be required 
to conduct clinical trials to demonstrate the safety and effectiveness 
of a product reformulated to include phenylephrine in place of 
pseudoephedrine. Applicants would instead be able to demonstrate the 
bioequivalence of the new product in humans compared to reference 
standards, a lesser demand on applicant resources.

    Question 22. Through the appropriations process, Congress has 
directed the FDA Commissioner to encourage, expedite, and support the 
filing, review, and final action on any new drug application, or 
supplement to a new drug application, seeking approval of a combination 
of active ingredients previously-approved as safe and effective, that 
would replace or provide a therapeutic alternative to a currently-
marketed drug product that contains an active ingredient that currently 
is the subject of diversion and/or abuse outside regulated channels of 
commerce.
    In light of this directive, would you please delineate for the 
committee the steps that FDA has taken to enhance access to new 
prescription combinations of safe and effective marketed drugs that 
could provide alternative therapies to replace pseudoephedrine-
containing products and address major public health and safety concerns 
arising from meth production?
    Answer 22. Products which require New Drug Applications (NDA) or a 
supplement to an NDA (SNDA) may qualify for a priority review. We will 
meet with applicants to determine if such applications qualify to be 
considered under priority review. The ability to actually develop such 
a formulation and provide data to demonstrate that it is abuse 
resistant (and not simply defeatable by another mechanism) is complex. 
We interact with such applicants to ensure that only essential testing 
is required to demonstrate that the reformulations will be safe and 
effective. For instance, clinical trials are not required in any 
instance in which a demonstration of bioequivalence in humans can be 
appropriately applied. This may help shorten the time necessary to 
provide data for the NDA or SNDA. We also will respond to submissions 
and meeting requests quickly so that access is not delayed based upon 
the ability of a company to get feedback or to interact with the 
Agency.
                            quinine sulfate
    Question 23. This past June, the FDA published a guidance document 
regarding drugs that are widely marketed without FDA approval which 
stated that the marketing of these drugs is unsafe and illegal because, 
``unapproved drugs have bypassed the Agency approval process through 
which FDA ensures, based on reliable scientific data, that marketed 
drugs are safe, effective, properly manufactured, and accurately 
labeled.''

    The FDA also stated,

        ``FDA is dedicated and determined to meet our drug safety 
        mission and to ensure that ALL drugs marketed in the United 
        States meet safety, effectiveness, manufacturing, and labeling 
        standards.''

    Quinine sulfate was one of the marketed drugs that had never been 
approved by FDA, but a year ago FDA granted approval to one company and 
required that its labeling include expanded safety information to 
address the serious risks of this drug. The company was also granted a 
7-year Orphan Drug Exclusivity meaning it is the only company legally 
allowed to sell quinine during this period. However, FDA has continued 
to allow the importation and marketing of numerous unapproved quinine 
products with outdated safety labeling.
    Dr. von Eschenbach, in light of the serious safety risks of 
unapproved quinine products, when will FDA begin taking enforcement 
action against these illegal products?
    What have been the barriers to FDA enforcement against domestic 
sales of unapproved quinine sulfate?
    Answer 23. While the FDA drug approval system is widely recognized 
for bringing safe and effective new drugs to the market, it is 
unfortunate that many older or existing drug products continue to be 
marketed in this country without required FDA approval. The Marketed 
Unapproved Drugs Compliance Policy Guide (CPG) (http://www.fda.gov/
cder/guidance/6911fnl.pdf) published in June addresses this issue and 
is a significant step forward for our drug safety initiative.
    Because it is impossible for the Agency to simultaneously and 
immediately remove all unlawfully marketed, unapproved products from 
the market, the CPG outlines a prioritized, risk-based enforcement 
approach that encourages companies to independently comply with the 
drug approval process and ensure the safety and efficacy of their 
marketed products. The CPG discusses how the Agency will bring 
unapproved drugs into the approval process, while making every effort 
to avoid adversely affecting public health, imposing undue burdens on 
consumers, or unnecessarily disrupting patient access to drugs that may 
provide important health benefits. The Agency's enforcement resources 
are limited and need to be used strategically to maximize the 
protection of the public health.
    With regard to quinine, FDA is aware of both the approved and 
unapproved quinine sulfate drug products on the market. FDA is 
evaluating the unapproved quinine drug products that are currently 
being marketed and will consider enforcement action consistent with the 
CPG.
  Response to Questions of Senator Harkin by Andrew C. von Eschenbach
    Question 1a. The FDA has made significant strides the past couple 
of years in implementing and enforcing DSHEA. Some people have been 
critical of DSHEA saying that it does not give FDA the tools it needs 
to ensure the safety of dietary supplements. Do you believe DSHEA gives 
the FDA sufficient authority to regulate dietary supplements?
    Answer 1a. The Dietary Supplement Health and Education Act of 1994, 
or DSHEA, provides FDA the authority to act against dietary supplements 
that carry unsubstantiated claims or claim to treat diseases, that are 
unsafe, or that are otherwise adulterated or misbranded. We believe 
that the current statute provides the necessary authority and FDA is 
focused on effective implementation and oversight of dietary 
supplements.
    On August 17, 2006, the U.S. Court of Appeals for the Tenth Circuit 
in Denver upheld the Food and Drug Administration's (FDA) final rule 
declaring all dietary supplements containing ephedrine alkaloids 
adulterated, and therefore illegal for marketing in the United States, 
reversing a decision by the U.S. District Court for the District of 
Utah. The Tenth Circuit Court of Appeals' ruling demonstrates the 
soundness of FDA's decision to ban dietary supplements containing 
ephedrine alkaloids, consistent with DSHEA.
    On November 4, 2004, FDA published a Regulatory Strategy for the 
Further Implementation and Enforcement of DSHEA, in which FDA detailed 
specific steps for the further implementation of DSHEA. This Regulatory 
Strategy identified three specific initiatives: (1) monitoring and 
evaluating product and ingredient safety, (2) assuring product quality 
through CGMP regulations, and (3) monitoring and evaluating product 
labeling. With this strategy, FDA intends to improve the transparency, 
predictability, and consistency both of the Agency's scientific 
evaluations of dietary supplement product and ingredient safety, and of 
its regulatory actions to protect consumers against unsafe dietary 
supplements.

    Question 1b. When we had Dr. Crawford's nomination hearing, he 
assured me that Good Manufacturing Practices for dietary supplements 
would be released ``very soon.'' In addition, when you came before the 
Agriculture Appropriations sub-committee earlier this year, I asked you 
when they would be released. You replied that they were at OMB. DSHEA 
was passed in 1994. That means it's been 12 years and still we do not 
have GMPs for dietary supplements. Can you give us a definitive date as 
to when the final GMP regulations for dietary supplements will be 
published in the Federal Register?
    Answer 1b. FDA is committed to publishing this final rule. I can 
assure you that there has been significant work done on the final rule 
since the comment period for the proposed rule ended in August 2003.
    Since we are still in the rulemaking process, I can not tell you 
what specific issues are being discussed, but I can tell you that the 
issues have been complex, legally and substantively, and in some cases, 
novel. The final rule is under review by the Office of Management and 
Budget.
    We have expended significant internal resources on reviewing and 
preparing responses to the comments received. We also have worked 
extremely hard to draft the final rule in order to assure quality 
products for the consumer while minimizing the economic impact to the 
dietary supplement industry. I can assure you that full attention is 
being given to the completion of the rule as soon as possible.
                             fda resources
    Question 2. Over the past several years, I have become increasingly 
concerned that FDA does not have the resources to adequately do its 
job. FDA regulates 25 cents of every dollar spent in the United States. 
Yet, in many areas, it seems FDA cannot keep up with its workload. For 
example, approval of generic drugs, and cuts at the Center for Food 
Safety and Applied Nutrition. You have new responsibilities with avian 
flu and threats to the food supply. At the same time, Congress is 
continuing to put new responsibilities on FDA. For example, last week 
we had a hearing in this committee on a National Food Uniformity bill 
that would increase the burden on FDA. And we will consider legislation 
next year that will give FDA more authority to do post-market 
surveillance of drugs.
    You have been at FDA for almost a year now. In your candid opinion, 
does FDA have the resources to do its job effectively, efficiently, and 
quickly? If you look at the Agency, what specific areas do you think 
require more funding from Congress?
    Answer 2. At FDA, our goal is to maximize the benefits of, and 
minimize the risks associated with the wide variety of products we 
regulate. The President's fiscal year 2007 budget proposes increases to 
respond to a number of high priority public health concerns. These 
increases reflect the areas of FDA responsibility that require 
increased funding from Congress. FDA has requested fiscal year 2007 
increases for pandemic preparedness, food defense, critical path, drug 
safety, tissue safety, funding to meet user fee triggers, pay increases 
for cost of living, and increases to support our essential 
infrastructure needs. In the months since the President released the 
fiscal year 2007 budget, I have been working with the members of the 
House and Senate Appropriations Committees and others in Congress to 
secure these important funding increases.
                  fda authority over tobacco products
    Question 3. As you know, tobacco use is the leading preventable 
cause of death in the United States, killing more than 400,000 people 
every year. Thirty percent of all cancer deaths are attributable to 
tobacco use. Nearly 4,000 children have their first cigarette everyday, 
and 1,500 of them become daily smokers. Senator DeWine has introduced 
legislation that would give the FDA the legal authority to regulate 
tobacco. The Senate has passed this legislation once and polls show 
overwhelming public support for this legislation. Do you support giving 
the FDA regulatory authority over tobacco products?
    Answer 3. I share your concern that tobacco use is a vital public 
health issue. As you know, on March 21, 2000, the U.S. Supreme Court 
affirmed the decision of the U.S. Court of Appeals for the Fourth 
Circuit that the Food and Drug Administration (FDA) lacks jurisdiction 
under the Federal Food, Drug, and Cosmetic Act to regulate cigarettes 
and smokeless tobacco products.
 Response to Questions of Senator Mikulski by Andrew C. von Eschenbach
    Question 1. GAO said in their recent report that the process for 
assuring the safety of drugs on the market is deeply flawed. They do 
not believe the Offices of Drug Safety, the Office of New Drugs, nor 
the Drug Safety Board are effectively addressing safety issues. Many, 
including Senators Grassley and Dodd with their legislation, have 
suggested an independent agency to provide the necessary oversight.
    What do you think of the establishment of an independent watchdog 
body to ensure ongoing safety? How can the FDA be a watchdog of itself? 
Given the GAO report, please outline what changes you will make to 
assure the safety of drugs after they have been approved for the 
public?
    Answer 1. Senator, we continue to believe that our current basic 
organizational structure which keeps the debate about the safety and 
efficacy of a product in one Center is appropriate and effective. In 
the past year, however, we have moved to strengthen that structure by 
ensuring that epidemiologists and post-market safety experts have equal 
organizational representation and stature within the Center. Prior to 
the Center reorganization, the Director of the ``Office of Drug 
Safety'' reported to the Director of the Office of Pharmacoepidemiology 
and Statistical Science; whereas, the Director of the Office of New 
Drugs reported directly to the Center Director. With the 
reorganization, we established an Office of Surveillance and 
Epidemiology (OSE) that is responsible for most of the functions 
formerly managed by the Office of Drug Safety. This new name more 
appropriately represents the functions handled by the office and 
alleviates some of the confusion and misconception that drug safety 
issues are handled solely by one office in CDER. Further, the Director 
of OSE now reports directly to the Center Director, thus putting the 
OSE Director on the same footing with the OND Director when negotiating 
business and management issues including requests for resources. With 
this organizational change, we believe that our current structure 
fosters a proper environment for a fair assessment of the effectiveness 
and risk of a product.
    You refer to the GAO Report on Drug Safety. Overall, FDA believes 
that the report is well done and that the conclusions reached are 
reasonable and consistent with actions we already have underway or 
planned. In particular, CDER has several initiatives that are discussed 
in the GAO report and are in the process of being implemented. These 
initiatives are aimed at strengthening the management of identified 
safety issues to assure that the decisions are made promptly, and are 
based on all of the relevant expertise in CDER, including the staff in 
OND and ODS.
    While two separate and independent centers may be a logical 
organizational structure for distinct pre-approval and post-approval 
regulatory activities, the nature of our knowledge of a drug's safety 
profile and the expertise required for the ongoing assessment of a 
drug's risk-benefit balance demand that these two activities be housed 
in a single center. Our knowledge of a drug's safety profile proceeds 
along a continuum, which begins with in vitro and animal studies 
(before the drug is ever administered to humans), continues to grow 
through rigorous clinical trials, and is further refined after a drug 
is marketed. It is the review and synthesis of this cumulative 
knowledge base that leads to the most accurate assessment of the drug's 
safety profile. In CDER, Office of New Drug (OND) staff is the most 
knowledgeable about the pre-marketing safety data, while Office of 
Surveillance and Epidemiology (OSE) staff specializes in the post-
marketing safety issues. Staff from the OSE and OND work closely in the 
analysis of appropriate regulatory actions, together they take into 
consideration both risk and benefit information from pre- and post-
approval sources. If pre-approval and post-approval functions were 
split, there would be a loss of continuity in the review of risks and 
benefits.
    Additionally, separating these two activities into two centers 
would be very costly, because of the duplication of the wide range of 
expertise involved. Medical officers in OND whose areas of expertise 
include the affected patient population(s), medical conditions, and 
treatments, know the results of animal and clinical studies that 
supported approval of the product; in addition, they review studies 
with products that are used in the same patient populations, and 
products, some still in the investigational phase, from drugs in the 
same or related classes. This expert knowledge of the patients' medical 
conditions, availability of alternative therapies, and safety profiles 
from IND and NDA submissions is a crucial component in the review of 
newly identified risks and how they may impact benefits. OSE personnel 
provide expertise in the areas of epidemiological studies of large 
populations, evaluation of data from AERS (that is, spontaneous adverse 
event reporting) and large external data sets purchased for adverse 
event tracking and evaluation in specific populations, medication error 
prevention, and risk management techniques.
    If the responsibilities were split into two centers, the safety 
center would have to duplicate the expertise of OND staff, with expert 
knowledge of patient populations, medical conditions, alternative 
therapies, and safety profiles from investigational new drug 
applications and studies in marketing applications to support approval 
to enable the safety center to make appropriate risk-benefit decisions 
and the drug approval center would have to duplicate the expertise of 
the OSE staff. Cross-center consultation would be much more difficult, 
and therefore, less efficient, than with-in center collaboration.
    OND routinely meets with OSE staff to discuss the current or 
anticipated safety of marketed products. In addition, CDER has recently 
instituted safety meetings that are held periodically (monthly or bi-
monthly) to discuss new safety issues and the status of reviews and 
analysis of previously identified safety signals. Also, prior to 
approval of applications to market new molecular entities (NMEs), or 
nonNMEs, OND and OSE staff have pre-approval safety conferences. The 
OSE staff is also consulted by OND in many pre-approval activities that 
increase CDER's ability to understand and adequately monitor risk and 
benefit for marketed products such as medication error prevention and 
risk management plan review.
    For the reasons mentioned previously--resources, communication, 
collaboration, leadership, and shared responsibilities--I do not 
believe that two separate and independent centers would improve FDA's 
ability to fulfill its mission to protect the public health.

    Question 2. The FDA has always been the gold standard in 
maintaining drug safety, yet today, the Agency is being politicized and 
degraded. We have seen a persistent pattern of placing ideology before 
science.
    As commissioner, outline for me what you will do to ensure that the 
best possible science informs the decisions the FDA makes every day? 
What are your concerns that hundreds of scientists at the Agency are 
reporting such interference with their scientific work? What would you 
as a scientist and Commissioner do to ensure greater respect for 
science within the FDA? Will you commit to having a channel for dissent 
if there are other views?
    Answer 2. Senator, first and foremost, I am committed to ensuring 
FDA makes decisions based on sound science. I would like you to know 
that I will make myself personally available to staff who want to 
appeal decisions made by FDA management. I believe that the need to 
appeal to me will be rare, however, because I will ensure that there 
are strong policies and procedures in place for resolving issues 
involving dissenting opinions. Efforts toward that end will include 
promulgating new policies and procedures as necessary, and 
strengthening, by process improvement and best practices measures, many 
of those that are already in place.
    For example, we are working to ensure a rigorous ombudsman program 
through which staff are welcome to promulgate dissenting opinions. 
Staff may also invoke standard written procedures for facilitating and 
resolving differing professional opinions. In addition, at the 
direction of the Secretary, FDA, established a Drug Safety Oversight 
Board whose charter includes responsibility for deliberating on any 
dissenting opinions raised during evaluation of drug applications and 
surveillance of marketed products. Through these and other traditional 
management techniques, I believe we will successfully address any 
dissenting opinions, and I am committed to evaluating our processes and 
refining them as necessary to ensure that there is an open scientific 
debate of issues at FDA.

    Question 3. The scientists at the FDA are my constituents. In a 
recent survey done by the Union of Concerned Scientists, nearly half of 
them report their morale as ``poor'' or ``extremely poor.'' Over half 
say their personal job satisfaction at FDA has decreased over the past 
few years. Only one-third think the Agency is moving in the right 
direction.
    Dr. von Eschenbach--these are my constituents. As a scientist, what 
will you do to address their concerns? The FDA needs to re-establish 
its relationship with its own scientists. What will you do to ensure 
that the FDA will continue to recruit and retain the best and brightest 
employees?
    Answer 3. FDA's workforce is comprised of over 12,000 incredibly 
talented and highly trained professionals who epitomize the true 
meaning of the word public servant. It is important for everyone to 
know that if confirmed, their support and guidance will be my greatest 
asset in leading the FDA.
    As the FDA regulates almost 25 percent of all the products 
Americans consume, its talented and dedicated employees continue to set 
the Gold Standard that is emulated around the world but never equaled. 
This standard of achievement must not change. But the world around us 
is changing and the FDA of today is faced with new challenges and the 
FDA of tomorrow will encounter incredible opportunities.
    Senator, I am committed to recruiting and retaining top staff to 
face these new challenges and to support the Agency's important public 
health mission.

