[Senate Hearing 109-99]
[From the U.S. Government Publishing Office]



                                                         S. Hrg. 109-99

                    NOMINATION OF LESTER M. CRAWFORD

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

                                HEARING

                                 OF THE

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

                       ONE HUNDRED NINTH CONGRESS

                             FIRST SESSION

                                   ON

 TO BE COMMISSIONER, FOOD AND DRUG ADMINISTRATION, U.S. DEPARTMENT OF 
                       HEALTH AND HUMAN SERVICES

                               __________

                             MARCH 17, 2005

                               __________

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

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20-167                      WASHINGTON : 2005
_____________________________________________________________________________
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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

                             MARCH 17, 2005

                                                                   Page
Enzi, Hon. Michael B., Chairman, Committee on Health, Education, 
  Labor, and Pensions, opening statement.........................     1
Sessions, Hon. Jeff, a U.S. Senator from the State of Alabama....     4
Crawford, Lester M., D.V.M., Ph.D., to be Commissioner, Food and 
  Drug Administration, U.S. Department of Health and Human 
  Services.......................................................     6
    Prepared statement...........................................     8
Harkin, Tom, a U.S. Senator from the State of Iowa, prepared 
  statement......................................................    28

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Clinton, Hon. Hillary Rodham, a U.S. Senator from the State 
      of New York, prepared statement............................    37
    Jeffords, Hon. James M., a U.S. Senator from the State of 
      Vermont, prepared statement................................    38
    Mikulski, Hon. Barbara A., a U.S. Senator from the State of 
      Maryland, prepared statement...............................    38
    Letters of concern from various organizations................    39
    Letters of support from various organizations................    42
    Response to questions of Senator Bingaman by Dr. Crawford....    66
    Response to questions of Senator Burr by Dr. Crawford........    73
    Response to questions of Senator Clinton by Dr. Crawford.....    77
    Response to questions of Senator Ensign by Dr. Crawford......    82
    Response to questions of Senator Frist by Dr. Crawford.......    84
    Response to questions of Senator Jeffords by Dr. Crawford....    90
    Response to questions of Senator Roberts by Dr. Crawford.....    95
    Response to questions of Senator Gregg by Dr. Crawford.......    97
    Response to questions of Senator Harkin by Dr. Crawford......   103
    Response to questions of Senator Hatch by Dr. Crawford.......   107
    Response to questions of Senator Isakson by Dr. Crawford.....   112
    Response to questions of Senator Dodd by Dr. Crawford........   112
    Response to questions of Senators Kennedy/Mikulski by Dr. 
      Crawford...................................................   124
    Response to questions of Senator Kennedy by Dr. Crawford.....   128
    Response to questions of Senator Enzi by Dr. Crawford........   137

                                 (iii)

  

 
                    NOMINATION OF LESTER M. CRAWFORD

                              ----------                              


                        THURSDAY, MARCH 17, 2005

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 9:34 a.m., in 
room 430, Dirksen Senate Office Building, Senator Enzi, 
chairman of the committee, presiding.
    Present: Senators Enzi, Isakson, DeWine, Ensign, Hatch, 
Sessions, Roberts, Kennedy, Dodd, Harkin, Mikulski, Jeffords, 
Bingaman, Murray, and Clinton.

                   Opening Statement of Senator Enzi

    The Chairman. Good morning, and welcome to the confirmation 
hearing for Dr. Lester M. Crawford to be the Commissioner of 
the Food and Drug Administration.
    Recently when we met, it became obvious our shared 
commitment to protect and advance America's health. Clearly, we 
have a lot of work to do together.
    Dr. Crawford, the FDA is no stranger to you. In fact, over 
the last 30 years, you have been at the FDA four times, twice 
serving at the helm of the agency already. Next year will mark 
the 100th anniversary of the landmark legislation that ushered 
the FDA into the modern era. This is truly a historical 
milestone and a dramatic time for you to take up the reins of 
the agency.
    Back then, 100 years ago, there was a controversy--similar 
to today's drug controversy--that spurred the FDA's dramatic 
growth from a chemist at the Department of Agriculture to the 
full-fledged agency it is today. Back then, it was a crisis in 
food safety. Today, it is a concern with drug safety. The FDA 
weathered the previous storm. It will handle this one, too, 
with the same kind of talent, diligence, and hard work that 
solved the previous one.
    You will face some tough questions today, but I want to let 
you know that we will be asking these questions so that we can 
be sure the man chosen by President Bush to head the FDA at 
this critical juncture in its history is up to the task.
    The FDA has a very broad and critical mission in protecting 
the public health. You will be in charge of an agency that 
regulates $1 trillion worth of products a year. The FDA ensures 
the safety and effectiveness of all drugs, 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 will 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.
    The FDA has been without a confirmed Commissioner for over 
a year. You have been picking up the reins during that time and 
pulling it through.
    Earlier this year, 17 members of this committee sent a 
letter to the President urging him to nominate a Commissioner 
to provide the agency with greater clarity and certainty in its 
mission to protect our food and drug supplies. By having you 
before us today, it is clear that the President is committed to 
restoring the FDA to its fully mandated authority and we 
appreciate the promptness with which your nomination followed 
our letter.
    One of Congress's most important responsibilities is 
oversight. As Chairman, I have already held bipartisan hearings 
on drug safety and drug importation and I plan to continue to 
focus on these and other important areas.
    Dr. Crawford, you are as committed to government 
accountability and responsibility as I am, so I know you will 
welcome our participation in the process.
    In recent months, the FDA and its system for approving 
drugs and ensuring their safety have been on the front pages of 
our newspapers--quite often lately. The role of pharmaceuticals 
in health care has never been as vital to our health as it is 
today. That is why people need to be reassured that they can 
trust the FDA. Our bipartisan hearings to review the FDA's drug 
approval and postmarketing surveillance system examined the 
recent controversies and reviewed some options for 
strengthening our drug safety system. I trust you share our 
concerns and that you will continue to work with us to evaluate 
and eventually implement the necessary reforms to the system.
    We also need to look at last year's flu vaccine shortage 
and what steps we need to take to prevent this from happening 
again. Both the FDA and the Centers for Disease Control and 
Prevention have been criticized. I intend for this committee to 
review what happened and to determine how we, as legislators, 
should respond. One thing we must do, however, is attract 
companies back into the vaccine business. Relying on one or two 
companies to produce some of the most critical vaccines is a 
prescription for public health disaster. I would welcome your 
thoughts on how we can rebuild our domestic vaccine industry.
    With respect to food safety, I represent a State that has 
substantial agricultural interests. Issues of food safety and 
food labeling are critically important to me and my 
constituents. The FDA is responsible for the safety of a 
variety of our food products and I look forward to hearing from 
you what the agency plans to do to continue protecting the 
American food supply from outside threats.
    It will fall upon you to build on your record on behalf of 
President Bush, and I am confident that the President has 
chosen wisely in nominating you to be the Commissioner of the 
FDA. I look forward to working with you, with Senator Kennedy, 
and with the other members of the committee to protect and 
promote the public health and to maintain the FDA's status as 
one of the strongest regulatory agencies in the world.
    We all know the FDA has a storied past that made it the 
gold standard of the world. In previous hearings, we heard from 
members of your staff who spoke with pride of that designation. 
Recent events have called into question that standard in the 
eyes of some of the people in the public. I have no doubt that 
with the right leadership in place, the FDA will again be the 
gold standard and our regulatory process the envy of the world.
    I look forward to hearing your testimony today. I welcome 
your wife, Kathy, to the hearing, and I would turn the floor 
over to Senator Kennedy on this great Irish day.
    Senator Kennedy. You can keep going, St. Patrick's Day--
[Laughter.]
    Thank you very much, Mr. Chairman. I want to say how much 
we appreciate your calling the hearing this morning on the 
nomination of Lester Crawford to be the Commissioner of the 
Food and Drug Administration and I welcome Dr. Crawford and I 
look forward to hearing about his plans for leading the agency 
in the coming years and I join Senator Enzi in welcoming Mrs. 
Crawford, as well.
    Effective leadership of FDA is essential to protect the 
health of all Americans, and friends and colleagues speak 
highly of Dr. Crawford's dedication and commitment to public 
service. But our committee has a special responsibility to make 
a careful evaluation of the qualifications of any nominee for 
this critical position.
    As Acting Commissioner, Dr. Crawford has led FDA during 
troubled times. Serious side effects were belatedly discovered 
for several major drugs already on the market, raising alarming 
questions about the adequacy of FDA's review. And there have 
been significant failures by FDA to disclose and manage 
conflicts of interest on scientific advisory panels. Over half 
of the Nation's flu vaccine was lost to contamination. And 
disturbing allegations have been raised that FDA has prevented 
open scientific discussion of important drug safety issues, has 
disregarded science that conflicts with ideology, and has 
retaliated against whistleblowers. And just today, the New 
England Journal of Medicine published an article stating that 
at FDA, there is an atmosphere that stifles debate and 
discourages some employees from expressing scientific concerns 
about drugs.
    It is essential to address these serious issues and for Dr. 
Crawford to present a clear plan to restore the Nation's trust 
in the ability of FDA to do its job. FDA, as our chairman has 
pointed out, oversees about a quarter of all products purchased 
by American consumers. Whether FDA does its job effectively can 
mean the difference between whether the infant formula you feed 
your child is safe or not, or whether the prescription drug you 
take does more harm than good.
    Doubts have risen about the agency's effectiveness in the 
wake of Merck's withdrawal of its pain-killing drug Vioxx from 
the market because of estimates that tens of thousands of 
patients may have suffered heart attack or stroke because of 
it.
    And last October, we learned that half of last year's flu 
vaccine was lost because of poor manufacturing conditions at a 
plant in Britain, and we were surprised to learn that FDA had 
not actively inspected the plant and then compounded the 
problem by doing too little after it learned that some of the 
vaccine had been contaminated.
    Last year, the agency declined to approve emergency 
contraception for over-the-counter use after a nearly unanimous 
advisory group recommended such approval, and the agency is now 
2 months late in ruling on a revised request for such use.
    The agency has also prohibited or discouraged some of its 
medical officials from presenting their studies at advisory 
committee hearings, at scientific meetings, or in respected 
journals. The agency also chose not to disclose in advance 
potential conflicts of interest by members of the advisory 
committee who reconsidered Vioxx and related drugs a few weeks 
ago and approved their continuation on the market.
    As the President's nominee, Dr. Crawford owes this 
committee, the Senate, and the American people his assurance 
that if the committee confirms him as Commissioner, there will 
not be more of the same. The stakes could not be higher. No 
patient who takes a pill should have to worry whether the drug 
inside is safe or whether the decisions to approve the drug 
were based on politics or profits instead of science. It is a 
tragedy that the FDA's recent failures have caused millions of 
patients to ask those questions now. It would be far worse if 
we don't insist on clear answers.
    We know that Dr. Crawford is here to answer these questions 
and other questions of the committee and I look forward to his 
response and I thank you very much, Mr. Chairman, for holding 
these hearings.
    The Chairman. Thank you, Senator Kennedy.
    I would mention that we are doing a little different 
seating arrangement on this side. Since we allow people to ask 
questions in the order in which they arrive after the gavel has 
sounded, we are just moving everybody up here in that order on 
this side.
    This morning, we have the Senator from Alabama to do an 
introduction, Senator Sessions.

STATEMENT OF HON. JEFF SESSIONS, A U.S. SENATOR FROM THE STATE 
                           OF ALABAMA

    Senator Sessions. Thank you, Mr. Chairman. It is an honor 
to be before you as chairman of this committee. We came to the 
Senate together and you have moved up more rapidly than most of 
us to chair this august body and I couldn't be more proud of 
you. You have the right instincts for public service, the 
professional commitment to doing things right, and the work 
ethic that is necessary to deal with the complex issues that 
come before us.
    Mr. Chairman, it is my honor and privilege to introduce my 
fellow Alabamian, Dr. Lester Crawford, to this committee. I am 
addressing the committee today not only because Dr. Crawford 
hails from Demopolis, AL, which was the original vine and olive 
colony founded by a group of Napoleon losers who had to flee 
France and established on the river there in Alabama the vine 
and olive colony. I am not sure it succeeded as a vine and 
olive colony, but it has succeeded as a wonderful community 
that sets a good example in that whole region of the State.
    He received his Doctorate of Veterinary Medicine at Auburn 
University, one of the Nation's great universities. But I am 
also here because this nominee is a recognized scientist, 
scholar, and academic, a public servant of unassailable 
personal integrity who brings with him the perspective of 
personal experience in academia, government, private practice, 
and industry. Most importantly, he combines openness, good 
humor, and a commitment to the common good.
    Dr. Crawford brings to the agency expertise in a remarkable 
range of relevant fields. We frequently forget that in addition 
to authority to regulate drugs, the FDA is charged with 
overseeing foods, biological products, medical devices, animal 
feed and drugs, among other responsibilities. I don't know that 
you could find another candidate with his degree of expertise, 
not only in pharmacology and issues related to drugs and 
biologics, but also food safety, and in the era of ``mad cow'' 
disease and avian flu, the fields of agriculture and veterinary 
medicines, which are proving ever more crucial to the public 
health. In fact, he has a particular expertise in mad cow 
disease.
    At a time when rising to the substantial challenges will 
require innovation and interdisciplinary thinking, a man who 
brings this quintessentially interdisciplinary training and 
experience could not be more appropriate.
    In addition to his substantial academic and professional 
achievements, Dr. Crawford has demonstrated a tremendous 
dedication to public service during more than 13 years at the 
Food and Drug Administration and the United States Department 
of Agriculture. Colleagues who have worked with Dr. Crawford 
over the years unfailingly note his exemplary personal 
qualities, as well. Integrity, dedication, and enthusiasm have 
been hallmarks throughout his training and career.
    Dr. Timothy Boosinger, Dean of Auburn University's 
nationally recognized College of Veterinary Medicine, called 
yesterday to share his own and Auburn's unreserved endorsement 
of Dr. Crawford as a scientist and administrator, a leader, and 
a man. He is really one of our most distinguished alumni. 
Auburn is proud of the contribution he is making to all our 
lives, he said.
    I think that his own advice to a recent class of veterinary 
graduates is telling. He noted that he has always tried to let 
his own life be guided by the Latin phrase, I credo, I believe. 
The point is, he explained, when you have talent, you have to 
develop it and practice it. Develop your own credo and live by 
it. And Dr. Crawford has throughout his career demonstrated not 
only remarkable talent, but a consistent dedication to honing 
and applying that talent for the public good.
    In summary, I believe that Dr. Lester Crawford is a man of 
great knowledge, talent, dedication, and integrity. As 
Commissioner, he will be even better able to bring these 
qualities to bear in the service of the safety and well-being 
of the American people. I urge you to join me in working to 
enable this superb nominee to get to his essential task as soon 
as possible.
    Thank you, Mr. Chairman. I am honored to be with Dr. 
Crawford.
    The Chairman. Thank you, Senator.
    We welcome Dr. Crawford. I would mention that the committee 
has received over 100 letters and statements of support for Dr. 
Crawford's nomination from individuals and organizations around 
the country. We received one letter with some concerns, that if 
they are not addressed at the hearing, we will ask that you 
address following the hearing. I would ask unanimous consent 
that all of those letters be entered into the record, without 
objection.
    The Chairman. Dr. Crawford, we look forward to hearing your 
testimony.

     STATEMENT OF LESTER M. CRAWFORD, D.V.M., PH.D., TO BE 
COMMISSIONER, FOOD AND DRUG ADMINISTRATION, U.S. DEPARTMENT OF 
                   HEALTH AND HUMAN SERVICES

    Dr. Crawford. Thank you very much, Mr. Chairman. First, I 
would like to introduce my wife, who is seated over here. This 
is my wife, Katherine, who is from Birmingham, Alabama, and is 
the mother of my two daughters and the grandmother of my four 
grandchildren.
    The Chairman. Welcome.
    Dr. Crawford. I would like to thank the committee for 
inviting me here today. I am honored to be here and I 
appreciate the opportunity to tell you about myself and share 
ideas for how we can strengthen and advance the Nation's public 
health.
    FDA is the Nation's principal consumer protection agency 
when it comes to food, drugs, and medical devices. The agency 
impacts the lives of all Americans every day. We ensure the 
safety and efficacy of the medicines they consume. We regulate 
80 percent of the food Americans eat. FDA regulated products 
account for approximately 20 cents out of every dollar in the 
economy. American consumers rely on FDA to protect and advance 
the Nation's public health while people around the world share 
the view that the agency upholds the gold standard in terms of 
public health protection.
    I have had the opportunity over the course of my career to 
serve four different tenures at FDA. This is the second time I 
have served as Acting Commissioner of the agency. I previously 
served as FDA Deputy Commissioner from 2002 to 2004, and as 
Director of FDA's Center for Veterinary Medicine from 1982 to 
1985. Prior to that, I held several different positions, 
including Director in the former FDA Bureau of Veterinary 
Medicine in 1970s.
    My career outside of FDA has likewise been dedicated to 
advancing public health. I served as Administrator of the Food 
Safety and Inspection Service, or FSIS, at the U.S. Department 
of Agriculture from 1987 to 1991. Prior to that, I was Chair of 
the Department of Physiology-Pharmacology at the University of 
Georgia and held the position of Associate Dean for several 
different offices at the University of Georgia's College of 
Veterinary Medicine.
    More recently, from 1997 to 2002, I was Director of the 
Center for Food and Nutrition Policy at Georgetown University 
and at Virginia Tech, where it moved in 2001. I also served as 
the Executive Director of the Association of American 
Veterinary Medical Colleges.
    I am a member of several professional and scientific 
societies. I am a member of the National Academy of Sciences 
Institute of Medicine, a Fellow of the Royal Society of 
Medicine in the United Kingdom, and a Fellow of the 
International Society of Food Science and Technology. In 1984, 
I was inducted into the French Academy of Veterinary Medicine 
and I received the Wooldridge Award, the British Veterinary 
Association's highest award, in 1991. Additionally, I have been 
an advisor to the World Health Organization of the United 
Nations.
    In terms of academic training, I received my Veterinary 
degree from Auburn, my Ph.D. in Pharmacology from the 
University of Georgia, and I have an Honorary Doctorate from 
Budapest University.
    Throughout my diverse career, I have had the unique 
opportunity to contribute to a number of groundbreaking public 
health initiatives. For example, I played major roles in the 
development of mandatory nutrition labeling and the control of 
chemical and microbiological contaminants of food. In recent 
years at FDA, I have led efforts to combat the obesity 
epidemic, counterterrorist threats through new food security 
regulations, and revitalized the regulation of biomedical and 
food industries through the development of current good 
manufacturing practices. I also played a role in designing 
FDA's Critical Path Initiative, a new cutting-edge approach to 
advancing medical innovation that seeks to bridge the so-called 
gap between bench and bedside.
    Going forward, as Commissioner of the Food and Drug 
Administration, if confirmed, I look forward to the opportunity 
to build on these initiatives to help America reach new levels 
of public health protection and innovation.
    This is a critical time for the Nation's health. We face 
exciting opportunities from new cross-cutting science and 
biomedical innovation, but at the same time, we are confronted 
with profound challenges of every shape and size--emerging 
diseases, product safety concerns, the threat of bioterrorism, 
and much more.
    Our success and the Nation's health are continually 
challenged by these emerging threats, changes in technology and 
global market forces. At the same time, FDA's responsibilities 
are growing in scope and complexity. To overcome these growing 
challenges and to truly capitalize on the boundless 
opportunities presented by modern science, we need a vision for 
the future, a vision for a 21st century FDA.
    I would like to tell you briefly about my vision for the 
future of FDA. It is one of transformation. Internally at FDA, 
we are transforming from domestic-focused, paper-based 
processes employing yesterday's technologies to global, 
electronic data-driven decisions that apply the latest science. 
And we are transforming our culture to one of transparency, 
collaboration, and cutting-edge thinking.
    We are going to tap into new technologies and new ways of 
thinking and build upon collaborations with a broad network of 
partners, public and private, U.S. and international. By 
capitalizing on 21st century innovation, information 
technology, and regulatory process innovation, we can leverage 
public investment in FDA to yield an even greater level of 
public health protection and a more efficient and predictable 
critical path to innovation. By adopting a quality systems 
approach in all our operations, we will increase productivity 
and promote better health outcomes.
    In particular, I am committed to addressing existing 
concerns regarding postmarket safety of FDA-regulated products, 
both in medical products and food, respectively. I remain 
focused on bioterrorism and on minimizing the threat of 
terrorist attacks both through heightened food security and 
through the development of new medical countermeasures.
    As we confront 21st century challenges, 21st century 
solutions are key. That is why innovation will be at the center 
of everything FDA does in the time ahead. I look forward to 
helping lead the way as we enter a new era of individualized 
medicine and electronic health.
    Finally, we need to continue to do more to empower our 
citizens with better health information about the foods they 
eat, the medicines they use, and the other health products they 
consume. Under my leadership, I will see to it that FDA 
continues to provide all Americans with the tools they need to 
make informed choices about their health so that they can live 
longer, happier, and healthy lives.
    These issues affect us all and I look forward to being part 
of the solution to these problems. Thank you, Mr. Chairman.
    The Chairman. Thank you, Dr. Crawford.
    [The prepared statement of Dr. Crawford follows:]

        Prepared Statement of Lester M. Crawford, D.V.M., Ph.D.

    Mr. Chairman and members of the committee, I am Dr. Lester M. 
Crawford, D.V.M., Ph.D., Acting Commissioner of the Food and Drug 
Administration (FDA or the Agency). I would like to thank the Committee 
for inviting me here today. I am honored to be here, and I appreciate 
the opportunity to tell you about myself and share ideas for how we can 
strengthen and advance the Nation's public health.
    FDA is the Nation's principal consumer protection agency when it 
comes to food, drugs and medical devices. The Agency impacts the lives 
of all Americans every day. We ensure the safety and efficacy of the 
medicines they consume. We regulate 80 percent of the food Americans 
eat. FDA-regulated products account for approximately 20 cents out of 
every dollar in the economy. American consumers rely on FDA to protect 
and advance the Nation's public health while people around the world 
share the view that the Agency upholds the gold standard in terms of 
public health protection.
    I have had the extraordinary opportunity over the course of my 
career to serve four different tenures at FDA. This is the second time 
I have served as Acting Commissioner of the Agency. I previously served 
as FDA Deputy Commissioner from 2002 to 2004 and as Director of FDA's 
Center for Veterinary Medicine from 1982 to 1985. Prior to that, I held 
several different positions --including Director--in the former FDA 
Bureau of Veterinary Medicine in the 1970s.
    My career outside of FDA has likewise been dedicated to advancing 
the public health. I served as Administrator of the Food Safety and 
Inspection Service at the U.S. Department of Agriculture from 1987 to 
1991. Prior to that, I was Chair of the Department of Physiology-
Pharmacology at the University of Georgia, and held the position of 
Associate Dean for several different offices at the University of 
Georgia College of Veterinary Medicine.
    More recently, from 1997-2002, I was Director of the Center for 
Food and Nutrition Policy at Georgetown University and at Virginia 
Tech, where it moved in 2001. I also served as Executive Director of 
the Association of American Veterinary Medical Colleges from 1993 to 
1997.
    I am a member of various professional societies. I am a Member of 
the National Academy of Sciences Institute of Medicine, a Fellow of the 
Royal Society of Medicine (UK), and a Fellow of the International 
Society of Food Science and Technology. In 1984, I was inducted into 
the French Academy of Veterinary Medicine. In 1991, I received the 
Wooldridge Award, the British Veterinary Associations highest award. 
Additionally, I have been an advisor to the World Health Organization 
of the United Nations for much of my career.
    In terms of academic training, I received my Doctor of Veterinary 
Medicine (D.V.M.) from Auburn University, my Ph.D. in pharmacology from 
the University of Georgia, and an Honorary Doctorate (M.D.V.) from 
Budapest University.
    Throughout my diverse career, I have had the unique opportunity to 
contribute to a number of groundbreaking public health initiatives. For 
example, I played major roles in the development of mandatory nutrition 
labeling and the control of chemical and microbiological contaminants 
of food. In recent years at FDA, I have led efforts to combat the 
obesity epidemic, counter terrorist threats through new food security 
regulations, and revitalize the regulation of biomedical and food 
industries through the development of current good manufacturing 
practices. I also played a key role in designing FDA's ``Critical 
Path'' initiative, a new cutting-edge approach to advancing medical 
innovation that seeks to bridge the so-called gap between bench and 
bedside.
    Going forward, as Commissioner of the Food and Drug Administration, 
if confirmed, I look forward to the opportunity to build on these 
initiatives and help America reach new levels of public health 
protection and innovation.
    This is a critical time for the Nation's health. We face exciting 
opportunities from new cross-cutting science and biomedical innovation, 
but at the same time we are confronted with profound challenges of 
every shape and size--emerging diseases, product safety concerns, the 
threat of bioterrorism, and much, much more.
    Our success--and the Nation's health--are continually challenged by 
these emerging threats, changes in technology, and global market 
forces. At the same time, FDA's responsibilities are growing in scope 
and complexity. To overcome these growing challenges, and to truly 
capitalize on the boundless opportunities presented by modern science, 
we need a vision for the future--a vision for a 21st century FDA.
    I would like to tell you briefly about my vision for FDA and my 
priorities for the time ahead. The FDA of today understands, perhaps 
better than ever, the need for both protecting and advancing the public 
health, and we are focusing on new and better ways to perform our core 
mission.
    My vision for the future of FDA is one of transformation. 
Internally at FDA, we're transforming from domestic-focused, paper-
based processes, employing yesterday's technologies, to global, 
electronic-data driven decisions that apply the latest science. And 
we're transforming our culture to one of transparency, collaboration, 
and cutting-edge thinking.
    We're going to tap into new technologies and new ways of thinking, 
and build upon collaborations with a broad network of partners--public 
and private, U.S. and international. By capitalizing on 21st century 
information technology and regulatory process innovation, we can 
leverage public investment in FDA to yield an even greater level of 
public health protection, and a more efficient and predictable critical 
path to innovation. By adopting a quality systems approach in all of 
our operations, we will increase productivity and promote better health 
outcomes.
    In particular, I am committed to addressing existing concerns 
regarding post-market safety of FDA-regulated products, both in medical 
products and food, respectively. I remain focused on bioterrorism and 
on minimizing the threat of terrorist attack both through heightened 
food security and through the development of new medical 
countermeasures. As we confront 21st century challenges, 21st century 
solutions are key; that is why ``innovation'' will be at the center of 
everything FDA does in the time ahead. I look forward to helping lead 
the way as we enter a new era of individualized medicine and e-health. 
Finally, we need to continue to do more to empower our citizens with 
better health information about the foods they eat, the medicines they 
use, and the other health products they consume. Under my leadership, I 
will see to it that FDA continues to provide all Americans with the 
tools they need to make informed choices about their health, so that 
they can live longer, healthier, and happier lives.
    These issues impact us all. I know that the members of this 
committee are genuinely focused on doing all you can to address these 
public health challenges and capitalize on our public health 
opportunities. I am truly honored to have worked with you in the past 
to advance FDA's public health mission, and I look forward to 
continuing to work with each and every one of you to better protect and 
advance the public health in the time ahead. Thank you.