    Question 4. The FDA has always been the gold standard in 
maintaining drug safety, yet today, the Agency is being politicized and 
degraded. We have seen a persistent pattern of placing politics before 
science stifling scientists whose findings do not meet political 
objectives making decisions based on politics--rather than sound 
science. The FDA needs a major overall and a culture change at the 
highest levels in order to continue to meet its mission.
    Dr. von Eschenbach, do I have your commitment that you will 
transform the FDA back into the proud agency it once was? What will you 
do, or have you done in your role as Acting Commissioner, to 
demonstrate a commitment to change?
    Answer 4. I am committed to maintaining the long-standing 
traditions and values of an Agency whose processes and decisions are 
guided by sound science and vigorous analysis of evidence and based on 
the best interests of the patients and public we serve.
    This year, FDA celebrates 100 years of successes in becoming the 
world's gold standard for assuring the drugs we give our children, the 
medical devices we use to treat disease and the food we eat is safe and 
effective. With more than 12,000 employees, FDA is committed to 
continuously improving and becoming even better as we enter our second 
century. FDA is as committed as ever to its time-honored tradition of 
encouraging vigorous debate among experts who use disciplined processes 
to arrive at consensus and conclusions.
    Much work remains to fully equip FDA to face the challenges and 
seize the opportunities ahead, but I am confident that we are on the 
right path. I believe I can provide the leadership and management that 
will guide this important public health agency proudly and effectively 
into its second century of service.
  Response to Question of Senator Jeffords by Andrew C. von Eschenbach
    Question 1. You have had a very distinguished career and are a top 
scientist. What are your reasons for wanting the top FDA slot?
    Answer 1. Throughout my career as a physician I have endeavored to 
devote my skills and effort to serving the needs of patients. In my 
career as a researcher, educator and administrator, I have witnessed 
remarkable achievements in science and technology that now hold the 
promise for extraordinary breakthroughs in conquering disease and 
assuring health for all. The FDA is the critical link between that 
phenomenal progress and its availability for the benefit of patients 
and the public. The FDA must assure that safe and effective life saving 
and health enhancing interventions are made available in the shortest 
possible time. The next few years are crucial to creating the FDA of 
the 21st century--an FDA that uses the tools of modern molecular 
science to facilitate the regulation of the food, drugs, devices and 
products that society will require to lead long and healthy lives. The 
Agency must swiftly adopt modern management tools to enhance the 
efficiency and reliability of the regulatory process to continue to 
fulfill its covenant to protect and promote public health. It would be 
my lifelong professional dream come true for me to be confirmed by the 
U.S. Senate, and to have the privilege to serve as the Commissioner of 
the FDA as it embraces these opportunities and challenges.
 Response to Questions of Senator Bingaman by Andrew C. von Eschenbach
                         lead in imported candy
    Question 1. For some time, those of us concerned about the health 
and well-being of Hispanic children (both in the United States and in 
Mexico) have eagerly awaited action by the Food and Drug Administration 
(FDA) to reduce the acceptable level of lead in candy to ensure that 
children's exposure to lead is minimized, as the Agency committed to do 
in Spring 2004. We have been concerned particularly about imported 
candy from Mexico. Therefore, in a letter I wrote you in January, I 
explained that I was pleased to see that, through its December 2005 
draft guidance, the FDA has proposed that acceptable levels of lead in 
candy be reduced from no more than 0.5 part per million (ppm) to 0.1 
ppm, while also maintaining the enforcement policy toward the use by 
industry of lead-based printing ink on candy wrappers. I expressed my 
strong support for both of these actions.
    However, I have been deeply disturbed by the fact that, while FDA 
states it will maintain its enforcement policy against industry use of 
lead-based printing ink on candy wrappers, it appears to be gutting its 
enforcement policy with respect to the acceptable level of lead in the 
candy itself. Dropping the stated acceptable level from no more than 
0.5 ppm to 0.1 ppm is meaningless if FDA does not intend to enforce the 
lower standard. The public documents on enforcement of the new 0.1 ppm 
standard appear to indicate just that--FDA is abrogating its current 
enforcement policy without replacing it with anything other than a 
``recommendation'' with no teeth.
    The notice published in the Federal Register on December 27, 2005, 
reads, ``. . . FDA is rescinding previous guidance provided in a 1995 
letter to the industry regarding an enforcement level.'' That would not 
be disturbing, in and of itself, if the guidance being rescinded were 
being replaced with new enforcement policy. However, the draft guidance 
and supporting documents make clear that is not the case.
    As the draft guidance entitled, ``Lead in Candy Likely To Be 
Consumed Frequently by Small Children: Recommended Maximum Level and 
Enforcement Policy'' reads,

          ``The 0.1 ppm recommended maximum lead level is not an 
        enforcement guideline. FDA intends to consider several factors 
        in bringing enforcement actions regarding lead in candy . . ., 
        including the level of lead present and the best available 
        consumption data.''

    The 0.1 ppm level is further undermined by the draft guidance's 
clarification that ``FDA's guidance documents, including this guidance, 
do not establish legally enforceable responsibilities. Instead 
guidances describe the Agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or 
statutory requirements are cited. The use of the word should in Agency 
guidances means that something is suggested or recommended, but not 
required.''
    In addition, the supporting document for the guidance takes it one 
step further by stating, ``The draft guidance also rescinds the 0.5 ppm 
guideline for considering enforcement action and does not announce a 
new enforcement guideline.''
    Further to the point, the Baltimore Sun (December 23, 2005) quotes 
Michael Kashtock, ``a senior adviser at the FDA,'' as stating:

          ``The guidance doesn't include enforcement because it's too 
        difficult to have a `one-size-fits-all approach' to various 
        candies'' and that `the agency has met with Mexican officials 
        and is hoping to prevent tainted candy from coming across the 
        border.' FDA enforcement policy should not be based on `hope.' 
        ''

    In sharp contrast, the 1995 enforcement guidance read:

        . . . we have the authority to take regulatory action against 
        any food product that contains a poisonous or deleterious 
        substance that may render the product injurious to individuals. 
        We also have regulations that require that ingredients used to 
        manufacture food be safe, which requires that they be of a 
        suitable degree of parity for their intended use. Further, our 
        regulations require that equipment and utensils used in the 
        production of food be designed and used in a manner that 
        precludes contamination of the food with unsafe substances.

    The statute clearly anticipates that FDA will set acceptable levels 
of contaminates, such as lead, in food products, and that, once such 
levels are established and exceeded, the product is adulterated and 
subject to enforcement action.
    FDA's press release on the guidance stated that the Agency will

        ``[c]ontinue to closely monitor the lead levels in Mexican 
        candy and other domestic and imported candy products, work with 
        our Mexican counterpart regulatory agencies, and take 
        appropriate regulatory action. . . .''

    Since FDA has apparently now rescinded the 1995 enforcement 
guidance, I asked that you take immediate action to clarify what the 
Agency means by ``appropriate regulatory action.'' Further, I asked 
that you explain both how FDA will take action against manufacturers, 
importers, and distributors of candy that exceeds 0.1 ppm of lead, 
whether domestic or imported, and how the Agency will identify the most 
likely sources of violations and set enforcement priorities. This 
clarification is essential so we can be assured that you intend to 
protect our Nation's children, particularly Hispanic children and 
children along the U.S.-Mexico border, from dangerous lead exposure.
    Furthermore, as part of that effort, I urged that FDA work in close 
partnership with the U.S.-Mexico Border Health Commission (USMBHC) to 
protect the health of children in both the United States and Mexico. 
FDA participated in a meeting in El Paso, Texas, on January 26-27, 
2006. However, it is unclear whether any additional action has taken 
place in the last 6 months.
    We know that elevated BLLs can have, as the California Senate 
Committee on Health and Human Services has found, ``dramatic and 
devastating effects, particularly on children.'' The committee adds,

          ``It affects the liver, kidneys, lungs, spleen, muscles, 
        heart, and central nervous system. At high levels, lead 
        poisoning can cause kidney problems, seizures, coma, 
        miscarriages in pregnant women and low sperm counts in men, and 
        even death. Once eaten, it stays in the bloodstream and bones. 
        Even low levels of lead are harmful and are associated with 
        decreased intelligence, impaired behavioral development, 
        stunted growth, and impaired hearing.''

    Therefore, I once again urge your immediate attention to this 
important matter. It is crucial for our children that you immediately 
make public real enforcement policies and ensure appropriate regulatory 
action in cases where there is failure to comply with the new 0.1 ppm 
standard. Anything less will fail many of our Nation's children and 
force individual States to take action, as California and Illinois 
already have done, to protect their children.
    With respect to California, while FDA has failed to take action, a 
lawsuit in California resulted in a settlement in June by California 
Attorney General Bill Lockyer in which three candy manufacturers agreed 
to substantially reduce the amount of lead found in imported Mexican 
candies that are popular with children.
    As the Associated Press reported,

          ``The attorney general's office led a coalition of government 
        agencies and nonprofit groups who sued candy makers under a 
        State law that requires warning labels on anything that could 
        cause cancer, birth defects or other reproductive harm.''

    What actions will the FDA take to ensure that all children are 
protected from lead in candy?
    Furthermore, wouldn't the Food Uniformity Act that is currently 
moving its way through Congress have preempted the very action that the 
State of California used to protect the health and well-being of its 
children from lead in imported candy?
    Answer 1. FDA is giving a high priority to its monitoring and 
enforcement activities aimed at imported and domestic candy products 
with potentially harmful levels of lead. FDA will take enforcement 
action whenever it encounters a candy product that contains potentially 
hazardous lead levels. Current findings of violative products are 
infrequent and have significantly decreased compared to the period 
prior to 2005-2006.
    We have had meetings with industry representatives of Mexican candy 
companies. Mexican candy manufacturers are well aware of the importance 
of reducing lead levels in their products, and in anticipation of FDA's 
pending lower recommended maximum lead level, are likely to obtain 
washed chili for use in their products (unwashed chili was the major 
cause of elevated lead levels in candy containing chili).
    FDA is continuing to work with the United States-Mexico Border 
Health Commission (USMBHC) on the issue of lead in candy, and also on 
other lead containing products such as pottery and folk remedies. 
USMBHC plans to hold a Bi-national Lead Meeting on September 28 and 29 
in San Diego to:

    1. Share information on the public health impact of exposure to 
lead in Mexican ceramics, cookware, candy and home remedies in the 
United States and Mexico,
    2. Identify problematic issues for the United States and Mexico-
related to these sources of lead, and
    3. Identify collaborative binational initiatives to:

        a.  Identify specific products posing health risks in the 
        United States and Mexico because they are sources of lead 
        exposure; and
        b.  Identify nonlead based alternatives, and promote their 
        manufacture and export to the United States.

    FDA contributed to the data summary report on lead in candy that 
the United States will exchange with our Mexican colleagues from the 
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS) 
and discuss at the San Diego meeting. FDA subject matter experts will 
participate in the meeting, and FDA will be involved in the ongoing 
activities of the USMBHC.
    Finally, the Food Uniformity Act, if signed into law as currently 
written, would preempt a State of California food safety warning 
notification requirement unless it is an identical requirement, meaning 
substantially the same language as a comparable provision under the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) and that any 
differences in language do not result in the imposition of materially 
different requirements.
                      scientific integrity at fda
    Question 2. It was a pleasure to work with you during your tenure 
at the National Cancer Institute. As you are aware in your new position 
at the Food and Drug Administration (FDA), there is a crisis of morale 
and adherence to science at the Agency. For example, according to a 
survey conducted by the Union of Concerned Scientists recently, a 
significant number of FDA professional staff and scientists responded 
that they have been asked ``for nonscientific reasons, to 
inappropriately exclude or alter technical information or conclusions 
in a FDA scientific document'' and that the public safety is not being 
adequately protected by the FDA, even within the Agency without fear of 
retaliation.
    Are you concerned that hundreds of senior level scientists and 
professional staff at the Agency are reporting interference with their 
scientific work? Also, what do you propose to do to help restore 
confidence in scientific integrity within the FDA?
    Answer 2. Senator, first and foremost, I am committed to ensuring 
FDA makes decisions based on sound science. I would like you to know 
that I will make myself personally available to staff who want to 
appeal decisions made by FDA management. I believe that the need to 
appeal to me will be rare, however, because I will ensure that there 
are strong policies and procedures in place for resolving issues 
involving dissenting opinions. Efforts toward that end will include 
promulgating new policies and procedures as necessary, and 
strengthening, by process improvement and best practices measures, many 
of those that are already in place.
    For example, we are working to ensure a rigorous ombudsman program 
through which staff are welcome to promulgate dissenting opinions. 
Staff may also invoke standard written procedures for facilitating and 
resolving differing professional opinions. In addition, our Center for 
Drug Evaluation and Research established a Drug Safety Oversight Board 
whose charter includes responsibility for deliberating on any 
dissenting opinions raised during evaluation of drug applications and 
surveillance of marketed products. Through these and other traditional 
management techniques, I believe we will successfully address any 
dissenting opinions, and I am committed to evaluating our processes and 
refining them as necessary to ensure that there is a healthy, open, 
unsuppressed scientific debate of issues at FDA.

    Question 3. In further response to the Union of Concerned 
Scientists survey, scientists at every Center within FDA responded that 
they felt pressure to approve products within FDA despite concerns 
about safety. I urge you to review those statements carefully, as they 
include threats and bullying behavior that may be at the expense of the 
public's health.
    In any quality organization, the goal is to seek continuous quality 
improvement and to constantly reassess one's practices, policies, and 
work. Unfortunately, the responses from FDA have, instead, in instances 
such as their response to Dr. David Graham's concerns about the safety 
of certain drugs, been dismissive of criticism or stated concerns and 
have largely ignored many of the serious problems that we have all 
witnessed with the FDA in the past few years.
    What will you do to ensure a culture of openness so that management 
fosters an environment where scientific disagreements are acknowledged 
as being a necessary part of the scientific process and where science 
is not set aside for ideological purposes or due to industry pressure?
    Answer 3. Please be assured that FDA is committed to providing an 
open and welcome culture for its employees and the vigorous scientific 
discourse that we rely on. As members of a scientific Agency composed 
of many scientific disciplines, FDA staff regularly engage in 
discussion, debate, and even disagreement on regulatory issues and FDA 
actions, much like the peer-review process used by scientists 
throughout the world. Such deliberation and disagreements are standard, 
expected, and wholeheartedly valued and encouraged by FDA management. 
They are a critical part of the process of scientific deliberation and 
discourse that is not unique to FDA--other Federal agencies operate 
this way, as do academic medical centers and institutes of higher 
learning, and many others.
    FDA is as dedicated as ever to its time-honored tradition of 
encouraging vigorous debate among experts who use disciplined processes 
to arrive at consensus and conclusions. Data must be adequate and 
valid. Methods must be statistically valid and conclusions must be 
supported by facts. When FDA staff have serious scientific 
disagreements, the Agency has a formal scientific dispute resolution 
process that may be invoked to resolve disagreement.
    Additionally, I want to assure you I, personally, am committed to 
ensuring FDA makes decisions based on sound science. I would like you 
to know that I will make myself personally available to staff who want 
to appeal decisions made by FDA management. I believe that the need to 
appeal to me will be rare, however, because I will ensure that there 
are strong policies and procedures in place for resolving issues 
involving dissenting opinions.
    Many of these policies and procedures are already in place. For 
example, staff in our product Centers may seek help through their 
ombudsmen or by invoking written standard procedures for facilitating 
and resolving differing professional opinions. In addition, at the 
direction of the Secretary, FDA established a Drug Safety Oversight 
Board whose charter includes responsibility for deliberating on any 
dissenting opinions raised during evaluation of drug applications and 
surveillance of marketed products. Through these and other traditional 
management techniques, I believe we will successfully address any 
dissenting opinions, and I am committed to evaluating our processes and 
refining them as necessary to ensure that there is an open scientific 
debate of issues at FDA.
                              drug safety
    Question 4. Public confidence in the safety of prescription drugs 
and the process at the FDA has been fundamentally shaken in recent 
years. It's critical for the public health that we restore this 
confidence, but I'm very concerned that the scientists who are most 
familiar with the safety data on these drugs, and therefore in the best 
position to ensure that the drugs be labeled and made available in the 
safest possible manner, are being prevented from doing the part of 
their job that could make safer use of approved drugs possible. Over 80 
percent of survey respondents to the Union of Concerned Scientists 
survey agreed that the ``public would be better served if the 
independence and authority of FDA post-market safety systems were 
strengthened.''
    How will you ensure that the FDA staff responsible for monitoring 
the safety of drugs once they are on the market will have the 
independence within the Agency and the resources necessary to protect 
the public's health?
    Answer 4. The decisionmaking processes at FDA incorporates science 
at all levels. FDA medical reviewers and scientists make regulatory 
judgments based on scientific data during both the drug review and 
post-market evaluation processes. The Agency makes, and will continue 
to make, these decisions in an open, transparent, and collaborative 
environment that offers several mechanisms for resolving differing 
scientific opinions. We weigh the scientific data regarding the 
inherent benefits of a product against its risks, and based upon the 
judgment of our medical reviewers, experts, and management about what 
that data tell us, we ultimately make a regulatory decision about that 
product. Over time, as the science underpinning our decisions changes 
and as we get new information regarding the basis and standards for our 
decisions, we move to re-visit our processes and respond to the new 
scientific information as appropriate and as necessary.
    I am committed to continuing FDA's proud tradition of dedicated, 
highly qualified Agency employees, making science-based decisions to 
further our mission of protecting and promoting public health.

    Question 5. In the Vioxx situation, FDA was expanding approval for 
Vioxx to juveniles at the very same time that Merck was rapidly moving 
in the opposite direction and withdrew the drug from the market just a 
month later. Paradoxically, Merck took an action through the withdrawal 
of Vioxx from the market in the interest of patient safety while FDA's 
last action was in the direct opposite direction.
    What lessons has FDA learned from this experience and what steps 
are you taking to ensure that FDA is properly protecting the public's 
health, including juveniles, with respect to drug safety? What steps 
are you taking to ensure that the Office of Drug Safety (ODS) has more 
independence from the Office of New Drugs (OND) than currently is the 
case?
    Answer 5. On August 19, 2004, we approved a supplemental 
application for the approval of Vioxx for the treatment of patients 
with juvenile rheumatoid arthritis (JRA), a chronic debilitating 
disease for which additional therapeutic options are needed. The 
approval decision was made taking into account the available data on 
the efficacy and safety of the drug as it was known at that time. Based 
on a careful review of those data, we concluded that the potential 
benefits of Vioxx outweighed the potential risks when used according to 
the approved labeling instructions. Subsequent to that approval, on 
September 27, 2004, Merck informed us of preliminary data from a large 
on-going study of Vioxx in the prevention of colon polyps in adults 
(the APPROVe trial), which showed an increased risk of serious 
cardiovascular adverse events in patients treated with Vioxx compared 
to placebo. Based on these new data, Merck voluntarily withdrew Vioxx 
from marketing worldwide on September 30, 2004. It was not possible for 
us to have considered the data from the APPROVe trial at the time the 
decision regarding approval of Vioxx for JRA was made because the data 
were not yet available.
    We have always taken our responsibility for the protection of pubic 
health very seriously, and continue to do so. In recent years we have 
taken additional steps to further improve our review and oversight of 
safety information for approved drugs. For example, FDA has:

     Commissioned a study by the Institute of Medicine (IOM) to 
evaluate the entire current U.S. drug safety system, with an emphasis 
on the effectiveness of post-marketing surveillance;
     Implemented a formal program that fosters discussion and 
resolution of dissenting scientific opinions about drug safety as part 
of our decisionmaking during the product approval process;
     Conducted an open public hearing to solicit input from the 
public about our communications on drug safety concerns and held 31 
advisory committee meetings (14 focused on risk or safety and 17 
focused on the safety and efficacy of new drug applications) to discuss 
complex drug safety and risk management issues with foremost experts in 
the U.S. health care community;
     Established the Drug Safety Oversight Board to provide 
independent oversight and advice to the CDER's Center Director on the 
management of important drug safety issues and to manage the 
dissemination of certain safety information through FDA's Website to 
healthcare professionals and patients. I believe that the DSB continues 
to create a culture of openness and enhanced oversight around safety 
issues within CDER. During the past year, we have issued 16 Public 
Health Advisories about important drug safety issues. In 2005, the DSB, 
met 5 times and discussed critical safety issues;
     Published draft guidance about how we intend to increase 
the availability of the latest drug safety information to the public 
(FDA's ``Drug Watch'' for Emerging Drug Safety Information''). We are 
reviewing and addressing all submitted comments on the draft guidance 
and intends to issue a final guidance on disseminating emerging safety 
information.
     Awarded four contracts that give us access to databases 
containing pharmacoepidemiologic information. These data will be used 
to study the association of various medications with serious adverse 
effects; and
     Elevated the Office of Surveillance and Epidemiology 
(formerly the Office of Drug Safety) to report directly to CDER's 
Center Director and appointed an Associate Center Director for Safety 
Policy and Communication in order to sustain a multidisciplinary, 
cross-center approach to drug safety.

    In addition, the Agency is working on:

     Improving our Adverse Events Reporting System (AERS), a 
computerized information database that supports our post-marketing 
safety surveillance; and
     Improving the Critical Path of Drug Discovery, a 
collaborative project designed to modernize drug development with the 
use of technologies such as pharmacoge-
nomic tests and imaging techniques to assess the overall safety and 
effectiveness of new medicines.

    With respect to a separate drug safety office, the nature of our 
knowledge of a drug's safety profile and the expertise required for the 
ongoing assessment of a drug's risk-benefit balance demand that these 
two activities be housed in a single center. Our knowledge of a drug's 
safety profile proceeds along a continuum, which begins with in vitro 
and animal studies (before the drug is ever administered to humans), 
continues to grow through rigorous clinical trials, and is further 
refined after a drug is marketed. It is the review and synthesis of 
this cumulative knowledge base that leads to the most accurate 
assessment of the drug's safety profile. In CDER, Office of New Drug 
(OND) staff is the most knowledgeable about the pre-marketing safety 
data, while Office of Surveillance and Epidemiology (OSE) staff 
specializes in the post-marketing safety issues. Staff from the OSE and 
OND work closely in the analysis of appropriate regulatory actions, 
together they take into consideration both risk and benefit information 
from pre-approval and post-approval sources. If pre-approval and post-
approval functions were split, there would be a loss of continuity in 
the review of risks and benefits.
    Additionally, separating these two activities into two centers 
would be very costly, because of the duplication of the wide range of 
expertise involved. Medical officers in OND whose areas of expertise 
include the affected patient population(s), medical conditions, and 
treatments, know the results of animal and clinical studies that 
supported approval of the product; in addition, they review studies 
with products that are used in the same patient populations, and 
products, some still in the investigational phase, from drugs in the 
same or related classes. This expert knowledge of the patients' medical 
conditions, availability of alternative therapies, and safety profiles 
from IND and NDA submissions is a crucial component in the review of 
newly identified risks and how they may impact benefits. OSE personnel 
provide expertise in the areas of epidemiological studies of large 
populations, evaluation of data from AERS (that is, spontaneous adverse 
event reporting) and large external data sets purchased for adverse 
event tracking and evaluation in specific populations, medication error 
prevention, and risk management techniques.
    If the responsibilities were split into two centers, the safety 
center would have to duplicate the expertise of OND staff, with expert 
knowledge of patient populations, medical conditions, alternative 
therapies, and safety profiles from investigational new drug 
applications and studies in marketing applications to support approval 
to enable the safety center to make appropriate risk-benefit decisions 
and the drug approval center would have to duplicate the expertise of 
the OSE staff. Cross-center consultation would be much more difficult, 
and therefore, less efficient, than within center collaboration.
    OND routinely meets with OSE staff to discuss the current or 
anticipated safety of marketed products. In addition, CDER has recently 
instituted safety meetings that are held periodically (monthly or 
bimonthly) to discuss new safety issues and the status of reviews and 
analysis of previously identified safety signals. Also, prior to 
approval of applications to market new molecular entities (NMEs), or 
nonNMEs, OND and OSE staff have pre-approval safety conferences. The 
OSE staff is also consulted by OND in many pre-approval activities that 
increase CDER's ability to understand and adequately monitor risk and 
benefit for marketed products such as medication error prevention and 
risk management plan review.
    For the reasons mentioned previously--resources, communication, 
collaboration, leadership, and shared responsibilities--I do not 
believe that two separate and independent centers would improve FDA's 
ability to fulfill its mission to protect the public health.

    Question 6. What action has FDA taken since 2004 with respect to 
reassessment of the safety of Meridia, Crestor, Accutane, Bestra, and 
Serevent?
    Answer 6. Meridia (sibutramine hydrochloride monohydrate).--We 
continue to receive 6-month safety assessments from the Data Safety 
Monitoring Board (DSMB) for the Sibutramine Cardiovascular Outcome 
Trial (SCOUT)--a large controlled trial examining the safety of 
sibutramine in obese patients at risk for cardiovascular disease. Thus 
far, the DSMB continues to recommend that the trial proceed as planned. 
On July 29, 2005, we approved a labeling supplement that incorporated 
additional information for patients with renal impairment or renal 
insufficiency.
    Crestor (rosuvastatin calcium).--On March 2, 2005, we provided 
information about the risks associated with the use of Crestor via a 
Public Health Advisory, Press Release, Patient Information Sheet, and 
Healthcare Professional Sheet. In addition, the labeling for Crestor 
was revised to highlight important information on the safe use of 
Crestor to reduce the risk for serious muscle toxicity (myopathy/
rhabdomyolysis), especially at the highest approved dose of 40 mg. The 
labeling was also revised to reflect the results of a large 
pharmacokinetic study involving a diverse population of Asian patients 
compared with a Caucasian control group that found drug levels to be 
elevated approximately twofold in the Asian population studied.
    We continue to perform regular assessments of Crestor's safety, 
with a focus on kidney function and potential serious adverse effects 
on muscle through monitoring of adverse events from controlled trials 
and spontaneously submitted reports. We are also tracking the patterns 
of use of Crestor, in particular the 40 mg dose, through prescription 
use data.
    Accutane (isotretinoin).--In July 2005, we provided information 
about potential risks (suicidal thoughts or actions) associated with 
the use of Accutane via Patient Information and Healthcare Professional 
Sheets. In addition, on August 12, 2005, we approved new labeling for 
Accutane including a strengthened risk management program, called 
iPLEDGE. The sponsors agreed to implement this risk management program 
that requires registration (in the iPLEDGE program) of wholesalers, 
prescribers, pharmacies, and patients who agree to accept specific 
responsibilities designed to minimize pregnancy exposures in order to 
distribute, prescribe, dispense and use Accutane. This information was 
relayed to consumers and healthcare professionals via a Public Health 
Advisory and Questions and Answers posted on our Website. On March 23, 
2006, we posted information regarding the iPLEDGE program and 
frequently asked questions regarding this program. The iPLEDGE 
restricted distribution program was fully implemented in the first 
quarter of 2006. This unprecedented program has the full participation 
of all manufacturers of the drug, and requires that wholesalers, 
distributors, pharmacies, prescribers and patients participate in order 
to have access to the drug. FDA has worked extensively with the 
sponsors of the program, their contractor and the American Academy of 
Dermatology to ensure that iPLEDGE is implemented in a manner that 
maximizes safe use of isotretinoin, but still ensures that patients who 
need the medication have access to it.
    Bextra (valdecoxib).--On April 7, 2005, we asked Pfizer to 
voluntarily remove Bextra from the U.S. market because we concluded 
that the overall risk versus benefit profile was unfavorable. Pfizer 
agreed to suspend sales and marketing of Bextra in the United States, 
pending further discussion with us. This conclusion was based on the 
potential increased risk for serious cardiovascular adverse events, an 
increased risk of serious skin reactions compared to other nonsteroidal 
anti-inflammatory (NSAIDs), and the fact that Bextra has not been shown 
to offer any unique advantages over the other available NSAIDs.
    Serevent Diskus (salmeterol xinafoate).--On July 13, 2005, the 
Pulmonary-Allergy Drugs Advisory Committee held a public meeting to 
discuss the implications of recently available data related to the 
safety of long-acting betaagonist bronchodilators, including 
salmeterol. On November 18, 2005, we alerted healthcare professionals 
and patients that several long-acting bronchodilator medicines, 
including salmeterol, have been associated with possible increased risk 
of asthma-related deaths and worsening of asthma in some patients with 
asthma, and requested that manufacturers update warnings in their 
existing product labeling. On March 2, 2006, FDA approved new safety 
labeling and Medication Guides for patients for drugs containing 
salmeterol. There are two products containing salmeterol in the U.S. 
market: Serevent (salmeterol) and Advair (salmeterol and formoterol).
                        fda advisory committees
    Question 7. The FDA acted to remove Dr. Curt Furberg from a FDA 
advisory committee for alleged conflict of interest due to his citing 
concerns about a Pfizer drug. This is in contrast to the continued 
participation of numerous other advisory panel members who are linked 
in a positive manner to drug and device companies, report conflicts of 
interest, and have made statements in favor of the class of drugs being 
reviewed. It raises the question why industry critics appear to be held 
to a higher standard for removal than those who frequently consult for 
industry.
    Recently, the deputy director of the FDA announced that the Agency 
will be redrawing its guidelines for staffing advisory committees. He 
said the Agency will make greater efforts to exclude scientists with 
conflicts of interest who currently get waivers to serve on these 
committees. He also suggested the process will become more open to 
outside participation and have increased transparency.
    Could you please share with us the specifics in each of these 
areas: which conflicts of interest will still be eligible for waivers, 
and which will be grounds for automatic exclusion under the new 
guidelines? How will the Agency encourage greater public participation 
in the staffing of these committees? And how will it become more 
transparent? Will there be more consumer and ethicists represented on 
these advisory committees?
    Answer 7. Dr. Curt Furberg was not removed from the COX-2 meeting 
in February 2005. Dr. Furberg participated fully in that meeting, 
consistent with applicable statutes, rules, and guidance regarding the 
evaluation and granting of conflict of interest waivers. We do not hold 
industry critics to a higher standard for removal than those who 
frequently consult for industry.
    In a speech given July 24, 2006, Deputy Commissioner Dr. Gottlieb 
discussed efforts to revise guidelines detailing the kind of industry 
ties that are permitted for those who serve on our advisory committees 
(see http://www.fda.gov/oc/speeches/2006/conference0724.html). More 
specifically, we plan to revise the guidance documents used to 
determine how potential conflicts are evaluated, how waivers are 
granted, and how information regarding conflicts and waivers is 
disclosed. The goal is to make the process more transparent and clarify 
more of the case-by-case qualitative judgments we make when we evaluate 
each potential conflict. We do not plan to re-write existing rules, but 
instead to provide additional guidance and clarity regarding 
implementation of the existing statutory and regulatory framework 
regarding conflicts of interest. The revision process is currently 
underway and is a high FDA priority. We will make public the revised 
guidances as soon as they are completed.
    We believe that these administrative changes will substantially 
improve the transparency of the process of managing our advisory 
committees, evaluating potential conflicts, and granting waivers where 
appropriate.

    Question 8. In the Union of Concerned Scientists survey, one FDA 
scientist wrote about subtle ways that the FDA and applicants can 
manipulate the advisory committee process in favor of approval. He or 
she wrote that division directors can schedule committee meetings at 
inconvenient times to intentionally exclude certain members, that 
division directors and office directors can withhold damaging 
information from the Advisory Committee Briefing Document, and that 
management can ``pressure reviewers to soften advisory committee 
presentations.'' He or she wrote that pharmaceutical companies hire as 
consultants as many scientists as possible with relevant expertise to 
render them ineligible for relevant committee meeting participation.
    What will you do to mitigate these subtle but significant 
influences that bias the advisory committee process?
    Answer 8. We are committed to an open and transparent advisory 
committee process that brings the best available scientific advice to 
the Agency in a public manner, consistent with relevant statutes and 
regulations. Our public meetings are open to anyone who wants to attend 
and anyone can ask questions. In these meetings FDA is put to the test, 
to explain and defend its scientific thinking in public. These public 
meetings are before a panel of experts with the breadth and depth of 
experience that enables them to dissect the results and to challenge 
our thinking. We believe that the best protection from undue influence 
is openness and transparency, which we are committed to provide.
                fda intervention in pre-emption lawsuits
    Question 9. FDA has intervened in cases on behalf of pharmaceutical 
companies claiming that FDA's authority preempted lawsuits in matters 
of drug safety. Lester Crawford, former FDA Commissioner, defended such 
actions by the FDA in a memo he wrote on November 16, 2004, to all FDA 
employees announcing the resignation of Daniel Troy, Chief Counsel of 
FDA. He wrote,

          ``Dan has also put his personal reputation on the line 
        defending the Agency's prerogatives from intrusion by courts 
        applying State law in product liability actions. I endorse this 
        practice, and believe the policy is the correct one for the 
        public health.''

    Rep. Maurice Hinchey called for Troy's resignation in July and 
noted Pfizer paid Troy's firm $358,000 for Troy's services on the 
company's behalf in 2001 just before he was hired at FDA. Then FDA 
spent 622 hours working on court briefings filed on behalf of drug 
manufacturers. As the wife of a man who committed suicide after taking 
an antidepressant drug said in a July 2004 New York Times article said,

          ``I do not believe in frivolous lawsuits, but it's ridiculous 
        that the government is filing legal briefs on the side of the 
        drug companies when it's supposed to be protecting the 
        public.''