    The Chairman. We will now have a series of 5-minute rounds 
to give everybody a chance to ask some questions. We appreciate 
your being here today. We appreciate the turnout of the members 
of the committee. This is the first round of the NCAA 
tournament, a great Irish day, and also the hearings on the 
House side on baseball steroids, which has some relationship to 
this. [Laughter.]
    I have 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 a hasty or unwise decision. I assume 
you disagree with this perspective, so would you please explain 
to the committee the importance of PDUFA and the way you will 
ensure, as Commissioner, that there will continue to be no 
compromise on FDA's standards in reviewing products covered by 
user fees?
    Dr. Crawford. Yes. Thank you, sir. As you know, the 
Prescription Drug User Fee Act was enacted in the early 1990s 
and it is reenacted as it sunsets every 5 years. The two times 
that it has been up for review, changes have been made and so 
we anticipate that, based on experience, probably we will be 
entertaining some new proposals.
    Virtually every country in the world has a user fee system. 
The question is how they utilize that user fee system.
    We think the goal letter that we develop between the 
industry that we regulate and FDA gives us an indication of 
what is coming down the pike, what new kinds of drugs and drug 
classes are coming and what the load will be upon FDA. And so 
we are--and as you know, that goal letter is ratified by the 
Congress as we finish it.
    The second part is is that because of the Prescription Drug 
User Fee Act, we get funding to increase our staff and to be 
more efficient in the drug approval process. That has worked 
well for FDA under the years of PDUFA. One particular year in 
the mid-1990s, we approved more drugs than any other year in 
history, and I think we are doing a better job of reviewing 
them. Some drugs are not approved. Some need more work. But 
what the companies pay for is the review itself, and I think on 
balance that it is working well.
    The Chairman. Thank you. Most of the questions today will 
shift gears pretty fast so that we can cover a wide range of 
things.
    The GAO report released earlier this week indicates serious 
breaches in the FDA's oversight of the 1997 ban on the feeding 
of meat and bone meal from livestock to other livestock. This 
ban is intended to guard against the spread of mad cow disease 
in the United States. This report follows up on a 2002 report 
that also found gaps in the FDA's enforcement of this 
regulation. GAO also noted that the FDA may not even have 
enough information to assess compliance rates. What are you 
planning to do to improve the enforcement and compliance with 
this and other food safety regulations?
    Dr. Crawford. We are in the process of analyzing the GAO 
report. As you know, we worked with them through the 2-year 
process that they employed to come up with the report. There 
are some suggestions in there that we think are very good and 
we intend to implement them.
    The report does say that we made improvements since the 
last report, and we appreciate that. There are more 
improvements to be made. We now know that there are about a 
million people in the United States that feed one or more 
cattle. We have to adopt a program that both educates them 
about the use of the prohibited material in feed and also 
encourages them to be very careful about what they mix in their 
cattle feed. We now know that that is a menace FDA has to stay 
on top of, so we appreciate the report and we will adopt the 
recommendation.
    The Chairman. Thank you. I do want to also discuss the 
FDA's action on the abortion drug RU-486. I don't believe that 
the FDA should spend time and resources reviewing products that 
are intended solely to end life. I am also very concerned that 
a number of deaths have been linked to RU-486.
    In August 2002, a number of organizations sent a citizen 
petition to the FDA asking that the FDA revoke its approval of 
RU-486. The petition argues that FDA violated drug law and its 
own regulations and standards in approving the RU-486 for 
medical abortion. Now, these are pretty serious allegations, 
and 18 months later, the FDA has yet to give a final response. 
Can you assure me that the FDA will respond to this petition 
sooner rather than later?
    Dr. Crawford. As you know, the issues raised in the 
petition are very complex, indeed. We are still working through 
those. We are in the final stages of that. I can assure you we 
will respond to the petition. I can't give an exact date, but 
we are in the final stages of it.
    The Chairman. Thank you. My time has almost expired.
    Senator Kennedy.
    Senator Kennedy. Thank you, Mr. Chairman.
    As we all know, the FDA should be the gold standard for 
objective science and unwavering commitment to the public 
health. On Plan B, emergency contraception there are serious 
concerns the FDA was guided more by ideology than by sound 
science.
    In your testimony on March 11, 2004, before the House 
Appropriations Committee, you said that the Scientific Advisory 
Committee on Plan B was all over the board, but that is not 
really the case, I don't think. Isn't it the reality that the 
Advisory Board voted 24 to three to approve OTC status for Plan 
B?
    Dr. Crawford. That is correct.
    Senator Kennedy. Yet the FDA rejected the recommendation?
    Dr. Crawford. Actually, what we did was we evaluated the 
then-application and we could not approve it. But the company 
has now submitted a second one. We also have, just in the last 
few weeks, been sued on the original decision, so we are 
evaluating what the impact of that is and we are also 
considering the application that is before the agency at the 
present time. We are continuing to evaluate both as we go 
forward.
    Senator Kennedy. Well, in response to the question from 
Representative Farr at the March 2004 hearing, you said the 
FDA's deadline for acting on the resubmitted application was 
January 22 of this year. Is it usual for FDA to miss the 
deadlines by months, and who is responsible for the hold-up?
    Dr. Crawford. We usually don't miss the deadlines. In this 
case, it is very complex. We have a kind of application that 
the company is seeking which we have never approved before, and 
so it is taking a little longer than it would have in the past.
    Senator Kennedy. Well, do we want to leave it there? The 
problems, as you indicated in your earlier answer were the 
difficulty in the application and then the review of the legal 
issues and the suit, and you are unable to indicate to us when 
you are going to act?
    Dr. Crawford. I can't give a date, but it won't be very 
much longer.
    Senator Kennedy. Well, are we talking days? Are we talking 
weeks?
    Dr. Crawford. I wouldn't want to say days, Senator. I would 
say weeks.
    Senator Kennedy. I want to move on. On the drug safety 
issue, we have talked about this and you have commented on it, 
so it is an old issue, but I want to get answers today. Last 
year, Merck withdrew Vioxx from the market because the drug 
doubled the risk of a heart attack or stroke, but that was more 
than 5 years after the FDA approved the drug and after 20 
million Americans had used it. As a result, tens of thousands 
of Americans needlessly suffered heart attack or stroke and 
many died. It is the single largest drug safety failure the 
Nation has ever faced. It simply should not take that long, nor 
should so many people use a drug before such a significant 
safety risk is discovered.
    If a similar disaster had happened through fire or flood or 
terrorism, we would be moving heaven and earth to make sure 
that such a catastrophe never happened again, yet the FDA has 
so far recommended only minimal adjustments to its procedures.
    In our hearings on drug safety earlier this year, the FDA 
witness, Dr. Kweder, admitted that there had been lapses in how 
the FDA handled this tragedy. Do you agree that there were 
lapses, that mistakes were made?
    Dr. Crawford. When these drugs entered the marketplace, as 
you mentioned, in the late 1990s and early parts of this 
decade, they held great promise. As they were used over time, 
and particularly in two NIH trials at higher doses for longer 
durations of therapy, some problems did show up. They could not 
have been anticipated, we do not believe, until that time. We 
had ordered earlier warnings and we were monitoring the drug 
very carefully, but it was only the very large, very long, 
high-dosage trials at NIH that revealed the problem.
    Senator Kennedy. ``They can't be anticipated'' is rather an 
ominous response when you have put at risk so many people on a 
prescription drug. I want to know whether this is going to be 
business as usual out at FDA or whether you are setting up some 
kind of system that will be able to flag these issues. I mean, 
we have just gone through one of the great, great, lapses for 
whatever reasons. I am not sure the American people are going 
to be satisfied that there are a number of situations that 
can't be anticipated and, therefore, that is the way it is 
going to be. That is not the answer that the American people, 
or certainly I, would like to hear.
    We heard Dr. Kweder indicate that there had been lapses, 
and I think most of us believe there had been, and the real 
issue is what the agency is going to do to deal with those 
lapses. I think, first of all, there has to be a recognition 
that there is a serious problem, and if there is, what are you 
going to do about the problem, is what I would like to direct 
your attention to.
    Dr. Crawford. To make sure there aren't lapses in the 
future, what we are going to do is like a multipronged 
approach. We are instituting a Drug Safety Board which will, 
when we get these signals, such as we did on Vioxx and some of 
those other kinds of drugs, we will put it in to the board. 
They will prescribe for us what we should do in order to find 
out whether or not this is a false signal, that is a false 
alarm, or whether it is something real. We will announce that 
at that point, not wait, and the Drug Safety Board's 
deliberations will be public, and we will also advise the 
Nation's physicians as well as consumers, that is patients, of 
what we have found at that point and what we are doing in order 
to get to the bottom of the matter. Then we will establish a 
drug watch so that we will list that drug so that it is 
accessible on our websites and elsewhere to the American people 
and we will have a progress report as we go forward.
    And then the other things we have asked the National 
Academy of Sciences Institute of Medicine to evaluate and 
affect the FDA culture. We want to figure out a system that is 
more transparent for decision making. We also want to 
effectuate a system so that minority opinions are involved. It 
is true that in the culture and milieu of FDA, there is a lot 
of give and take on these decisions based on the science, but 
we want to honor that and also to record what the minority 
opinions are.
    Senator Kennedy. My time is up, Mr. Chairman. I would just 
ask about that recent advisory board, you know, there were 
questions about the conflicts of interest. Are you committed 
when you publish the members of the board to also indicate the 
background of each?
    Dr. Crawford. We will. We are going to change those 
procedures. There is disclosure, but there should be easier 
disclosure for the press and others to get access to. We are 
going to change that entirely.
    Senator Kennedy. My time is up. Thank you, Mr. Chairman.
    The Chairman. Thank you. Senator Sessions.
    Senator Sessions. Thank you, Chairman Enzi.
    You have a difficult challenge. Delaying an effective drug 
from coming on the market because of concerns that prove to be 
insubstantial can cost hundreds, maybe thousands, of lives. And 
likewise, if a drug is approved too rapidly, it turns out to 
have side effects unexpected, it can also cost lives. So I know 
it is a very challenging position for you. Sometimes, the only 
way we can know for certain is to see a drug actually operate 
over a period of years and the costs then are weighed against 
the benefits and you can make the best decision insofar as 
possible.
    But your challenge is to identify in advance what will 
work, what will not work, and make those decisions that are 
best. I think your integrity, experience, and background will 
lead you to make good decisions, and that is what we expect and 
that is all we can ask. We can't expect perfection.
    Dr. Crawford, I have an interest in generics. I asked you 
about it as we talked yesterday, about let us not create a 
situation in which generics are delayed too long because that 
keeps the price higher for the public. A generic drug will come 
in at a lower cost, normally. You provided some information on 
that. I would like to get your philosophy about generics and 
what we can do to bring those on at the appropriate time.
    Dr. Crawford. Three years ago, when we began to address 
this problem, we found that generics were taking about 19 
months to be approved or disapproved, that is, to be reviewed. 
We have now been able to shorten that down to 12 months, and 
what that has resulted in is the approval of a new generic drug 
in America every day. We are now trending toward somewhere 
between 400 and 500 generic drug approvals for this coming 
year.
    Generic drugs cost less, and not only that, they cost less 
in America than they do in other countries around the world. 
The key thing, though, I think, in terms of our efforts with 
generics is that now, about half of all prescriptions are for 
generic drugs. Generic drugs, we are pledged to make sure are 
as safe and as effective and as potent as any other drug that 
is on the market, including the prescription counterparts in 
cases.
    So we are very pleased with this. We continue to work with 
generic drugs in order to get them on the market and also to 
have them be an appreciable percentage of the prescription 
drugs that are used by the American people.
    Senator Sessions. I think that is good progress, and I 
salute you for it. I think we ought not to have unnecessary 
delays in the time between an expiration of a drug 
manufacturer's patent and the approval of generic products. 
That just costs the purchasers of those drugs extra money, and 
I salute you for the progress that you made there.
    Would you share with us any thoughts you may have 
concerning the problem that lawsuits, liability questions, have 
with regard to establishing effective vaccines' availability in 
this country? It is something that seems to me to be rather 
significant and we need to deal with it or we may never get the 
vaccine problem settled.
    Dr. Crawford. Well, as you know, we have had a number of 
hearings on the subject, starting back in 2002. The main focus 
of that hearing in Congress was to expose the fact that the 
vaccine industry was extremely fragile. We predicted then that 
we would have only one supplier by this past flu season, this 
flu season that we are in, and there was a great deal of 
discussion about how to incentivize and indemnify the industry. 
The result of that hearing was some extra funding in order to 
develop alternative vaccine production methods which would make 
for a more viable industry, but not much was done with respect 
to liability.
    That is not an area that I testified on, not an area that I 
am expert in. It was, I believe, the report of that hearing and 
also two of these hearings that we have had recently did 
explore that, but I am not sure if conclusions were made.
    Senator Sessions. I think it is a factor in the declining 
number of suppliers, and I think it is something we are going 
to have to deal with.
    Thank you, Mr. Chairman.
    The Chairman. Thank you. The next Senator is Senator 
Clinton.
    Senator Clinton. Thank you, Mr. Chairman. If I could, I 
would like to submit additional questions for the record.
    The Chairman. Yes. The record will be held open so that 
people can submit questions.
    Senator Clinton. Thank you very much, and welcome, Dr. 
Crawford. There are a number of issues that are of concern to 
me, ranging from the flu vaccine, which was mentioned, the 
eventual decision on the COX-2 issue, and others which I will 
submit, but I want to zero in on this emergency contraception 
issue.
    Back on July 8, I, along with six of my colleagues on this 
committee, sent a letter asking that you and Dr. Galson meet 
with us to discuss this matter. My staff followed up 
repeatedly, but we were never able to establish a meeting time.
    So my first question, very simply, is can I have your 
assurance that in the future, you will make yourself available 
to meet with members of this committee to discuss matters that 
are of great importance to us?
    Dr. Crawford. Absolutely. I think that might have turned 
into a briefing, but I apologize for not meeting with you 
personally and that will not happen again.
    Senator Clinton. Thank you. Now, Dr. Crawford, I would like 
to ask a simple, straightforward question that may help to 
illuminate a great deal of the concern and confusion in the 
press and elsewhere about what exactly emergency contraception 
is and what it isn't.
    The label for Plan B says the method is indicated, and I 
quote, ``for the prevention of pregnancy after unprotected sex 
if a contraceptive fails or if no contraception was used,'' 
unquote. Would you clarify for the committee that emergency 
contraception is a method for prevention of pregnancy, not the 
termination of pregnancy?
    Dr. Crawford. I can certainly clarify. I may need to confer 
with the experts in the FDA about exactly what the physiology 
of it is, but the label will say prevention.
    Senator Clinton. Well, in fact, as the FDA's own questions 
and answers on Plan B released in May 2004 say, and I quote 
again, ``Plan B works like other birth control pills to prevent 
pregnancy. Plan B acts primarily by stopping ovulation. It may 
prevent fertilization. If fertilization occurs, Plan B may 
prevent a fertilized egg from attaching to the womb.''
    So just to be clear, are you confirming that FDA, in its 
own printed information which I have a copy of here, in 
response to questions that people legitimately have from both 
the public and other points of view, that it says explicitly 
what is emergency contraception, and I quote, ``emergency 
contraception is a method of preventing pregnancy.'' That is 
the FDA position, is that correct, Dr. Crawford?
    Dr. Crawford. We haven't finally finished the label, but 
that is what is before us at the present time and we have not 
at this present time finally decided. We have no real dispute 
with the label at this point. But as you know, the product is 
not approved and so I can't say how it will finally turn out.
    If I may answer that for the record, I can give some of the 
scientific interpretations of what happens at conceptus and 
whether or not--the term of art here is called nidation, 
whether or not the conceptus attaches to the wall of the 
uterus. But I would like, if I may, to consult with the experts 
in the Center and----
    Senator Clinton. Well, in fact, though, Dr. Crawford, the 
experts at FDA have made their recommendation, that emergency 
contraception should be available and it should be available 
over the counter and that the studies on it and the assessment 
of it confirm that it is as described, emergency contraception, 
a method of preventing pregnancy.
    And what has disturbed many of us is what appears to be 
political interference in a scientific process. For those of us 
who believe that prevention is the key for decreasing the 
number of abortions, it is somewhat disturbing to see the 
injection of political concerns. I think it is perfectly 
appropriate for citizens to petition, to send letters, to ask 
questions, but there must be a scientific basis for these 
decisions.
    And insofar as we are aware, the experts at the FDA and the 
outside experts have voted overwhelmingly in favor of making 
this drug available. More than 70 organizations, including the 
American Academy of Physicians, Family Physicians, 
Obstetricians and Gynecologists, the American Medical 
Association submitted testimony. If we are going to return the 
FDA to the gold standard, then it is perfectly appropriate for 
people to say, don't use this or that it is somehow 
inappropriate and to be in any way involved in the public 
debate over it, but not to politicize the science, and that is 
what I want your assurance of, Dr. Crawford.
    It is deeply disturbing to me. We rely on the FDA for 
everything we take. I am hopeful that we will reverse what 
appears to be a dangerous slide into political opinion as 
opposed to scientific evidence.
    Dr. Crawford. Well, I can assure you that this decision 
will not be based on politics. It will be based on science. It 
is delayed, and I think that is the way to look at it, because 
it is a very complex approval process that the company has 
proposed. And so we are working through the legality of that. 
But I am not aware of political pressure to make the decision 
one way or the other.
    You are absolutely correct about the Advisory Committee, so 
I think the science part is generally done. We are just now 
down to how the label will look. This is going to be a very 
unusual sort of approval and it is delayed and I apologize for 
that, but----
    Senator Clinton. When might we expect the approval to be 
forthcoming?
    Dr. Crawford. I can't say for sure because we--Mike could 
have predicted it, but the lawsuit has complicated it a little 
bit. We have to work through that. It is for the prior 
approval, and what effect it has on it, I can't really say at 
this time. But I don't think it is going to be a long delay.
    Senator Clinton. Thank you. Thank you, Mr. Chairman.
    The Chairman. Thank you. Senator DeWine.
    Senator DeWine. Thank you, Mr. Chairman.
    Dr. Crawford, like drugs, for too long, we assumed that 
children were small adults and could just take reduced doses of 
adult products. We are finding that many essential medical 
devices used extensively by pediatricians are really 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 to even 10 years behind those for adults. That 
is really not acceptable. Could you tell us, under your 
leadership, what the Food and Drug Administration will be able 
to do to ensure that devices used in children are designed and 
sized for their use?
    Dr. Crawford. Thank you for the question. When I came on as 
acting in 2002, we had just gotten the Best Pharmaceuticals for 
Children Act, as you know, and it was my privilege to implement 
that and it has gone forward. After that time, we had the 
codification of our regulation on labeling for pediatric uses 
of existing drugs. We had a regulation that was overturned in 
the courts. We pursued that. The Congress codified the 
regulation, thereby making it legal.
    And what has happened since that time is for those drugs 
that are on patent, the ones that have exclusivity, we have 
gotten a lot of activity and there have been multiple changes 
in the labeling, and also as the products go on the market, 
more and more, they do show pediatric indications. Not all 
drugs can be used in children, but many can and many more are 
as a result of these two pieces of legislation.
    The other thing is those drugs that are off-patent, 
however, we haven't made as much progress with because we 
actually need the National Institutes of Health to do some work 
on those products in order to make sure they are okay for 
pediatric uses. As you may know, Secretary Thompson and the 
past administration did order some funding for this particular 
project and it has yielded some results, but not enough at this 
point.
    Senator DeWine. Doctor, my question--I appreciate that. My 
question was about devices, though, which is a new area. What 
can you do in that area?
    Dr. Crawford. We are going to have the same people who work 
in my office that have spearheaded this effort with the drugs 
do it also with the devices. They have essentially the same 
kind of scheme, the same authorities in order to get it done, 
and I expect--you have my assurance that I am fully committed 
to that project. I will make the resources available for it, 
and I expect the same kind of results, and we will hold them to 
that expectation.
    Senator DeWine. What is your timing on that?
    Dr. Crawford. The timing on setting up the office is within 
this fiscal year, so it should be done within a month or two.
    Senator DeWine. Setting up the office?
    Dr. Crawford. The office is already set up, basically. We 
have to recharge it----
    Senator DeWine. What will be done within a couple months?
    Dr. Crawford. The office will be fully charged to do 
devices evaluation, the same as it did in drugs.
    Senator DeWine. Let me go on to another question. 
Currently, few programs specifically target the treatment of 
children with HIV/AIDS in developing countries. A primary 
reason, of course, is the lack of appropriate pharmaceuticals 
for use in children. We all know that children do need special 
drugs. With 2.5 million children infected with HIV/AIDS around 
the world, it is essential that we have appropriate medications 
to treat them.
    Let me ask you, Doctor, how do you plan to ensure that HIV/
AIDS drugs, both generic and brand name, approved by the FDA 
expedited process also include pediatric formulations as well 
as important dosing information needed for treating the 
different age groups?
    Dr. Crawford. We are actually using these same authorities 
that I mentioned in the drug area. As you know, the President 
has made $15 billion available over a period of time for the 
use of these kinds of therapies in Africa and elsewhere. We 
have had to put in, with great dispatch, an FDA quick approval 
process for those kinds of products that will be used in 
Africa. We had many countries willing to enter that market once 
the amount of funding was made available. However, we have 
insisted that they be FDA approved, and the fact that they go 
through an abbreviated approval process also means that the 
Best Pharmaceuticals for Children Act and so forth will be 
applicable. So we will try to use that mechanism to make sure 
it works.
    Senator DeWine. Doctor, you are looking at the--you have 
been looking at the issue of salt in what is called healthy 
food products. When could we expect those guidelines, or what 
are you doing in that area?
    Dr. Crawford. Essentially, what has happened there is that 
we gave the industry, that is the food industry, a grace period 
of 6 years to try to reformulate the products that they would 
be drastically reducing the salt content of so that they would 
be palatable and also that they would be at the same nutrition 
level.
    The industry has had a hard time doing that, and yet we 
have some notable brands that have materially reduced the salt. 
We think that is good for public health. We don't want to in 
any sense invalidate those procedures, what they have done, and 
the progress that has been made, so we are considering now the 
finalization of a regulation which will enable them to label 
correctly and also to proceed with those efforts.
    That will be done sometime this summer, but there has been 
some concern that we might take action against companies in the 
salt area. I assure you that we are working with them. If there 
is too much salt, we will also be working with them. But those 
that are genuinely trying to reduce the salt and maintain the 
nutrition level, we will have a place for them.
    Senator DeWine. But something will happen this summer?
    Dr. Crawford. Yes.
    Senator DeWine. Thank you, Mr. Chairman.
    The Chairman. Thank you. Senator Murray.
    Senator Murray. Thank you, Mr. Chairman, and first, let me 
commend Senator DeWine for his work on pediatric labeling. I 
share his concern and agree with him that we need to really 
make sure we are moving forward on that.
    Dr. Crawford, thank you for coming before this committee at 
a very troubling time for FDA, where across this country, we 
are seeing allegations of safety lapses, of political 
interference, conflict of interest. It is extremely important 
that FDA's reputation remain sterling and that the public can 
count on FDA to give us the best scientific information and 
approve drugs and let consumers make decisions for themselves, 
and we have heard that on this committee many times as we have 
had discussions about safety over the last several weeks, on 
the COX-2 drugs, for example, that patients need to know about 
the drug, but they need to have the right to make decisions 
about it themselves.
    So within that context, I just want to follow up on a 
comment that was made earlier on this committee on RU-486. RU-
486 is not about ending life, it is about protecting women's 
health, and, in fact, FDA has approved this drug as safe and 