    In light of all the other problems and lack of resources that FDA 
has to do its fundamental job, do you think that is an appropriate use 
of FDA's time and energy to file briefs in such cases on behalf of drug 
companies?
    Answer 9. FDA's regulation of prescription drugs is designed to 
ensure each drug's optimal use through requiring scientifically 
substantiated warnings. Under the Federal Food, Drug, and Cosmetic Act, 
FDA is the public health agency charged with ensuring that drugs and 
devices are safe and effective, and that the labeling of drugs and 
devices adequately inform users of the risks and benefits of the 
product. FDA employs scientists and other experts who review the 
information submitted by the manufacturer on a product's risks and 
carefully titrate the warnings, etc. that should be placed on the 
labeling. FDA continuously works to evaluate the latest available 
scientific information to monitor the safety of products and to 
incorporate information into the product's labeling when appropriate. 
The public health risks associated with overwarning are as great as--if 
not greater than--the health risks associated with underwarning. 
Overwarning can cause patients not to take beneficial drugs and doctors 
not to prescribe them. Under-utilization of a drug based on 
dissemination of scientifically unsubstantiated warnings, so as to 
deprive patients of beneficial, possibly lifesaving treatment, could 
well frustrate the purposes of Federal regulation as much as over-
utilization resulting from a failure to disclose a drug's 
scientifically demonstrable adverse effects. Further, allowing 
unsubstantiated warnings may also diminish the impact of valid warnings 
by creating an unnecessary distraction and making even valid warnings 
less credible. FDA considers itself to be the final arbiter of the 
content of drug and device labeling, and believes this is further 
substantiated by the courts in response to briefs filed by the Agency 
in support of preemption dating back to at least 1977.
    With respect to the role of Mr. Troy at the FDA, I would have the 
following comment. It is my understanding, that upon joining the FDA, 
Mr. Troy consulted with agency ethics officials who worked with him to 
ensure that he was in compliance with all ethical requirements of 
Federal law, and he recused himself with respect to particular matters 
in which his former firm or former clients were a party or represented 
a party. Any allegations or suggestions that he did not conduct himself 
in compliance with applicable legal and ethical rules are false.
    I believe that assisting the Department of Justice in cases in 
which the government believes that State law conflicts with the Federal 
Food, Drug, and Cosmetic Act (the act) is an appropriate use of FDA's 
resources. The Supremacy Clause of the U.S. Constitution mandates 
Federal preemption of State law in such cases. FDA has intervened to 
protect the public health by asserting its jurisdiction to make the 
final public health determinations for FDA-approved products.
    To clarify, the Department of Justice has asserted Federal 
preemption in regard to drug labeling/advertising and device approvals/
labeling in several court cases, often at the request of the courts 
themselves. In many cases, FDA used an implied conflict preemption 
analysis under the Supremacy Clause. FDA argued standard preemption 
principles that State law must yield to Federal law when application of 
State law makes it impossible to comply with both Federal and State 
law, or when State law acts as an obstacle to accomplishing Congress's 
objectives as expressed in the act. FDA believes that State law should 
not be used to second-guess its determinations, particularly where FDA 
reviewed the claims or warnings at issue, and rendered a judgment about 
whether they are false or misleading.
    In the device context, FDA argued that State tort law claims are 
expressly preempted where FDA has approved an application for pre-
market approval for a medical device, and further argued that Congress 
charged FDA with determining issues that the lower court in a specific 
case identified as issues for the jury. FDA asserted that State law 
should not be used to second-guess FDA's determination as to the 
correct regulatory pathway for a medical device. In another case, FDA 
argued that Plaintiffs State tort law claims were expressly preempted 
by section 521(a) of the act, which preempts State device requirements 
that are different from or in addition to any requirement under the 
act.
                           off-label drug use
    Question 10. The Archives of Internal Medicine recently published 
an article that estimated 21 percent of drugs are prescribed off-label 
and that, for about 73 percent of those prescriptions, there is little 
or no science to justify that prescription.
    Could you describe what could be done to improve the quality of 
knowledge and safety about off-label use. For example, if the FDA 
determines that a drug is being heavily used off-label, could you 
require a company to conduct a post-market approval safety study?
    Answer 10. Once a drug product has been approved by FDA for 
marketing for one indication, a physician may prescribe it for uses or 
in treatment regimens or patient populations that are not included in 
approved labeling, i.e., for ``off-label use.'' Physicians under their 
own responsibility may exercise judgment for the use of an approved 
drug for unlabeled indications when they are satisfied there is medical 
and scientific support that such use may benefit their patients.
    The appropriateness of off-label use is highly variable, and it is 
difficult to evaluate. We routinely discuss post-marketing studies with 
companies and urge them to perform such studies regarding off-label 
uses when we believe it is appropriate. We monitor post-marketing 
safety information for all uses of every drug, whether they are 
approved and labeled or not, and take any necessary action to revise 
labeling based on the available scientific data, including data 
accumulated since the drugs were approved. There are examples in which 
labeling includes important safety information in populations for which 
the drug is not approved when it is known that the drug is used off-
label in those populations. Regulations require a brief description of 
major limitations of use of a drug (for example, the lack of efficacy 
of the drug in particular subsets of the population).
                           generic biologics
    Question 11. The European Union has moved to provide guidance on 
how generic biologics can be approved through a combination of 
nonclinical and clinical trials on a biologic-by-biologic basis. In the 
United States, other than one court-order approval, the FDA has not 
provided such guidance. Are you considering adopting an approach, such 
as the European Union approach, that will allow generic biologics to 
come to market and possibly result in billions of dollars of savings to 
consumers in the future?
    Answer 11. FDA has determined that it would be appropriate to 
initially publish guidance that is more broadly applicable to follow-on 
protein products in general, rather than beginning with product-
specific guidance. FDA expects that this approach will provide useful 
guidance to the industry, while ensuring that we do not stifle 
innovation and the utilization of state-of-the-art technologies. In 
addition, a sponsor may contact the Agency to request advice on a case-
specific basis regarding the development of a follow-on protein 
product.
    Even as guidance documents on follow-on protein products are being 
developed, the Agency has been moving forward with the review and 
approval of those follow-on protein products requlated as drugs for 
which the sponsors have met the statutory and regulatory approval 
requirements under section 505 of the FD&C Act. Most recently, we have 
approved Fortical (calcitonin salmon recombinant) Nasal Spray in August 
2005, Hylenex (hyaluronidase recombinant human) in December 2005, and 
Omnitrope (somatropin [rDNA origin]) in May 2006.
    It should be noted that currently there is no abbreviated approval 
pathway analogous to sections 505(b)(2) or 505(j) of the FD&C Act for 
several protein products for which the EMEA has provided guidance, as 
those products (recombinant human erythropoietin, recombinant 
interferon alpha, and recombinant human granulocyte-colony stimulating 
factor) are licensed under section 351 of the PHS Act.
  Response to Questions of Senator Murray by Andrew C. von Eschenbach
    Question 1. In response to questions at the Senate HELP Committee 
nomination hearing, you responded to my question about your 
determination that 18 years of age was the appropriate age restriction 
for Plan B OTC. As I pointed out at the hearing, there seems to be a 
shift at FDA from 16 to 17 now 18 years of age. However, there does not 
appear to be any justification for this shift. Does the Agency have 
additional scientific data showing that young women under 18 could not 
use Plan B safely and effectively as an OTC product? What information 
did you receive that resulted in your determination that 18 was the 
appropriate age? Did you consult with the original members of the FDA's 
Advisory Committee in reaching this decision or did you consult with 
health care providers that provide care to younger women?
    Answer 1. I did not receive any additional scientific data nor did 
I consult an FDA Advisory Committee in reaching the decision that age 
18 was the appropriate age. Dr. Galson, the Director of the Center for 
Drug Evaluation and Research, had previously concluded that the sponsor 
had not established that Plan B could be used safely and effectively 
without a prescription by young adolescents, women age 16 and younger 
(i.e., that it was appropriate for OTC use for women age 17 and older). 
In considering the difficulty of enforcing an age-based restriction on 
the availability of this oral hormonal contraceptive, I have concluded 
that 18 (rather than 17) is the more appropriate cutoff to best promote 
and protect the public health. The State-regulated pharmacies that will 
be dispensing Plan B under Barr's voluntary Convenient 
Access, Responsible Education (CARE) program (as well as society as a 
whole) are more familiar with 18 as a cutoff age. I understand that in 
all 50 States, 18 is the age of majority (i.e., the legal delineation 
between minor and adult), and retail outlets, including pharmacies, are 
familiar with using 18 as the age of restriction for the sale of 
certain products. With regard to the sale of certain drug products, the 
legal age to purchase FDA-approved nonprescription nicotine replacement 
therapy products is 18. Moreover, I understand that as a matter of 
State law, many products routinely sold by pharmacies, e.g., tobacco 
products and nonprescription cough-cold products like pseudoephedrine 
are restricted to consumers 18 and older. The approach builds on well-
established State and private sector infrastructures to restrict 
certain products to consumers 18 and older. This approach should, 
therefore, help ensure safe and effective use of Plan B.

    Question 2. Based on FDA's decision to place an age restriction on 
an OTC product due to safety, can we assume that all OTC applications 
will be considered under these circumstances? I know that the Agency is 
currently reviewing a weight loss medication OTC application. Will FDA 
be requesting data on the safety of this product for younger patients? 
Will FDA be reviewing this application to determine how this product 
may affect behavior? And, finally will FDA be asking the manufacturer 
how to ensure that this medication can be taken safely without a 
physician's supervision?
    Answer 2. In any request to switch a prescription product to OTC 
status, FDA applies the statutory standard and considers available data 
to determine whether prescription dispensing is ``not necessary'' for 
the protection of the public health by reason of the drug's toxicity or 
other potentiality for harmful effect, or the method of its use, or the 
collateral measures necessary to its use, and . . . the drug is safe 
and effective for use in self-medication as directed in proposed 
labeling.
    Such switch applications generally include data from actual use and 
labeling comprehension studies to demonstrate that the product can be 
safely and effectively used without the supervision of a practitioner 
licensed by law to administer the drug. FDA may approve an NDA 
application only when, among other things, the investigations submitted 
in the application include adequate tests showing whether or not the 
drug is safe for use under the conditions prescribed, recommended, or 
suggested in the proposed labeling and when there is sufficient 
information to determine from the application whether the drug is safe 
for use. FDA will apply these statutory standards to any switch 
application submitted to it.
    Furthermore, Dr. Galson, the Director, Center for Drug Evaluation 
and Research, has indicated that he intends to work with FDA's 
scientific staff to initiate a process to further develop the Agency's 
understanding about pediatric use of OTC drugs. One of the questions he 
intends to address will be how to establish the data requirements 
regarding use patterns in these special age groups in which age is not 
merely a chronologic deterrent, but also a biologic deterrent.

    Question 3. When FDA approved the original Plan B application for 
prescription in 1999 as an emergency contraceptive, did the Agency 
request additional data on younger women? Was there a distinction made 
between the safety and efficacy for women over 18 and women under 18? 
Was the issue or concern about behavior part of the approval process?
    Answer 3. FDA did not request additional data on younger women as 
part of the original approval process for Plan B as a prescription 
product. Prescription Plan B was reviewed in a manner similar to that 
for all hormonal contraceptives. Prescription oral contraceptives have 
been determined to be safe and effective, for all women after they have 
passed through menarche and are having menstrual cycles, when used 
following the direction of a healthcare provider. The issue or concern 
about age was not a significant consideration during the original 
approval process for prescription Plan B since woman could only obtain 
the product with a prescription from a healthcare provider. The issue 
regarding additional data for younger women arose in the sponsor's 
actual use and labeling comprehension studies submitted to support the 
switch to OTC, not in the original prescription application.

    Question 4a. In the announcement of July 31, 2006, FDA indicated 
that they would be working with the manufacturer of Plan B to determine 
appropriate enforcement mechanisms for ensuring that women under 18 did 
not receive the product as an OTC. How does FDA currently enforce risk 
management responsibilities?
    Answer 4a. For prescription Plan B, there are no special procedures 
or responsibilities beyond those normally required for all prescription 
drug products. In this case, the company proposed to market 
prescription Plan B and nonprescription Plan B in the same box. 
Therefore, certain marketing restrictions are appropriate to ensure 
that Plan B is made available to one population on a prescription basis 
and another population on a nonprescription basis. Both FDA and 
manufacturers are involved in ensuring that restrictions on 
distribution and use are followed. Manufacturers typically submit, as 
part of their application, a plan to address any marketing 
restrictions, which often includes, as here, education and monitoring. 
Enforcement of risk management responsibilities for other products 
varies depending on the specific drug product.

    Question 4b. As I mentioned at the hearing Accutane has a number of 
label safety restrictions for women due to the documented risk of 
miscarriage and birth defects. Women have to prove that they are in 
fact not pregnant and they are currently using two forms of birth 
control. How does FDA ensure that women under 18 are able to comprehend 
this labeling restriction and effectively use 2 forms of birth control? 
I realize this is a prescription medication, but it is taken every day 
without physician supervision.
    Answer 4b. The sponsor's iPLEDGE program for Accutane is aimed at 
preventing use of the drug during pregnancy. To obtain the drug, in 
addition to registering with iPLEDGE, patients must comply with a 
number of key requirements that include completing an informed consent 
form, obtaining counseling about the risks and requirements for safe 
use of the drug, and, for women of childbearing age, complying with 
necessary pregnancy testing. Prescribing physicians, responsible for 
administering the informed consent, are also responsible for judging 
their patients' comprehension of the restrictions.
    To convey important information about risk-reduction to women of 
child-bearing potential, iPLEDGE provides the following education 
materials: the iPLEDGE Patient Introductory Information Brochure, the 
iPLEDGE Program Isotretinoin Educational Kit for Female Patients who 
Can Get Pregnant (which includes the Guide to Isotretinoin for Female 
Patients Who Can Get Pregnant, Birth Control Workbook, Contraception 
Referral Form and Contraception Counseling Guide, Patient 
Identification Card, Patient Information and Informed Consent form, and 
Patient Flowchart), and a Medication Guide.
    In addition, the patient, in interacting with the iPLEDGE system, 
is queried to ensure her understanding of the risks of the drug and the 
importance of using effective contraception. If there is any suggestion 
that she does not have a complete understanding, she is not cleared for 
dispensing of isotretinoin through the system, but is instead referred 
back to her physician.

    Question 4c. Finally, would Plan B be recommended for women taking 
this medication as a method of birth control?
    Answer 4c. Plan B should not be used as one of the 2 forms of birth 
control recommended for users of Accutane. Plan B is not approved for 
routine contraception use. It is only approved for emergency use. 
Labeling for Plan B (both nonprescription and prescription) does/will 
not recommend the use of Plan B in conjunction with Accutane.

    Question 5a. One of my major concerns about the Plan B OTC 
application process has been the appearance that political forces, not 
science have dictated this process. Have you discussed this process or 
your July 31st announcement with individuals at the White House?
    Answer 5a. I have never discussed the Plan B application process 
with anyone at the White House.

    Question 5b. How many current applications at FDA from drug 
approvals to medical devices to OTC applications do you personally 
decide? What is the percentage of decisions issued by FDA regarding 
food safety, drugs or devices that you personally sign?
    Answer 5b. Under the act, the authority to approve drug and device 
applications is specifically assigned to the Secretary of Health and 
Human Services. That authority, in turn, has been delegated to the 
Commissioner of the FDA and redelegated to the Directors of CDER, CBER, 
and CDRH. Therefore, it is appropriate for a Commissioner to directly 
act on a drug or device application. That said, the decision to approve 
Barr's supplemental new drug application for Plan B was made by CDER. 
Prior to the Center's decision on the application, I determined that 
further rulemaking by the Agency was not required to address the unique 
regulatory issues related to this particular application. I determined 
this was an appropriate resolution to the Advance Notice of Proposed 
Rulemaking (ANPRM) process that was put in place by my predecessor. I 
also determined that 18 was the appropriate age to enforce the partial 
OTC switch requested by Barr. While I am unaware of any pending 
applications on which I would make decisions regarding approval, it is 
customary for a Commissioner to be briefed and updated on high-profile 
decisions before the Agency, and to exercise his/her authorities when 
appropriate.

    Question 5c. And, finally it has come to my attention that there 
are a large number of political appointees now serving the 
Commissioner's office. Can you please provide to me the current number 
of political appointees within the FDA and does this number represent 
an increase or decrease from past Administrations?
    Answer 5c. Of the more than 10,000 FDA employees, only five are 
political appointees, including myself. It is my understanding that 
this number is generally consistent with past Administrations.

    Question 6. In 2002 and 2003 when we enacted the MDUFMA and the 
technical corrections legislation, I was very interested in the need to 
provide additional incentives to improve pediatric labeling of medical 
devices. As a strong supporter of the Better Pharmaceuticals Act for 
Children and the FDA Pediatric Rule, I believe we can provide 
incentives to encourage manufacturers to seek on label approval for 
pediatric drugs and devices. However, the task of determining the 
appropriate mechanism for medical devices has proven to be difficult. I 
recognize the differences between drugs and devices but I do believe we 
can do more to address this inequity. I would be interested in your 
insights as a practitioner and as the Acting Commissioner on what steps 
we can take to ensure greater pediatric labeling of medical devices.
    Answer 6. Labeling devices for pediatric use is of significant 
interest to FDA, and the Center for Devices and Radiological Health 
(CDRH) has taken important steps to ensure that devices have pediatric 
labeling, as needed. It is important to note, however, that although 
some medical devices are specifically designed for use on infants and 
children, such as infant incubators and infant radiant warmers, the 
majority of devices going to market are indicated for the general 
population. As such, although the labeling does not indicate the device 
for pediatric use, it does not exclude such use. Because these devices 
can be used in both the pediatric and adult populations, they are not 
specifically labeled as pediatric devices.
    There are many challenges influencing the development of pediatric 
devices. Due to natural growth and development of a child, long-term or 
permanent implants would need to ``grow'' with the subject or at least 
remain functional while the child develops. Because of the young age of 
the patients, the devices would also need to have a longer life span. 
In general, the smaller size of children requires smaller devices, 
oftentimes requiring that the entire product would need to be re-
engineered to ensure that the functionality remains consistent when the 
size changes or as the child grows.
    To address these issues, CDRH has taken a number of important 
initial steps. These include: (1) a guidance for pediatric devices 
which identifies the types of information needed to support marketing 
and discusses labeling issues for pediatric devices (cite to name of 
guidance--``Pre-market Assessment of Pediatric Medical Devices--
Guidance for Industry and FDA Staff ''), (2) encouraging sponsors to 
consider pediatric populations during meetings where trial designs and 
indications for use are discussed, and (3) instituting a policy to 
encourage the discussion of pediatric issues at Advisory Committee 
meetings.
    Recently, CDRH formed a pediatric steering committee (SC) to 
oversee pediatric issues throughout the Center. Its functions include 
facilitating and encouraging pediatric pre-market reviews and consults. 
The SC has also set up a process to allow the Center to track pediatric 
PMAs and HDEs (Humanitarian Device Exemptions) and has developed a 
checklist to be used during the review of pediatric study protocols to 
ensure key information is captured.
    MDUFMA allows for a user fee exemption for device submissions 
solely for pediatric use. This is intended to encourage pediatric 
device development. In addition, HDEs do not require a user fee, and 
several products specifically for use in pediatrics, including life-
saving cardiovascular technologies, have been approved as HDEs.
    CDRH hopes that through a combination of greater awareness of the 
medical need, more open interactions with industry and pediatric 
societies, and minimizing financial burdens to manufacturers, the 
Agency can help ensure greater interest in pediatric labeling of 
medical devices.

    Question 7. When we look toward reauthorization of the PDUFA, one 
of the areas that I would like to see modernized is the issue of 
clinical trials. For many orphan or rare diseases or even some 
pediatric diseases, it is very difficult to meet the current threshold 
for clinical trials. I realize that the Agency has an obligation to 
protect patients but many times it is difficult to conduct a broad-
based clinical trial as the population is too small or the costs too 
great. Is there a way that we can use new technology to address this 
concern without jeopardizing patient safety?
    Answer 7. We think that new bioinformatic technologies, 
particularly model-based product development, hold potential to 
transform clinical trial design. In the Critical Path Opportunities 
Report and List, which we published in March 2006, we note that many 
rare diseases are hard to study due to the difficulty of enrolling 
subjects, and note the potential that databases recording the natural 
history of patients with rare diseases, incorporating observations of 
clinical progression and biomarkers could assist in creating disease 
models to support better designed clinical programs. No one company, 
university, or governmental agency has the necessary information to 
create computer models sufficiently robust to accomplish these and 
other goals. The effort will require new strategies for information 
sharing and safe information housing, and a commitment to collaborative 
approaches. FDA is actively considering, under the Critical Path 
initiative, a variety of study designs, methods of analysis and uses of 
data from other studies to improve decisionmaking and the rate of 
success of studies. We continuously evaluate new clinical trial designs 
that hold the promise of more efficient drug development as well as 
nontraditional statistical approaches that may lead to more efficient 
drug development. For example, the appropriate use and applicability of 
historical controls in which the effect of a new treatment in a group 
of patients is compared to well-documented experience from other 
studies is considered in detail in the International Conference on 
Harmonization (ICH) guidance E-10 (Choice of Control Group and Related 
Issues in Clinical Trials.), and in certain circumstances such trials 
designs are employed to expedite drug development.
    Under certain circumstances, we also have the authority to base a 
finding of substantial evidence of effectiveness on the results of a 
single adequate and well controlled clinical study rather than the more 
traditional two-study standard. This standard can help speed important 
new therapies to market by reducing the number of trials that must be 
performed to gain marketing approval. Also, under certain 
circumstances, we can approve drugs on the basis of their effects on a 
marker that is reasonably likely to predict a clinical benefit, 
provided that we are able to obtain evidence after approval to 
establish that the drug had clinical benefit. This approach is reserved 
for serious or life-threatening illnesses for which there are 
inadequate available treatments. Although there are difficulties with 
this approach and it must be used with caution, where appropriate, it 
can drastically reduce the time to market for important new drugs.

    Question 8. While both drugs and medical devices are used to 
diagnose and treat human illness, there are significant differences 
between the two categories of FDA-regulated products recognized by 
Congress in their respective statutory frameworks. Will you continue to 
treat medical device issues on their own merits and tailor medical 
device policies to recognize their unique features and unique role in 
medical practice?
    Answer 8. FDA recognizes that there are important inherent 
differences between drugs and devices and these differences require 
unique regulatory approaches.
    Whereas small changes in a drug compound can often have profound 
effects on its mechanism of action and therefore the product's safety 
and effectiveness, minor changes in devices can often be made without 
greatly altering the function of the device. CDRH's 510(k) premarket 
notification regulations for lower risk devices allow many products 
which are ``substantially equivalent'' to existing, legally marketed 
devices, to reach the marketplace in an efficient manner, for example, 
based on pre-clinical bench and/or animal data alone. Every year CDRH 
clears thousands of new devices through this less-burdensome mechanism. 
FDA has also succeeded in applying the appropriate level of regulatory 
controls to assure the safety and effectiveness of combination products 
where there is a merging of devices and drugs.
    How devices are used also requires us to tailor device-specific 
policies. For example, most drugs are administered orally or 
intravenously and a placebo is often indistinguishable to the patient 
and/or clinician in a clinical trial. However, devices often require 
surgical implantation or cause a physical reaction to the body which a 
patient and physician would be well aware of. In addition, device use 
(and hence safety and effectiveness) can often be affected by the 
experience and skill level of the user. These and other issues make 
device trial design and data interpretation especially challenging.
    We also recognize the financial burden on sponsors when clinical 
trials require expensive operations or where the nature of the device 
requires particularly long follow-up. FDA's regulations and policies 
allow us to take these issues into consideration by providing ample 
latitude in defining what constitutes ``valid scientific evidence.''
    In summary, our current device classification system allows us to 
apply different policies and regulations to products depending on their 
associated risk and/or equivalence to other similar products in a least 
burdensome way, thus enabling FDA to address the unique issues 
associated with medical devices.

    Question 9. The FDA's Critical Path Initiative has potential to 
improve the development process for medical technologies and bring 
better devices to market faster. Yet most of FDA's projects under the 
Critical Path initiative are focused on drugs--very few are dedicated 
to medical technology development. Given that the device development 
process for drugs and devices are vastly different, will you work to 
ensure the Agency dedicates more projects to device issues?
    Answer 9. Device sciences are front and center in FDA's Critical 
Path Initiative; however, I would caution against a narrow view of 
which projects will help improve device development. The List is 
divided into six priority areas, rather than into product types, 
because these priorities--and many of these projects--apply across 
product areas and will require collaboration among experts in the 
development of drugs, devices, and biologics in order to succeed. For 
example, work to improve clinical trial design or to develop a robust 
clinical bioinformatics infrastructure will improve development of all 
medical products. Similarly, the full potential of genomic biomarkers 
cannot be achieved without new approaches not only to development of 
the drug or biologic therapy, but also to development of the partner in 
vitro diagnostic device needed to identify the presence or absence of 
the biomarker in an individual.
    The release of the list marks a starting point in identifying 
priorities to be accomplished under the Critical Path Initiative. It is 
meant to spur a continued discussion among industry, academia, patient 
and professional groups and government organizations about the research 
priorities that need to be accomplished in our effort to modernize the 
medical product development process. The List was compiled from ideas 
we received during nearly 2 years of outreach, including an open public 
docket and meetings with companies and trade associations. Device 
interests were well represented. We look forward to additional input 
from device interests.

    Question 10. Women and other minorities have consistently been 
under-represented in clinical trials, causing most of the assumptions 
about a drug's effectiveness and side-effect profile to be based on 
predominate experience in men. Given the recent biologic evidence that 
gender may be important in determining a drug's effectiveness and/or 
side-effect profile, the committee would appreciate your comments on 
whether the FDA should require--or at the very least encourage--the 
exploration of gender differences in clinical trials and the drug 
approval process.
    Answer 10. We are continuing to meet and work with various groups 
to encourage sponsors to study and report the effects of drugs in a 
population that is representative of the population the drugs will be 
used in, including men and women. To this end, we finalized a guidance 
to recommend categories for collecting data regarding race and 
ethnicity (``A Guidance for Industry--Collection of Race and Ethnicity 
Data in Clinical Trials,'') in September 2005. A copy can be found at: 
//www.fda.gov/cder/guidance/5656fnl.pdf.
    On July 22, 1993, we also published the ``Guideline for the Study 
and Evaluation of Gender Differences in the Clinical Evaluation of 
Drugs'' that explicitly describes our expectation that women should be 
included in all phases of drug development. Current regulations permit 
the Agency to prevent a clinical trial from proceeding if ``. . . men 
or women with reproductive potential who have the disease or condition 
being studied are excluded from eligibility because of a risk or 
potential risk . . . of reproductive toxicity.'' See 21 CFR 312.42. 
This reflects the Agency's view that women should not be excluded from 
clinical trials simply because they are biologically capable of 
becoming pregnant (women who are pregnant are not covered by this 
regulation). In addition, the Agency is developing a model and protocol 
standards that would allow gender, age, and race to be captured as 
demographic variables and enhance Agency monitoring of participation 
based on these characteristics from clinical trial data submissions. We 
will consider other guidance and initiatives as the need becomes 
apparent.

    Question 11. Given the FDA's acknowledged support for the concept 
of personalized medicine, is it your view, as the head of the FDA, that 
gender-based medicine should be included within that concept?
    Answer 11. Yes. Personalized medicine requires the assumption that 
parameters measured for an individual, including information associated 
with his or her genome, can accurately predict therapeutic response. 
Gender-based medicine is part of personalized medicine. For example, 
only 20-25 percent of women with breast cancer have tumors that over-
express HER2 and thus would be good candidates for herceptin therapy. 
Treating women with herceptin based only on their gender would result 
in no benefit to the subset of women (75-80 percent) whose tumors do 
not over-express HER2. However, with a greater understanding of the 
molecular basis of disease and drug response than we have today, we can 
do better. Thus, the FDA's commitment and support for personalized 
medicine is to go beyond gender and race. FDA is working to facilitate 
development of genomic tools that can increase the precision by which 
personalized medicine can be delivered to patients to improve the 
overall benefit/risk profile of drug treatments.
    It is important that these considerations continue to be included 
in our agency-wide efforts to bring personalized medicine to consumers. 
The FDA has a dedicated office, the Office of Women's Health, 
addressing questions specifically related to gender-based medicine. 
This office is working closely with other parts of the FDA on a number 
of projects that will help us to better understand, and take action on, 
issues related to gender-based differences in drug response.

    Question 12. The issue of gender bias in research is one that FDA 
needs to be vigilant in addressing. I applaud the steps taken by both 
FDA and NIH in working to eliminate gender bias in research and 
development of new therapies. However, much more needs to be done that 
new drug therapies are properly labeled for women. I am also very 
concerned about the impact of an expedited FDA approval process as 
envisioned under Bioshield. I realize that getting new life saving 
vaccines and antivirals is critical in preparing for a pandemic or 
bioterrorist attack, but we must also ensure that these treatments are 
in fact safe. FDA must ensure that special populations like women, 
pregnant women and children are not forgotten. It's essential that any 
review process for new vaccines or antivirals include data on safety 
for these populations. Can you provide to me the measures you have 
taken to ensure that at-risk or special populations are part of the FDA 
approval process for new vaccines and drug treatments to protect 
against a pandemic or bioterrorist attack?
    Answer 12. Attention to potential gender, age, racial and ethnic 
differences in response to medical products is part of a larger effort 
by the FDA to ensure that the safety and efficacy of medical products 
are adequately studied in people who represent the full range of 
patients who will receive the products after approval. Our regulations 
and guidance encourage the participation of women and individuals from 
underrepresented racial and ethnic groups in all phases of product 
development. FDA also promotes collection of gender, age, and race-
related data during research and development, and recommends analysis 
of the data for demographic effects.
    These principles also apply to FDA's efforts to facilitate the 
development and availability of safe and effective medical 
countermeasures against threat agents. The legal standards for product 
approval, licensure, and clearance under the Federal Food, Drug, and 
Cosmetic Act (the act) and the Public Health Service Act apply equally 
to countermeasures and to other medical products. Recent legislation 
has established an authority to allow temporary access to unapproved 
medical countermeasures during an emergency. Specifically, the Project 
BioShield Act of 2004 authorizes the use of certain unapproved medical 
products or unapproved uses of approved medical products during 
declared emergencies. Before the Commissioner can issue an Emergency 
Use Authorization (EUA) for a particular product, the HHS Secretary 
must first declare that the emergency justifies issuance of an 
authorization. Moreover, the Commissioner must determine that the 
product meets the statutory criteria for issuance, which include a 
consideration of whether the known and potential benefits of the use 
outweigh the known and potential risks of the product. The 
determination of risks and benefits is a product-specific and 
circumstance-
dependant analysis that may involve a number of factors, including the 
needs of special populations.
   Response to Questions of Senator Reed by Andrew C. von Eschenbach
    Question 1a. Dr. Von Eschenbach, last fall you reconvened the 
Counterfeit Drug Task Force to examine the progress that has been made 
in the adoption of electronic tracking technology, commonly referred to 
as radio frequency identification (RFID), to protect the integrity of 
our drug supply. Like you, I am alarmed by the proliferation of 
increasingly sophisticated counterfeit medications that are finding 
their way to the marketplace. However, I am also concerned about the 
slow pace of implementation of this tracking technology as well as the 
fact that FDA has not utilized authority under the Prescription Drug 
Marketing Act (PDMA) to push manufacturers and distributors to 
accelerate its deployment. What prompted you to reconvene the task 
force?
    Answer 1a. As FDA continued to monitor the adoption and 
implementation 
of e-pedigree and electronic track and trace technology, we recognized 
that adoption across the U.S. drug supply chain was slower than 
originally anticipated, so we reconvened the task force to evaluate 
appropriate steps to take.

    Question 1b. Could you please comment on the findings of the task 
force?
    Answer 1b. In June 2006, in its Counterfeit Drug Task Force 
Report--2006 Update, FDA announced new steps to strengthen existing 
protections against the growing problem of counterfeit drugs. The 
measures emphasize certain regulatory actions and the use of new 
technologies for safeguarding the integrity of the U.S. drug supply.
    Among other new measures, FDA will fully implement regulations 
related to the Prescription Drug Marketing Act of 1987, which requires 
drug distributors to provide documentation of the chain of custody of 
drug products (a pedigree) throughout the distribution system. A 
potential new measure to safeguard the drug supply is the use of 
electronic track and trace technology, such as radio-frequency 
identification (RFID), which creates an electronic pedigree (e-
pedigree) for tracking the movement of the drug through the supply 
chain. FDA had expected this technology to be in widespread use in the 
drug supply chain by 2007. In early 2004 FDA delayed the effective date 
of the regulatory provisions regarding pedigrees to allow the industry 
time to adopt this technology. However, it now appears that FDA's 
expectations for adoption of the technology by 2007 will not be met. 
FDA therefore has determined it can no longer justify delaying 
implementation of the pedigree regulations.
    FDA also announced that, during the next year, its enforcement of 
the pedigree regulations will focus on products most susceptible to 
counterfeiting and diversion. FDA announced in the Federal Register the 
availability of a draft compliance policy guide (CPG) for public 
comment describing this enforcement approach.
    The Task Force report also underlines FDA's belief that widespread 
use of e-pedigrees using electronic track and trace technology, 
including RFID, would provide an electronic safety net for our Nation's 
drug supply. The report therefore recommends that stakeholders continue 
to work expeditiously toward that goal, and that their implementation 
of RFID technology be used first on products most susceptible to 
counterfeiting and diversion.
    Additional topics discussed in the Task Force's report include the 
following key issues related to electronic track-and-trace that are in 
need of resolution:

     Technical aspects of the mass serialization of marketed 
drugs by assigning a unique identifier or serial number to each drug 
package as the initial step in development of track and trace 
technology.
     Protection of consumer privacy to prevent unauthorized 
disclosure of information stored in RFID tags when RFID-tagged drug 
products are dispensed to consumers.
     Consumer education about RFID and the labeling of RFID-
tagged drug products, to disclose to consumers when they are receiving 
RFID-tagged products and to inform consumers of the benefits of RFID 
technology and how consumers' privacy is being protected.

    Question 1c. Should you become commissioner, would you exercise the 
authority under PDMA to ensure the integrity of our domestic drug 
supply?
    Answer 1c. We will continue to use all of the authority that 
Congress has granted FDA to ensure the integrity of our domestic drug 
supply. As we noted in our statements, FDA will no longer delay the 
effective date of the pedigree regulations and has published a draft 
CPG that describes our enforcement approach. Further, FDA's Office of 
Criminal Investigations (OCT) has been pursuing violations of the PDMA 
since OCI's inception and will continue to do so.
        citizens petitions and the delay of generic competition
    Question 2a. FDA regulations permit any interested person to file a 
citizen petition requesting FDA ``to issue, amend, or revoke a 
regulation or order, or to take or refrain from taking any other form 
of administrative action'' (Title 21, Code of Federal Regulations 10.25 
and 10.30). Citizen petitions may be submitted at any time. I 
understand that the backlog of citizen petitions has grown in recent 
years, particularly as they pertain to generic drugs. It has been 
reported that these requests for agency action are being misused by 
brand-name drug manufacturers to stave off generic competition.
    Could you please tell the committee what increases the FDA has seen 
in the number of citizen petitions that have been filed in recent 
years, and what the Agency is doing to work through the growing 
backlog?
    Answer 2a. The Center for Drug Evaluation and Research (CDER) is 
responsible for responding to citizen petitions relating to certain 
drug products, including generic drugs. Within CDER, the Office of 
Regulatory Policy (ORP) has primary responsibility for drafting 
responses to citizen petitions, except for petitions relating to over-
the-counter drug monographs or ``suitability'' petitions (see 21 CFR 
314.93). Recently, CDER has seen a significant increase in petitions. 
For example, ORP saw a 50 percent increase in petitions received in 
calendar year 2004 over calendar year 2003. ORP received 70 citizen 
petitions in 2004, and 65 in 2005. For calendar year 2006, we 
anticipate a greater increase because ORP has already received 53 
petitions as of July 31, 2006. This increase includes not only citizen 
petitions relating to Abbreviated New Drug Applications (ANDAs) or 
generic drug applications, but also an increasing number of petitions 
raising drug safety issues.
    In response to the increase in petitions and an increasing backlog 
of pending petitions, ORP initiated an extensive review of processes 
for responding to petitions. As a result, CDER instituted a number of 
changes, including:

     ORP has been increasing its early interactions with other 
offices to better coordinate responses.
     All parties involved in responding to petitions have 
attempted to increase communications to avoid misunderstandings, wasted 
efforts, or unnecessary delays.
     ORP and the Office of Generic Drugs (OGD) regularly 
discuss priorities and anticipated timetables, so responses can be 
coordinated with ANDA approval actions.

    In addition, OGD has made organizational changes to improve the 
petition response process. OGD has dedicated a group of highly skilled 
scientists to address complex scientific issues related to review of 
ANDAs and citizen petitions. This change is expected to increase the 
consistency, quality and speed of OGD's input on petition responses.

    Question 2b. Similarly, what is the FDA doing to address the 
allegation that brand name drugmakers are using the citizen petition 
process to delay the introduction of generic products?
    Answer 2b. With respect to allegations that petitions are used to 
delay competition, FDA plans to review petitions from innovator and 
generic drug manufacturers that have been denied. We will consider such 
factors as the timing of the petition and the nature and age of the 
data supporting the petition. Should we believe that further 
investigation into potentially anti-competitive behavior may be 
warranted, we intend to refer the cases to the Federal Trade 
Commission.
                     uva/uvb labeling for sunscreen
    Question 3. The fiscal year 2006 Agriculture Appropriations 
conference report included language directing the FDA to complete the 
sunscreen monograph, which will guide UVA and UVB labeling information 
for over-the-counter (OTC) sunscreen products, within 6 months of 
passage of the agriculture appropriations bill. That bill was signed 
into law on November 10, 2005. We are now approaching 3 months that 
this provision is past due and still no sunscreen monograph. The FDA 
began drafting a monograph for sunscreen products in 1978 and has yet 
to complete it. Please provide the committee with the following 
information:

    (a) an accurate time-line detailing a plan of action for completing 
the monograph;
    (b) any perceived or acknowledged obstacles to completing the 
monograph by the end of calendar year 2006; and
    (c) an explanation as to why the monograph has not been completed.

    Answer 3. It is anticipated that a rulemaking will be issued by the 
end of calendar year 2006 to propose new testing and labeling, 
primarily for products that contain ingredients that block UVA rays. 
FDA drafted this proposed rule after asking for comments specific to 
this topic in a June 2000 Federal Register notice. As the Agency 
developed the rule new issues emerged that needed to be addressed. For 
example, recently FDA received a citizen petition requesting that the 
Agency amend the OTC sunscreen drug monograph to consider OTC sunscreen 
drug products containing nanoparticles as not covered under the 
monograph and instead treat them as new drugs. The proposed rule is 
currently in clearance.
    The period for public posting of comments associated with the 
proposed rulemaking, once published, is 90 days and FDA will 
subsequently issue a Final Rule. The time to publication of the final 
rule is dependent on the number and content of the comments submitted 
in response to the proposed rule and the Agency's clearance process.

    Question 4. Similarly, the current FDA-mandated warning label on 
indoor tanning equipment has not been updated since 1979. Yet, the 
Department of Health and Human Services (HHS) has declared UV 
radiation, including that which is emitted by indoor tanning devices, 
as a known carcinogen. The FDA claims the delay in updating the label 
is due to the need to harmonize the label with international standards. 
In the mean time, on average more than one million people visit tanning 
salons every day with 30 million people tanning indoors in the United 
States each year. Of those 30 million, 2.3 million are teens. The World 
Health Organization has even suggested a ban on minors accessing this 
equipment.
    Where do revisions to the current label stand and what is the 
Agency's time-line for making the new label available for public 
comment?
    Answer 4. Sunlamp products are Class I medical devices, classified 
as ultraviolet lamps for tanning. They are subject to the general 
controls for medical devices, including registration/listing and 
quality system regulation requirements. They also are subject to the 
electronic products performance standard for sunlamp products (21 CFR 
1040.20). The current FDA warning statement required on sunlamps 
(tanning beds and tanning booths) and in their user instructions is as 
follows:

          ``DANGER--Ultraviolet radiation. Follow instructions. Avoid 
        overexposure. As with natural sunlight, overexposure can cause 
        eye and skin injury and allergic reactions. Repeated exposure 
        may cause premature aging of the skin and skin cancer. WEAR 
        PROTECTIVE EYEWEAR; FAILURE TO MAY RESULT IN SEVERE BURNS OR 
        LONG-TERM INJURY TO THE EYES. Medications or cosmetics may 
        increase your sensitivity to the ultraviolet radiation. Consult 
        physician before using sunlamp if you are using medications or 
        have a history of skin problems or believe yourself especially 
        sensitive to sunlight. If you do not tan in the sun, you are 
        unlikely to tan from the use of this product.''