effective, is that not correct?
    Dr. Crawford. That is correct.
    Senator Murray. Thank you. I just want that for the record.
    Now, on the emergency contraceptives, Plan B and emergency 
contraceptives, I heard you say that this is unusual. You have 
a panel that has recommended 24 to 3 to approve this. I know 
you said a court filing has been made, but what is unusual? Are 
there other times that it's 24 to 3 and it is not approved?
    Dr. Crawford. Yes. There have been times when we have 
overturned the Advisory Committee. I think it is important for 
me to state that we have a decision pending with respect to the 
product you asked about and we are moving forward. What is 
unusual is the kind of application that the company has filed 
with us----
    Senator Murray. In what way?
    Dr. Crawford. I can't--I am really not supposed to discuss 
what they have filed, but it is complex and it has never been 
done before, so it is taking us a little longer. I am not 
saying we are going to deny it, but we are moving toward a 
decision. But it is a unique application.
    Senator Murray. You may or may not know, but Washington 
State is one of the four States that currently have an over-
the-counter agreement on emergency contraceptives. It is based 
on good science. It is based on good public health policy. It 
allows consumers to make their own decisions. And I, frankly, 
think that is part of what we need to do to make sure that FDA 
is something that all of us have confidence in, that it is not 
political decisions, it is based on good health, good public 
health, and good science.
    So I just want to ask you, you said that a decision is 
coming, a decision is coming. Will this committee know by the 
time we vote on your confirmation--I believe it is April 13--
either what that decision is or an exact time line of when that 
decision will be made?
    Dr. Crawford. I can't commit to that.
    Senator Murray. Well, I find that troubling because this is 
an issue that is extremely important. I think many of us on 
this committee care deeply that FDA make decisions based on 
good science, good public health policy, and that troubles me 
greatly that we won't have that answer.
    Senator Mikulski. Would the gentlelady yield? Perhaps, I 
wonder if Dr. Crawford could share--he can't say this at a 
hearing. Could he say this at a briefing, perhaps with you and 
I and Senator Clinton and the leadership of the committee?
    Dr. Crawford. Yes. I would be happy to meet with you.
    Senator Murray. Then I would request that we have that time 
and that briefing before this committee votes on this 
nomination, if I could ask the chairman for his approval of 
that.
    The Chairman. We will work on that.
    Senator Murray. OK, and I think there are a number of us 
who would like to----
    The Chairman. We will work on having that happen. We have a 
little bit of time to----
    Senator Murray. I appreciate that.
    The Chairman. We have a number of people to get together. I 
hope we are not counting on all of them being there all at the 
same time, if that is what presents the difficulty.
    Senator Murray. I think we are asking for a specific 
briefing from Dr. Crawford before this committee votes on his 
nomination to give us the reason why he believes that the 
request on the Plan B emergency contraceptives is unusual.
    Senator Mikulski. And the relevant people will be Senator 
Clinton, you and I, the leadership of the committee if it 
wishes to participate, and, of course, your staff being 
present, Senator.
    The Chairman. Certainly. The point that I am making, 
though, is that if we have to coordinate all of those people to 
be at the same place at the same time----
    Senator Mikulski. We will be there.
    Senator Murray. We will be there.
    The Chairman. [continuing]. As opposed to setting up a 
time----
    Senator Murray. You tell us the time.
    The Chairman. OK.
    Senator Murray. All right. We will work on that with you. I 
have other questions I will submit for the record, and I thank 
the chairman.
    The Chairman. Thank you. Senator Hatch.
    Senator Hatch. Dr. Crawford, welcome to the committee. 
Congratulations on this nomination. I have been around here a 
long time and watched all kinds of FDA Commissioners come 
through. I have to say, you are as qualified as anybody who has 
ever been nominated for this position. I know that you have 
done an excellent job during the time that you have been there 
as Acting Commissioner, but also in other capacities, as well. 
So I am grateful for your willingness to serve and expect you 
to be a great Chairman.
    I look forward to working with you on a wide variety of 
issues, including drug safety, Hatch-Waxman reform, DSHEA, the 
White Oak facility, which, of course, I take a great interest 
in, as you know, and so many other issues. And I agree with 
those who have spoken for you and have mentioned your 
integrity, your capacity, the background, the education, and 
all the things that you have that would add, I think, a great 
deal to this position.
    Let me just ask you this. Would you please take just a few 
minutes to talk about your plan to ensure the safety of our 
food supply against bioterrorist threats?
    Dr. Crawford. Thank you, Senator. We were blessed when I 
came on board in 2002 with the fact that the Bioterrorism Act, 
which I know you and other members worked on, was about to be 
passed. The President signed it into law in June of that year 
and we immediately went to the four regulations that 
implemented that law. They are now, I am happy to report, are 
all in place.
    For the first time in its history, FDA has a thoroughly 
effective legislative authority to protect the food supply. We 
deployed a number of our inspectors in specific areas. At the 
time of the passage of the law, we were only at 35 ports of 
entry. We are now at basically half of them, which is well over 
100. We are also able to order companies to tell us when they 
are having food come into the United States. We are also able 
to debar them, to prevent them from entering. We can condemn 
the food. We have a very strong food safety net both 
domestically and internally.
    I think the proof of the pie is in the pudding. We have 
been able to prevent these kinds of attacks and we also are 
doing a better job at essential food safety, because each time 
there is a major outbreak of any kind, we ask ourselves first, 
could this be a terrorist attack, and because of that, our 
people are in tune with looking very much more carefully at 
food safety events than they were in the past.
    So I think the system is working very well and a lot of it 
has to do with that law.
    Senator Hatch. Thank you so much. I would like to talk a 
little bit about your broad view of drug safety and basically 
how we should approach this issue so that consumers are better 
informed. Senator Kennedy referred to serious lapses on the 
FDA's part and specifically mentioned Vioxx, as you know. Dr. 
Crawford, how many serious lapses do you believe have taken 
place at the FDA on drug safety review and how do you feel 
about the creation of an independent Board on Drug Safety? Is 
that really a good solution?
    Our HELP Committee hearings on drug safety heard from a lot 
of people who did not think that an independent board was a 
very good solution or approach. Instead, they supported keeping 
the drug safety review within the FDA so that those overseeing 
drug safety could directly communicate with those who reviewed 
the drug application. I would just like to have your thoughts 
on these areas.
    Dr. Crawford. Well, the Drug Safety Board will be within 
FDA. There was some interest in having it placed outside the 
agency. That is not something we are considering. We want to 
take advantage of the critical mass of personnel in the 
scientific and medical areas that we have in FDA when these 
problems come up. So the Drug Safety Board will be appointed by 
the Commissioner and will report within FDA. So I think that is 
the way to do it.
    The other thing that we have to do in concert with that is 
be more open, to inform the public what we have under 
consideration, and also to have a better system of 
communicating with physicians.
    Senator Hatch. Thank you. My time is just about up. Let me 
just ask one last question, but it is a very important one. As 
you know, I take a great interest, as does Senator Mikulski and 
others on this committee, in the White Oak facility that is 
being built pursuant to the bill that I passed a long time ago 
on this committee, the FDA Revitalization Act. I am watching 
its progress closely. Could you provide us with a progress 
report on the work done to date, your projected time table for 
the future, and the cost estimates of the remaining work? Is 
the necessary funding to complete work at White Oak 
contemplated in the President's budget?
    Dr. Crawford. Yes. We are now about halfway through at 
White Oak and we want to thank you, Senator Mikulski, and 
others for the FDA Revitalization Act. That was the stimulus 
that got us where we are today. FDA is in 55 different 
buildings in the Washington area. It is very difficult to 
manage the agency like it is. Once White Oak is open, which 
will be 2010, it will be a far more effective and efficient 
FDA.
    We have about half of the funding that we need. We need 
just under a billion dollars total. We have already had 
committed by the Congress between--slightly over $500 million, 
and we do ask for the recommended amount in this upcoming 
budget. We haven't had the budget hearings yet, but we have 
made public the President's budget for 2006 and we do include 
the increment that we need to stay on course for occupying the 
building fully in 2010.
    Senator Hatch. Thank you so much. I appreciate it, Mr. 
Chairman.
    The Chairman. Thank you. Senator Jeffords.
    Senator Jeffords. Before I go on to my questions, Dr. 
Crawford, I want to say that I share the same concerns as 
Senators Kennedy, Murray, and Clinton about the FDA's handling 
of Plan B.
    Dr. Crawford, there have been concerns raised that having 
both the Office of Drug Safety and the Office of New Drugs in 
the same component of the FDA creates conflicts. What are your 
thoughts on taking ODS out of CDER and putting it elsewhere 
within the FDA?
    Dr. Crawford. Well, that is one of the suggestions that has 
been made. The Office of Drug Safety, we have over the past, 
actually, about 5 years, we have doubled the number of people 
and also doubled its budget and made it a separate unit. It 
does report to the same director as the people that are in the 
pre-approval process and we are still looking into that.
    But the Drug Safety Board that I mentioned that will 
oversee all this will not include people that are primary 
reviewers, that is, those people that evaluate the drugs before 
they come on the market. We have heard it said, and we believe 
it could be true, that they may have an affinity with a drug 
that probably doesn't look good, at the very minimum, so we are 
going to make that separation of personnel. But we have not 
decided to move it outside of FDA, change its location, at the 
present time.
    Senator Jeffords. Would you give us some ideas of the 
things that you would do to increase the FDA's commitment to 
drug safety?
    Dr. Crawford. Yes. I think we need to continue to build up 
the Office of Drug Safety. Ten years ago, it had very few 
personnel and virtually no funding. It now is--I would call it 
fully funded, and we are adding more funds this year in the 
President's budget, also more personnel--in fact, an 
appreciable increase in personnel if the budget is accepted. I 
think the strength of the Office of Drug Safety is very 
important and they need to be carefully monitored by me and the 
other leadership in FDA to make sure that they are truly 
experts in drug epidemiology, in other words, figuring out the 
early signals that would make us either bring about a labeling 
change or in some cases suspend marketing or take the drug off 
the market. They need to have that mentality and they also need 
to have the tools to do it. So that is what we are committed to 
doing.
    Senator Jeffords. Relative to PDUFA, in the past, the 
Congress has authorized the FDA to accept user fees to augment 
its ability to review drug and medical device products. Some 
have urged that a portion of these fees should be directed 
toward ensuring the safety of these products. Thus far, the 
Congress has agreed with the industry's position that 
postmarket product safety review is the responsibility of the 
government and should be paid for through general revenues.
    Dr. Crawford. That is correct. That has been what the 
situation is now. I understand that there are people that think 
that some of these funds should come out of PDUFA, and as you 
know, we are reauthorizing that particular law--hopefully we 
are reauthorizing it in a year and a half, I think it is. So I 
suspect that will be under consideration.
    Senator Jeffords. I would like to hear your thoughts on how 
you plan to provide funding for postmarket product safety. 
Failing the availability of appropriations, would some portion 
of user fees be a reasonable source of funding?
    Dr. Crawford. Right now, the law as constructed doesn't 
really provide for that. However, we have always generally been 
able to redirect funds, with the permission of the appropriate 
Appropriations Committees on Capitol Hill, to take care of 
these kinds of exigencies, and we will continue to--we will 
keep it funded. The funding profile of the Office of Drug 
Safety has been steadily improving.
    Senator Jeffords. Dr. Crawford, clinical trials are an 
important part of the drug approval and use process. 
Information that comes out of clinical trials continues to be a 
vital concern to doctors, patients, manufacturers, and 
regulators. To that end, it seems like a good idea to expand 
the amount of information about trials that is available. What 
is the response to the idea of creating a mandatory clinical 
trials registry?
    Dr. Crawford. We have been working with the National 
Institutes of Health and other entities both in the government 
and outside to consider that. We have heard the unalloyed 
message from the public that they want to know about those 
clinical trials. They want to be able to read about them, air 
them if possible, and they think there ought to be a common 
source. So that is a charge to keep that we have and we will 
move forward with that as best we can.
    It may take some funding, but I think that funding would 
probably come through NIH and not FDA because they maintain the 
database. Nonetheless, I think it is a good idea and it is one 
we are pursuing.
    Senator Jeffords. Dr. Crawford, you will likely be the 
third Commissioner of the FDA since the Congress first passed 
legislation allowing for the reimportation of prescription 
drugs. The FDA helped draft that bill almost 6 years ago, but 
since then, the agency has opposed any efforts to allow 
reimportation. I would like you to tell me that you are ready 
to change that situation.
    Dr. Crawford. Well, that has a history, as you know, within 
FDA. When the Prescription Drug Marketing Act of 1987 was 
passed, it basically made reimportation illegal. But then after 
that, you are absolutely correct, another bill was passed which 
called on first Secretary Shalala and then Secretary Thompson 
to affirm that this process would be safe. Neither of them were 
able to affirm that it would be safe, so as Acting 
Commissioner, I was guided by the determination that these 
products were not safe.
    Our concern is safety. FDA has been into the cost debate. 
That is not something that we have authority over. As far as 
the drugs being safe, that worries me a lot. We have to be very 
concerned about it. I am not trying to stonewall the situation, 
but we are not at this time able to tell you that the 
government is changing its position.
    Senator Jeffords. Well, are you willing to work with us?
    Dr. Crawford. I am certainly willing to work with you, and 
as a matter of fact, as we have gone around prior to this 
hearing, a number of Senators have said that they have bills 
pending or they are thinking about it and we offered FDA's 
expertise in evaluating that in terms of safety and those 
responsibilities that we have. So yes, we are open to that.
    Senator Jeffords. Thank you, Mr. Chairman.
    The Chairman. Thank you. Senator Isakson.
    Senator Isakson. Thank you, Mr. Chairman. First of all, Mr. 
Chairman, I would like the record to reflect that Dr. Crawford 
has his Ph.D. in Pharmacology from the University of Georgia, 
and further, serves as the head of the Department of Physiology 
and Pharmacology, which in and of itself should certify his 
complete competence to serve in this capacity. [Laughter.]
    I say that as a Senator from Georgia who is very proud of 
your nomination.
    Dr. Crawford. Thank you, sir.
    Senator Isakson. Following up a little bit on some of the 
questions, the Office of Drug Safety is a postapproval office, 
is that correct?
    Dr. Crawford. That is correct.
    Senator Isakson. And it collects data from drugs that have 
been approved from various sources to determine whether there 
is a safety problem.
    Dr. Crawford. That is right.
    Senator Isakson. How do you collect that data?
    Dr. Crawford. What we do is there are about three major 
sources. There are databases. For example, the Veterans' 
Administration has a very complex and very useful database 
where they keep records on adverse reactions and so forth. So 
do some of the HMOs, Kaiser Permanente, the National Institutes 
of Health, and we tap into those databases.
    The second thing is that there are scientific reports that 
appear in the scientific literature around the world. We comb 
through that.
    And then we receive adverse event reports each and every 
day of the year and we compile all of that.
    So those are the three main sources of information, and 
then once we get one of those signals that something may be 
wrong, it is up to the Office of Drug Safety to evaluate 
whether it is a false alarm or the real thing.
    Senator Isakson. Is that collection system 
institutionalized within the agency or does someone just have 
the responsibility of going to these three sources and asking 
if they have information?
    Dr. Crawford. No, it is institutionalized in the agency. 
There is an Office of Drug Safety. I would say that prior to 10 
years ago, prior to 1995, it was not institutionalized, but it 
was at that point, and gradually over the years the funding and 
the number of people in that office have improved both in terms 
of what they do and what their expertise is, and we are asking 
this year in the President's budget for more personnel. I think 
this is the biggest increase we have asked for. We are also 
asking for more funding for the office. I am taking a personal 
interest in it, as is the rest of FDA's leadership.
    Senator Isakson. Is any of that collection electronic?
    Dr. Crawford. Not as much of it as it should be. What we 
are working with--I met with the Secretary of Veterans' Affairs 
just recently and what we are hoping to do is get online with 
their medical databases. We also want to do that with NIH. And 
I think we are very close. But right now, it is a little bit of 
both.
    Senator Isakson. The reason I asked the question is that 
life experiences are the best teachers. My sister's life was 
saved through a field trial where she was a volunteer and she 
had a very serious, complex case of cancer. And so I am fully 
an advocate of getting drugs to the marketplace and 
technologies as expeditiously as possible for the benefit of 
those who suffer from terribly crippling diseases or other 
effects.
    I am equally committed to ensuring that we have good 
safety, and it seems to me like two things. One, drug safety 
ought to remain within the agency. If you get into sending it 
outside, that doesn't seem to make any sense at all except to 
maybe be symbolic of something that I don't think needs to be 
symbolized.
    But second, it would appear to me that the timely 
collection from all sources of adverse effects or some 
commonality of reoccurrences of those on different drugs or 
taking different treatments postapproval would serve to be a 
great second certification of what a field trial in itself does 
from the beginning.
    And I guess my comment is--I am not really asking you a 
question, but after the two hearings I have attended on this 
and conversations I have had and my personal experience, it 
would seem like to me if the Department--and it may be doing 
this--could initiate or institutionalize electronic collection 
from all sources--Veterans' Administration is a great source 
and you have great reliability in the information, but once you 
go beyond that, like Kaiser Permanente or an HMO or maybe this 
drug program or that drug program, it seems to me like it is 
probably as comprehensive as you can get given what you have 
but not as comprehensive as we probably ought to have.
    And so I would hope you all would look toward initiating 
whatever you can to expedite the collection of all that data 
from its various sources, and I think then the post safety 
process will be that much better and certainly that much more 
timely. Spoken as one who has no degree in any chemistry or 
pharmacology, but just based on what I have heard.
    The Chairman. Thank you. Senator Mikulski?
    Senator Mikulski. Thank you very much, Mr. Chairman, and 
good morning to you, Dr. Crawford.
    First, I want to associate myself with Senators Clinton and 
Murray on the issues raised by Plan B and look forward to a 
briefing with you and discussing it in an appropriate forum, 
recognizing your legal and regulatory constraints.
    I am really proud that FDA is a Maryland agency. Nine 
thousand people work there, and what a great cornucopia, to 
have NIH down Route 270 and you up there in FDA, and hopefully 
with the move to White Oak, then to have these surrounded by 
the great academic centers that do research, like Hopkins and 
Maryland and Georgetown. So we are really very, very, very 
proud of it.
    And we worked on a nonpartisan basis here on FDA reform. 
Some of the greatest advocates for making sure that the 
employees who work so hard and are so diligent have the best 
facilities, the move to White Oak has been jointly with myself, 
Senator Hatch, and Senator Frist. So you see where we are.
    Looking at where we are, though, with FDA, there is a 
crisis of confidence over drug safety in the public's mind and 
even with some clinicians. Looking at page three of your 
testimony, you talk about transformation, which I think we 
would want to support, but I was puzzled why the number one 
issue wouldn't be to restore in the public's mind the integrity 
of FDA. So I am going to come back to that and ask for your 
elaboration about the drug safety issue so that patients, 
doctors who don't want to get their advice from a drug 
salesperson need to know FDA is there.
    You talked about this independent agency, a separate group. 
Would you give us your views on whether or not, in all candor, 
you think that within the agency itself, no matter how 
diligent, there can be that independent review, because it is 
not a change of buildings. Your own staff, Dr. Graham, has 
recommended an independent agency, a watchdog agency separate 
from FDA and almost a devil's advocate approach to watching 
this to ensure ongoing safety.
    Could you share with us, do you think that FDA can truly be 
a watchdog of itself, recognizing the professionalism of the 
people who work there, but do you think we need not a watchdog 
system in a different building or a different block on an 
organizational chart, but a truly independent agency with its 
own staff and no ties to the industry?
    Dr. Crawford. Well, thank you for the question. It is up, I 
think, to me to make sure that they act independently, that 
they are not intimidated, that the conclusions of the Office of 
Drug Safety are given the kind of emphasis that they should be. 
FDA, as you mentioned, is a large organization, about 10,000 
people all told, so I think it is possible, and I think it is 
being done, to have the Office of Drug Safety serve in a place 
in the organizational chart and also physically so that they 
are not subsumed by the primary drug reviewers and the other 
parts of the Center for Drugs.
    I believe they are operating independently. I believe we 
need to do more work, though, on what you referred to earlier, 
which essentially is the culture of FDA. I think that decision 
making is not understood by the public. I think it is 
basically, like most scientific--when scientists get together, 
they sort of shout each other down. We need to have it very 
different, because we are talking about something other than 
scientific debate. We are talking about the safety of the drugs 
that are on the market, and so we need to work on making that 
transparent. The National Academy of Sciences Institute of 
Medicine is advising us on how to make that sea change in how 
we do business.
    Senator Mikulski. Doctor, I am going to ask you to walk me 
through it. First of all, the public wants two things. No. 1, 
they want those dazzling cures available as quickly as we can, 
that our colleague, Senator Isakson's, sister would be able to 
be cured of cancer, but anyone else facing it--my dear father 
with Alzheimer's, though he has since passed away, my mother, 
who had a chronic condition like diabetes, to be able to find 
either a cure or even more drugs to help people not develop all 
the complications of it. So the public wants it and so do the 
clinicians and the practitioners, and we want them in America.
    The other, though, is they want to be safe when they take 
it. So there is the dual pressure. It is a dual pressure, and 
FDA has served us well. That is why they are the gold standard. 
Emerging democracies that could never afford to have an FDA 
look to us.
    So, again, how mechanically would that be? Are you going to 
have a separate office? Is it going to have a separate staff? 
Who is that person responsible to? How will they be held 
accountable, and yet then not get entwined with the other 
administrative or bureaucratic assets? How do you envision 
that?
    Dr. Crawford. Well, the Office of Drug Safety, as it is 
being changed, will be a separate entity entirely with its own 
director. We are about ready to announce the appointment of the 
director----
    Senator Mikulski. Is that person--will that person only be 
responsible to you?
    Dr. Crawford. The person will be responsible to me, but 
through the Center Director for Drugs. So he will go through 
that person to me.
    Senator Mikulski. Can I ask you why? First of all, I know 
that you are busy. I mean, an FDA Commissioner's job is really, 
between food safety and drug safety, it is really three jobs. 
But why not to you directly, because doesn't that again give 
them one more layer of bureaucracy, one more justification when 
we want intellectual rigor, scientific scrutiny, transparency?
    Dr. Crawford. Well, I think it is up to me to make sure 
that I am intimately involved in what they do. If the person 
reported to me, which is always something that we can consider 
and we are open to, I would essentially have to be the person 
who did their job evaluations, take care of their budget 
amendments----
    Senator Mikulski. But that is the crux of it.
    Dr. Crawford. Yes, I know.
    Senator Mikulski. That is the crux of it.
    Dr. Crawford. Well, I am not closed to that----
    Senator Mikulski. Who is going to evaluate it--the chicken, 
the egg, do you see?
    Dr. Crawford. Mm-hmm.
    Senator Mikulski. That is the point. I am not saying, let 
us create a whole new independent agency. Senator, I know my 
time is up, but that is the crux of it. Who evaluates them? Who 
decides whether they get the promotion? Who decides whether 
they keep the job?
    Dr. Crawford, I know you are a professional person. You 
stood in twice now as acting. We need a permanent Commissioner 
of FDA. We are proud of FDA. And I am not saying that person in 
between you and the drugs, the watchdog department, would not 
be faithful as you intend to be. But I am telling you, I really 
strongly recommend that if it is going to be independent, it 
has got to be independent of the entire bureaucracy, 
responsible to the Commissioner to whom we then hold 
responsible.
    Dr. Crawford. Maybe we could talk further about that.
    Senator Mikulski. Thank you very much.
    Mr. Chairman, you have been very indulgent. I appreciate 
it.
    The Chairman. Thank you. Senator Harkin.
    Senator Harkin. Thank you very much, Mr. Chairman, and 
welcome, Dr. Crawford. I would ask that my statement be made a 
part of the record, Mr. Chairman.
    The Chairman. Without objection.
    [The prepared statement of Senator Harkin follows:]