    The purpose of the warning statement is to provide information 
necessary for consumers to make an informed decision regarding the 
risks of using sunlamp products. The warning statement must be legible 
and readily accessible to view by the person being exposed immediately 
before use of the product.
    FDA staff have worked closely with the International 
Electrotechnical Commission (IEC) to amend the IEC standard for 
``Household and similar electrical appliances--particular requirements 
for appliances for skin exposure to ultraviolet and infrared radiation 
products.'' Amendment 2 is scheduled for the Final Draft International 
Standard (FDIS) stage in August 2006.
    The FDA intends to consider whether amendments to the performance 
standard for sunlamp products should be undertaken to achieve closer 
agreement with the IEC standards. Any proposal initiated would likely 
include proposed changes to the required warning statement to improve 
readability and to increase the likelihood that the warning will reach 
consumers.
                         safety of flu vaccines
    Question 5. A couple of years ago, FDA inspectors discovered 
manufacturing problems at the Liverpool vaccine facility of Chiron. 
Yet, these problems did not become public until several months later 
when the British government declared 40 million doses of the vaccine 
unusable just prior to the start of flu season. This announcement left 
many States without adequate supplies for the season and left many 
questioning FDA's ability to respond swiftly and effectively to 
problems that may arise during annual flu vaccine production.
    What steps has FDA taken to ensure that this level of communication 
breakdown doesn't happen again? Why did it come down to the British 
government barring the shipment of the contaminated vaccine and not the 
FDA?
    Answer 5. The Agency has made significant changes to address a 
number of issues. For example, FDA now conducts inspections of 
influenza vaccine manufacturers on an annual basis. The Agency is 
completing or has completed agreements that allow information sharing 
with numerous foreign regulatory agencies. In addition, FDA has 
recently engaged in a confidentiality agreement with U.K. Medicines and 
Healthcare Products Regulatory Agency (MHRA) that covers exchange of 
information for all inspections.
  Response to Questions of Senator Clinton by Andrew C. von Eschenbach
    Question 1. Dr. von Eschenbach, as you know, the FDA has had this 
application for over 3 years--since April 21, 2003--and we appear to be 
no closer to having a resolution than we were the day it was filed. We 
had a promise from Secretary Leavitt that we would have a decision on 
this application by September 1st and today, almost an entire year 
later, we are still waiting. We have been clear all along that we are 
not asking for a specific outcome--we are simply asking for a decision. 
When are we going to have a decision from the FDA?
    Answer 1. On August 24, 2006, FDA approved the amended sNDA from 
Barr Laboratories allowing OTC sale of Plan B to adults 18 and older. 
Plan B will be available to patients 17 and younger by prescription.

    Question 2a. In your letter to Mr. Carrado, you also discuss the 
CARESM Program, a program proposed by Duramed outlining the marketing, 
education, distribution, and monitoring for the OTC version of Plan B. 
Specifically, you express the FDA's strong interest in Duramed's 
enforcement strategy if a pharmacy fails to comply with regulations to 
keep Plan B behind the counter and to require that patients show photo 
identification to obtain the drug. Is it considered standard procedure 
to hold pharmaceutical companies liable for the actions of independent 
pharmacies?
    Answer 2a. The approval of Plan B does not hold Duramed liable for 
the actions of independent pharmacies. Duramed provided revisions to 
its CARESM program that satisfied FDA that it would take steps to 
monitor the implementation of the program and report to FDA 
periodically regarding the results of its monitoring program. The 
program also provides that the sponsor will report repeat violators of 
the age restriction to the appropriate State Boards of Pharmacy. FDA 
intends to monitor the program's effectiveness so that we can discuss 
with the sponsor further modifications, if necessary, to prevent 
inappropriate use of Plan B.

    Question 2b. Later on in your letter, you write,

          ``If after our discussions we conclude that the CARESM 
        Program isn't sufficiently rigorous to prevent the OTC version 
        of Plan B from being used by young girls who can't safely use 
        the product without the supervision of a practitioner licensed 
        by law to administer the drug, Plan B will remain Rx-only for 
        women of all ages.''

    What, in your opinion, constitutes a ``sufficiently rigorous'' 
program? How much evidence would you need to support a decision to deny 
Plan B's OTC application entirely--considering the overwhelming 
scientific evidence demonstrating its safety and efficacy, in addition 
to over 70 from major medical organizations?
    Answer 2b. Duramed provided revisions to its CARESM program that 
were considered to be ``sufficiently rigorous'' by the Agency. Duramed 
satisfied FDA that it would take steps to monitor the implementation of 
the program and report to FDA periodically regarding the results of its 
monitoring program. FDA intends to monitor the program's effectiveness 
so that we can discuss with the sponsor further modifications if 
necessary to prevent inappropriate use of Plan B.

    Question 3. A consequence of the FDA's refusal to make a decision 
on Plan B has been a deterioration of trust in the integrity of this 
Agency. Last year, The New England Journal of Medicine published a 
damning op-ed titled ``A Sad Day for Science at the FDA.'' And the GAO 
report made clear that the FDA process and decisionmaking process was 
highly atypical and suspect. Out of 67 over-the-counter applications 
made in the past decade, this was the only one that was not approved 
after the advisory committee recommended approval and the only one in 
which the action letter was signed by the Director of the Center for 
Drug Evaluation and Research.
    The Journal article labels the Plan B controversy as ``a mockery of 
the process of evaluating scientific evidence,''and concludes with a 
haunting question, ``Will we ever again be able to believe in the FDA's 
independence? '' Given the recent actions of the FDA leadership, I fear 
I cannot dismiss this question with confidence.
    An editorial in the New York Times from March 25 of this year said 
the following of the FDA's nondecision on Plan B:

          ``We don't generally approve of holding nominations hostage 
        to other political objectives. But Senators Hillary Clinton and 
        Patty Murray surely have good cause to block a vote on the 
        nomination of Dr. Andrew von Eschenbach to become commissioner 
        of the Food and Drug Administration until the Agency makes a 
        final decision on the morning-after pill. There is no excuse 
        for the administration's endless obfuscation and delays on 
        making the pill available without a prescription when the 
        overwhelming bulk of expert opinion says it is safe to do so.''

    Dr. von Eschenbach, the bottom line here is that the public health 
community and much of the general public has begun to question the 
allegiances of the FDA. For the sake of the Agency's reputation and 
good standing in the public, which directly impacts its effectiveness. 
What can the FDA do and what can Members in this chamber do to further 
expedite this already long-overdue decisionmaking process?
    Answer 3. On August 24, 2006, FDA approved the amended sNDA from 
Barr Laboratories allowing OTC sale of Plan B to adults 18 and older. 
Plan B will be available to women 17 and younger by prescription.

    Question 4a. We know that the FDA's advisory panel voted 
overwhelmingly (23 to 4) that this drug should be available over the 
counter. We know that ACOG, the America Academy of Pediatrics, the 
American Medical Association and more than 70 other major medical 
organizations have recommended that the application should be approved. 
And we know that the New England Journal of Medicine believes what has 
taken place flies in the face of science.
    When I questioned Mr. Crawford in March 2005 regarding Plan B's 
application, he told this committee and I quote: ``I can assure you 
that this decision will not be based on politics, it will be based on 
science . . . I don't think it's going to be a long delay.''
    It's been almost a year and a half since Mr. Crawford made these 
claims and sadly we can see his promises have not been kept.
    What principles do you believe should guide the FDA when it makes 
decisions about what drugs may be available over the counter?
    Answer 4a. The statutory standards established by Congress and the 
provisions of FDA's regulations guide the FDA when it makes decisions 
about what drugs may be available over the counter. FDA's regulations 
provide that FDA will approve a switch to OTC use when it finds that 
prescription dispensing is ``not necessary for the protection of the 
public health by reason of the drug's toxicity or other potentiality 
for harmful effect, or the method of its use, or the collateral 
measures necessary to its use, and . . . the drug is safe and effective 
for use in self-medication as directed in proposed labeling.''
    Such switch applications generally include data from actual use and 
labeling comprehension studies to demonstrate that the product can be 
safely and effectively used without the supervision of a practitioner 
licensed by law to administer the drug. FDA may approve an NDA 
application only when, among other things, the investigations submitted 
in the application include adequate tests showing whether or not the 
drug is safe for use under the conditions prescribed, recommended, or 
suggested in the proposed labeling and when there is sufficient 
information to determine from the application whether the drug is safe 
for use. FDA will apply these statutory standards to any switch 
application submitted to it.

    Question 4b. Under what circumstances do you believe it is 
appropriate for the FDA to override such strong scientific evidence in 
making such decisions? What more information does the FDA need to make 
a decision on Plan B?
    Answer 4b. On August 24, 2006, FDA approved the amended sNDA from 
Barr Laboratories allowing OTC sale of Plan B to adults 18 and older. 
Plan B will be available to patients 17 and younger by prescription.

    Question 5. Dr. von Eschenbach, I can't help but notice a gradual 
increase in the age deemed acceptable for appropriate use of Plan B. 
Allow me to describe the following timeline of this age discussion:
    In July 1999, the U.S. Food and Drug Administration approved Plan 
B, finding it safe and effective for women of all ages to use as a 
prescription product. On December 16, 2003, the FDA's independent panel 
of experts votes 23 to 4 to recommend Plan B be made available OTC, 
with no age restriction. The panel also voted unanimously that Plan B 
is safe for nonprescription use.
    Despite these findings, on May 6, 2004, Dr. Steven Galson, Acting 
Director of the Center for Drug Evaluation and Research overrode FDA 
professional staff recommendations and issues a ``not approvable'' 
letter to Plan B's manufacturer, citing concerns about young teens 
using the drugs.
    Two months later, [July 22, 2004] Barr Pharmaceuticals submitted a 
revised OTC proposal to FDA, which would make it available to women 16 
and older without a prescription while requiring one for women 15 and 
under. Despite this response to their stated concerns, the FDA failed 
to make a decision within the deadline imposed under Federal law 
governing performance standards.
    In 2005, Mr. Crawford wrote a letter to a Mr. Joseph Carrado, 
Senior Director of Regulatory Affairs at Duramed Research, a subsidiary 
of Barr Pharmaceuticals. Within the text of his letter, Crawford 
explicitly states that the Center for Drug Evaluation and Research 
(CDER)'s findings ``support the safe use of Plan B as an OTC product, 
but only for women who are 17 years of age and older.''
    This year, however, in a letter to Mr. Carrado, written just 
yesterday, you state that the FDA believes the ``appropriate age for 
OTC access [for Plan B] is 18.''
    Dr. von Eschenbach, what prompted the addition of a year to the 
FDA's criteria for what constitutes the ``appropriate age'' for Plan B? 
Did new scientific research lead to your move from 17 to 18 years of 
age? If not, how do you explain your departure from Mr. Crawford's 
words just a year ago?
    Answer 5. The Center for Drug Evaluation and Research (CDER) at FDA 
determined that the data submitted by the sponsor (Duramed or Barr) in 
its 2004 application supported OTC use for women 17 and older. In 
considering the difficulty of enforcing an age-based restriction on the 
availability of this oral hormonal contraceptive, however, I have 
concluded that 18 (rather than 17) is the more appropriate cutoff to 
best promote and protect the public health. The State-regulated 
pharmacies that will be dispensing Plan B under Barr's voluntary 
Convenient Access, Responsible Education (CARE) program (as well as 
society as a whole) are more familiar with 18 as a cutoff age. I 
understand that in all 50 States, 18 is the age of majority (i.e., the 
legal delineation between minor and adult), and retail outlets, 
including pharmacies, are familiar with using 18 as the age of 
restriction for the sale of certain products. With regard to the sale 
of certain drug products, the legal age to purchase FDA-approved non-
prescription nicotine replacement therapy products is 18. Moreover, I 
understand that as a matter of State law, many products routinely sold 
by pharmacies, e.g., tobacco products and nonprescription cough-cold 
products like pseudoephedrine are restricted to consumers 18 and older. 
The approach builds on well-established State and private sector 
infrastructures to restrict certain products to consumers 18 and older. 
This approach should, therefore, help ensure safe and effective use of 
Plan B.
                             fda authority
    Question 6. Several questions have been raised as to whether the 
FDA has the legislative and regulatory authority it needs to carry out 
its mission of ensuring the safety of food and drugs used by American 
consumers. What additional authority would you identify as necessary to 
enable the FDA to ensure the safety and efficacy of the drugs, medical 
devices and foods manufactured and sold in our Nation?
    Answer 6. FDA is fully capable of carrying out its mission under 
its current statutory and regulatory authority.

    Question 7. In light of concern that FDA activities are influenced 
unduly by factors other than science, what assurances can you provide 
that your leadership and your leadership team will pursue a science-
based agenda, rather than an ideological-based agenda? What 
qualifications are most important to you when assembling your 
leadership team? Who are you considering as possible members of your 
leadership team?
    Answer 7. Throughout my career as a physician, I have believed that 
only the discipline of scientific inquiry could provide an accurate and 
reliable understanding of disease and guide the development and 
application of interventions. This is a belief that I have embraced as 
an administrator. To embrace scientific research not as an end but as a 
means to illuminate a path to future progress is the ideology that must 
guide FDA's decisions regarding the effectiveness and safety of the 
innovative products that will impact the health and welfare of the 
public. The leadership of FDA who are responsible for the integrity of 
the regulatory process must be dedicated to providing the tools of 
modern science and assuring the application of the rigor and discipline 
of the scientific method. This leadership team must be comprised of a 
diverse group of experts in both the science and policy components of 
the regulatory process. In addition to their professional 
qualifications, I believe their commitment to collaboration and placing 
the Agency before personal agendas as well as their devotion to 
integrity and public service are essential requirements. At present 
there are no pending candidates for the senior leadership team.

    Question 8. Over 1,000 scientists at the FDA recently responded to 
a survey conducted by the Union of Concerned Scientists, who were 
seeking information about the ways in which career scientists felt they 
were able to conduct their work without undue political or commercial 
interference. Forty percent of the employees who responded noted that 
their morale was poor or very poor. What steps do you plan to take to 
restore morale among the career employees at the FDA?
    Answer 8. FDA's workforce is comprised of over 12,000 incredibly 
talented and highly trained professionals who epitomize the true 
meaning of the word public servant. It is important for everyone to 
know that if confirmed, their support and guidance will be my greatest 
asset in leading the FDA.
    As the FDA regulates almost 25 percent of all the products 
Americans consume, its talented and dedicated employees continue to set 
the Gold Standard that is emulated around the world but never equaled. 
This standard of achievement must not change. But the world around us 
is changing and the FDA of today is faced with new challenges and the 
FDA of tomorrow will encounter incredible opportunities.
    I am committed to recruiting and retaining top staff to face these 
new challenges and to support the Agency's important public health 
mission.
                              biogenerics
    Question 9. I would like to followup with you on an issue I raised 
with Gary Buehler, Director of the FDA Office of Generics, at a recent 
Aging hearing regarding generic biologics.
    I recognize that the FDA has been very public about its belief that 
it does not have the legislative authority to develop a pathway that 
would allow the vast majority of generic biologics to enter the market. 
However, the FDA began working on drug-specific guidance documents 7 
years ago--during the Clinton administration--to provide information to 
companies about 2 biologics--insulin and growth hormone--drugs that you 
have asserted authority over. While these guidance documents are not an 
explicit pathway, they would certainly facilitate bringing a biogeneric 
for each of these drugs to the market. But just last month, after 7 
years, the FDA announced that it is reversing course and will instead 
begin all over again and develop industry-wide guidance on this issue.
    So now even where the FDA has accepted authority to facilitate 
bringing a generic to the market, you have spent 7 years and missed the 
opportunity to save millions of dollars for consumers and taxpayers. In 
fact, just for insulin and growth hormone, the Medicaid program spent 
$752 million in 2005 (calculation based on CMS data). If a biogeneric 
had been on the market in 2005, the Medicaid program could have saved 
over $100 million on these two drugs alone. And of course the savings 
to Medicare and the health system overall would be much greater.
    Why after 7 years did the FDA decide to change course? What 
happened to the insulin and growth hormone specific documents you were 
working on, and will you release documentation of their development to 
the HELP Committee? In light of the significant opportunity for cost-
savings, will you release these two guidance documents? What action 
will you take to provide industry-wide guidance and how will you make 
it specific enough to be helpful to companies considering biogeneric 
development for drugs as different as insulin and growth hormone?
    Answer 9. Protein products may be approved as drugs by FDA under 
section 505 of the Federal Food, Drug, and Cosmetic (FD&C) Act or 
licensed as biological products under section 351 of the Public Health 
Service (PHS) Act. For products approved under section 505 of the FD&C 
Act, we believe there is existing authority to allow applications for 
follow-on protein products to be approved under sections 505(b)(2) or 
505(j) of the FD&C Act where scientifically appropriate. There is no 
abbreviated approval pathway for protein products licensed under 351 of 
the PHS Act analogous to sections 505(b)(2) or 505(j) of the FD&C Act 
for drugs.
    Please be assured FDA's consideration of regulatory issues related 
to follow-on protein products is progressing. FDA held two public 
meetings (September 2004 and February 2005) and co-sponsored a workshop 
(December 2005) on scientific issues related to follow-on protein 
products. These meetings resulted in a large number of comments and 
concerns from the interested parties that are being considered as we 
develop policies for regulating these products, including forms of 
insulin and human growth hormone.
    The Agency has reconsidered issuing, at this time, the draft 
guidance documents on human growth hormone and insulin that you 
referenced for a number of reasons. After re-assessing these ``product-
specific'' draft documents, FDA has determined that it would be more 
appropriate to initially publish guidances that are more broadly 
applicable to follow-on protein products in general. FDA expects that 
this approach will provide useful guidance to the industry, while 
ensuring that we do not stifle innovation and the utilization of state-
of-the-art technologies. In addition, a sponsor may contact the Agency 
to request advice on a case-specific basis regarding the development of 
a follow-on protein product for submission in an application under 
section 505 of the FD&C Act.
    With regard to your request for the Agency to release its 
preliminary draft guidance documents on human growth hormone and 
insulin, I note that these internal draft documents were never 
finalized and were not cleared by Center for Drug Evaluation and 
Research (CDER) management, thus they do not necessarily reflect CDER's 
current thinking on these topics. For this reason, we would not 
disseminate these deliberative documents outside FDA.
    I do want you to know, however, that even as guidance documents on 
follow-on protein products are being developed, the Agency has been 
moving forward with the review and approval of those follow-on protein 
products regulated as drugs for which the sponsors have met the 
statutory and regulatory approval requirements under section 505. Most 
recently, we have approved Fortical (calcitonin salmon recombinant) 
Nasal Spray in August 2005, Hylenex (hyaluronidase recombinant human) 
in December 2005, and Omnitrope (somatropin [rDNA origin]) in May 2006.

    Question 10. Since 2004, the FDA has been studying the issue of 
follow-on protein products, which refers to proteins and peptides that 
are intended to be sufficiently similar to already approved products--
essentially, generic versions of biologic protein products that may 
already be on the market. Although the FDA was supposed to release a 
White Paper to provide further guidance on this topic in 2005, nothing 
has yet been released. When will you release this guidance?
    Answer 10. The Agency has been studying the issue of follow-on 
protein products because of the important public health objectives that 
are advanced by an approval system for such products. Applications that 
rely on existing scientific knowledge, subject to the protection of 
intellectual property rights, can avoid unnecessary duplication of 
research and lead to decreased costs to consumers, industry, and FDA. 
Further, such reliance on existing knowledge obviates certain ethical 
concerns related to medically or scientifically unjustified preclinical 
and clinical testing.
    We generally use the term follow-on protein products rather than 
generic biologics to refer to protein and peptide products that are 
intended to be sufficiently similar to a product already approved or 
licensed to permit the applicant to rely for approval on certain 
existing scientific knowledge about the safety and effectiveness of the 
approved protein product. Your question refers to ``generic versions of 
protein products.'' FDA generally uses the term ``generic'' to refer to 
drugs approved under section 505(j) of the FD&C Act, which are 
therapeutically equivalent to, and therefore substitutable for, the 
innovator product. Although the generic drug approval pathway set forth 
in section 505(j) of the FD&C Act may be used to approve follow-on 
protein products where the State of the science is adequate to 
demonstrate ``sameness'' of the active ingredient, and for which 
clinical safety and effectiveness studies are not necessary, most 
follow-on protein products are expected to be reviewed in section 
505(b)(2) applications.
    Numerous protein products, however, are licensed as biological 
products under section 351 of the Public Health Service (PHS) Act, and 
are not approved as drugs under the FD&C Act. There is no abbreviated 
approval pathway for protein products licensed under section 351 of the 
PHS Act analogous to sections 505(b)(2) or 505(j) of the FD&C Act for 
drugs.
    Please be assured that FDA's consideration of regulatory 
requirements for follow-on protein products is progressing. FDA has 
sought input from stakeholders and conducted an extensive public 
discussion on scientific issues relating to the development and 
approval of follow-on protein products, including two public meetings 
(September 2004 and February 2005) and a co-sponsored workshop 
(December 2005). The public meetings resulted in a large number of 
comments and concerns from interested parties that are being considered 
further as we develop policies for regulating follow-on protein 
products. FDA recognizes that guidance for industry would be helpful, 
and intends to publish guidance broadly applicable to follow-on protein 
products in a timely manner. FDA expects that this approach will 
provide useful guidance to the industry, while ensuring that we do not 
stifle innovation and the utilization of state-of-the-art technologies. 
In addition, a sponsor may contact the Agency to request advice on a 
case-specific basis regarding the development of a follow-on protein 
product for submission in an application under section 505 of the FD&C 
Act.
    I do want you to know, however, that even as guidance documents on 
follow-on protein products are being developed, the Agency has been 
moving forward with the review and approval of those follow-on protein 
products for which the sponsors have met the statutory and regulatory 
approval requirements under section 505. Most recently, we have 
approved Fortical (calcitonin salmon recombinant) Nasal Spray in August 
2005, Hylenex (hyaluronidase recombinant human) in December 2005, and 
Omnitrope (somatropin [rDNA origin]) in May 2006.

    Question 11. We know that a number of brand biopharmaceuticals are 
now eligible to have generic competition or will be eligible over the 
next few years. Yet, there seems to be very little movement by FDA to 
bring affordable generic biologics to the market in the United States. 
Without FDA action, naming organizations in both the United States and 
Europe are delaying action on regulations which will guide the 
marketing of these types of biogenerics. As a result, consumers 
worldwide are denied access to generics that are proven safe, but cost 
less.
    At the upcoming World Health Organization meeting of global 
regulatory agencies, will the FDA help to resolve questions around the 
naming of biogenerics to ensure that Americans and patients around the 
world will soon have access to affordable medicine?
    Answer 11. FDA has been moving forward with the review and approval 
of those follow-on protein products for which the sponsors have met the 
statutory and regulatory approval requirements under section 505 of the 
FD&C Act. Most recently, we approved Fortical (calcitonin salmon 
recombinant) Nasal Spray in August 2005, Hylenex (hyaluronidase 
recombinant human) in December 2005, and Omnitrope (somatropin [rDNA 
origin]) in May 2006.
    We have considered issues related to the established 
(nonproprietary) name of follow-on protein products on a case-specific 
basis, informed by our public meetings on scientific considerations 
related to follow-on protein products in September 2004 and February 
2005. The Agency is not aware of any delay in marketing a follow-on 
protein product attributable to a question regarding the appropriate 
established name for the product, which typically is resolved during 
the review process and prior to product approval. It should be noted, 
however, that a common established name does not necessarily indicate 
therapeutic equivalence (and therefore substitutability or 
interchangeability) of two drug products absent an ``A'' therapeutic 
equivalence rating in FDA's ``Approved Drug Products with Therapeutic 
Equivalence Evaluations'' (the ``Orange Book'').
    FDA looks forward to participating in the upcoming World Health 
Organization meeting of global regulatory agencies and discussing its 
issues related to the international nonproprietary name selection 
process for ``biosimilar'' or follow-on protein products.
                              flu vaccine
    Question 12. Following the flu vaccine shortage that occurred in 
fall 2004, which was the third shortage experienced by our Nation since 
2000, several questions were raised about the FDA's oversight of 
vaccine manufacturing facilities, especially after it was revealed that 
the Agency had been aware of contamination issues at the Chiron 
facility prior to the shutdown of this facility by British drug 
regulators. With the loss of this production capacity, the U.S. vaccine 
supply for the 2004 flu season was effectively cut in half.
    How will you work to ensure, from the regulatory standpoint, that 
future flu shortages do not occur? What activities will you undertake 
to assist manufacturers who are currently in or who enter the flu 
vaccine market with producing a safe, reliable and uncontaminated 
vaccine product? What other steps can the FDA take to ensure an 
adequate supply of flu vaccine on an annual basis?
    Answer 12. While there are significant elements of risk in the 
industry that are beyond FDA's control, in particular underlying market 
forces and the inherent uncertainties and complexities of flu vaccine 
production, the Agency has made significant changes in certain areas in 
an effort to help prevent future problems. Since 2004, FDA has conduced 
inspections of influenza vaccine manufacturers on an annual basis, and 
the Agency is completing or has completed agreements that allow 
information sharing with numerous foreign regulatory agencies. The 
Agency also interacts extensively with licensed manufacturers to 
address issues that may arise during annual production. FDA has also 
reached out to manufacturers to share important technical information 
and to encourage preventive approaches that specifically address 
quality in vaccine manufacturing.
    FDA is also working to facilitate increased diversification and 
capacity in flu vaccine manufacturing. FDA has contacted major 
manufacturers of influenza vaccine throughout the world to stimulate 
interest in producing vaccine for the U.S. market. In March 2006, FDA 
released the guidance document, ``Draft Guidance for Industry, Clinical 
Data Needed to Support the Licensure of Trivalent Inactivated Influenza 
Vaccines.'' For new vaccine developers, the document recommends clear 
pathways for both traditional and accelerated approval approaches. 
Accelerated approval allows for evaluation based on biological 
indicators (e.g., the immune response to the vaccine) likely to 
demonstrate effectiveness. This outreach to manufacturers and the 
availability of accelerated approval has resulted in one additional 
vaccine product approval for the 2005-2006 season, and the possibility 
for others in future flu seasons.
    A major factor contributing to current risks in flu vaccine 
manufacturing is the inherent nature of current, egg-based 
technologies. FDA is therefore undertaking efforts to facilitate 
development of influenza vaccines using new technologies, including 
cell based, and other novel types such as DNA and synthetic peptide, 
and is working closely with HHS, NIH and product developers to help 
advance and evaluate such promising new technologies.
                             pediatric rule
    Question 13. I believe that it's extremely important to ensure that 
the drugs we give to our children have been proven to be safe for use 
in children, which is why I worked with Senator DeWine and my other 
colleagues in the Senate to pass the Pediatric Research Equity Act to 
codify the pediatric rule--the FDA guideline that required such 
testing, and which was promulgated during the Clinton administration.
    The Pediatric Research Equity Act, in conjunction with the Best 
Pharmaceuticals for Children Act (BPCA), which provides pediatric 
exclusivity incentives to manufacturers that conduct pediatric studies, 
have worked to improve confidence in the safety of the drugs that we 
provide to children.
    The FDA allows companies to request waivers from requirements to 
conduct pediatric studies for drugs that are not likely to be used in 
the overall pediatric population, such as drugs for ovarian cancer. 
Some companies that should be seeking waivers are instead conducting 
pediatric studies to receive the 6 months of exclusivity made available 
under the BPCA. Such abuse of the system undermines support for this 
important incentive and needs to be addressed.
    What actions should the FDA take to ensure that drugs that are 
obviously not geared for pediatric populations do not qualify for the 
exclusivity incentives under the BPCA?
    Answer 13. I can assure you that FDA carefully considers the 
potential for public health benefit of a given drug in pediatric 
patients before issuing a Written Request to a sponsor for pediatric 
studies under BPCA. FDA would not issue a Written Request for studies 
in children when there is evidence that strongly suggests the drug 
would be ineffective or unsafe in pediatric patients; when the studies 
would be ethically controversial (unless the potential public health 
need is so great that studies are warranted); or when there is 
insufficient safety information for studies to be conducted. Written 
Requests are typically reviewed by a multidisciplinary committee prior 
to being issued; this review further ensures that Written Requests are 
appropriately issued.
    There are several reasons why a Written Request might be issued 
under BPCA even though studies were waived or deferred under PREA. 
BPCA, like PREA, allows FDA to request pediatric studies for any and/or 
all approved adult indications that apply to the pediatric age group. 
However, in contrast to PREA, BPCA also allows FDA to request pediatric 
studies for indications that are not approved in the adult population. 
For example, a product that is used to treat hypertension in adults 
may, by its mechanism of action, also be useful to treat pulmonary 
hypertension in newborns. Under PREA, there is no way to obtain those 
studies in newborns because PREA is limited to indications for which 
the sponsor has obtained or is seeking approval in adults. Under BPCA, 
we could issue a Written Request to the sponsor asking that they submit 
studies for pulmonary hypertension in newborns. We could issue the 
Written Request at any time and not have to wait until a sponsor 
informs us they want to study the product in the adult population.
    Products for orphan indications (those indications occurring in 
fewer than 200,000 patients) may be studied under BPCA, but are exempt 
from the requirements of PREA. This provision was included in BPCA to 
ensure that treatments for rare diseases are studied in the pediatric 
population. In some cases, a drug with an approved indication that does 
not occur in the pediatric population may be used off-label in 
pediatric patients to treat rare childhood diseases such as McCune-
Albright Syndrome or osteogenesis imperfecta. When possible in these 
cases, we want to have information that can be included in the label 
and studies under BPCA are often the only way to get this information.

    Question 14. There has been much controversy over the use of 
antidepressant medications in pediatric populations because several 
studies linked this medication to increased risk of suicidal ideation. 
While the FDA has little control over the off-label use of drugs, the 
Pediatric Rule, if applied to its fullest extent, could have helped 
prevent much of the controversy around pediatric antidepressant safety. 
Could you please tell me how you plan to increase FDA reliance upon the 
Pediatric Rule, as well as the Best Pharmaceuticals for Children Act, 
as tools to increase the safety of drugs for Americans?
    Answer 14. The use of psychotropic medications in children and 
adolescents is an issue of major concern to FDA. BPCA, in particular, 
has contributed to the development of important information. Over the 
past few years, we have taken a number of actions related to the use of 
selective serotonin reuptake inhibitors (SSRIs) and other anti-
depressants in children and adolescents. These actions were based 
largely on FDA's review of clinical trials conducted in children under 
the pediatric exclusivity incentives. Review of these study data 
contributed toward FDA's conclusion that antidepressants are associated 
with an increased risk of suicidal thinking and actions in adolescents 
with certain psychiatric disorders. This conclusion led to issuance of 
public health advisories, revised labeling for all SSRIs and other 
antidepressants, and patient medication guides. The FDA 
Psychopharmacologic Drugs and Pediatric Advisory Committees reviewed 
these actions and considered them appropriate. BPCA has stimulated 
studies of other psychotropic drugs as well and has identified that 
many of these products that work for depression in adults do not appear 
to have the same magnitude of effect in children. Without these studies 
it is doubtful we would ever have been able to develop the level of 
information that we did regarding how children react differently than 
other patient populations.
                             generic drugs
    Question 15. There has been a well-publicized backlog of generic 
drug approvals at the FDA. What action will you take to clear this 
backlog? What additional authority or resources do you need to reduce 
the amount of time it takes to bring safe, generic pharmaceuticals to 
market?
    Answer 15. We share your interest in speeding the availability of 
generic drugs. FDA has taken a number of significant steps to provide 
greater access to affordable prescription medications, including 
unprecedented steps to lower drug costs by helping to speed the 
development and approval of low-cost generic drugs after legitimate 
patents have expired on branded drugs. Generic drugs typically cost 50 
to 70 percent less than their brand-name counterparts. In 2003, FDA 
published a final rule to improve access to generic drugs and lower 
prescription drug costs for millions of Americans. The rule limits an 
innovator drug company to only one 30-month stay of a generic drug 
applicant's entry into the market for resolution of a patent challenge. 
These changes will save Americans over $35 billion in drug costs over 
the next 10 years, and will also provide billions in savings for the 
Medicare and Medicaid programs. We were pleased that elements of this 
rule were codified as part of the Medicare law and that, with FDA's 
technical assistance, the law added additional mechanisms to enhance 
generic competition in the marketplace.
    In addition, since fiscal year 2001, the Administration and 
Congress have increased funding for FDA's generic drug program by 66 
percent, a clear sign of the important role played by OGD. These 
increases have enabled FDA to hire additional expert staff to review 
generic drug applications more quickly and initiate targeted research 
to expand the range of generic drugs available to consumers. While 
there remains work to be done, as I will discuss, we have been able to 
produce significant reductions in approval times for generic drugs 
since 2002 that consequently will save consumers billions by generally 
reducing the time for developing generic drugs and making them 
available.
    In addition, our Office of Generic Drugs (OGD) has worked 
tirelessly to find efficiencies in the generic drug application review 
process. OGD is incorporating several changes in the process to reduce 
review time, including:

     Reviewing Drug Master Files (DMFs) prior to the time the 
related ANDAs are assigned since the DMF evaluation is often the 
limiting factor in completing the ANDA review.
     Utilizing telephone conversations with ANDA sponsors, when 
appropriate, to resolve deficiencies more efficiently and 
expeditiously.
     Assigning applications to reviewers with related expertise 
or experience with a particular drug class.
     Utilizing a new format for the chemistry review called 
question based review. It is based on the structure of the 
International Conference on Harmonization Common Technical Document for 
the chemistry review.
     Utilizing a team review approach for ``clusters'' of 
applications for the same product.

    OGD continues to seek ways to make the review processes and 
interactions with industry more efficient, including seeking better 
information technology solutions.
                              drug safety
    Question 16. In April, you engaged a consulting firm to evaluate 
post-marketing study commitment process. The report from that firm is 
not expected for another year. In the meantime, what action will you be 
taking to ensure that companies engage in post-marketing studies?
    Answer 16. As noted in your question, FDA is in the process of 
undertaking a review of the decisionmaking process behind requests for 
Post-marketing Study Commitments (PMCs) for human drugs, including 
biological drugs. An outside contractor has been hired to evaluate how 
different review divisions decide to request PMCs, decisions 
surrounding what kinds of PMCs to request, and what are reasonable 
timeframes for completing PMCs. The study will serve to assist FDA in 
determining if better guidance is needed for industry and to ensure 
there is standardization of the procedures. While this study is being 
conducted, the Centers within FDA have undertaken activities in the 
meantime to improve the response on post-marketing and post-approval 
studies for human drugs (including biological drugs).
    Post-marketing study commitments (PMCs) for approved drug products 
are studies that a sponsor either is required or agrees to conduct 
after FDA has approved a product for marketing to further define the 
safety, efficacy, or optimal use of a product. In some cases, the 
studies can take years to complete, even if everything is going 
according to schedule. In other cases, there are considerable obstacles 
(e.g., difficulty in recruiting patients and investigators to 
participate in a clinical trial when an approved therapy is available) 
that must be addressed before the studies can be completed. In these 
cases, FDA works closely with sponsors to address these obstacles. It 
should also be noted that approximately 38 percent of the currently 
pending PMCs for new drug applications were established in applications 
approved between October 1, 2003, and September 30, 2005, and thus, 
depending on the complexity of the study, FDA would expect that many of 
these studies would not have been initiated yet.
    FDA takes its statutory obligations under the Food and Drug 
Administration Modernization Act of 1997 (FDAMA) to track and monitor 
the progress of PMCs very seriously. FDA recently published a final 
guidance to industry to describe in greater detail the content, format, 
and timing of PMC annual status reports submitted by the drug industry. 
Furthermore, FDA reports annually in the Federal Register on the 
performance of applicants in conducting their PMCs and maintains a 
public Website that contains the information that FDA is required under 
FDAMA to make available to the public. These initiatives, along with 
other FDA internal procedures, are all intended to ensure that industry 
undertakes their commitments and completes them in a timely manner.