                  Prepared Statement of Senator Harkin

    Thank you, Mr. Chairman. And I also thank Dr. Crawford for 
appearing before us today. Dr. Crawford and I have a long, 
positive history of working together on issues at the Food and 
Drug Administration. And I am pleased to see him here.
    I'd like to take this opportunity to bring up two issues.
    First, as you know, Dr. Crawford, Congress passed the 
Dietary Supplement Health and Education Act (DSHEA) to ensure 
the availability and safety of dietary supplements that 
millions of Americans rely on. Under the leadership of Dr. 
McClellan as Commissioner and you as Acting Commissioner, the 
FDA has made significant progress in implementing and enforcing 
DSHEA. I look forward to continuing to work with FDA to fully 
implement DSHEA, and to make sure that U.S. consumers have 
access to safe, effective, and affordable dietary supplements.
    Second, as you know, Dr. Crawford, our Nation is 
confronting a major obesity epidemic, among both adults and 
children. While obesity is a complex condidtion with many 
contributing factors, that fact is that we need a comprehensive 
approach to combating it--with an active role by government, 
parents, communities, and also the food and restaurant 
industries. Last year HHS/FDA released a report titled, 
``Counting Calories: Report of the Working Group on Obesity.'' 
It notes that food consumed away from home--mostly food from 
restaurants--has increased dramatically over the last 3 
decades. In 1970, this accounted for 33 percent of the average 
consumer's food budget. By 2002, it accounted for 47 percent. 
But while people are eating out more and more, they have little 
or no information available to make informed food choices in 
restaurants. I am sponsoring legislation, the Healthy 
Lifestyles and Prevention Act, which would require mandatory 
nutritional labeling on menues and menu boards in chain 
resyaurants.
    I have questions on both these issues, and several 
additional questions for the record.
    Senator Harkin. First of all, Dr. Crawford, I would like to 
commend you on your work as Acting Commissioner in an area in 
which I have a great deal of interest and have since I was one 
of the authors of the Dietary Health and Supplement Education 
Act, but your work on vitamins, minerals, and dietary 
supplements. The FDA has made significant strides in the past 
couple of years in implementing and enforcing what is known as 
DSHEA and I look forward to working with you to ensure that we 
continue to make this progress.
    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 that the Dietary Supplement 
and Health Education Act gives the FDA sufficient authority to 
regulate dietary supplements, vitamins, and minerals?
    Dr. Crawford. Yes. We need to go ahead and make solid 
this--the GMP part of it. It has not been finalized, and I know 
that is your next question. Until we do that, it is not really 
possible to thoroughly answer that question, but it is my 
belief that once we get that done, we will have the authority 
we need.
    Senator Harkin. Let me ask a follow-up on that question, 
then. Do you believe that the Dietary Health and Supplement 
Education Act gives the FDA the authority to remove harmful 
items from the shelves?
    Dr. Crawford. Yes. As you know, we have done that with 
ephedra and also with andro and some other products, and so 
obviously we do have the authority.
    Senator Harkin. So looking back to the first question, 
then, you said that as soon as the GMPs, the Good Manufacturing 
Practices, are promulgated, you will have sufficient authority 
then. Your predecessors have answered that question by saying 
that they thought they had sufficient authority. But then 
again, we have waited 10 years--10 years, the FDA has drug its 
feet on getting the Good Manufacturing Practices out. Can you 
inform the committee, or provide us with a more definitive date 
as to when the final Good Manufacturing Practices regulations 
will be published in the Federal Register?
    Dr. Crawford. I hope to be able to do that within--to tell 
you the exact date within a few days. I cannot at this point, 
but if I can follow up in writing, I will do what I can do.
    Senator Harkin. I would appreciate it, because your 
predecessors going back to 1995, when the law was passed, and I 
have sat here and asked every one of them, they have said, oh, 
yes, we are going to get the GMPs out. Then they get confirmed 
and that is the end of it. And so I really want to try to pin 
you down as much as I can.
    Dr. Crawford. Well, you can pin me down and I will agree 
that 10 years is too long to wait for it.
    Senator Harkin. Right.
    Dr. Crawford. So I am on track to try to get it out as 
quickly as I can.
    Senator Harkin. I appreciate that. And you will let us 
know----
    Dr. Crawford. Absolutely.
    Senator Harkin. [continuing]. Sometime, when, the next 
couple of months? Sixty days?
    Dr. Crawford. I can't really say, but it is sooner rather 
than later, for sure. You have heard that before, too, Senator, 
and I really can't answer that. I just don't have a publication 
date.
    Senator Harkin. Before the end of the year?
    Dr. Crawford. Yes.
    Senator Harkin. Thank you. That is great. I finally got it 
before the end of the year. [Laughter.]
    My second question, Dr. Crawford, last year, the FDA 
released a report on obesity, and I certainly again appreciate 
your work on this issue. You have been in the forefront on 
this. But I am concerned by the fact that many of the 
recommendations that pertain to the food industry, especially 
restaurant foods, are voluntary rather than mandatory. The FDA 
report notes that food consumed away from home, mostly from 
restaurants, increased significantly from 33 percent of 
consumers' food budget in 1970 to 47 percent in 2002. Over the 
same period, total calories consumed from food purchased 
outside the home increased from 18 percent to 32 percent. So we 
know that consumers eat more when they are out and they are 
less aware of nutritional information.
    The report that came out of FDA had specific 
recommendations for the industry, and specifically, the FDA 
urged the restaurant industry to launch, quote, ``a nationwide 
voluntary and point-of-sale nutrition information campaign for 
customers,'' end quote. Can you tell me about the progress the 
restaurant industry has made toward that recommendation?
    Dr. Crawford. Yes. I think certain segments, and like fast 
food corporations and also chain restaurants that have an 
identifiable name, have made progress with it. When we unveiled 
the Obesity Working Group Report, which was called ``Calories 
Count,'' you recall that Secretary Thompson did say that we 
were going to try the voluntary approach for a while. If it 
didn't work, we were going to have to do something else.
    So I think some progress has been made. It has been uneven. 
Not every chain restaurant you go into and not every fast food 
restaurant has the material available, and it is voluntary. As 
you remember, the NLEA was silent on that subject, so we don't 
have the authority to require it. I have been encouraged by 
comments from restaurants, though, that seem to think that it 
is working and that it is good for them.
    Senator Harkin. Of course, as you know, NLEA was mandatory, 
and I don't know that we want to go back and say that all of 
the information that shoppers, now they go into a food store 
and you look at all the nutritional--and by the way, the FDA is 
doing some good work there in standardizing that, too, so that 
is good. But we know that consumers are using those labels now 
and they are reading them. But they don't have that kind of 
information when they go to a restaurant. And now that we know 
there is an obesity epidemic--there was just a new study that 
was just published today again.
    And if you have voluntary guidelines, I am all for 
voluntary if they will do it. But then that leads to one chain 
having one sort of set of guidelines and another one having 
another set of guidelines and who do you know? At least with 
NLEA, we have got some basic standards by which you can measure 
different items in packages or cans or bottles and stuff like 
that. But how do you know when you go in a restaurant? You 
really don't.
    So voluntary is fine, but it seems to me the FDA really has 
got to step in here and design an information system that will 
be helpful to consumers when they go out to eat.
    Dr. Crawford. You mean try to standardize it? Yes, I think 
you are right.
    Senator Harkin. Something like that so that it is across 
the board so they know what they are getting, something like 
that. I don't know how much longer we are going to go with the 
voluntary. Again, a few of the chains have done a pretty darn 
good job, but then the others haven't, so what do you wind up 
with here? There is kind of a mishmash of stuff out there.
    And again, because of the obesity epidemic, because of the 
onset of diabetes earlier and earlier, we just may have to have 
the FDA come up with standardization guidelines and with some 
mandatory provisions for these restaurants to all at least put 
it out there in understandable form for people to read and 
understand.
    Thank you very much, Dr. Crawford.
    The Chairman. Thank you. Senator Dodd.
    Senator Dodd. Thank you very much, Mr. Chairman, and Dr. 
Crawford, welcome to the committee. I appreciate your 
willingness to take on this job.
    Let me, before our colleague from Iowa leaves, on his last 
point of questioning, the obesity issue, I think the papers 
this morning indicate that we may be looking at the first 
generation of Americans who will live shorter lifespans than 
their parents because of this issue, and I think too often in 
the past, it has been sort of ridiculed a bit.
    I know when Senator Frist and I, along with Jeff Bingaman, 
introduced legislation a year or so ago dealing with improved 
nutrition and physical activity, really sort of a harmless 
piece of legislation that passed the Senate, we weren't able to 
get it out of the House, there was some sense of sort of 
ridiculing, here is the Federal Government sort of telling 
people whether they can go to fast food restaurants or not, 
which is obviously not the case of what we were trying to do.
    But I would hope the FDA would take this issue seriously. 
Too often, I think there is a negative association with this 
issue. There have been a lot of studies and a lot of news 
reports and so forth indicating the seriousness of this issue, 
and particularly when you consider some of these food producing 
companies that are getting exclusive rights in schools by 
offering poor schools significant money if they can put their 
vending machines in those schools for use during the day. It is 
dangerous and it is a serious problem. It really deserves 
someone like yourself to really champion this issue and make 
something of it, so I would hope you would do that. Senator 
Harkin raised a very good point.
    Second, I just want to raise--I know Mike DeWine was here 
earlier, but he and I have worked a long time on the pediatric 
testing issues, as you know, and the Better and Best 
Pharmaceutical Acts for Children, which were adopted a number 
of years ago. I just want to, again, I want to comment quickly 
and go ahead, but we would like you to continue to work on 
expanding pediatric testing. The SSRI issue certainly 
highlights the importance, and I know there were tests done on 
those--many of them were inconclusive with younger children and 
adolescents particularly. But pediatric testing is something 
that is very, very important, and I presume you agree with 
that, as well.
    Dr. Crawford. I do agree completely.
    Senator Dodd. And we will talk about expanding the 
opportunities for pediatric testing.
    Dr. Crawford. We are, and we are going to make sure that 
both on the exclusive side, where there is a patent, and off-
patent that we get the same kind of penetration with those 
firms as they move forward with labeling.
    Senator Dodd. Let me come back, I know Senator Mikulski, 
and she had to leave, and I believe Senator Kennedy, certainly 
Senator Jeffords in the time I was sitting here, talked about 
the Office of Drug Safety issue. I am going to be a little bit 
repetitive here, but I think it is an important issue, and 
maybe because I am going back over some of this ground again 
you get some sense of the importance of this issue.
    Senator Grassley and I are planning to introduce as I think 
you are aware--you and I talked on the phone about this----
    Dr. Crawford. We did, yes.
    Senator Dodd. Legislation to create an independent office 
within FDA to deal with this issue, and you have expressed your 
views on this a bit already, but I want to continue to make the 
point to you here.
    Let me, as a backdrop, underscore the point that I am sure 
all of my colleagues have made here. There is nothing like, 
when you travel around the world and you go out to buy a 
product someplace in a store in some foreign country and you 
see on the shelves, ``product approved by the FDA.'' It is the 
gold standard, still all over the world. That Good Housekeeping 
Seal of Approval, that this is a product approved by the Food 
and Drug Administration of the United States, is incredibly 
important. And obviously, the issues of Vioxx and the SSRI 
issues and so forth have raised some serious questions.
    So as a backdrop to all of this, and I know you feel this 
way, as well, but I think it is important to be stated here. We 
really need to make sure that the reputation of this incredible 
agency that has done so much to put products in the marketplace 
that have changed people's lives, extended lives, the quality 
of lives, as well as protecting people from adverse effects of 
those products that either are approved or those that shouldn't 
be approved. So there is a tremendously important critical 
moment we are at here and I am worried that if we don't get 
this right in the next couple of years, we could see this gold 
standard be diminished, and then I think we all suffer terribly 
as a result of that.
    So this Office of Drug Safety idea, the idea of making it 
more independent so that you don't have to go through a 2-year 
period with Vioxx where literally tens of thousands of people 
have lost their lives--and I don't blame the FDA for this, but 
the ability to have someone that can say, outside of the group 
that has approved the product in the first instance, to make 
the decision to take it off the shelf, we think is very, very 
important.
    I wonder if you would share just sort of your general 
thoughts about this. Is there a sense, and let me just give you 
an opportunity, I presume there is, but a sense of this FDA 
standard approval being tarnished a bit by all of this, and 
what steps do you envision, maybe going a little bit further, 
to make the point that we are not going to allow this to 
happen, particularly on your watch?
    Dr. Crawford. We are not going to allow it to happen. I 
don't think we have been tarnished. Checking with our 
international colleagues and also checking with various polls 
that are done, it looks like the American people have full 
confidence in the FDA.
    I don't want to see it happen, though, and you are 
absolutely correct. That specter has been raised over the past 
few months and I pledge to you that I will do everything in my 
power to stem the tide by doing the right thing and I look 
forward to working with you, Senator Grassley, and whoever else 
has some legislation in this regard.
    I am open to solutions. I don't want on my watch FDA to be 
tarnished in any sense. I want us to move forward strongly and 
better than ever. We have some special challenges with the 500 
percent increase in food trade and now a great increase in drug 
trade that is occurring. However, an independent Office of Drug 
Safety is something I am certainly open to discuss and I look 
forward to spending time with you on that.
    Senator Dodd. Obviously, we are talking to people, and 
Senator Enzi and Senator Kennedy and others are interested, as 
well, on the subject matter.
    There was an internal study, as you know, conducted by the 
Health and Human Services Office of the Inspector General in 
2002--I know you are aware of this--that revealed that 
approximately one-fifth of drug reviewers had been pressured to 
approve a drug despite concerns about safety, efficacy, or 
quality. In addition, more than one-third said, and I am 
quoting, ``they were not at all or only somewhat confident that 
initial decisions of the Center for Drug Evaluation and 
Research adequately assessed the safety.''
    That seems to have been the case with Dr. Mosholder, if I 
am pronouncing his name correctly, when he had data to suggest 
that certain anti-depressants might increase the risk of 
suicide in children and adolescents. And as with Dr. David 
Graham when he had data to suggest that Vioxx was connected 
with cardiovascular problems.
    I wonder if you might just, whether or not you would agree 
that mistakes were made in the handling of both of these two 
cases or not.
    Dr. Crawford. Well, I came on board when that report came 
out that you mentioned from the Office of the Inspector General 
and it was my responsibility to try to make sure that that part 
was fixed and remedied, and what we did was we put more funding 
in the Office of Drug Safety, gave them a bit more authority, 
and we continue to do that.
    I think that the key to it is my own personal involvement. 
I mean, I have got--nothing is more important at FDA right now 
than this drug safety issue and I will continue to monitor it 
and we will also continue to enhance not only the number of 
personnel and the resources in the Office of Drug Safety, but 
the kinds of people. We need these epidemiologists that I 
mentioned earlier and we are building them up. I am going to 
monitor it very closely myself because if there is one thing 
that we are vulnerable in right now in terms of our reputation 
worldwide, that is it.
    Senator Dodd. Yes, you have hit it on the head. The 
transparency issue is related to this, obviously, and I would 
love at some point to be able to talk with you about that.
    Mr. Chairman, I appreciate this and we will look forward to 
working with you on this, because obviously, doing it right is 
going to be tremendously important. The point that Senator 
Mikulski raised, and again, you are overburdened as it is, but 
that transparency issue, that sense of competence is going to 
be tremendously important, that whatever the entity is that we 
create, that there is going to be a sense they can act and act 
intelligently when these matters arise. So I look forward to 
working with you.
    I should mention, as well, Senator Grassley and I also 
introduced legislation dealing with clinical trials, which I 
know you have an interest in and we want to work with you on 
that, as well.
    Dr. Crawford. Absolutely.
    Senator Dodd. Thank you, Mr. Chairman, very much. I 
appreciate it very much.
    The Chairman. Thank you, and since I allowed an average of 
two-and-a-half extra minutes per person on this side for 
questioning, is there one last quick question from either of 
you?
    Senator Hatch. I won't ask a question, because I know the 
questioning is over for now, but I want to tell you how 
strongly I support you for this position.
    Dr. Crawford. Thank you, sir.
    Senator Hatch. I know you will do a good job, but one last 
thing: Congress has appropriated funds to support a national 
inventory of high-quality cord blood units, an especially 
important resource for ethnic minority patients. It is my 
understanding the FDA has been collecting data on the 
therapeutic use of cord blood for some time, yet it has not 
issued regulations that would address the need for a set of 
standards or licensing to assure that cord blood units 
collected for therapeutic use are meeting the high quality 
expected of a biological product.
    So what I would like you to think about under your 
leadership is to a way of assuring the quality and safety of 
cord blood and issuing regulations as soon as you can. Cord 
blood looks to me as though it may have remarkable stem cell 
advantages over adult stem cells and maybe help us resolve some 
of the conflicts and problems with regard to the whole 
embryonic stem cell area, as well.
    So I hope you will give some real thought to that. It is 
important. I think it is important for you to make that a major 
part of your work. I won't ask you any questions on it, but I 
just wanted to ask you to really get into that, because what I 
am studying and what I am reviewing shows some tremendous 
promise.
    Senator Dodd. Would my colleague yield on this point?
    Senator Hatch. I am happy to.
    Senator Dodd. I want to totally support Senator Hatch's 
point on this. Being the father of a 2-week-old, with my first 
child and second child, we took the cord blood. It is 
complicated to do this. There are private operators that do it, 
but a lot of them don't last very long.
    Senator Hatch. That is right.
    Senator Dodd. The ones that do, we used the one out in 
Berkeley, California, which is a university-associated one, to 
send the child's cord blood, to go through it so you are part 
of the test, everything has to be done exactly right. I had to 
have a person on the phone making sure the packaging was all 
done properly.
    But Senator Hatch is absolutely correct in this. There are 
some tremendous opportunities, I think, with the cord blood 
issue, much more so than people even thought a few years ago. I 
would like to support you in every effort you make along those 
lines.
    Senator Hatch. Thank you, and I appreciate you jumping on 
that, because----
    Senator Dodd. It is a great point. Thanks.
    Senator Hatch. Well, thanks. Thank you. We support you 
strongly.
    The Chairman. Senator Isakson.
    Senator Isakson. I will be quick, Mr. Chairman, but I want 
to go back to the obesity and the labeling thing. What 
percentage of that flier that I get when I get a prescription 
filled, the thing with the real small print, what percentage of 
all that information is dictated by the FDA after the approval 
of a drug?
    Dr. Crawford. You mean what is on the----
    Senator Isakson. Just as a guess.
    Dr. Crawford. [continuing]. On the bottle itself?
    Senator Isakson. Well, not just the bottle, but the inside 
stuff.
    Dr. Crawford. A hundred percent.
    Senator Isakson. A hundred percent?
    Dr. Crawford. Mm-hmm.
    Senator Isakson. OK. My comment is this, and I mean this 
very sincerely. I respect what Senator Harkin said about 
labeling on prepared foods and about the issue of obesity, but 
our first responsibility is to instill more personal 
responsibility in people than self-satisfy ourselves that we 
can label them into better health habits, particularly in 
something like the food issue.
    CDC in Atlanta is doing a marvelous job, I think, on the 
obesity issue and you all are working in concert with them, but 
before we succumb to making ourselves feel good that we get 
into the mandatory labeling of menus as addressing the problem 
of obesity, let us do more to inform people so they make good 
decisions for themselves as advocates in the public sector, and 
that is the only thing I wanted to say, Mr. Chairman.
    The Chairman. Thank you very much.
    I appreciate Dr. Crawford's testimony. Unless there is 
objection, we will end the rounds of oral questions, but we 
leave it open for written questions.
    I would mention that in regard--there was a lot of emphasis 
on an independent safety panel, a lot on the independence, and 
we covered that in one of the FDA hearings that we held. There 
was a lot of concern by a wide variety of panelists that if it 
is really independent, people watch ads on television and there 
are always some things that they ought to watch out for. And if 
you are in an office where your only job is safety, those may 
all sound like really bad things, and so you could end the drug 
if you have total independence. There are a lot of people 
relying on some of those drugs, even though they know the side 
effects, even though they know that it has affected people in 
their own family previously. For pain, they think that it is 
essential even though they know they will have heart problems 
from it.
    So I am hoping there is some balance, as there always has 
been in FDA, of realizing that some people actually rely on 
these things even knowing the consequences. We even talked a 
little bit about how that affects the clinical trials and at 
what point ethically you can have people that were not in the 
actual test group begin to get the medicine.
    So I hope everybody will review the results of that hearing 
and it will provide a little bit of a balance that I think you 
covered well in your testimony, but we will have some follow-up 
questions to do that.
    Members of the committee may submit questions in writing. 
Per an agreement between myself and Senator Kennedy, we will be 
submitting our written requests to Dr. Crawford by Friday, 
March 18. That is tomorrow. Members will be notified of this, 
and we ask them to respectfully submit their written questions 
by that same date. And then, accordingly, it is my 
understanding that Dr. Crawford will answer the questions 
before we return from recess.
    We will schedule the briefing that was talked about this 
morning so that to the degree that you can talk about an 
application prior to action on the application, you can brief 
us on what the status is and what the complications are.
    I want to compliment the staff for, since this is St. 
Patrick's Day, for using the green tablecloth--which we always 
use--[Laughter.]
    Thank you all very much for your participation and 
attendance. The hearing is now adjourned.
    [Additional material follows:]

                          ADDITIONAL MATERIAL

                 Prepared Statement of Senator Clinton

    Thank you, Chairman Enzi and Senator Kennedy. And thank you 
to Dr. Crawford for appearing before the HELP Committee this 
morning.
    I know that two of your colleagues--Dr. Sandra Kweder and 
Dr. Janet Woodcock--have recently appeared before this 
committee to testify about issues of drug safety, primarily in 
response to the controversies surrounding Cox-2 drugs and 
pediatric use of antidepressants. These drug safety 
controversies occurred during your tenure as Acting 
Commissioner of the FDA, and, quite frankly, I was disappointed 
by your response to them. I think that the American public lost 
a great deal of confidence in the ability of the agency to 
ensure the safety of their medications.
    As someone who has worked to give the FDA the authority to 
increase the safety of drugs, particularly pediatric drugs, I 
would like additional assurances that you will use such 
authority to guarantee the safety and effectiveness of our drug 
supply.
    Today, I will be looking for assurances that you will seek 
to strengthen the FDA's commitment to drug safety and increase 
the use of already-existing enforcement tools like the 
Pediatric Rule.
    In addition to drug safety issues, I am concerned about the 
way that the FDA is letting political considerations interfere 
with scientific treatment decisions. During your tenure at FDA, 
you denied an application to make emergency contraception (EC) 
available for sale over the counter, despite the fact that the 
FDA's own advisory committees and career professionals at the 
agency had made such a recommendation.
    The New York Times reported that several former FDA 
officials said they had never seen the recommendations of both 
staff and an advisory committee overruled in such a manner 
prior to the rejection of this EC application. The notion that 
politics might have entered into any decision about a drug 
approval is deeply disturbing and alarming.
    During your tenure, the Nation also experienced its third 
influenza vaccine shortage since 2000, after the British 
government's drug safety agency closed down a contaminated 
vaccine manufacturing plant in Liverpool. While the FDA was 
aware of the problems that existed at this plant prior to the 
shutdown, it failed to alert the rest of the government about 
the possibility of a shortage.
    Dr. Crawford, the FDA is a demoralized agency. It needs a 
strong leader with a clear vision of ways to restore its 
reputation. Today, you have the opportunity to present us with 
your ideas as to how to improve the FDA. More importantly, you 
have the opportunity to demonstrate what you have learned from 
the mistakes that have occurred during your tenure at the FDA, 
and what actions you will take to keep such mistakes from 
happening in the future. Our citizens look to the FDA to give 
its good housekeeping seal of approval. They need to trust that 
the Agency is looking out for their well being. I'm afraid that 
the gold standard which FDA has held for so long is in 
jeopardy. We need real leadership to ensure that our citizens 
can have faith that decisions being made are in their best 
interests. I look forward to hearing your testimony and answers 
to the committee today.

                 Prepared Statement of Senator Jeffords

    Mr. Chairman, I want to join you in welcoming Dr. Crawford 
before the HELP Committee. I've had the opportunity to meet 
with Dr. Crawford, and although there are some serious issues 
that need to be raised about the agency's ability to meet it's 
fundamental mission, I fully expect to support his nomination 
and to vote in favor of his appointment as the new Commissioner 
of the Food and Drug Administration.
    Dr. Crawford, you may be the most important presidential 
appointee whose nomination this committee will have the 
opportunity to consider during this Congress. The members of 
this committee know well of the vital role that the Food and 
Drug Administration plays in the health and well being of our 
citizens, and we are also well aware of the impact the agency 
has on the industries you are charged to regulate.
    The FDA also holds a special significance for many of us 
because of our involvement with passage of the FDA 
Modernization Act; a measure intended to guide the FDA in its 
mission to protect the American public. That act emerged after 
several years of debate over the appropriate role the FDA 
should have in approving the products it regulates
    Many in industry and some in the consumer community argued 
that the agency was taking too long to approve new life saving 
medical devices and medicines; that the agency was acting as a 
roadblock to progress. More recently, new charges are emerging 
that the FDA is being too lax in its oversight of industry and 
that some of the products being approved are unsafe. What we 
need at the agency, and what I hope you will bring with your 
leadership is a better balance between these competing 
interests.
    I had the privilege of being chairman of this committee 
when FDAMA passed and I continue to believe that that measure 
made substantial improvements to the agency. But, I will say 
again what I said then--I stand ready to work with FDA and my 
colleagues to ensure that the agency is able to meet its 
mission.
    In some respects I view your, and the agency's, role to 
that of a traffic cop whose job is not just to stop the bad 
drivers, but is also to ensure that the good drivers get 
through unimpeded. This is not an easy task but I expect to 
hear you tell and convince this committee that you are up to 
that challenge.

                 Prepared Statement of Senator Mikulski

    Thank you for calling this prompt hearing on the vitally 
important nomination of Dr. Lester Crawford to be the 
Commissioner of the Food and Drug Administration (FDA).
    The position of FDA Commissioner is critically important to 
the public health of the United States but it has been vacant 
for nearly 1 year. I am so pleased that Maryland is home to the 
FDA. FDA makes sure that safe and effective drugs, biologics, 
and devices come to the market to help save lives, help 
patients live longer, and help improve the quality of their 
lives.
    FDA also plays a critical role in ensuring the safety and 
security of our country's food supply. FDA affects the lives of 
Americans everyday whether it is a pill you take or the food 
you eat. FDA-regulated products account for about 25 cents of 
every consumer dollar spent--a total of $1 trillion per year.
    Criteria--My criteria for looking at each nomination are 
competence, integrity, and commitment to the mission of the 
agency.
    I look forward to hearing from Dr. Crawford today about his 
vision and qualifications.
    Competence--As head of the agency that regulates everything 
from food to the latest medication for heart disease, the FDA 
Commissioner must be knowledgeable about medicine and science. 
Management expertise is essential to effectively run FDA 
without red tape and bureaucracy.
    FDA has over 9,000 dedicated employees. FDA has a budget of 
close to $1.8 billion and about 9,000 employees. Strong 
management skills and leadership to ensure that FDA can 
efficiently and effectively carry out its many 
responsibilities.
    Recruiting and retaining the best and brightest employees 
at FDA is especially important as products reviewed by FDA 
become increasingly more complex and advanced.
    Integrity--Well respected by patient/consumer groups and 
the industry so that FDA commands the respect of the public and 
the industry it regulates.
    Honest broker and listener who can make tough calls on 
contentious issues.
    Commitment to the Mission of the Agency--Decisions based on 
sound science and public health, not ideology. Maintaining the 
FDA gold standard of safety and efficacy. Ensuring timely 
approval of new therapies to save lives, help patients live 
longer, and improve their quality of life. Continual 
improvement in mammography quality and ensuring access to new 
screening and detection tools. Ensuring safety of our food 
supply.

Closing

    While Dr. Crawford may have an unusual background for 
Commissioner of FDA. He could also bring a fresh perspective 
with new thinking and new ideas. I will evaluate Dr. Crawford, 
as I do each and every nominee, based on his competence, 
integrity, and commitment to the mission of the agency. Thank 
you again, Mr. Chairman, for convening this hearing on this 
critically important nomination to the health of this country.
                                ------                                

                           Letters of Concern
                                                     March 4, 2005.

    Dear Senator: We write to share our serious concerns about the 
President's nomination of Dr. Lester Crawford to serve as Commissioner 
of the U.S. Food and Drug Administration. The continued delay on a 
decision to make Plan B emergency contraception available without a 
prescription undermines public confidence in the Acting Commissioner's 
commitment to promoting the public's health and welfare.
    Overwhelming scientific evidence shows that making emergency 
contraception easier to obtain would substantially reduce the incidence 
of unintended pregnancy and need for abortion. A recent study published 
in the Journal of the American Medical Association provides the latest 
evidence that Plan B should be made readily available by demonstrating 
that using emergency contraception does not lead to more risky sexual 
behavior or other health risks for women.
    In December 2003, following review of hundreds of studies, the FDA 
independent advisory committees voted 23-4 to approve Plan B for over-
the-counter status. Based on FDA guidelines, a decision was anticipated 
in February 2004. Following a 90-day delay, on May 6, 2004 the FDA 
issued a non-approvable letter to Barr Pharmaceuticals, citing the lack 
of data concerning use in adolescents under age 16. The final decision 
was made by Acting Center Director Dr. Steven Galson, contrary to the 
recommendations of his own professional staff.
    Barr Pharmaceuticals responded in good faith with a revised 
application supporting the marketing of Plan B as a prescription-only 
product for women 15 years of age and younger, and a non-prescription 
product for women 16 years of age and older. A decision was due on 
January 21, 2005, but instead the agency only gave notice of another 
delay and provided no reason for delay or date for completion of 
review.
    Each day that this decision is delayed increases the serious health 
implications for women. The agency needs a leader who will ensure FDA 
decisions are based on scientific evidence and not political interests. 
To restore public confidence in the agency's integrity, Dr. Crawford 
must provide a full account of the decision processes that caused the 
FDA to go against the recommendations of the review panel and 
professional staff, share his assessment of the current situation, and 
provide assurances that a decision will be made on Plan B over-the-
counter based totally on science and not politics. Until he provides 
this information and assurances, we urge you not to confirm him as 
Commissioner.
            Sincerely,
                       National Partnership for Women and Families,
                          Reproductive Health Technologies Project.

    Organizations: Advocates for Youth; American College of 
Obstetricians and Gynecologists; American Society for Emergency 
Contraception; Association of Reproductive Health Professionals; 
Campaign for Access to Emergency Contraception (Champaign, IL); Center 
for Reproductive Rights Center for Women Policy Studies; Champaign 
County Health Care Consumers; Clara Bell Duvall Project, ACLU of 
Pennsylvania; Family Planning Advocates of New York State; Family 
Planning Council (Philadelphia, PA) Feminist Majority Foundation; 
Florida NOW Young Feminist Taskforce; Gainesville Area National 
Organization for Women; Gainesville Women's Liberation Gynuity Health 
Projects; Ibis Reproductive Health; Institute for Reproductive Health 
Access; Massachusetts Emergency Contraception Network; Morning-After 
Pill Conspiracy; NARAL Pro-Choice America; NARAL Pro-Choice Colorado; 
NARAL Pro-Choice Massachusetts; NARAL Pro-Choice Texas; National 
Abortion Federation; National Association of Nurse Practitioners in 
Women's Health; National Family Planning and Reproductive Health 
Association; National Latina Institute for Reproductive Health; 
National Organization for Women; National Women's Health Network; 
National Women's Law Center; New York State Reproductive Rights 
Taskforce; People for the American Way; Pharmacy Access 
Partnership;Physicians for Reproductive Choice and Health; Planned 
Parenthood Federation of America; Population Connection; Redstockings 
Allies and Veterans, New York City; Religious Coalition for 
Reproductive Choice; Sexuality Information and Education Council of the 
United States (SIECUS); Students for Access to Emergency Contraception 
(IL); University of Florida Campus NOW; Women's Health Task Force (IL).
    Individuals: Philip Corfman, M.D. (Bethesda, MD); Betty Farrell, 
CNM, MPH (Brooklyn, NY); Diana Romero, Ph.D. (Mailman School of Public 
Health, Columbia University.
                                 ______
                                 
                                   Consumers Union,
                    Consumer Federation of America,
               U.S. Public Interest Research Group,
                                                    March 15, 2005.
Hon. Michael Enzi,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.

    Dear Mr. Chairman: This Thursday, the Senate Committee on Health, 
Education, Labor, and Pensions will consider the nomination of Dr. 
Lester Crawford to be the Commissioner of the Food and Drug 
Administration.
    Before voting on his nomination, we urge you to ask, and get 
answers to, important questions about Dr. Crawford's record at FDA and 
his plans to achieve meaningful drug safety reform as Commissioner.
    Dr. Crawford has served at the helm of FDA, as either Deputy or 
Acting Commissioner, for the last 3 years. During that time, the 
agency's high profile missteps and failure to take timely action to 
protect consumers from unreasonable drug safety risks have raised 
serious questions about his leadership, his ability to manage 
interagency conflicts and willingness to act in the best interest of 
consumers.
    Dr. Crawford and Secretary of Health and Human Services Michael 
Leavitt recently announced the creation of an independent drug safety 
oversight board at FDA. Unfortunately the move offers no true 
substantive reform and bears little resemblance to the ``emboldened new 
vision'' it is supposed to represent. The Drug Safety Board does 
nothing to improve the agency's weak regulatory capacity or to address 
the inherent internal conflicts of interest that prevent FDA from 
identifying unreasonable safety risks and taking timely action to 
protect the public from them.
    The agency's recent high-profile failings on the safety of widely 
used painkillers and antidepressants are symptoms of a larger problem 
that can only be resolved with critically needed new laws. First, FDA 
lacks authority to require drug companies to conduct safety studies 
once a drug is approved and to require timely protective action when 
unreasonable risks arise.
    Second, the organizational structure of the FDA suffers from 
inherent conflicts of interest by allowing reviewers in the Office of 
New Drugs to make important determinations about the post-market safety 
of drugs they approve. In 2004, these conflicts discouraged public 
release of findings by reviewers in the Office of Drug Safety, who have 
no authority to take action on their own, nor even the right to ensure 
that FDA advisory committees, doctors and patients have access to their 
findings.
    And third, patients and doctors don't have access to all clinical 
trial results, both good and bad, for widely prescribed medications. 
Meanwhile, drug makers are free to publish the positive results in 
medical journals, while downplaying less favorable findings.
    In the face of widely publicized regulatory shortcomings at FDA, 
Dr. Crawford has not acknowledged the need for substantive changes to 
increase the FDA's ability to protect consumers.
    Though he claims to have a bold vision for the FDA, the question is 
whether or not Dr. Crawford is committed to achieving substantive 
rather than symbolic drug safety reform. Such reforms must include full 
public disclosure of all clinical trial results, greater independence 
for the Office of Drug Safety, stronger authority to require additional 
studies on the safety of approved drugs, and increased capacity to take 
action to mitigate unreasonable risks when they arise.
    Before the Senate HELP Committee reports his nomination, we urge 
you to compel Dr. Crawford to enumerate steps he will take to change 
the agency's culture and achieve meaningful administrative and 
legislative reforms to FDA's drug safety system.
            Sincerely,
                                           Jeannine Kenney,
                                             Senior Policy Analyst,
                                                   Consumers Union.
                                           Travis Plunkett,
                                              Legislative Director,
                                    Consumer Federation of America.
                                           Lindsey Johnson,
                                                 Consumer Advocate,
                               U.S. Public Interest Research Group.
                                 ______
                                 
                           Letters of Support



          University of Georgia Alumni Association,
                                     Athens, GA 30602-6372,
                                                 February 17, 2005.
Lester M. Crawford,
U.S. Food and Drug Administration,
Rockville, MD 20852.

    Dear Dr. Crawford: Congratulations on being named Commissioner of 
the Food and Drug Administration. I wish you the best as you move 
forward with your appointment.
    On behalf of the University of Georgia Alumni Association, I would 
like to extend our appreciation for your commitment to excellence. You 
bring honor to your alma mater.
    If I may ever be of service, please do not hesitate to contact me.
            Sincerely,
                                       Deborah A. Dietzler,
                                                Executive Director.
                                 ______
                                 
    American Society of Health-System Pharmacists,
                                        Bethesda, MD 20814,
                                                 February 16, 2005.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.

    Dear Chairman Enzi: The American Society of Health-System 
Pharmacists (ASHP) is writing today to applaud the President's 
nomination of Lester M. Crawford to be Commissioner of the Food and 
Drug Administration (FDA). For more than 60 years, ASHP has helped 
pharmacists who practice in hospitals and health systems improve 
medication use and enhance patient safety. The Society's 30,000 members 
include pharmacists and pharmacy technicians who practice in inpatient, 
outpatient, home-care, and long-term-care settings, as well as pharmacy 
students.
    The FDA has the enormous task of safeguarding our Nation's drug 
supply, ensuring that safe and effective products reach the market in a 
timely manner, monitoring products for continued safety after they are 
in use, and securing accurate, science-based information about these 
products for consumers. Despite extraordinary efforts on the part of 
the FDA, more can and should be done. As a result, the FDA has come 
under significant fire in recent times to strengthen its focus on 
public health and safety.
    The confirmation of a permanent FDA commissioner is an important 
step in positioning the FDA to fulfill its role. Dr. Crawford has 
exhibited the knowledge and leadership qualities that make him the 
right person for the job. During the confirmation process, we hope that 
you will request that Dr. Crawford put forward his plan for achieving 
this important goal. ASHP is particularly interested in FDA plans to 
enhance confidence in the integrity of the drug products reaching the 
pharmacy, increase drug safety information available to health 
professionals and the public, and facilitate the exchange of 
information to providers in times of product shortages or public health 
emergencies.
    ASHP looks forward to continuing our work with Dr. Crawford in his 
new position. We encourage the committee and the Senate to confirm him 
quickly. PIease feel free to contact us at any time if we can be of 
assistance. Kathleen Cantwell, ASHP's Director of Federal Legislative 
Affairs and Government Affairs Counsel can be reached via e-mail at 
[email protected] or by phone at 301-664-8710.
            Sincerely,
                                     Henri R. Manasse, Jr.,
                                              Ph.D., Sc.D.,
                                       Executive Vice President and
                                           Chief Executive Officer.
                                 ______
                                 
                   National Restaurant Association,
                                                    March 16, 2005.

Committee on Health, Education, Labor and Pensions,
U.S. Senate.

    Dear Chairman Enzi: I am writing to express the support of the 
National Restaurant Association for Dr. Lester Crawford, the nominee 
for Commissioner of the Food and Drug Administration. We hope the 
Senate Health Committee, without hesitation, will approve Dr. Crawford.
    As Administrator of the USDA's Food Safety and Inspection Service, 
Dr. Crawford has an unique perspective on the important oversight role 
that both the FDA and USDA provide in maintaining a safe food supply--
this is of the utmost importance to the National Restaurant 
Association.
    In addition, Dr. Crawford's experience in life science, coupled 
with a laudable record of public service focused on those issues makes 
him the ideal candidate for this position. His previous roles as Acting 
FDA Commissioner, and Director for the FDA's Center for Veterinary 
Medicine, give him an unprecedented familiarity with roles and 
responsibilities of the FDA.
    His commendable track record of successes in a variety of settings 
is ample evidence of Dr. Crawford's capabilities. We hope that the 
members of the Senate Health Committee, and the Senate overall, will 
confirm Dr. Crawford as FDA Commissioner.
            Sincerely,
                                        Steven C. Anderson,
                                                   President & CEO.
                                 ______
                                 
                    Strock-Wise Animal Clinic P.A.,
                                      Charleston, SC 29412,
                                                 February 28, 2005.
Dr. Lester Crawford,
U.S. Food and Drug Administration,
Rockville, MD 20857-0001.

    Dr. Lester Crawford: Congratualtions on your appointment to 
Commissioner of the FDA, I have been following your many 
accomplishments in the city by the Potomac and wanted to tell you what 
a great representative of the veterinary profession you have been 
throughout your professional career. If you are ever in Charleston, SC, 
please look me up.
    I spoke with Roger Wilbur the other day; he sends his regards and 
congratulations also. Keep up the good work.
                                               Wilbur Wise.
                                 ______
                                 
                           The 60 Plus Association,
                                       Arlington, VA 22209,
                                                    March 16, 2005.
Hon. Michael B. Enzi,
U.S. Senate,
Washington, D.C. 20510-5004.

    Dear Senator Enzi: I am writing to express my support for Dr. 
Lester Crawford as the next Commissioner of the Food and Drug 
Administration. Dr. Crawford brings to the post a successful 1-year 
tenure as Acting Commissioner of the FDA as well as unique credentials 
and noteworthy achievements that qualify him for leadership of the 
agency's many and varied responsibilities.
    As you may know, Dr. Crawford previously led the FDA as Deputy 
Commissioner as the agency stepped up to counter the threat of 
bioterrorism. He also served the FDA two other times in the past 30 
years, as director of the agency's Center for Veterinary Medicine, from 
1978 to 1980 and again from 1982 to 1985. Dr. Crawford's credentials 
are unmatched. He has dedicated his career to promoting safer products 
for the public; his vast experience positions him well to lead the 
agency going forward.
    Today, the FDA's plate is full, brimming with challenges that when 
successfully accomplished will help 21st century Americans live longer, 
healthier and happier lives. Dr. Crawford has already demonstrated his 
leadership skills and his ability to deliver on the agency's core 
objectives, as measured by the FDA's unprecedented achievements toward 
its comprehensive strategic action plan.
    In 2004, thanks to Dr. Crawford's inspired leadership, the FDA 
improved consumer protection by employing new bioterrorism 
countermeasures. The agency created regulations for safer dietary 
supplements. By applying innovative technologies, the agency bolstered 
protections against medical errors. And the FDA gave consumers the keys 
for improving their own health by educating people with better 
information about the foods they eat and the medicines they take. Of 
paramount importance to the 5 million senior citizens I represent, in 
2004 the FDA gave citizens faster access to safe and affordable 
medicines.
    But there's much more to be done. The FDA estimates it has 
completed about one-third of the work detailed in its strategic action 
plan. The agency has committed to completing three-quarters of the 
remaining work this year. A tall order, yes, but Dr. Crawford is the 
right leader at the right time, one who can focus the FDA's work and 
ensure that the FDA is not given burdensome responsibilities outside of 
its core mission that would dilute its purpose.
    For example, the FDA has worked hard to reduce the time and expense 
of new drug approvals, steadily increasing the speed of its processes 
since the 1990s. But more improvements are needed, as the demand for 
safe, fast and affordable medication escalates, especially among 
seniors. Companies today may spend as much as $800 million to bring a 
new drug to market. That cost is prohibitive and discourages 
innovation, a problem that must be resolved.
    In its role as health educator, the FDA should teach the American 
public, seniors in particular, about current discounts for prescription 
drugs. Discounts are available but not yet well understood by citizens. 
If the FDA were to leverage its credibility as the Nation's public 
health agency and primary consumer protection agency, it could launch 
an information campaign to advise citizens the best ways to avail 
themselves of the best prices on prescription medicines, and 
simultaneously cool down the drug reimportation issue.
    Dr. Crawford's experience in regulating medical, agricultural and 
food product safety will serve well the FDA and the Nation. We welcome 
his vision, focus and leadership on the agency's fundamental 
imperatives, and hope that you will approve his nomination as the next 
Commissioner of the Food and Drug Administration.
    60 Plus is an 11-year-old nonpartisan group with a less government, 
less taxes approach to seniors' issues. 60 Plus has become one of the 
fastest growing seniors groups in the country, doubling then tripling 
its support in the past year. 60 Plus now calls on support from nearly 
4.5 million citizen lobbyists to print and mail millions of letters and 
petitions. 60 Plus publishes a newsletter, SENIOR VOICE, and a 
SCORECARD, bestowing a GUARDIAN OF SENIORS' RIGHTS award on lawmakers 
in both parties who vote ``pro-senior.'' 60 Plus has been called ``not 
only an increasingly influential lobbying group for the elderly,'' but 
also `` the conservative alternative to the AARP.
            Sincerely,
                                                Jim Martin,
                                                         President.
                                 ______
                                 
                             University of Florida,
                    College of Veterinary Medicine,
                                 Gainsville, FL 32610-0136,
                                                 February 25, 2005.
Dr. Lester Crawford,
U.S. Food and Drug Administration,
Department of Health and Human Services,
Rockville, MD 20857.

    Dear Dr. Crawford: Congratulations! I am excited that you were 
nominated by President George Bush for the position of Commissioner of 
the Food and Drug Administration. This is a tremendous accomplishment 
and demonstrates your hard work and dedication to our Nation. I am sure 
President Bush made a very wise choice and that you will excel in your 
new role as Commissioner.
    Please accept my congratulations on your nomination and my very 
best wishes for your continuing success.
            Sincerely,
                                         Dr. Eleanor Green,
                                      DVM, Dipl DACVIM, Dipl DABVP,
                               Professor and Chair, Chief of Staff.
                                 ______
                                 
        Association of American Veterinary Medical 
                                          Colleges,
                               Washington, D.C. 20005-3536,
                                                     March 7, 2005.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.

    Dear Mr. Chairman: The Association of American Veterinary Medical 
Colleges strongly supports President Bush's nomination of Dr. Lester M. 
Crawford to be Commissioner of the Food and Drug Administration. Dr. 
Crawford's unequaled experience, including his current tenure as Acting 
Commissioner and his previous positions as Deputy Commissioner and 
Director of the FDA's Center for Veterinary Medicine, make him 
eminently qualified for this position.
    Dr. Crawford is one of the Nation's preeminent scientists and a 
world renowned leader in the veterinary medical profession. His recent 
election to the Institute of Medicine is evidence of his significant 
contributions to the advancement of the medical sciences and public 
health. In addition, Dr. Crawford's extensive experience in achieving 
cooperation and communication among numerous Federal Agencies and 
private organizations underscores his qualification for high public 
office.
    The FDA is facing unprecedented challenges in ensuring the safety 
of foods, drugs and medical devices for all Americans. It is imperative 
to name a Commissioner with proven leadership ability and impeccable 
scientific acumen. Dr. Crawford embodies these traits and his 
appointment would provide the proper scientific basis of operation and 
exceptional communication skills in the position.
    On behalf of the Nation's 28 colleges of veterinary medicine, the 
AAVMC urges the Senate to confirm Dr. Crawford's appointment as FDA 
Commissioner without delay.
            Sincerely,
                           Lawrence E. Heider, DVM, DACVPM,
                                                Executive Director.
                                 ______
                                 
                   Canadian Food Inspection Agency,
                                                 February 23, 2005.
Dr. Lester M. Crawford,
Commissioner,
Department of Health & Human Services,
Food and Drug Administration,
Rockville, MD 20857.

    Dear Lester: This is just a quick note to congratulate you on your 
appointment as Commissioner. The task will be a difficult one but I am 
certain you will do very well.
    The follow-up to our Argentina PAHO Veterinary Project continues--
next session will be in June 2005. Enclosed is a paper which Enrique 
collaborated on. I am sure you will be interested in the 
recommendations.
            Kind Regards,
                                            Anne MacKenzie,
                                   Science Advisor, Science Branch,
                                   Canadian Food Inspection Agency.
                                 ______
                                 
                                        RetireSafe,
                                          Oakton, VA 22124.
                                                    March 15, 2005.
Hon. Michael B. Enzi,
Chairman,
Hon. Edward M. Kennedy,
Ranking Minority Member,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, DC 20510.

    Dear Senator Enzi and Senator Kennedy: On behalf of RetireSafe's 
300,000 senior citizen supporters across America, I write to express 
our strong support for the nomination of Dr. Lester Crawford, Jr. to be 
the next Commissioner of the U.S. Food and Drug Administration (FDA). 
We believe the older Americans we represent, and the Nation as a whole, 
will be extremely well served by Dr. Crawford in his new role as FDA 
Commissioner. RetireSafe applauds Dr. Crawford's appointment by 
President Bush, and urges your swift confirmation of his nomination to 
this critical post.
    Today, the FDA faces a host of challenges, as well as an expansion 
of responsibilities. It is vitally important that this agency have the 
benefit of a strong, experienced leader. Dr. Crawford, now serving as 
Acting Commissioner of the FDA, is more than qualified to fill that 
need. He is truly a champion of both food and drug safety, exactly the 
kind of individual FDA needs at the helm. This is evidenced by Dr. 
Crawford's work as an advisor to the World Health Organization and the 
United Nations, and as a leader in mandatory nutrition labeling and the 
control of chemical and microbiological contaminants of food.
    Dr. Crawford's prior service at the FDA, as the Administrator of 
the Food Safety and Inspection Service (USDA), as Chair of the 
Physiology-Pharmacology Department at the University of Georgia, and as 
Director of the Center for Food and Nutrition Policy at Georgetown 
University and at Virginia Tech, all indicate that he is a person 
superbly qualified to head the FDA. As a Member of the National Academy 
of Science, a Fellow of the Royal Society of Medicine, and a Fellow of 
the International Society of Food Science and Technology, Dr. Crawford 
is very well respected in the scientific community.
    With these outstanding qualifications, Dr. Lester Crawford is an 
excellent choice to serve as the Commissioner of the FDA. RetireSafe 
urges your strong support of Dr. Crawford, and the swiftest possible 
confirmation of his nomination.
            Sincerely,
                                         Charles G. Hardin,
                                                         President.
                                 ______
                                 
                 LUPUS Foundation of America, Inc.,
                                    Washington, D.C. 20036,
                                                    March 16, 2005.
Hon. Mike Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.

    Dear Mr. Chairman: On behalf of the Lupus Foundation of America, 
which represents the more than 1.5 million Americans with the disease 
lupus, their families and their health professionals, we are writing to 
express our enthusiastic support for the confirmation of Dr. Lester M. 
Crawford as Commissioner of the U.S. Food and Drug Administration 
(FDA). As Acting Commissioner, Dr. Crawford's focused leadership has 
served the Agency and the Nation well during this period of transition.
    While many national nonprofit voluntary health organizations have 
reason to provide input regarding this important position, the Lupus 
Foundation of America has a unique interest in the individual who will 
be confirmed by the Senate. As you may know, the FDA has not approved a 
new lupus medication in nearly 40 years. In recent years, drug 
development for lupus has entered a critical period in which an 
increasing number of biotechnology and pharmaceutical companies are 
developing new therapies for lupus. For individuals with lupus, the 
decisions of the FDA will have a great impact on their quality of life 
and survival.
    Dr. Crawford has included lupus among the diseases that are part of 
the FDA's Critical Path Initiative that seeks to address unmet medical 
needs. Additionally, the Agency is preparing to release the first-ever 
industry guidance document on lupus. Under Dr. Crawford's on-going 
leadership, we believe the FDA will continue to take steps to ensure 
that patients with lupus will soon have access to new life-saving 
medicines aimed at bringing the disease under control. We applaud these 
efforts and look forward to working with him.
    We urge you to confirm Dr. Crawford as the next Commissioner of the 
U.S. Food and Drug Administration. Thank you for your consideration of 
our views. Please let us know if we can be of assistance on this issue 
or any other matters.
            Sincerely,
                                         Sandra C. Raymond,
                                                   President & CEO.
                                 ______
                                 
                                        WomenHeart,
                                    Washington, D.C. 20006,
                                                 February 15, 2005.

 WomenHeart Endorses Appointment of Lester Crawford as FDA Commissioner
    Washington, D.C. (February 15)--WomenHeart: the National Coalition 
for Women and Heart Disease applauds President Bush's selection of 
Lester Crawford as the new Food and Drug Administration (FDA) 
Commissioner. It also urges Congress to swiftly approve his 
appointment.
    ``Dr. Crawford has many years of experience at FDA safeguarding the 
Nation's prescription drug and medical device approval processes, as 
well as our food supply,'' said Nancy Loving, WomenHeart's executive 
director. ``We have worked very well with him on many important patient 
safety issues, including the need to include more women in clinical 
trials. He is an exceptional public servant.''
    Crawford, she noted, supported the Bioshield Act that ensured rapid 
FDA action for medical technologies that could improve the Nation's 
defense against bioterrorism threats and also efficiently secured 
sources to provide added flu vaccine in the 2004/2005 flu season.
    WomenHeart is the Nation's only patient advocacy organization 
serving the 8,000,000 American women living with heart disease and 
provides them support, information and advocacy services. It is a 
public charity headquartered in Washington, D.C. Visit online at 
www.womenheart.org.
                                 ______
                                 
                  Pan American Health Organization,
                               Washington, D.C. 20037-2895,
                                                 February 18, 2005.
Lester Crawford, D.V.M., Ph.D.,
Acting Commissioner,
U.S. Food and Drug Administration (FDA),
Rockville, MD, 20857-1706.

    Dear Dr. Crawford: I am writing to congratulate you on your 
nomination as Commissioner of the Food and Drug Administration. Your 
advice and support of the Veterinary Public Health Program in PAHO has 
been greatly valued over the years, and I have also very much enjoyed 
our personal discussions.
    It is a pleasure to see this recognition of your abilities. Best 
wishes for successful nomination hearings and subsequent work in your 
new role.
            Sincerely,
                                      Stephen Corber, M.D.,
                                                      Area Manager,
                                    Disease Prevention and Control.
                                 ______
                                 
                  Pan American Health Organization,
                               Washington, D.C. 20037-2895,
                                                 February 18, 2005.
Lester M. Crawford, D.V.M., Ph.D.,
Commissioner-Designate,
U.S. Food and Drug Administration,
Rockville, MD, 20557-1706.

    Dear Dr. Crawford: I wish to congratulate you on your recent 
nomination as Commissioner of the United States Food and Drug 
Administration (USFDA) by President George W. Bush.
    I share the opinion of the Health and Human Services Secretary, Mr. 
Mike Leavitt, that you are ``an outstanding choice'' for the post. I am 
highly honored to have the head of one of the most important and 
prestigious U.S. health agencies as a friend who has provided steadfast 
advice to the Pan American Health Organization/World Health 
Organization (PAHO/WHO).
    Please accept my best wishes for continued success in your new 
position.
            Sincerely yours,
                                       Mirta Roses Periago,
                                                          Director.
                                 ______
                                 
             Massachusetts Institute of Technology,
                                     Bedford, MA 01730 USA,
                                                 February 26, 2005.
Lester M. Crawford, D.V.M., Ph.D.,
Office of the Commissioner,
Food and Drug Administration,
Washington, D.C. 20204.

    Dear Doctor Crawford: I wish to congratulate you on your many 
accomplishments and superb service to the government and society in 
general over the many years since you left the ``lovliest village'' of 
the plains in Auburn. Particularly significant is the most recent 
appointment at the FDA, a confirmation of your commitment to the 
protection and improvement of the health and well-being of all of us 
citizens. In all of the many assignments you have had you have brought, 
among other things, wisdom, integrity, and humor to sometimes difficult 
situations. For this, I for one, and for the entire Veterinary 
Profession in general thank you.
    One event which affected me personally and which I've not forgotten 
was a meeting you were chairing somewhere in the western United States 
in the late 1970s. I presented the results on nitrate/nitrite studies 
conducted at MIT under contract to the FDA. Members of the pork 
producers in the audience was ready to tar and feather me for 
suggesting that the food industry might do as well with a little less 
nitrates and nitrites in our foods. You saved me from that rather 
miserable and unfortunate event and for that I have been eternally 
grateful.
    I look forward to following your continuing remarkable career and 
to observe how you grapple with FDA problems, especially with what 
sometimes seems to be a pharmaceutical industry out of control. I've 
worked with the industry all of my active career and came to recognize 
many of their problems. However, if I were limited to only one 
suggestion as to how to improve the current situation in that regard, 
it would be to reduce the amount of direct to consumer advertising; 
this probably contributes more than any other single action to problems 
now under consideration by the Agency (i.e., cox-2 pain killers). As 
our old Professor, Will Bailey would say ``you've done us proud.'' Keep 
up the good work and my best wishes.
            Sincerely,
                                          Paul M. Newberne,
                                               D.V.M. M.Sc., Ph.D.,
                                                Professor Emeritus,
                                             Nutritional Pathology.
                                 ______
                                 
                                     Health Canada,
                                   Ottawa, Ontario K1A 0L2,
                                                 February 17, 2005.
Dr. Lester M. Crawford, D.V.M., Ph.D.,
Acting Commissioner,
Food and Drug Administration,
Rockville, MD 20857-0001.

    Dear Dr. Crawford: On behalf of the Health Products and Food Branch 
of Health Canada, I would like to congratulate you on your nomination 
as FDA Commissioner, a position of enormous importance in the United 
States.
    You come to this position with a very distinguished and outstanding 
career, and the FDA is fortunate to have your leadership in this 
position.We welcome your nomination and believe that you will continue 
to bring to the FDA programs, the vision and energy that had made you a 
success as FDA's Acting Commissioner over the past years.
    Once again, I offer my sincere congratulations to you and look 
forward to a continued collaboration between our two organizations on a 
number of issues, and want you to know how much we have appreciated 
your leadership, support and insights in the past.
            Yours sincerely,
                                           Diane C. Gorman,
                                         Assistant Deputy Minister.
                                 ______
                                 
                            The Tipton Group, Inc.,
                                    Washington, D.C. 20003,
                                                 February 23, 2005.
Dr. Lester M. Crawford,
Acting Commissioner,
Food and Drug Administration,
Rockville, MD 20857.

    Dear Les: Congratulations! I am most pleased that President Bush 
has nominated you to be Commissioner of the Food and Drug 
Administration. In my view, you are clearly the correct choice, and you 
should have been nominated to the position much sooner.
    I am already telling my friends on the Hill that you are the right 
person to take over leadership of FDA. If I can ever be of help to you 
on any specific issues or with Members of Congress, I would like the 
opportunity to try.
    Again, my sincerest congratulations!
            My best regards,
                                         E. Linwood Tipton,
                                                    Chairman & CEO.
                                 ______
                                 
                          Food Marketing Institute,
                               Washington, D.C. 20005-5701,
                                                    March 16, 2005.
Senator Mike Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510-6300.