    Question 17. For months, Tysabri, a drug used to treat multiple 
sclerosis, was unavailable to patients, after several patients in 
clinical trials developed a serious brain infection that proved fatal 
in two cases. It is estimated that 1 in 1000 patients who take Tysabri 
will experience such complications.
    Although Tysabri was returned to the market earlier this year under 
a special distribution program, many MS patients, including several of 
my constituents, who had experienced treatment gains with Tysabri were 
concerned at the sudden withdrawal of this drug. Some argued that they 
understood the treatment risks, and would like to have had the option 
to continue taking a drug which helped them halt progression of an 
ultimately fatal disease.
    As new therapies for debilitating chronic diseases like MS emerge 
on the market, how will you work with patient groups to balance 
concerns over safety with the desire to get a clinically effective but 
potential risky drug to a population that will benefit from it?
    Answer 17. Under the Federal Food, Drug, and Cosmetic (FDC) Act and 
related statutes, the Government has a vitally important role in 
helping to ensure that the medical products upon which patients and 
their health care practitioners rely are both safe and effective. These 
safeguards are particularly important for our most vulnerable citizens, 
those who are desperately ill. We believe the existing programs under 
which patients can obtain access to experimental therapies, and those 
under which we expedite approval of such therapies, establish the 
appropriate framework for achieving our mutual goal of providing 
patients with serious and life-threatening diseases the earliest 
reasonable access to promising therapies. These programs were codified 
in the ``Food and Drug Administration Modernization Act of 1997.''
    Of course, we recognize the value of even more effective access 
programs, and we are open to improving the effectiveness of these 
processes. FDA's Office of Special Health Issues works with patients 
and their advocates to encourage and support their active participation 
in the formulation of FDA's regulatory policy. The staff is familiar 
with the concerns confronting patients and families dealing with life-
threatening and debilitating illnesses.
    CDER routinely consults with the American people in making its 
decisions about the drugs that they use. It holds public meetings to 
incorporate expert and consumer input into its decisions. The center 
also announces many of its decisions in advance so that members of the 
public, academia, industry, trade associations, consumer groups, and 
professional societies can comment and make suggestions before 
decisions become final. In addition, CDER holds annual public meetings 
with consumer and patient groups, professional societies, and 
pharmaceutical trade associations to obtain enhanced public input into 
its planning and priority-setting practices. The Agency's public health 
mission remains constant: to ensure that the benefits of drug products 
made available to the public outweigh known risks.
                  pregnant women--pregnancy registries
    Question 18. The FDA Website contains information about pregnancy 
registries--surveillance studies to help determine the safety of drugs 
in utero. These types of studies are extremely important so that we can 
develop guidelines that help us not only prevent adverse health impacts 
in the womb, but also to help women with health concerns, such as 
cancer, depression, or other chronic diseases, maintain good health 
during and after their pregnancies. However, your Website has not 
updated information on these types of registries since July 2004. How 
will you improve the ability of the Agency to make women aware of these 
studies and their results? How will you work with manufacturers to 
encourage them to engage in these types of studies and disseminate 
their results?
    Answer 18. Our Office of Women's Health will be updating the 
pregnancy registries Website within the next 12 months. FDA issued an 
industry guidance document, ``Establishing Pregnancy Exposure 
Registries,'' in August 2002. When a pregnancy registry is implemented, 
FDA works with the sponsor of the registry to ensure that healthcare 
providers and patients who may be eligible for participation are aware 
of it. This may be done through a variety of measures, including 
publication of the registry contact information in labeling, patient 
package inserts, notification of teratogen information services in 
States, and even use of the product's detail sales force. Additionally, 
in April 2005, FDA finalized guidance to staff, entitled ``Evaluating 
the Risks of Drug Exposure in Human Pregnancies,'' to assist them in 
evaluating human fetal outcome data generated after medical product 
exposures during pregnancy.
    Unfortunately, the current system of having a separate registry for 
every drug for which a pregnancy registry is implemented is highly 
inefficient and makes communication regarding, and even participation 
in, registries cumbersome at every level. FDA continues to work with 
other agencies, especially the CDC, to find ways to build a more 
consistent, robust system of capturing data on the safety of drugs used 
in pregnancy.
                            ipledge program
    Question 19. Isotretinoin, also known as Accutane, is a drug used 
to treat severe acne, has been found to cause miscarriages and birth 
defects. According to a study by Roche, nearly 2,000 women have become 
pregnant while on the drug since it was approved over 20 years ago. 
Three hundred and eighty-three gave birth, with half of those children 
being born with birth defects.
    In order to prevent pregnancy from occurring while on this drug, 
the FDA established the iPledge program in March of this year. This 
Internet-based program tracks compliance with prescription 
requirements, which include mandates to ensure female patients use two 
forms of birth control and take monthly pregnancy tests. All patients 
must also undergo tests to monitor other conditions, including 
cholesterol and liver function. These important safety protections help 
to ensure that health will not be endangered.
    However, the administrative requirements of the iPledge program 
have made it more difficult for patients to access this drug, and 
physicians report long wait times in seeking assistance from iPledge 
personnel. What actions will you take to reform the iPledge program so 
as to protect women's health while reducing the administrative burden 
for both patients and physicians? Will you be releasing data on the 
number of pregnancies that may occur with this system, so that we can 
judge its effectiveness?
    Answer 19. FDA has worked closely with isotretinoin sponsors and 
their vendor, Covance Inc., to maintain a critical balance between 
access to the drug by patients who need it and ensuring its safe use. 
In response to concerns raised by dermatologists and pharmacists in 
recent weeks, FDA has ensured that rapid and significant progress has 
been made by the sponsors and Covance to address operational aspects of 
the program. The specific measures taken include an increase in iPLEDGE 
call center staffing to handle the expected increases in call volume 
and user questions, as well as an enhanced system to process requests 
for new passwords by users who have forgotten or lost their original 
passwords.
                            minority health
    Question 20. In 2005, the FDA approved BiDil, the first race-
specific drug. BiDil is a combination of two drugs--75 milligrams of 
hydralazine and 40 milligrams of isosorbide dinitrate--used to treat 
high blood pressure and chest pain. Non-race specific generic versions 
of these two drugs are available. Since BiDil was approved, significant 
concerns have been raised about the ethics of developing and marketing 
race-specific drugs. What will you do to address these concerns when 
other race-
specific drugs are submitted for approval? How will you work with 
patient populations to ensure that such concerns are heard by your 
agency, especially since there is no currently existing Office of 
Minority Health at the FDA?
    Answer 20. The growing interest in targeted therapy could lead to 
cases in which an effect is shown for a narrow group, but there is very 
little information about the rest of the population. Thus, when a 
therapy is shown to be effective for a responsive subgroup, the 
following critical questions to be considered include: (1) how much 
data should be expected on the drug's effects in other groups, (2) how 
small an effect needs to be detected or excluded in those groups, (3) 
when should the data on those other groups be expected (before or after 
approval, and how long after), and (4) to what extent can FDA require 
further studies. It is important to note, however, that it is 
appropriate to approve a product for a specific race or demographic 
group when the legal standard for approval is met, given adequate 
attention to the points above.
                      food safety--mercury in fish
    Question 21. In 2004, the FDA and the EPA released the Joint 
Federal Advisory for Mercury in Fish, which provided information on 
levels of mercury in fish to help guide the diet choices for pregnant 
women, parents, and others. Recent data has uncovered higher than 
expected levels of mercury in both imported tuna, which makes up about 
half the American tuna market, and other types of fish, such as mahi 
mahi, that were thought to be low in mercury. Yet despite this new 
data, the FDA has not updated its advisory. How will you ensure that 
such updated information is made available to consumers on a more 
timely basis?
    Answer 21. In March 2004 FDA and EPA issued a joint advisory to 
help women who may become pregnant, pregnant women, nursing mothers, 
and parents of young children get the health benefits of eating fish 
and shellfish while reducing prenatal and early childhood exposure to 
mercury. The advisory, based on data collected from various brands of 
tuna and other species of fish from both domestic and international 
sources, provides specific recommendations about portion sizes of fish 
with low and moderate mercury levels, and recommends against 
consumption of specific fish species with higher levels of mercury. 
These recommendations remain valid. We continue to collect and analyze 
data on mercury levels in fish.
    The consumer advisory is being aggressively disseminated. For 
example, FDA and EPA are jointly sponsoring a public education campaign 
to reach women planning on becoming pregnant, pregnant women, nursing 
mothers, and parents of young children about the methylmercury 
advisory. FDA's outreach includes over 9,000 media outlets, including 
those that specialize in reaching women. In addition, information about 
the advisory has been sent to over 50 health-care provider 
organizations.
    An ongoing national survey conducted by the Centers for Disease 
Control and Prevention shows that about 94 percent of U.S. women of 
childbearing age have less methylmercury in their bodies than the EPA 
Reference Dose, a level of exposure established with a substantial 
margin of safety to protect the fetus from neurological harm. The 
remaining approximately 6 percent of women in the target population 
are, for the most part, only slightly over the Reference Dose, and 
still retain most of the substantial margin of safety that is built 
into it. Because a Reference Dose is not intended to separate safe 
levels from unsafe levels, we would not anticipate the risk for those 
who are exposed slightly over the Reference Dose to be significantly 
different than it is for those who are exposed at or below the 
Reference Dose.

    Question 22. In a letter I sent to you in February of this year, I 
urged you to take the following steps to address concerns around levels 
in mercury in fish, especially questions about the methodology used by 
the FDA to take mercury samples:

     Expand the testing system and increase sampling sizes for 
commonly consumed fish. We need a better baseline to ensure that we can 
better detect high levels when they do occur.
     Perform further investigations into samples that do 
register high levels of mercury. From the data available on the FDA's 
Website, there is no way to determine what factors might contribute to 
the increase in mercury levels found in 6 percent of the samples of 
light tuna--such as possible inclusion of yellowfin tuna in the sample.
     Provide clear, detailed summaries of the results of your 
monitoring program on your Website, in addition to providing the actual 
data available at http://www.cfsan.fda.gov/frf/seamehg2.html.

    What action have you taken to implement these steps at the FDA?
    Answer 22. Thank you for your suggestions. FDA will continue to 
provide summaries of the results of our monitoring program on our 
Website (http://www.cfsan.fda.gov/frf/seamehg.html). We have not 
implemented your other recommendations relating to our sampling program 
because, as explained in FDA's April 13 response to your letter, our 
findings of methylmercury concentrations in commercial fish are either 
within the variations in methylmercury that we know to exist or are not 
so high as to represent a significant public health issue. In response 
to your suggestion of expanding the monitoring program, FDA remains 
convinced that the number of samples collected for methylmercury 
analysis provides us with sufficient data to make appropriate risk 
management decisions and represents an appropriate allocation of our 
public health resources. As it is currently designed, the monitoring 
program allows us to track mercury levels in those fish species that 
tend to have the higher levels and are the most frequently consumed.
    It is important to recognize that fish consumption is typically so 
low in this country that exposure to methylmercury, as revealed by 
national survey data from the Centers for Disease Control and 
Prevention, remains low for most people regardless of the variations in 
the methylmercury concentrations of the fish they eat. Actual exposure 
to methylmercury, i.e., the amount of methylmercury that people have in 
their bodies, is a key public health indicator relative to the 
concentration of methylmercury that might be in any given fish.
    We know of no confirmed cases of adverse effect from methylmercury 
from eating commercial fish in the United States. However, it is 
essential that we develop a better understanding of the likelihood of 
adverse effects at the relatively low levels of exposure generally 
experienced by U.S. consumers. For that reason, we are in the process 
of upgrading our understanding of risk within the U.S. population. This 
effort involves examining the likelihood of adverse effects through the 
range of exposures being experienced by U.S. consumers. We look forward 
to sharing the results with you as soon as they are available.
                   collaboration between the fda/cpsc
    Question 23. The FDA and the Consumer Product Safety Commission 
(CPSC) have collaborated on several occasions to address safety risks 
from food and packaging. Yet while there has been cooperation on 
specific issues, such as the threat posed by conjac gel candies, there 
is no standard mechanism to spur greater cooperation. The lack of 
cooperation leads to jurisdictional issues around items like jumbo mint 
balls, which caused choking deaths in New York. How will you formalize 
the relationship between your agency and the CPSC in order to set up a 
permanent mechanism through which to improve the ability to regulate 
both foods and their packaging?
    Answer 23. FDA has had a close relationship with the Consumer 
Products Safety Commission (CPSC) since its creation in 1973. This is 
especially true since some FDA functions and personnel were transferred 
to CPSC upon its creation. In 1976, FDA and CPSC signed a Memorandum of 
Understanding (MOU) delineating the areas of jurisdiction of the 
respective agencies including those involving food and food contact 
materials. Both agencies continue to operate under that MOU and to 
closely cooperate in matters where jurisdictional questions may occur. 
In fact, representatives from FDA's foods program have met with 
representatives of CPSC as recently as August 14, 2006, to discuss 
closer cooperation on matters involving food and food contact material. 
FDA expects to continue these discussions as necessary and to take 
whatever other steps are appropriate to maintain and improve our 
ability to work with CPSC to accomplish our respective consumer 
protection missions. In the coming months, FDA and CPSC will examine 
the existing MOU on jurisdiction and work to revise it as needed.
                             lead in candy
    Question 24. In December 2005, the FDA released a draft guidance 
entitled ``Lead in Candy Likely To Be Consumed Frequently by Small 
Children: Recommended Maximum Level and Enforcement Policy.'' While 
this guidance recommends that levels of lead in candy not exceed 0.1 
parts per million, it also states that ``FDA's guidance documents, 
including this guidance, do not establish legally enforceable 
responsibilities.'' Why hasn't the FDA taken stronger action against 
candy that contains higher levels of lead? If the FDA does not have 
such enforcement authority, what additional authority do you need in 
order to ensure that no lead exists in candy sold to American children?
    Answer 24. FDA is giving a high priority to its monitoring and 
enforcement activities aimed at keeping candy products with potentially 
harmful levels of lead from reaching U.S. consumers. Under the Federal 
Food, Drug and Cosmetic Act, FDA can take action against any food, 
including candy, which is contaminated with lead at levels that may 
render the food injurious to health. FDA monitors candy for lead at 
points of entry into the United States and in domestic commerce. FDA 
will take enforcement action whenever it encounters a candy product 
that contains potentially hazardous lead levels.
    Enforcement actions available to FDA include seizure for foods in 
domestic commerce and refusal of entry for foods offered for import 
into the United States Also, future entries of an imported candy 
product found to be contaminated would be detained without physical 
examination until the contamination problem was corrected. FDA can also 
pursue voluntary recall for food that has been distributed 
domestically. FDA has, in the past, refused entry into the United 
States for imported candy products that have been found to contain 
elevated lead levels.
    To further reduce the exposure of children to lead from candy 
products, FDA plans to issue a guidance, which has been released in 
draft for comment. When it is issued, the final guidance on lead in 
candy will provide guidance on the maximum lead level we would expect 
in candy produced under good manufacturing practices. The guidance will 
list specific actions candy makers can take to ensure that their 
products do not exceed the recommended maximum level.

    Question 25. In New York City, local legislators passed a law 
banning candy containing lead, because of the lack of regulation on 
this issue at the Federal level. How do you plan to improve the 
responsiveness of the FDA to food safety issues so that national safety 
standards are as strong as those at the local level?
    Answer 25. FDA is able to and does take prompt action in response 
to food safety concerns under its regulatory authority, including the 
Federal Food, Drug and Cosmetic Act, the Public Health Service Act, and 
the Bioterrorism Act of 2002. For example, FDA can take action against 
any food that contains lead, or other added contaminants, at levels 
that may render the food injurious to health. Enforcement actions 
available to FDA include seizure of foods in interstate commerce and 
refusal of entry for foods offered for import into the United States. 
Future entries of an imported food product previously found to be 
contaminated would be detained without physical examination until the 
contamination problem was corrected. FDA can also pursue voluntary 
recall for food that has been distributed domestically.
    FDA plays a leadership role in food safety through cooperative 
efforts with our State partners. For example, the Conference for Food 
Protection is a cooperative FDA-State program, pursuant to which FDA 
issues nonbinding guidelines that States can adopt under State law and 
regulatory processes. FDA has similar cooperative provisions for milk 
and shellfish. In addition, FDA often develops guidance for the 
regulated community on food safety matters. While these guidance 
documents are not binding on the regulated community, the regulated 
community may use them as informal standards, even when they are in the 
draft, rather than final, stage.
    In terms of setting enforceable national standards, FDA frequently 
issues regulations to address food safety issues. The speed with which 
such actions can become final and enforceable regulatory requirements 
is influenced by staff and resource limitations and competing public 
health priorities, and by our need and desire to fully comply with 
controlling procedural and policy requirements, including the 
Administrative Procedures Act, Executive Order 12866, the Small 
Business Reform Act, the Unfunded Mandates Act, the Paperwork Reduction 
Act, and other requirements.
    With respect specifically to lead in candy, please see our response 
to your previous question (#24) for information regarding FDA's 
actions.

    Question 26. The FDA is currently considering approving the pre-
market applications (PMAs) of Mentor and Inamed Corporations for their 
silicone breast implants (SBI). However, the FDA is also conducting a 
criminal investigation of Mentor, including allegations that Mentor 
provided inaccurate data to hide design problems and higher rupture 
rates. Has the FDA completed its investigation? If not, will the FDA 
conclude its investigation before issuing a final decision on the PMAs?
    Answer 26. FDA has completed its investigation of Mentor and the 
case was closed in June. If information arises in the future that 
causes FDA to question the validity of data in an application, the 
Agency would not consider approving a PMA without considering how the 
information may affect our ability to assess safety and effectiveness. 
In addition, as part of the PMA review process, FDA performs 
Bioresearch Monitoring (BIMO) and Manufacturing inspections. The BIMO 
inspection of the sponsor and some investigational sites includes, for 
example, the review of records to assure the integrity of the data 
submitted. Any decision we make on the PMA will be made on the basis of 
a complete evaluation of the safety and effectiveness of the silicone 
breast implants.
                                 ______
                                 
              Additional Questions of Senator Clinton for 
                        Andrew C. von Eschenbach
    Question 1. The FDA regulates the promotion of prescription drugs, 
including the content of DTC advertisements. A 2002 GAO report 
highlighted a change in HHS procedure for reviewing draft regulatory 
letters that resulted in the issuance of regulatory letters after the 
misleading advertising campaign was completed. What has the FDA done to 
correct this problem and ensure that regulatory letters are issued 
timely?

    Question 2. What actions has FDA taken to prevent pharmaceutical 
companies who have received regulator letters from disseminating new 
misleading advertising for the same drug?

    Question 3. What are FDA's personnel and budgetary commitments for 
the oversight and regulation of the promotion of prescription drugs, 
including DTC?

    Question 4. Does the FDA review prescription drug advertising on 
the Internet? What differences have you found with regulation of 
advertising in that medium compared to broadcast or print?

    [Editors Note: The responses to additional questions from Senator 
Clinton were not available at time of print.]

    [Whereupon, at 12:20 p.m., the hearing was adjourned.]

                                    

      
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