    Chairman Enzi: The Food Marketing Institute would like to offer its 
support for the nomination of Dr. Lester Crawford to be Commissioner of 
the Food and Drug Administration (FDA). FMI works with FDA on issues 
related to food safety, food security and nutrition on behalf of its 
1,500 member companies--food retailers and wholesalers--in the United 
States and around the world. FMI's U.S. members--large multi-store 
chains, regional firms and independent supermarkets--operate 
approximately 26,000 retail food stores with a combined annual sales 
volume of $340 billion. Its international membership includes 200 
companies from 50 countries.
    Because of Dr. Crawford's present position as Acting Commissioner, 
as well as his previous experience as FDA's deputy commissioner, he 
would bring an unprecedented depth of knowledge to the job. His past 
experience as the U.S. Department of Agriculture's Food Safety 
Inspection Service (FSIS) Administrator and his tenure at FDA guarantee 
that he understands the need for uniformity in food safety policy as 
well as how vital it is for FDA's Center for Food Safety and Applied 
Nutrition to work in tandem with its sister food safety department, 
FSIS.
    Dr. Crawford also brings a unique perspective to the job of 
commissioner as he has a global view that he applies to U.S. food 
policy. He has seen firsthand how the amount of food products imported 
into the U.S. has increased and understands that developing food policy 
that applies only within our borders is no longer viable. His 
experience gives him the ability to see things with a wider lense, for 
example, he was instrumental in the formation of the World Trade 
Organization and has been an advisor to the World Health Organization 
of the United Nations for much of his career. He is a Fellow of the 
Royal Society of Medicine (UK) and a Fellow of the International 
Society of Food Science and Technology.
    Not only does he have a special perspective on the world's food 
supply, he is also a scientist. He was Chair of the Department of 
Physiology-Pharmacology at the University of Georgia and he was the 
Director of the Center for Food and Nutrition Policy at Georgetown 
University and at Virginia Tech (where it moved in 2001). With his 
extensive knowledge regarding the control of chemical and 
microbiological contaminants of foods, Dr. Crawford is able to take his 
science background and use it to create practical solutions for food 
safety issues. In addition, he has also been involved with many of the 
major food safety initiatives in recent history; two of which were 
mandatory nutrition labeling and the recent bioterrorism act.
    Dr. Crawford's distinguished career has also included his induction 
into the French Academy of Veterinary Medicine and he has been a 
recipient of the Wooldridge Award, the British Veterinary Association's 
highest award. Having a commissioner with a background in veterinary 
medicine is most timely as we face such critical issues as regulating 
animal feed and the rise of antimicrobial resistant stains of bacteria.
    With Dr. Crawford's well-rounded career in food science and food 
policy it ensures that food issues will be given proper attention at 
FDA. Once confirmed, the food industry will look forward to sound, 
science-based policy and regulatory decisions under Dr. Crawford's 
guidance.
            Sincerely,
                                              Tim Hammonds,
                                                 President and CEO,
                                          Food Marketing Institute.
                                 ______
                                 
          Medical Device Manufacturers Association,
                                    Washington, D.C. 20006,
                                                    March 18, 2005.
Hon. Michael Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.

    Dear Chairman Enzi: On behalf of the Medical Device Manufacturers 
Association and the hundreds of manufacturers of medical devices, 
diagnostic products and health care information systems we represent, I 
wish to convey strong support for the prompt confirmation of Dr. Lester 
Crawford to be the Commissioner of the Food and Drug Administration so 
he can continue the important work of ensuring the public health safety 
of the Nation's citizens.
    As a representative of the innovative sector of the medical 
technology industry, MDMA has worked closely with Dr. Crawford 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. Crawford, as both a veterinarian and dedicated 
public servant, is uniquely suited to lead the FDA. With rapidly 
developing technologies and advancements in medicine it is imperative 
that FDA is led by a Commissioner who has the ability, dedication and 
integrity to lead the agency. Dr. Crawford has exhibited these 
qualities and it is our sincere hope that the Senate will move quickly 
to confirm him as the next FDA Commissioner.
            Sincerely,
                                               Mark Leahey,
                                                Executive Director.
                                 ______
                                 
          Consumer Healthcare Products Association,
                                    Washington, D.C. 20006,
                                                     March 1, 2005.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.
    Dear Senator Enzi: The Consumer Healthcare Products Association 
(CHPA) sends this letter to express its support for the Senate 
confirmation of Dr. Lester M. Crawford to be Commissioner of Food and 
Drugs.
    Dr. Crawford has devoted most of his career to public service, 
including his current term as Acting FDA Commissioner. The Food and 
Drug Administration has been hampered for too long by having an acting 
head.
    Dr. Crawford is very familiar with the public health policy issues 
confronting the agency and his appointment will assure continuity in 
the leadership of FDA at a critical juncture. He has demonstrated a 
willingness to work cooperatively with stakeholders on important 
matters, and we believe that collaboration is a key to the credibility 
of the regulatory process. We urge the committee to give prompt 
consideration to Dr. Crawford's nomination.
            Sincerely yours,
                                           Linda A. Suydam,
                                                         President.
                                 ______
                                 
                   University of California, Davis,
                              Davis, California 95616-8558,
                                                 February 24, 2005.
Commissioner Les Crawford,
Federal Drug Administration,
Rockville, MD 20857.

Re: Western U.S. FDA Center of Excellence

    Dear Commissioner Crawford: First, let me congratulate you on your 
nomination as Commissioner of the Food and Drug Administration (FDA). 
Your continued interest and investment in the future of our Nation's 
food supply certainly qualifies you for this critical leadership 
position. I look forward to working with you in the future.
    As Chancellor of the University of California, Davis, I am very 
supportive of the opportunity to develop an FDA Center of Excellence on 
the Davis campus. As we lend our support for an added FDA research 
center of excellence, I would like to seek information from you 
regarding the FDA's level of interest in and priority for such an 
endeavor in the Western United States.
    UC Davis established the Western Institute for Food Safety and 
Security (WIFSS) in 2002 to enhance our ability to provide a secure 
food supply by developing a research and training program in food 
defense. Through the Department of Homeland Security (OHS) cooperative 
agreement, we have been developing a region-wide training program for 
individuals and groups that are invested in the safety of our food 
supply, including the import of workers and food from Mexico, Canada, 
and the Pacific Rim.
    Could you share with me those focus areas in which FDA would have a 
specific interest in a western FDA Center of Excellence?
    The University of California, Davis has a long history for 
supporting agriculture and the extensive food systems in California 
through education, research and outreach. The University has been 
essential to California maintaining its leadership as the premier 
agricultural State in the Nation for over 50 years, We look forward to 
an opportunity to develop a strong collaborative research program with 
FDA in California.
    The University recognizes its obligation to help the public, 
through industry, address the extraordinary challenges of improving and 
assuring food safety and food defense. For several years we have 
supported the California food industries' efforts to establish a FDA 
research center of excellence in the Western United States. By joining 
the talents we have assembled at the Western Institute for Food Safety 
and Security with those of FDA, we will be able to efficiently and 
effectively address the threats to our Nation's food systems and those 
that accompany the movement of food across our borders.
    Again, I look forward to working with you on this endeavor and any 
focus areas in which FDA would have a specific interest in a western 
FDA Center of Excellence.
            Sincerely,
                                       Larry N. Vanderhoef,
                                                        Chancellor.
                                 ______
                                 
 Advanced Medical Technology Association (AdvaMed),
                                                 February 15, 2005.
          Appointment of Permanent FDA Commissioner Applauded
    Washington, D.C.--AdvaMed welcomed the Bush Administration's 
appointment today of Lester M. Crawford as commissioner of the Food and 
Drug Administration. Crawford has served as Acting Commissioner since 
the departure of former FDA Commissioner Mark McClellan in March 2004.
    ``We look forward to continuing to work with Dr. Crawford,'' said 
Pamela G. Bailey, AdvaMed President. He understands the unique 
characteristics of the medical technology industry.''
    ``Dr. Crawford's experience will be invaluable as Congress and FDA 
craft legislation this year that will add predictability and stability 
to the medical device user fee program and allow for the program's 
continuation beyond the current fiscal year,'' Bailey said.
    Crawford served as Acting FDA Commissioner before Dr. McClellan 
joined the Agency in November 2002 and was involved in key negotiations 
that led to the landmark ``Medical Device User Fee and Modernization 
Act of 2002.''
    AdvaMed is the world's largest association representing 
manufacturers of medical devices, diagnostic products, and medical 
information systems AdvaMed's more than 1,300 members and subsidiaries 
manufacture nearly 90 percent of the $75 billion of health care 
technology products purchased annually in the United States, and more 
than 50 percent of the $175 billion purchased annually around the 
world. AdvaMed members range from the largest to the smallest medical 
technology innovators and companies. Nearly 70 percent of our members 
have fewer than $30 million in sales annually.
                                 ______
                                 
                       Alliance for Aging Research,
                                    Washington, D.C. 20001,
                                                 February 16, 2005.

 Alliance Endorses Dr. Lester Crawford's Nomination as FDA Commissioner
    Washington, D.C.: The Alliance for Aging Research, a not-for-profit 
organization, supports President Bush's nomination of Dr. Lester 
Crawford as the next FDA commissioner and encourages Congress to act 
swiftly in approving his appointment.
    ``Dr. Crawford is the perfect candidate to lead the FDA at this 
critical time,'' said Daniel Perry, Executive Director of the Alliance 
for Aging Research. ``We are confident that Dr. Crawford will enhance 
the lives of our Nation's aging population by promoting better medical 
practices and guaranteeing the safety of drugs that affect our most 
vulnerable population.''
    ``Dr. Crawford,'' continued Perry, ``will use sound judgment and 
good science when dealing with drug safety. We look forward to continue 
working with him at the FDA in assuring the safety and efficacy of the 
next generation of therapies and treatments.''
    Crawford has been acting commissioner of the FDA since March of 
2004 when Dr. Mark McClellan left the post to become administrator for 
the Centers for Medicare and Medicaid Services.
    Founded in 1986, the Alliance for Aging Research is a nonprofit 
independent organization dedicated to supporting and accelerating the 
pace of medical discoveries to vastly improve the universal experience 
of aging. The Alliance combines the interests of top scientists, public 
officials, business executives and foundation and academic leaders to 
promote a greater national investment in research and new technologies 
that will prepare our Nation for the coming senior boom, and improve 
the quality of life for older Americans. Visit online at 
www.agingresearch.org.
                                 ______
                                 
                    Alliance of Specialty Medicine.
Hon. Michael Leavitt,
Secretary,
U.S. Department of Health and Human Services,
Washington, D.C. 20201.

    Dear Secretary Leavitt: The Alliance of Specialty Medicine supports 
the nomination of Lester M. Crawford Jr. for Commissioner of the Food 
and Drug Administration and urges the Senate to confirm him. Dr. 
Crawford has served the FDA with distinction since be was named to 
serve as deputy commissioner in 2002 and more recently as Acting 
Commissioner.
    As specialty physicians, the more than 200,000 members of the 
Alliance of Specialty Medicine and the millions of patients they care 
for, support the critical role the FDA plays in assuring that the 
Nation's food is safe and properly labeled, The FDA also assures that 
pharmaceuticals, biological products and medical devices are safe, 
effective and properly labeled. Dr. Crawford has devoted his career to 
promoting safer products for the public. His leadership skills and 
experience equip him well for this important position.
    We hope the Agriculture, Nutrition and Forestry Committee and full 
Senate will vote favorably on this nomination.
            Sincerely.
                                 ______
                                 
           American Society for Microbiology (ASM),
                               Washington, D.C. 20036-2594,
                                                 February 22, 2005.
Lester M. Crawford, Ph.D.
Acting Commissioner,
Food and Drug Administration,
Rockville, M.D. 20857.

    Dear Dr. Crawford: We would like to thank you for the generous time 
you took to make such an excellent presentation to the ASM's Public and 
Scientific Affairs Board on February 11. Thank you for being so 
flexible with your schedule. Your presentation of issues and 
information related to the Food and Drug Administration was extremely 
valuable to ASM.
    We would like to congratulate you on your appointment as 
Commissioner of FDA. The Society stands ready to assist you and the FDA 
on issues and policy.
            With best wishes,
                                   Ruth L. Berkelman, M.D.,
                        Chair, Public and Scientific Affairs Board.
                                 ______
                                 
        Association of American Veterinary Medical 
                                          Colleges,
                                        Chicago, IL, 60610,
                                                     March 7, 2005.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510.

    Dear Mr. Chairman: The Association of American Veterinary Medical 
Colleges strongly supports President Bush's nomination of Dr. Lester M. 
Crawford to be Commissioner of the Food and Drug Administration. Dr. 
Crawford's unequaled experience, including his current tenure as Acting 
Commissioner and his previous positions as Deputy Commissioner and 
Director of the FDA's Center for Veterinary Medicine, make him 
eminently qualified for this position.
    Dr. Crawford is one of the Nation's preeminent scientists and a 
world renowned leader in the veterinary medical profession. His recent 
election to the Institute of Medicine is evidence of his significant 
contributions to the advancement of the medical sciences and public 
health. In addition, Dr. Crawford's extensive experience in achieving 
cooperation and communication among numerous Federal agencies and 
private organizations underscores his qualification for high public 
office.
    The FDA is facing unprecedented challenges in ensuring the safety 
of foods, drugs and medical devices for all Americans. It is imperative 
to name a Commissioner with proven leadership ability and impeccable 
scientific acumen. Dr. Crawford embodies these traits and his 
appointment would provide the proper scientific basis of operation and 
exceptional communication skills in the position.
    On behalf of the Nation's 28 colleges of veterinary medicine, the 
AAVMC urges the Senate to confirm Dr. Crawford's appointment as FDA 
Commissioner without delay.
            Sincerely,
                           Lawrence E. Heider, DVM, DACVPM,
                                                Executive Director.
                                 ______
                                 
           American Veterinary Medical Association,
                                 Schaumburg, IL 60173-4350,
                                                 February 17, 2005.
Hon. Michael Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
Washington, D.C. 20510.

    Dear Mr. Chairman: The American Veterinary Medical Association 
(AVMA), on behalf of its more than 72,000 members, strongly endorses 
President Bush's nomination of Dr. Lester M. Crawford to be 
commissioner of the Food and Drug Administration (FDA). Dr. Crawford's 
exemplary record of service and leadership in public health, food 
safety, and regulatory medicine brings invaluable experience and a 
myriad of accomplishments in government, academia, and industry to this 
most esteemed position.
    We echo Secretary Mike Leavitt's comments that Dr. Crawford is an 
``outstanding choice'' for commissioner, especially as the FDA enters a 
new era of medicine and rapidly developing science.
    Dr. Crawford's admirable public service at the FDA as Acting 
Commissioner mirrors his previous appointments as deputy commissioner 
of the FDA, director of the FDA Bureau of Veterinary Medicine, and 
director of the FDA Center for Veterinary Medicine. Noteworthy 
experience in his distinguished and varied Federal career is his 
appointment as administrator of the Food Safety and Inspection Service 
at the U.S. Department of Agriculture. Dr. Crawford's breadth and depth 
of experience in seeking out and facilitating cooperation and 
communication between numerous agencies and organizations underscores 
his qualifications for the office of commissioner.
    In the academic venue, Dr. Crawford has served as the head of the 
Center for Food and Nutrition Policy at Georgetown University and 
Virginia Tech, chairman of the University of Georgia's Department of 
Physiology-Pharmacology, and executive director of the Association of 
American Veterinary Medical Colleges.
    In addition, Dr. Crawford played a key role in the formation of the 
World Trade Organization has been an advisor to the World Health 
Organization of the United Nations for much career.
    The AVMA is the recognized voice of the veterinary profession in 
presenting its views on veterinary medicine, including its relationship 
to public health, biological science, and agriculture, to government, 
academia, agriculture, pet owners, the media, and other concerned 
publics. As such, we strongly endorse Dr. Crawford and encourage the 
Senate to confirm his appointment as FDA commissioner.
            Sincerely,
                                          Bonnie V. Beaver,
                                                BS, DVM, MS, DACVB,
                                                         President.
                                 ______
                                 
                      American Medical Association,
                                         Chicago, IL 60610,
                                                    March 15, 2005.
Hon. Michael B. Enzi,
Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C. 20510-6300.

    Dear Senator Enzi: On behalf of the American Medical Association, I 
write to strongly endorse the confirmation of Lester M. Crawford, 
D.V.M., Ph.D., as Commissioner of the Food and Drug Administration 
(FDA). The FDA Commissioner plays a crucial role in protecting the 
public from unsafe drugs and dangers associated with the Nation's food 
supply while ensuring that the United States remains a leader in 
medical innovation. Today's world of quickly evolving science and an 
increasing reliance on the healing power of prescription drugs calls 
for effective, seasoned leadership at the helm of the FDA. Dr. Crawford 
will provide that leadership.
    Dr. Crawford has dedicated his career to advancing the public 
health, is well known for his work in food safety, and is a first rate 
scientist committed to public service. He has shown a strong commitment 
to improving patient safety, something that we as physicians value most 
highly. As a member of the National Academy of Sciences' Institute of 
Medicine he has contributed to providing accurate, scientifically sound 
information to the public. Importantly, Dr. Crawford has held several 
assignments at the FDA, serving as Deputy Commissioner, and most 
recently as Acting Commissioner. His expertise and experience will 
serve him well as Commissioner.
    During his tenure as Acting Commissioner, Dr. Crawford has pursued 
initiatives to improve drug labeling standards to make it easier for 
physicians to read information critical to the safe and effective use 
of prescription drugs. He has continued the agency's increasing 
oversight of dietary supplements, and also has focused on slowing the 
growth of antibiotic resistance. Furthermore, he has worked to speed 
innovations to make medicines safer and more affordable to the American 
public. He has enhanced bioterrorism countermeasures to protect 
consumers, and is helping to empower Americans by providing more and 
better information about the medicines and food they consume every day, 
We have great confidence that Dr. Crawford's vision and leadership will 
continue to improve the FDA, and will benefit patients and the 
physicians we represent.
            Sincerely,
                                                      ABXD,
                                          Michael D. Mayes,
                                          Executive Vice President.
                                 ______
                                 
                     Additional Letters of Support
                                       Novartiz AG,
                                                 February 24, 2005.
Lester M. Crawford, D.V. M., Ph.D.
Commissioner Designee,
U.S. Department of Health and Human Services,
Food and Drug Administration,
Parklawn--Room 1471,
3600 Fishers Lane,
Rockville, MD 20857.

    Dear Dr. Crawford: It is with great pleasure that I extend sincere 
congratulations on the announcement of your nomination to the post of 
Commissioner of Food and Drugs. It is not only an honor to be named for 
this high post, but an expression by President George W. Bush of his 
confidence in your education, skills, experience and judgment. You have 
clearly demonstrated an abiding commitment to the health and safety of 
U.S. citizens.
    I wish for you a speedy and successful confirmation process and I 
look forward to continuing our cordial working relationship.
            Best personal regards,
                                        Daniel Vasella, MD.
                                 ______
                                 
                  U.S. Office of Government Ethics,
                                          Washington, D.C.,
                                                     March 1, 2005.
Mr. Lester M. Crawford,
Department of Health and Human Services,
Food and Drug Administration,
5600 Fishers Lane,
Rockville, MD.

    Dear Mr. Crawford: Congratulations on your nomination to the 
position of Commissioner, Food and Drug Administration, Department of 
Health and Human Services. I hope you will find that this position will 
be both challenging and rewarding.
    Enclosed for your information is a copy of the letter sent to the 
U.S. Senate stating that the Office of Government Ethics has reviewed 
your financial dlsclosure report and that you are in compliance with 
applicable laws and regulations governing conflicts of interest. Also 
enclosed is ``Ethics Starts Here: A Guide for Senior Officials'' to 
provide you with an introductory guide to the government ethics rules. 
We hope you will find this overview helpful.
    In addition, as you may already know, all Federal Agencies have a 
Designated Agency Ethics Official (DAEO). If, in the course of the 
confirmation process, you have any questions about conflicts of 
interest or other ethics related matters, you should contact your DAEO, 
Edgar M. Swindell, who can be reached at 202-690-7258.
    I wish you all the best as you proceed through the confirmation 
process.
            Sincerely,
                                          Marilyn L. Glynn,
                                                   Acting Director.
                                 ______
                                 
                  U.S. Office of Government Ethics,
                                          Washington, D.C.,
                                                     March 1, 2005.
Hon. Michael B. Enzi,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C.

    Dear Mr. Chairman: In accordance with the Ethics in Government Act 
of 1978, I enclose a copy of the financial disclosure report filed by 
Lester M. Crawford, who has been nominated by President Bush for the 
position of Commissloner, Food and Drug Administration, Department of 
Health and Human Services.
    We have reviewed the report and have also obtained advice from the 
Department of Health and Human Services concerning any possible 
conflict in light of its functions and the nominee's proposed duties.
    Based thereon, we believe that Mr. Crawford is in compliance with 
applicable laws and regulations governing conflicts of interest.
            Sincerely,
                                          Marilyn L. Glynn,
                                                   Acting Director.
                                 ______
                                 
   Center for Biosecurity, Food Safety, and Public 
                                            Health,
                                                     Lakeworth, FL.
Lester M Crawford, DVM, Ph.D.,
Acting Commissioner,
Food and Drug Administration,
Rockville, MD.

    Dear Lester: Congratulations and best wishes for a speedy 
confirmation. You have been an outstanding professional, a dedicated 
public servant, and a perfect exemplar of how members of the veterinary 
profession can contribute to benefit one medicine.
    You will be challenged daily in a manner that would test your inner 
strength. That is the price that you will pay as you continue to serve 
the needs of our Nation--it is a small price. Stay the course, but pace 
yourself and avoid as much as possible the stresses linked to the job. 
I wish you well. You are most deserving.
            Sincerely,
                                             Don A. Franco,
                                                         President.
                                 ______
                                 
                        Cystic Fibrosis Foundation,
                                          Washington, D.C.,
                                                 February 18, 2005.
Hon. Michael O. Leavitt,
Secretary of Health and Human Services,
U.S. Department of Health and Human Services,
Washington, D.C.

    Dear Sec. Leavitt: The Cystic Fibrosis Foundation supports the 
nomination of Dr. Lester Crawford as Commissioner of Food and Drugs. 
Representing 30,000 people with cystic fibrosis (CF) and their 
families, the CF Foundation is keenly aware of the importance of a 
strong leader at the FDA to ensure innovation and protect the public 
health.
    Cystic fibrosis is a chronic, progressive, life-threatening, 
genetic disease that makes breathing difficult and impairs digestion of 
food, It creates abnormally thick, sticky mucus in the lungs and 
pancreas, which results in persistent coughing and chronic lung 
infections, as well as poor weight gain. A bacterial or viral lung 
infection that has a minimal impact on a healthy person could be life-
threatening to someone with CF. While 30,000 people in the United 
States have CF, more than 10 million Americans are unknowing, 
symptomless carriers of a copy of the defective CF gene; individuals 
with CF have two copies of the gene.
    Several new drugs for CF that have been approved in the last decade 
are the result of key incentives, including the Orphan Drug Act and the 
fast track approval process for life-threatening diseases. These drugs 
are critical to the people with CF who desperately need more effective 
medications to enjoy longer, healthier lives with this disease. Though 
we believe the FDA plays a vital role to ensure the safety of all 
medications, our community is well aware of the risk/benefits required 
and the impact on their own health of delaying approval of new 
technology. We hope that as Commissioner, Dr. Crawford will provide the 
essential leadership that will enable the FDA to maintain the priority 
on the timely approval of drugs to treat life-threatening diseases, 
such as CF.
    We look forward to working with the Commissioner in the months and 
years ahead.
            Sincerely yours,
                                    Robert J. Beall, Ph.D.,
                                                 President and CEO.
                                 ______
                                 
                          Federation of American Hospitals,
                                                 February 16, 2004.

   Federation Commends Nomination of Dr. Lester M. Crawford for FDA 
                              Commissioner
    The Federation of American Hospitals commends President Bush's 
nomination of Dr. Lester M. Crawford as Commissioner of the Food and 
Drug Administration (FDA).
    Dr. Crawford has an exemplary record of public service, with both 
the FDA and the U.S. Department of Agriculture, and has performed 
admirably as acting FDA Commissioner. Furthermore, Dr. Crawford has an 
extensive background in consumer health and safety issues, including 
safety issues with medicine and food. We believe Dr. Crawford is an 
excellent choice for FDA Commissioner and look forward to working with 
him on regulatory issues of mutual interest.
                                                 Chip Kahn,
                                                         President.
                                 ______
                                 
                               5504 Goldsboro Road,
                                              Bethesda, MD,
                                                 February 14, 2005.
Lester Crawford, DVM, Ph.D.,
Commissioner,
Food and Drug Administration,
5600 Fishers Lane,
Rockville, MD.

    Dear Commissioner Crawford: Congratulations on your well deserved 
appointment. You join a very distinguished list of individuals to hold 
this position.
    It appears that this appointment will mark some significant 
firsts--first Deputy elevated to full Commissioner; first veterinarian 
trained professional to the post.
    If my accounting is correct, there will have been chemists, 
physicians, a pharmacist, a zoologist and now a veterinarian.
    My best wishes for success in what is one of the best and most 
difficult jobs in Washington.
            Sincerely,
                                           Sherwin Gardner.
                                 ______
                                 
                            Girl Scouts of the USA,
                                                    March 14, 2005.
Hon. Michael Leavitt,
Secretary,
U.S. Department of Health and Human Services,
200 Independence Avenue, SW,
Washington, D.C.

    Dear Mr. Secretary: On behalf of the Girl Scouts of the USA, I 
enthusiastically applaud the nomination of Dr. Lester Crawford to serve 
as the new Federal Drug Administration (FDA) Commissioner. Dr. Crawford 
has served the FDA with distinction as Deputy Commissioner and now 
Acting Commissioner, and we believe he will make an excellent 
Commissioner.
    Throughout our 93-year history we have offered girls innovative 
programs in sports, nutrition and health. Our long-standing commitment 
to the health and well-being of girls gives our organization a profound 
understanding of the complex issue of obesity. From the beginning of 
his tenure at the FDA, Dr. Crawford recognized the need to respond to 
the increase in adolescent obesity and was instrumental in creating our 
Healthy Living partnership between your agency and the GSUSA to educate 
girls and their families about nutrition and the importance of physical 
activity. His leadership and guidance will help to ensure that this and 
other FDA initiatives regarding the health and well-being of children 
and families are successful.
    We look forward to his confirmation and to continuing to work with 
Dr. Crawford to promote healthier lifestyles for all Americans.
            Sincerely,
                                           Kathy Cloninger,
                                           Chief Executive Officer.
                                 ______
                                 
                Generic Pharmaceutical Association,
                                                 February 14, 2005.
Hon. Lester Crawford,
FDA Commissioner.

    Arlington, VA, Feb. 14 Newswire--The Generic Pharmaceutical 
Association (GPhA) today welcomed the White House's nomination of Dr. 
Lester M. Crawford to be Commissioner of the Food and Drug 
Administration (FDA). Dr. Crawford has served as Acting Commissioner 
since 2004,
    ``We're pleased that the White House has decided to nominate Dr. 
Crawford to this key position, A permanent, fully confirmed 
Commissioner will have the authority to move forward on many of the 
important tasks facing the FDA.'' said GPhA President and CEO Kathleen 
Jaeger. ``GPhA has been working with Dr. Crawford in his current role 
and we are looking forward to continuing our conversations with him as 
the permanent Commissioner, once he is confirmed by the Senate.''
    Jaeger noted that because Dr. Crawford has served as Acting 
Commissioner for nearly 1 year, he already is familiar with many of the 
issues affecting the generic industry. Those include the development of 
an abbreviated approval pathway for generic biopharmaceuticals, an end 
to the practice of authorized generics, the timely approval of generic 
medicines, and concerns with price controls/reimportation.
    GPhA represents the manufacturers and distributors of finished 
generic pharmaceuticals, manufacturers and distributors of hulk active 
pharmaceutical chemicals, and suppliers of other goods and services to 
the generic drug industry. Generics represent 51 percent of the total 
prescriptions dispensed in the United States, but less than 8 percent 
of all dollars spent on prescription drugs. For further information, 
please contact GPhA at 703-647-2480, or visit our web site at http://
www.gphaonline.org/.
            Sincerely,
                                           Kathleen Jaeger,
                                                 President and CEO.
                                 ______
                                 
                                                 February 15, 2005.

    The undersigned organizations are writing to express our support 
for Dr. Lester Crawford as Commissioner of the Food and Drug 
Administration.
    Background: People with HIV/AIDS rely on the FDA for approval of a 
vast array of medical treatments. It is the major source of the 
prescription drugs that can forestall their illness and disability. It 
is also the major source of much of the diagnostic and preventive care, 
as well as treatment for those who become sick. We urge the 
confirmation of Dr. Crawford and look forward to his continued 
leadership.
            Sincerely,
    AIDS Action Project Northwest, AIDS Alliance for Children, Youth, 
AIDS Foundation of Chicago, AIDS Legal Council of Chicago, AIDS Project 
Los Angeles, AIDS Rochester, AIDS Services of Dallas, AIDS Survival 
Project, AIDS Treatment Activists Coalition, AIDS Treatment Data 
Network, 1AIDSmeds.com, Asian and Pacific Islander Wellness Center, 
Boulder County AIDS Project, Care for the Homeless, Cascade AIDS 
Project, Catholic Charities AIDS Services, Center for AIDS, Community 
HIV/AIDS Mobilization for Power (CHAMP), Critical Path AIDS Project, 
Doorways, an Interfaith AIDS Residence Program, Fenway Community Health 
Center, Florida Keys HIV Community Planning Partnership, foundation for 
Integrative AIDS Research (FIAR), Gay, Lesbian, Bisexual, and 
Transgender Community Center of Baltimore and Central Maryland, Harm 
Reduction Coalition, Health Education Resource Organization. Inc. 
(HERO), Hemophilia Association of New York, Hep-C Alert, Hepatitis C 
Action & Advocacy Coalition, Hepatitis C Caring Ambassadors Program, 
Hepatitis C Outreach Project, HIV/AIDS Alliance for Region Two, Inc, 
Housing Works, HUG-ME Program, Orlando Regional Healthcare, 
International Foundation for Alternative Research in AIDS (IFARA), Iris 
House, Inc. Latino Commission on AIDS, Latino Organization for Liver 
Awareness (LOLA), Lifelong AIDS Alliance, Long Island Association for 
AIDS Care (LIAAC), Metro St. Louis HIV Health Services Planning 
Council, McAuley Health Center, Minnesota AIDS Project, Montrose 
Clinic, Movable Feast, Inc., NAMES Project Foundation, Nashville CARES, 
National Healthcare for the Homeless Council, New York City AIDS 
Housing Network, Persons Living with HIV Action Network of Colorado, 
Philadelphia FIGHT, Positive Employment Options, Project Open Hand, 
Provincetown AIDS Support Group, Rochester Area Task Force on AIDS, San 
Francisco AIDS Foundation, San Mateo County AIDS Program, Seattle 
Treatment Education Project (STEP), Siouxland and Local Area AIDS 
Project, St. Louis Effort for AIDS, T.H.E. Clinic, Tennessee AIDS 
Support Services, Inc., The Health Association, Treatment Action Group, 
Treatment Access Expansion Project (TAEP), Vermont People With AIDS 
Coalition, Visionary Health Concepts, West Virginia HIV Care 
Consortium, Williamsburg/Greenpoint/Bushwick HIV CARE Network, Wilson 
Resource Center.
                                 ______
                                 
   Institute of Medicine of the National Academies,
                                          Washington, D.C.,
                                                 February 16, 2005.
Lester M. Crawford, Ph.D.,
Commissioner of Food and Drugs,
Food and Drug Administration,
5600 Fishers Lane,
Rockville, MD.

    Dear Les: What great news! Congratulations, and thanks for the 
continued leadership. It's terrific when good work is recognized, and 
that's clearly the case here. We all look forward to working with you. 
Meanwhile, warm wishes for great success.
            Sincerely,
                         J. Michael McGinnis, M.D., M.P.P.,
                                                    Senior Scholar.
                                 ______
                                 
  Interamerican College of Physicians and Surgeons,
                                          Washington, D.C.,
                                                 February 15, 2005.

    The Interamerican College of Physicians and Surgeons was founded in 
1979 to promote cooperation among U.S. Hispanic physicians and to 
advance their professional and educational needs. The ICPA reaches a 
vast majority of the Hispanic medical community in the United States 
and Puerto Rico--over 39,000 physicians--and a growing number of health 
professionals in Mexico, the Caribbean, Central and South America, and 
Spain. The ICPS is the largest association of Hispanic physicians in 
the Nation.
    Today, the ICPS is writing to express our support for the 
nomination of Dr. Lester Crawford as FDA Commissioner. Dr. Crawford has 
a long and distinguished record of bringing safe and effective new 
treatments to all patients. His leadership and expertise will continue 
to guide the FDA to ensure safe regulation of food and medical 
products.
    Again, ICPS urges confirmation of Dr. Crawford.
                                 ______
                                 
                         Kidney Cancer Association,
                                              Evanston, IL,
                                                 February 15, 2005.

    The Kidney Cancer Association is pleased to support the nomination 
of Lester M. Crawford to be Commissioner of Food and Drugs at the 
Department of Health and Human Services.
    Dr. Crawford's track record with regard to regulation of medical 
products and ensuring timely access to safe, effective new tests and 
treatments is an indication of his commitment to patient safety. In 
addition, his FDA service record combined with his science based 
leadership in medical regulation should enable him to serve all 
Americans well--especially the hundreds of thousands with life 
threatening illnesses, such as kidney cancer, demand safe and 
efficacious treatments.
            Sincerely,
                                            William P. Bro,
                                                               CEO.
                                 ______
                                 
            National Alliance for the Mentally Ill,
                                             Arlington, VA,
                                                 February 16, 2005.
Hon. Mike Enzi,
Hon. Edward M. Kennedy,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, D.C.

    Dear Chairman Enzi & Senator Kennedy: On behalf of the 210,000 
members and 1,200 affiliates of the National Alliance for the Mentally 
Ill (NAMI), I am writing to urge support for the nomination of Dr. 
Lester Crawford 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. Crawford brings unique qualifications to the 
important position of FDA Commissioner. He has a strong track record of 
working to ensure timely access to safe, effective new tests and 
treatments. This includes a long record of service at the FDA in both 
the Carter and Reagan administrations. He has a demonstrated record of 
effectiveness in promoting a science-based approach to patient safety.
    NAMI urges the HELP Committee to act swiftly on this important 
nomination. It is critically important that the FDA have a strong 
leader in place address challenges faced by the agency with respect to 
safety and monitoring of medications.
            Sincerely,
                               Michael J. Fitzpatrick, MSW,
                                                Executive Director.
                                 ______
                                 
                National Milk Producers Federation,
                                             Arlington, VA,
                                                     March 9, 2005.
Senate Committee on Health, Education, Labor, and Pensions.

    Dear Chairman Michael B. Enzi: I a writing to express the support 
of the National Milk Producers Federation for Dr. Lester Crawford, the 
nominee for Commissioner of the Food and Drug Administration. We hope 
the Senate Health Committee, following the necessary hearing and 
deliberations, will act quickly to approve Dr. Crawford.
    Few commissioners in the history of the FDA have the depth and 
breadth of Dr. Crawford's experience in life science and food safety 
issues, coupled with a laudable record of public service focused on 
those issues. His two recent stints as Acting FDA Commissioner, coupled 
with his previous service as Director for the FDA's Center for 
Veterinary Medicine, give him an unprecedented familiarity with roles 
and responsibilities of the FDA.
    By the same token, his past service as Administrator of the USDA's 
Food Safety and Inspection Service also provides him a unique 
perspective on the important oversight role that both the FDA and USDA 
provide in maintaining the public health.
    On a personal note, I had the privilege of serving at FDA with Dr. 
Crawford early in my career and I have first hand knowledge of his 
capabilities, statesmanship and leadership. His early life growing up 
on a dairy farm in Alabama also serves him as a man of character, 
discipline, and fortitude.
    His commendable track record of successes in a variety of settings 
is ample evidence of Dr. Crawford's capabilities. We hope that the 
members of the Senate Health Committee, and the Senate overall, will 
also acknowledge those capabilities by acting quickly to confirm Dr. 
Crawford as FDA Commissioner.
            Yours truly,
                                               Jerry Kozak,
                                                 President and CEO.
                                 ______
                                 
  Response to Questions of Senator Bingaman by Lester Crawford, DVM, 
                                 Ph.D.

(1) Response to Letters

    Question 1. We await responses to the March 2004 anthrax vaccine 
letter and the July 2004 letter sent with Senator Reed regarding drug 
trials. Can we obtain answers to these letters? What is the timeframe 
for such responses?
    Answer 1. On June 4, 2004, the Food and Drug Administration (FDA or 
the Agency) responded to your letter of March 7, 2004. Although the 
response was limited due to pending litigation, additional public 
information has become available since our June 2004 response.
    There is only one anthrax vaccine licensed in the United States, 
Anthrax Vaccine Adsorbed (AVA), also known as Biothrax, which is 
manufactured by BioPort Corporation, located in Lansing, Michigan. AVA 
was first licensed by NIH in November 1970. AVA is recommended for 
individuals who may come in contact with animal products that may be 
contaminated with Bacillus anthracis spores and for individuals engaged 
in diagnostic or investigational activities that may bring them in 
contact with Bacillus anthracis spores. It is also recommended for 
persons at high risk, such as veterinarians and others handling 
potentially infected animals.
    In an October 27, 2004 court order currently on appeal, the 
district court for the District of Columbia invalidated the January 5, 
2004, final rule referenced in your letter. On December 29, 2004, in 
deference to the court, FDA republished a proposed rule and proposed 
order to provide notice and comment to give interested persons an 
opportunity for input. Comments were due by March 29, 2005. The 
proposed rule and order can be accessed on FDA's website: http://
www.fda.gov/cber/vaccine/anthrax.htm.
    In the December 29, 2004, proposed rule and proposed order, FDA 
categorized those bacterial vaccines and toxoids licensed before July 
1972 according to the evidence of their safety and effectiveness, and 
issued a proposed response to recommendations made in an advisory 
panel's report. Pursuant to the FDA regulations Title 21, Code of 
Federal Regulations  601.25, the advisory panel was convened on July 
12, 1973, in an organizational meeting, followed by multiple working 
meetings until February 2, 1979. The Final Report of the advisory panel 
was completed in August 1979. The advisory panel's recommendations 
concern conditions relating to active components, labeling, tests 
required before release of product lots, product standards, or other 
conditions considered by the advisory panel to be necessary or 
appropriate for assuring the safety and effectiveness of the reviewed 
products.
    FDA will be considering all comments submitted in response to the 
December 29, 2004, proposed rule and proposed order.

(2) Office of Drug Safety

Background
    The Office of Drug Safety (ODS) is responsible for ensuring the 
safety of drugs already approved and on the market. It is housed within 
the Center for Drug Evaluation and Research (CDER). CDER is also home 
to the Office of New Drugs (OND), which is responsible for reviewing 
new drug applications and approving drugs for market.
    There have been allegations that having both ODS and OND in the 
same component of the FDA creates conflicts. These conflicts stem from 
the fact that both offices are subject to the same management, which 
may not want drugs it has approved for market to be the subject of too 
much scrutiny, and also from the fact that OND and ODS staff are 
colleagues, which may create situations in which less than complete and 
impartial review of safety concerns occurs. The co-location of ODS and 
OND within CDER may have a chilling effect on raising and addressing 
safety concerns.

    Question 2. Dr. Crawford, we have heard allegations about the 
conflicts that stem from the fact that the Office of Drug Safety (ODS) 
and the Office of New Drugs (OND) are co-located within the Center for 
Drug Evaluation and Research. There is some concern that drug safety 
concerns may not receive as much attention as they warrant given the 
potentially divergent missions of ODS and OND.
    What are your thoughts on taking ODS out of CDER and putting it 
elsewhere within the FDA, like the Office of the Commissioner? Will 
that help foster scientific debate about drug safety? Will moving the 
Office of Drug Safety help ensure that drug safety concerns receive the 
appropriate amount of attention?
    Are there other things that you would do to increase the FDA's 
commitment to drug safety? Are there other things you would suggest 
Congress do?
    How do you intend to balance the need to expediently approve 
innovative drugs while ensuring the safety of consumers? Are you 
supportive of an independent office of drug safety?
    Answer 2. Recently, I joined Secretary Leavitt to announce 
important efforts that we are undertaking with FDA to improve its 
ability to monitor and respond to emerging drug safety information. 
These steps will ensure both a better internal process of deliberation 
on drug safety issues that ensures appropriate and independent 
consideration of all issues, as well as a stronger ability to gather 
data about drug safety issues once a drug has been approved.
    Most importantly, we are moving to encourage more transparency and 
to ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent a possible.
    This is in addition to FDA's Five Point Plan to Improve Drug 
Safety, a major initiative designed to improve the monitoring of drug 
products recently approved for marketing. The major components of this 
initiative include:
     Sponsoring a major study of the Drug Safety System by the 
Institute of Medicine;
     Implement a Program for Adjudicating Differences of 
Professional Opinion;
     Conducting a nationwide search to identify a permanent 
director for the Office of Drug Safety;
     Conducting a series of workshops and meetings on drug 
safety and risk management; and
     Publishing risk management guidance.

    FDA's Office of Drug Safety (ODS), in the Center for Drug 
Evaluation and Research (CDER), is already an independent office 
separate from the Office of New Drugs, the office that reviews new drug 
applications. Both the Office of New Drugs and the Office of Drug 
Safety report directly to the Director of the CDER. ODS has independent 
authority to perform its own research and does so every day. To be 
valuable, this independent research must conform to widely accepted 
scientific standards and normal scientific procedures and peer review 
should not be bypassed. And when drug safety issues are identified, 
they must be factored into the risk-benefit equation so that safe and 
effective drugs remain available to patients who need them.
    FDA has a longstanding commitment to provide a strong resource base 
for its drug safety program. The budget for fiscal year 2006 continues 
this commitment. The President has proposed a 24 percent increase for 
FDA's post-market safety program to help further ensure that America's 
drug product supply is safe and effective, and of the highest quality. 
Under this proposal, CDER's ODS would receive increased funding to 
expand the Agency's ability to rapidly survey, identify and respond to 
potential safety concerns for drugs on the market. ODS will hire 
additional staff to manage and lead safety reviews, will increase the 
number of staff with expertise in critical areas such as risk 
management, risk communication and epidemiology, and will increase 
access to a wide range of clinical, pharmacy and administrative 
databases. Our commitment to increase resources available for post-
market safety will enhance the structural changes we are proposing to 
advance drug safety.

(3) Office of Orphan Products

Background
    The Director of the Office of Orphan Products Development (OOPD), 
Dr. Marlene Haffner, is a respected and accomplished leader of OOPD. 
She is a highly dedicated public servant, respected by the 
pharmaceutical and biotechnology industry, by patient organizations, 
researchers, and by national drug regulatory authorities not just in 
the United States but throughout the world.
    Through the office, there are 267 FDA approved orphan drugs and 
several ``humanitarian'' medical devices that treat at least 13 million 
Americans today--Americans who would otherwise have no treatment at 
all--and millions more throughout the world. Just last year, the FDA 
reported that the ``program is widely viewed as a major success in 
assisting in development of treatments for rare diseases, at a very 
modest investment. FDA is conducting an internal review of how the 
successes of Orphan Products development research might be applied to 
other kinds of critical path problems.''
    It is our understanding that Dr. Haffner does not want to retire 
and continues to serve in the Public Health Service (PHS). Under her 
leadership, the FDA's orphan drug program has led the rest of the world 
in an international cooperative effort to address these devastating 
diseases. When Dr. Haffner decides to retire, the FDA should conduct a 
nationwide search for an individual with medical and/or pharmacy 
background and extensive knowledge of orphan products and rare diseases 
to ensure the continued growth and international influence of the FDA's 
Office of Orphan Products Development.

    Question 3. The FDA Office of Orphan Drugs has a long successful 
history. It is my understanding that you are considering management 
changes in the office. If the office has been so successful, why are 
such changes being considered? What are your plans for ensuring that 
future management has the knowledge, subject expertise, and track-
record necessary to ensure continued office and program success, 
including expertise in orphan drugs, biologics, or humanitarian use 
devices?
    Answer 3. All FDA offices are required to have succession plans. 
The incumbent in the Office of Orphan Drugs has been in that position 
for 17 years. Traditionally, FDA leaders have rotated into other 
positions following lengthy periods in one position. This is the best 
for the institution and for the individual. No current Director, 
Associate Commissioner, or Deputy Commissioner has served for 17 years 
in one position. Finally, whenever FDA conducts recruitments for 
vacancies, we strive to identify individuals that have the relevant 
management and subject matter expertise for the position.

(4) Labeling

    The Food and Drug Administration's (FDA) Office of Nutritional 
Products, Labeling and Dietary Supplements (ONPLDS) is responsible for 
essential public health and consumer protection programs. ONPLDS 
develops policy and regulations for nutrition labeling, food standards, 
infant formula and medical foods. During hearings last year by the 
House Appropriations Subcommittee on Agriculture, Rural Development and 
Related Agencies, FDA stated that it would need 10-12 additional full 
time equivalents (FTEs) to complete five important projects, the 
majority of which are food labeling projects associated with reducing 
the costly rise in obesity among Americans. In addition, the Senate 
Committee on Appropriations last year recognized the important public 
health responsibilities of this Office and noted that its funding for 
activities other than the regulation of dietary supplements has 
remained level for several years. In Senate Report 108-340, the 
committee, therefore, encouraged ``FDA to determine if additional 
funding is necessary for ONPLDS to more effectively carry out its 
important responsibilities, and if appropriate, increase funding for 
this office in its fiscal 2006 budget request.''

    Questions 4. Why did FDA fail to request additional FTEs in its 
2006 budget for labeling activities when it told the House that it 
needed 10-12 additional FTEs and was encouraged by the Senate to 
determine if it needed more funding? If these matters are not 
addressed, how will FDA ensure that the market is not flooded with 
deceptive claims appealing to consumer's desire to control their weight 
especially in light of the cut in inspections?
    Answer 4. FDA's Office of Nutritional Products, Labeling and 
Dietary Supplements' (ONPLDS) responsibilities continue to grow, 
including initiatives on infant formula review notifications, better-
informed consumers, obesity, and allergen labeling. In addition, the 
Office has a continuing challenge to protect the safety and security of 
the food supply from tampering and from counterfeit products. The 
President's fiscal year 2006 budget request delineates FDA's priorities 
in this regard. FDA will continue to evaluate if additional funding is 
necessary for ONPLDS to more effectively carry out its important 
responsibilities.

(5) Food and Drug Administration Advisory Committees

    The FDA relies on advisory committees to evaluate the scientific 
evidence supporting applications for new drugs, biologics, medical 
devices, and foods. Advisory committees also play a key role when drug 
safety issues come to the fore, as they have in the past year with the 
use of antidepressants in children leading to suicide and the 
cardiovascular risk from the newer arthritis pain relief medicines 
known as COX-2 inhibitors. Though the Federal Advisory Committee Act 
(FACA) prohibits outside scientists recruited to serve on these 
advisory panels from having conflicts of interest with companies whose 
products are under review, the FDA staff routinely waives such 
conflicts. These waivers are allowed under the law. Moreover, the staff 
usually waits until the eve of the advisory panel's meeting to release 
the names of the scientists who will be serving on the panel and the 
questions they will be asked, thus making it almost impossible for the 
public to scrutinize their choices to determine if the agency has met 
FACA's requirements for eliminating conflicts of interest and assuring 
that the committee is balanced with regard to points of view. The use 
of waivers reached a nadir at the recently concluded advisory panel on 
COX-2 inhibitors, where at least 10 of the 32 scientists on the panel 
had financial relationships with the companies involved. These 
conflicts were not disclosed at the meeting. Moreover, the FDA claimed 
that they didn't need to be disclosed because it was just a general 
discussion of the issue and not specific to any one company even though 
at the end of the 3-day meeting, specific votes were taken on three 
drugs.

    Questions 5. Why did the FDA say at the advisory committee meeting 
that voted on specific COX-2 inhibitors that financial relationships 
with the companies making those drugs did not have to be disclosed? 
What efforts did the FDA make, prior to that COX-2 inhibitors meeting, 
to find additional experts who did not have a financial relationship 
with the manufacturers of those drugs? More generally, what do you 
intend to do at the FDA to clean up the advisory committee process for 
drugs, biologics, medical devices, and foods so that scientists who 
serve on your panels don't have conflicts of interest with the 
companies whose products are under review?
    Answer 5. FDA screened the Advisory Committee members and other 
invited special Government employees (SGEs) for conflicts of interest 
according to the same strict ethics guidelines FDA applies to all its 
advisory committees. This transparent process requires the Agency to 
carefully weigh any potential financial interest with the need for 
essential scientific expertise in order to protect and advance the 
public health. It is very difficult to obtain qualified advisory 
committee panel members who are totally free from any previous 
association with manufacturers. The Nation's experts (and in some 
cases, there are only a few experts on a particular topic) are sought 
after for consultation by both the Agency and industry because of the 
scarcity, and therefore the value, of their expertise. Utilizing less 
experienced or less highly qualified scientists in order to completely 
remove any potential conflict from the committee would hamper the 
Agency's ability to protect and advance the public health.
    The Agency's staff examines all potential financial interests. The 
Agency's process is to evaluate the potential financial interests of 
members and other invited special government employees. FDA makes a 
determination as to whether the participation of an individual with 
some financial ties outweighs the need for the agency to understand the 
science on the topic before the committee. Although the Agency has 
guidelines for this process (see Waiver Criteria Document 2000 on the 
FDA website: http://www.fda.aov/oc/advisory/conflictofinterest/
intro.html.), this is not a black and white process. It requires 
careful consideration of all facets of the issue in order to evaluate 
that balance. Congress, by permitting waivers for potential conflicts 
of interest, has ensured that the Agency and the public (through the 
advisory committee process) have access to the most knowledgeable 
individuals on the meeting topic.
    Although 18 U.S.C. Section 208 provides that a copy of any waiver 
determination is available to the public upon request, the Agency may 
withhold from disclosure information that would be exempt under the 
Freedom of Information Act, 5 U.S.C.  522(b). Under this provision, 
all of the information concerning conflicts of interest may be withheld 
as exempt pursuant to 5 U.S.C.  522(b)(3) because the Ethics in 
Government Act prohibits release of the information. Nevertheless, in 
order to provide meaningful disclosure of conflicts of interest 
information, the Office of Government Ethics has concluded that, under 
section 208, Federal agencies have discretion to disclose information 
concerning the waived conflict of interest absent a foreseeable harm to 
be caused by the disclosure. The Office of Legal Counsel, United States 
Department of Justice (OLC), concluded that FDA may exercise its 
discretion in making disclosure to avoid making the disclosure 
requirement so intrusive or onerous as to make outside experts 
unwilling to serve on advisory committees.
    In January 2002, the FDA issued draft guidance on ``Disclosure of 
Conflicts of Interest for Special Government Employees Participating in 
FDA Product Specific Advisory Committee.'' The guidance provides 
information on the type and amount of information that will be 
disclosed to the public when a member is granted a conflict of interest 
waiver with the topic to be discussed by the committee. The guidance 
applies only to those advisory committee meetings at which a particular 
matter relating to a particular product is discussed (product specific 
meetings). The guidance does not apply to advisory committee meetings 
that provide advice on topics of general applicability (i.e., those 
meetings that could affect a class of products and their sponsors) even 
if the members on the committee received general matters waivers 
covering their participation on the committee.
    The disclosure for particular matters identifies whether the 
interest is related to the sponsor or competitor that markets a product 
competing with the product at issue (without naming the competitor), 
the type of interest (stock, consulting, contracts/grants, patents/
royalties/trademarks, expert witness, teaching, speaking, or writing), 
and the magnitude of the interest is described as a range.
    After conducting the Agency's standard thorough review of the 
potential conflicts of interest for all potential members and invited 
SGEs on the advisory committee discussing the class of COX-2 
inhibitors, several types of conflicts of interest were found. At least 
one potential participant was recused from the meeting entirely. In 
other cases, FDA found the conflicts not to be of sufficient magnitude 
to outweigh the need for the SGEs' specific scientific expertise for 
this public meeting. Accordingly, the Agency approved waivers to allow 
the participation of 19 scientists. The additional 16 participants did 
not require waivers.
    SGEs who serve the public interest on advisory committee panels are 
world-class experts who are highly renowned and respected in their 
fields. Most consider it an honor and a privilege to serve on advisory 
committees. SGEs disclose all relevant personal and imputed financial 
information and members of the public may request copies of the waivers 
granted under 18 U.S.C. 208 through the Freedom of Information Act 
process. FDA has no reason to believe that any potential conflict 
affected the participant scientist's recommendations given our careful 
evaluation of all potential conflicts, selection of appropriate 
experts, and adherence to our standard process for granting and 
disclosing waivers where the need for essential scientific information 
for public discussion is so warranted.
    FDA's process of evaluating potential committee members for 
conflicts is very extensive and transparent. At the beginning of each 
meeting, a conflict of interest statement is read into the record, 
which summarizes the results of the conflicts of interest screening. 
FDA has been commended by the Office of Government Ethics (1997) for 
serving as ``a model for other Agencies to use in developing their own 
systems and procedures.'' Nonetheless it is always prudent to regularly 
assess the Agency program and determine if any improvements are 
warranted. In the near future, the Agency will review the advisory 
committee conflicts of interest disclosure process and consider if 
further improvements are necessary to make the disclosures more easily 
accessible to the public.

(6) Trans Fat in Partially Hydrogenated Vegetable Oils

    Trans fat in partially hydrogenated vegetable oils is a major 
public health problem because it promotes heart disease. In July 2002 
the Institute of Medicine (``IOM'') of the National Academy of Sciences 
concluded that the consumption of trans fat is at least as unhealthful 
as the consumption of saturated fat and that consumption of trans fat 
in any amount increases the risk of heart disease. In December 2003 the 
IOM concluded that it is feasible to exclude from the diet trans fat 
from partially hydrogenated vegetable oil. In April 2004 the Nutrition 
Subcommittee of the Food and Drug Administration (``FDA'') Food 
Advisory Committee concluded that trans fat is more conducive to 
coronary heart disease than is saturated fat. The January 2005 Dietary 
Guidelines recommended minimizing consumption of trans fat from both 
partially hydrogenated oils and meat and dairy products.

    Questions 6. In addition to inclusion of trans fat information on 
Nutrition Fact labels by 2006, what other measures will be taken by FDA 
to promote public health in regard to trans fat intake?
    Answer 6. FDA is requiring the declaration of trans fat amounts 
directly under the saturated fat line on the nutrition facts panel 
(without a %DV). This requirement goes into effect January 1, 2006. 
(The trans fat labeling rule, which was published on July 11, 2003, in 
the Federal Register, can be found at http://www.cfsan.fda.gov/-
acrobat/fr03711a.pdf). We believe this information will allow consumers 
to lower their intake of trans fat. We estimate that 3 years after the 
January 1, 2006 effective date, trans fat labeling will result in 
approximately 600 to 1,200 fewer cases of coronary heart disease and 
240-480 fewer deaths each year, saving $900 million to $1.8 billion per 
year in medical costs, lost productivity, and pain and suffering.
    FDA understands the important public health concern associated with 
the consumption of products that contain cholesterol-raising lipids 
such as trans fat which, in turn, may increase the risk of coronary 
heart disease. We encourage consumers to choose foods with lower 
amounts of saturated fat, trans fat and cholesterol as part of a 
healthy diet (see FDA's education material entitled ``Trans Fat Now 
Listed with Saturated Fat and Cholesterol on the Nutrition Facts 
Label'' on the web at http://www.cfsan.fda.gov/-dms/transfat.html). FDA 
also recommends that saturated and trans fats be replaced with mono- 
and polyunsaturated fats because mono- and polyunsaturated fats do not 
raise LDL (or ``bad'') cholesterol levels and have health benefits when 
eaten in moderation. The 2005 Dietary Guidelines for Americans contain 
these same recommendations. The FDA has worked closely with other 
offices within the Department of Health and Human Services to foster 
the incorporation of these messages into consumer education materials 
as it relates to nutrition labeling. To further disseminate FDA's 
consumer message about trans fat and other cholesterol raising fats, we 
are planning additional outreach efforts, including a Newsflash that 
can be incorporated into consumer magazines and other publications.
    The Agency has no regulation defining nutrient content claims or a 
reference value for trans fat. In the near future, we hope that we will 
be able to establish definitions for claims such as ``trans fat free'' 
and in response to an ANPRM that published the same day as the trans 
fat labeling final rule (http://wvvw.cfsan.fda.gov/-Ird/fr03711b.html). 
Soon, FDA will be conducting consumer research to determine consumer 
perception of trans fat labeling including nutrient content claims and 
a possible footnote statement. Currently, the label or labeling may 
contain a statement about the amount of trans fat provided the 
statement is not false or misleading and in no way characterizes the 
level of trans fat in the food. For example, ``0 g trans fat/per 
serving'' and ``2 g trans fat/per serving'' are appropriate when, in 
fact, the nutrition facts panel represents these same amounts of trans 
fat per serving.
    FDA is also working to develop educational strategies and 
partnerships to support appropriate messages and teach people, 
particularly children, how to lead healthier lives through better 
nutrition.
    Fostering the development of healthier food products for American 
consumers is an important aspect of public health. FDA is aware of the 
impact labeling trans fat has on the manufacturer (e.g., by creating an 
incentive to reformulate), and the alternative ingredients or 
processing techniques under consideration for reducing trans fat. FDA 
is monitoring industry progress in this effort.

(7) Nutrition Education Strategy

Background
    In commenting on the Calories Count report of March 2004, you (FDA 
Deputy Commissioner Lester M. Crawford, D.V.M., Ph.D.) said, ``Our 
report concludes that there is no substitute for the simple formula 
that ``calories in must equal calories out'' in order to control 
weight. We're going back to basics, designing a comprehensive effort to 
attack obesity through an aggressive, science-based, consumer-friendly 
program with the simple message that ``Calories Count.'' Thus far, we 
have seen that education campaign in the form of the updated nutrition 
facts label website and the consumer brochure that accompanied the 
release of the 2005 Dietary Guidelines for Americans.

    Question 7. What ``aggressive, science-based, consumer friendly'' 
strategies do you have planned for the future?
    Answer 7. FDA believes that all parties, including the packaged 
food industry, restaurants, academia, and other private and public 
sector organizations in addition to government agencies at all levels, 
have an essential role to play in communicating the report's messages 
to the public. FDA is focusing its science-based, consumer friendly 
strategies in 3 areas at this time:
     Developing education materials and partnerships to promote 
appropriate weight management messages.
     Evaluating the need for changes to the food label to make 
it easier for consumers to understand the calories and portion sizes 
they are consuming.
     Working with a third party facilitator to begin a national 
policy dialogue, seeking consensus-based solutions, on the obesity 
problem and away-from-home foods.
    FDA is working to develop educational strategies and partnerships 
to support appropriate messages and teach people, particularly 
children, how to lead healthier lives through better nutrition. We are 
starting work with the Girl Scouts of the USA, under terms of a 
Memorandum of Understanding signed this past fall, to provide outreach 
and education in a science-based initiative to focus on improving 
health, nutrition, and physical activity. In addition, FDA's field 
offices are participating in local partnerships to reach and teach 
children. For example, in Central Florida, FDA's SE Region is part of 
the Seminole County Healthy Kids Partnership to promote positive 
opportunities for school-aged children in Seminole County to learn 
healthy nutrition and the value of increased daily physical activity. 
These are examples of how FDA is working to leverage its ability to 
convey appropriate messages on obesity to the public with the goal of 
changing behavior and ultimately reversing obesity trends in the United 
States.
    FDA has published advance notices of proposed rulemaking (ANPRMs) 
addressing prominence of calories on the label and certain provisions 
of the nutrition labeling regulations related to serving size.
    FDA also stresses that the regulatory scheme for claims in food 
labeling, whether health claims, nutrient content claims, or other 
types of claims, must be science based. We continue to consider 
modifications to our regulations to keep up with recent scientific 
developments. A benefit of standardized, science-based terminology 
(e.g., terminology concerning fat content) is that it allows consumers 
to compare across products and it encourages manufacturers to compete 
based on the nutritional value of the food. FDA, however, does not 
regulate television and other media marketing of food products.
    In June 2004, FDA signed a contract with the Keystone Center, a 
nationally recognized facilitator for policy and scientific issues, to 
begin a dialogue on away-from-home foods and the pediatric obesity 
(education) issue. The goal of the away-from-home foods dialogue will 
be to consider what can be done, given the best available evidence to 
date, to support consumers' ability to manage energy intake with 
respect to preventing undue weight gain and obesity. The dialogue will 
produce a report to FDA and options for a range of actions by diverse 
stakeholders, including government, industry, voluntary health 
agencies, consumer organizations, and others. Keystone will convene its 
first plenary meeting of stakeholders, to include representatives from 
the restaurant industry, academia, consumer groups and government on 
April 26-27, 2005.
    The final Keystone report, and comments received on the two ANPRMs, 
in combination with other information, will provide FDA with 
information on which to base future activities.

(8) Scientific Evidence vs. Personal or Political Ideology

    Questions 8.  Do you have a personal commitment to keep politics or 
political ideology out of the FDA approval process? If so, how do you 
plan to accomplish this?
    Answer 8. The law is clear that FDA approval decisions should be 
based on science, and the requirements of the law, not ideology or 
opinion. Sometimes the science is not adequately developed to provide 
for a clear decision, and decisions have to be deferred until adequate 
information is available.
    I am committed, if confirmed, to ensuring that during my tenure as 
commissioner, FDA's decisions will be based on science and the 
requirements of the law and that the basis for FDA's decisions are open 
and transparent to the public.
    My vision for the future of FDA is one of transformation. And one 
aspect of that transformation will be ensuring an agency culture of 
transparency, collaboration, and cutting-edge thinking.
                                 ______
                                 
  Response to Questions of Senator Burr by Lester Crawford, DVM, Ph.D.
    Question 1. On Monday, March 14, 2005, the NIH inadvertently posted 
on its website at 2:22 p.m. the results of a large clinical trial that 
showed a Genentech drug helped certain lung-cancer patients live 
longer. The NIH was supposed to publish those results at 4 p.m., after 
the close of trading. Due to the mistake, Genentech's stock shot up 25 
percent and the NYSE halted trading in the shares just before 3:30 
p.m.--but in the preceding 10 minutes, 4.7 million shares had changed 
hands. There has been some discussion around the drug safety issue 
about putting more clinical trial data on the web. Shouldn't we 
consider examples like what happened on March 14 and think twice about 
putting more and more clinical trial data on the web?
    Answer 1. As you know, I recently joined Secretary Leavitt to 
announce important efforts that we are undertaking with FDA to improve 
its ability to monitor and respond to emerging drug safety information.
    These steps will ensure both a better internal process of 
deliberation on drug safety issues that ensures appropriate and 
independent consideration of all issues, as well as a stronger ability 
to gather data about drug safety issues once a drug has been approved.
    Most importantly, we are moving to encourage more transparency and 
to ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent as possible.
    You raise an important point, and I agree that it is important that 
we make this information available in a meaningful, accurate and 
responsible manner, and I hope to continue to work with this committee 
as we move forward.

    Question 2. FDA and USDA have joint responsibility over the Food 
Emergency Response Network. Who at the FDA will be in charge of working 
on that Network and how directly will they report to you?
    Answer 2. As you know, the Food Emergency Response Network (FERN) 
is a nationwide laboratory network that integrates existing Federal and 
State food testing laboratory resources by utilizing standardized 
diagnostic protocols and procedures. FERN is the collaborative work of 
USDA and FDA with support from the Department of Homeland Security 
(DHS), Centers for Disease Control and Prevention (CDC), Department of 
Defense (DOD), Federal Bureau of Investigation (FBI), Customs and 
Border Protection (CBP), and the Environmental Protection Agency (EPA). 
By increasing our laboratory search capacity, FERN will enhance the 
Nation's ability to respond swiftly to a terrorist attack.
    The FERN Steering Committee, which includes Federal and State 
representation, was established in September 2003 and is jointly 
chaired by Patrick C. McCaskey, Senior Executive for Laboratory 
Services within the Office of Public Health Sciences in USDA's Food 
Safety and Inspection Service and John R. Marzilli, Deputy Associate 
Commissioner for Regulatory Affairs in FDA's Office of Regulatory 
Affairs (ORA). FERN Subcommittees have also been formed which provide 
guidance and expertise regarding the development and implementation of 
FERN programs to Messrs. McCaskey and Marzilli specifically, and the 
steering committee, in general.
    Participating FERN laboratories fall within one of five 
geographically based Regional Coordination Centers (RCCs), otherwise 
known as regional ``hubs''. The regional hubs include the Northeast 
RCC, the Southwest RCC, the Southeast RCC, the Pacific RCC and the 
Central RCC. Each RCC is led by an Interdisciplinary Scientist who 
receives direction from, and reports directly to, the FERN National 
Program Office (NPO) located within FDA's/ORA's Division of Field 
Science. Scientists within the Division of Field Science who have 
oversight of FERN programs subsequently advise, inform and notify Mr. 
Marzilli of all issues involving FERN laboratories. FDA's Center for 
Food Safety and Applied Nutrition also assists the FERN initiative by 
providing specialized scientific expertise, laboratory capabilities, 
and research capabilities, as well as training, proficiency, and 
logistics support.
    Mr. Marzilli reports to his immediate supervisor, the Associate 
Commissioner for Regulatory Affairs who, in turn, reports directly to 
the Commissioner of Food and Drugs.

    Question 3. The DOD and USDA use the Carver Analytical Tool to 
perform threat assessments and understand where vulnerabilities are in 
a particular system. Will the FDA also use the Carver Analytical Tool 
on the food system? I would think that there could be better 
coordination between the DOD, USDA and FDA if everyone is using the 
same tool to perform threat assessments.
    Answer 3. I agree with your statements. To perform threat 
assessments, the Agency has been using the CARVER + Shock Analytical 
Tool since April 2003. In preparing for the CARVER + Shock analysis, 
FDA worked with DOD, CIA, FBI, and our colleagues at USDA/Food Safety 
Inspection Service to develop a design basis threat (i.e., what a party 
intent on doing damage could do based on their capability, intent, and 
past history). The CARVER + Shock analyses for two food products have 
now been classified as SECRET. Furthermore, seven other products under 
FDA jurisdiction are currently being finalized using the CARVER + Shock 
Analytical Tool. In addition to these assessments, FDA has been working 
with selected higher risk commodity industry groups to initiate threat 
assessment and identify preventive measure options using a CARVER + 
Shock approach. Also, FDA has collaborated with USDA using the CARVER + 
Shock Analytical Tool on specific commodities that are of joint 
interest in relation to the school lunch program.

    Question 4. The FDA's Core Mission covers a wide spectrum, 
including:
     Maintaining the safety of the Nation's food supply from 
threats such as BSE or ``mad-cow'' disease;
     Ensuring that vaccines are safe and in ready supply for 
the American public;
     Reviewing the safety and efficacy studies for new medical 
drugs and devices; and
     Monitoring approved medical drugs and devices for 
unforeseen health consequences, to name a few.

    Does FDA possess adequate resources and expertise to carry out 
these core missions?
    Do you believe there are other areas not currently within the 
agency's purview that it should address?
    If so, is the regulation of tobacco one of those areas?
    If there are other areas, how would you expect to allocate FDA's 
limited resources to address these new areas without impacting the 
agency's ability to carry out its core mission?
    Answer 4. FDA has a highly motivated and well-trained staff. Our 
resource levels have been sufficient to meet critical needs and 
requirements and have been augmented by Congress when new demands are 
identified as occurred, for example, with the fiscal year 2002 Counter 
Terrorism supplemental appropriations. Our mission involves the 
regulation of food and medical products that are valued at more than 20 
percent of every consumer dollar spent in the U.S. The Administration's 
budgets are set at a level to effectively accomplish FDA's core 
mission. If new needs arise, the Administration will work with Congress 
to address them.

    Question 5. Critics have argued that FDA cannot be trusted to 
safeguard the American drug supply and that we need to set up an 
independent drug safety office, separate from the FDA and the FDA 
personnel who review and approve drug products, to oversee drug safety. 
Do you believe that an independent drug safety is necessary? Is there, 
in fact, some benefit to having the drug safety review function remain 
within FDA even after approval? What is the FDA doing internally to 
enhance the independence of its drug safety oversight?
    Answer 5. Recently, I joined Secretary Leavitt to announce 
important efforts that we are undertaking with FDA to improve its 
ability to monitor and respond to emerging drug safety information.
    These steps will ensure both a better internal process of 
deliberation on drug safety issues that ensures appropriate and 
independent consideration of all issues, as well as a stronger ability 
to gather data about drug safety issues once a drug has been approved.
    Most importantly, we are moving to encourage more transparency and 
to ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent as possible.
    This is in addition to a major initiative designed to improve the 
monitoring of drug products recently approved for marketing. The major 
components of this initiative, including the IOM study, include:
     Conducting a nationwide search to identify a permanent 
director for the Office of Drug Safety;
     Conducting a series of workshops and meetings on drug 
safety and risk management; and
     Publishing risk management guidance.

    FDA has a longstanding commitment to provide a strong resource base 
for its drug safety program. The budget for fiscal year 2006 continues 
this commitment. The President has proposed a 24 percent increase for 
FDA's post-market safety program to help further ensure that America's 
drug product supply is safe and effective, and of the highest quality. 
Under this proposal, CDER's ODS would receive increased funding to 
expand the Agency's ability to rapidly survey, identify and respond to 
potential safety concerns for drugs on the market. ODS will hire 
additional staff to manage and lead safety reviews, will increase the 
number of staff with expertise in critical areas such as risk 
management, risk communication and epidemiology, and will increase 
access to a wide range of clinical, pharmacy and administrative 
databases. Our commitment to increase resources available for post-
market safety will enhance the structural changes we are proposing to 
advance drug safety.
    With regards to an independent drug safety office, FDA's Office of 
Drug Safety (ODS), in the Center for Drug Evaluation and Research 
(CDER), is already an independent office separate from the Office of 
New Drugs, the office that reviews new drug applications. Both the 
Office of New Drugs and the Office of Drug Safety report directly to 
the Director of the CDER. ODS has independent authority to perform its 
own research and does so every day. To be valuable, this independent 
research must conform to widely accepted scientific standards and 
normal scientific procedures and peer review should not be bypassed. 
And when drug safety issues are identified, they must be factored into 
the risk-benefit equation so that safe and effective drugs remain 
available to patients who need them.
    FDA will await the views and findings of the IOM study before 
making any major structural changes with regard to ODS. The benefits of 
having both OND and ODS under one FDA center are many. Most 
importantly, the current structure allows important risk information on 
drugs to be shared rapidly between the two offices that are most 
familiar with the benefits and risks of the drug. It is this close 
collaboration that allows FDA to make the critical decisions with 
regard to a drugs benefit-to-risk profile.

    Question 6. In November 2002, the FDA disbanded its Medical Imaging 
Drugs Advisory Committee (MIDAC), ending the 25 year existence of that 
body. Medical imaging drugs are now the only significant class of drugs 
for which FDA does not have a standing advisory committee. We 
understand that FDA is currently obtaining expert medical imaging 
advice by retaining medical imaging experts on an ad hoc basis and 
assigning them to existing standing committees as temporary members for 
particular meetings. In its notice terminating the MIDAC, FDA said this 
system would be ``more effective'' than a standing MIDAC, but did not 
explain why. It is difficult to understand how this ad hoc system would 
be more effective than having a cohesive group of imaging experts with 
appropriate continuity meeting as a standing committee at regular 
intervals. Please explain how the current system of assigning experts 
ad hoc to existing committees on a meeting-by-meeting basis is ``more 
effective'' than having a standing committee.
    Answer 6. The MIDAC met only infrequently in the preceding years. 
The decision to terminate MIDAC was based on several factors. We 
believe that the FDA advisory committee assessment of the risks and 
benefits to patients of a new imaging procedure is enhanced through the 
perspective of physicians who are providing direct care to patients, 
and, as part of that direct patient care, are ordering all imaging 
procedures for their patients. As part of the assessment of a patient's 
care, these attending physicians must determine the risk and benefit to 
their patients of all imaging procedures. As such, the current FDA 
advisory committee assessment of a new imaging procedure is performed 
by the advisory committee that represents the specialty of patient care 
physicians that will order the new imaging procedure, in conjunction 
with all other imaging procedures. We believe we can continue to obtain 
the essential external advice from imaging trained specialty physicians 
for the FDA advisory committees by supplementing the membership of our 
patient care specialty advisory committees. For example, medical 
imaging special government employees (SGEs) were part of the Pediatric 
Subcommittee of the Anti-Infective Drugs Advisory Committee that 
occurred in February 2004 to discuss the use of imaging drugs in 
conjunction with cardiac imaging procedures in the pediatric 
population. They were also part of the November 2002 meeting of the 
Peripheral and Central Nervous System Drugs Advisory Committee on the 
role of brain imaging as an outcome measure in Phase 3 drug trials in 
Alzheimer's disease. Most recently, they were also part of the March 
2005 Oncology Drugs Advisory Committee that assessed the performance of 
lymph node imaging in patients with possible metastatic cancer.
    Please be assured that the Agency believes it possesses the 
scientific expertise required to perform thorough reviews of 
applications pertaining to these drug products and make informed 
decisions, and can supplement that expertise with outside input. In 
addition, we are committed to resolving scientific issues regarding 
medical imaging in a timely manner.

    Question 7. I have always been concerned that a generic biologic 
would not pass the FDA's gold standard safety test, especially without 
the FDA using protected information from other companies' biologic 
applications. Where does the generic or follow-on biologic process 
stand at the FDA?
    Answer 7. As you know, FDA is conducting a public process to 
examine the many questions, including scientific and legal issues, that 
must be answered regarding these products and to ensure that all 
interested parties have an opportunity to comment. When this process is 
complete, FDA intends to provide guidance to industry to clarify, 
consistent with its legal authority, the approval pathway and 
principles for review of such products, which will protect the public 
health.

    Question 8. Since the implementation of the Generally Recognized as 
Safe (GRAS) notification process at the Center for Food Safety and 
Nutrition, what has been the number of full time employees (FTEs) 
involved in the review and safety evaluation of food ingredients before 
and after GRAS notification, how many food ingredients have been 
reviewed under GRAS notification compared to immediately prior to 
implementation of GRAS and what is the average review time for GRAS 
petitions submitted under GRAS notification before and after 
implementation? Would implementation of GRAS notification at the Center 
for Veterinary Medicine be possible? If not, please explain.
    Answer 8. FDA published a proposed rule to establish a GRAS 
notification program in 1997 (62 FR 18938; April 17, 1997; Substances 
Generally Recognized as Safe; the GRAS proposal). Under the GRAS 
proposal, FDA evaluates whether each submitted notice provides a 
sufficient basis for a GRAS determination and whether information in 
the notice or otherwise available to FDA raises issues that lead the 
Agency to question whether use of the substance is GRAS. Following this 
evaluation, FDA responds to the notifier by letter.
    The Center for Food Safety and Applied Nutrition (CFSAN) 
implemented a pilot GRAS notification program and received its first 
notice for a food ingredient in 1998. Through the end of 2004, CFSAN 
had filed 162 notices (ranging from 12 to 30 notices per year, with an 
average of 23 per year) and had completed its response to 155 of them. 
CFSAN has responded to 80 percent of the filed GRAS notices within 180 
days (ranging from 7 to 643 days, with an average of 163 days). Over 
the past 3 years, CFSAN estimates that approximately 7 to 8 FTE's were 
devoted to support the review of GRAS notices.
    In regard to review times of GRAS affirmation petitions submitted 
before and after implementation of the GRAS notification program, CFSAN 
last filed a GRAS affirmation petition in 1997 (62 FR 10285; March 6, 
1997). Prior to the implementation of the GRAS notification program, 
CFSAN published an average of 5 affirmations of GRAS status in the 
Federal Register per year for 1995 and 1996. The time elapsed since 
CFSAN filed the petition until CFSAN published the final rule ranged 
from just under 3 years to more than 13 years. CFSAN estimates that 
approximately 5 or fewer FTE's were devoted the GRAS affirmation 
petition process prior to implementation of the GRAS notification 
program (i.e., a time when CFSAN had re-allocated resources to reduce 
the backlog of food and color additive petitions). The GRAS affirmation 
petition process required rulemaking, and was far more resource-
intensive than the GRAS notification process, so that fewer responses 
were achieved per FTE.
    While it would be possible for the Center for Veterinary Medicine 
(CVM) to implement GRAS notification before publication of a final 
rule, CVM has not done so because an alternative process has existed 
for many years through establishment of feed ingredient definitions by 
the Association of American Feed Control Officials (AAFCO) and 
implementation of a notification program would require significant 
reallocation of resources currently allocated to high priority 
programs. CVM has participated in the AAFCO process by serving in a 
technical scientific review capacity ensuring that the listed 
ingredients are safe and function as claimed. No comparable process 
exists for human food. In addition, CVM traditionally has received only 
a small number of GRAS affirmation petitions and currently does not 
have resources dedicated for review of GRAS submissions. Implementation 
of a GRAS notification program at CVM also would be complicated by 
other issues. CVM, for example, is responsible for many animal species, 
and review of GRAS notices would need to address the different 
physiologies and the potential for toxicity in each species. CVM also 
would need to review whether a notified substance would produce 
residues that raise human food safety concerns when these substances 
are fed to livestock species. Addressing complex issues such as these 
would place significant additional demands on resources. Affected 
resources would include both personnel and implementation technologies, 
such as CVM computer systems, which would require modification and 
support to implement publicly available database of GRAS notices and 
their ultimate disposition. CVM has met recently with two major feed 
trade associations on GRAS notification and is reviewing its options, 
which may include implementing a notification program that uses longer 
timeframes in consideration of its resource limitations.
                                 ______
                                 
Response to Questions of Senator Clinton by Lester Crawford, DVM, Ph.D.
    Question 1. In your opinion, what are the appropriate roles of the 
scientific advisory committees and the senior staff of the FDA, if not 
to make recommendations about the safety and efficacy of drugs like 
Plan B?
    Answer 1. Advisory committees at the Food and Drug Administration 
(FDA or the Agency) are designed to offer a wide range of views on 
topics that are discussed in a public forum and to be advisory in 
nature. FDA seeks and appreciates the recommendations made by the 
committees. By law, however, the final determination on a drug 
application, however, remains with the Agency. Although the Agency 
frequently makes final decisions concerning a new drug application 
(NDA) that are consistent with an advisory committee's recommendations, 
FDA is not bound to follow their recommendations. Ultimately, a final 
decision is based on FDA's evaluation of the data, taking into account 
all of the views expressed.

    Question 2. In your opinion, under what circumstances is it 
appropriate for the FDA to overrule such a strong, united, 
scientifically-based recommendation?
    Answer 2. The Agency considers the recommendations made by advisory 
committees very carefully and takes the suggestions made very 
seriously. However, as noted above, by law, the Agency has final 
decision-making authority on a drug application. Although the Agency 
frequently makes final decisions about NDAs that are consistent with 
advisory committee recommendations, the recommendations are not 
binding, and FDA may make a different decision.
    Occasionally, there are differences of opinion among staff at the 
Agency on a particular issue. The scientific interchange of ideas is 
widely encouraged during the review process to ensure a thorough 
vetting of the issues. Decisions on drug reviews, however, cannot be 
made by simple majority or with the Agency feeling obligated to rubber 
stamp an advisory committee vote. None of the advisory committee 
members are permanent FDA employees with the same responsibilities as 
our permanent staff. Ultimately, a final decision must be made based on 
the Agency's evaluation of the scientific data, taking into account all 
of the views expressed. The greatest responsibility for a final 
decision concerning an NDA falls on the Center Director or other FDA 
staff who must put his or her signature on the final action on an NDA 
and will be the primary individual with the responsibility to defend 
that decision in the future.

    Question 3. As you may be aware, the agency's decision on the EC 
application last May was widely decried as politically influenced. In 
fact, my colleague Senator Kennedy and I organized 15 of our colleagues 
to initiate a GAO investigation into the process, and we are looking 
forward to the results. Can we count on you to ensure that the GAO has 
the FDA's full cooperation in the investigation? What steps will you 
take to ensure that medical and scientific evidence, not politics, is 
the basis for the agency's future decisions? Can we count on greater 
transparency in the FDA's decision-making process?
    Answer 3. The Agency makes every effort to fully cooperate with the 
GAO, and we are doing so with regards to the study that you and Senator 
Kennedy et al., initiated concerning the Barr/Plan B application.
    Additionally, FDA now publishes on its Internet site full 
information about the Agency's review process on an application if the 
application is approved. Included in this information is the medical 
and scientific evidence taken into account when reviewing the 
application.

    Question 4. On November 5, 2004, you pledged to fill the position 
of Director at the Office of Drug Safety. Can you please update us on 
the status of this search, over 4 months after you made this pledge?
    Answer 4. The Agency has experienced difficulty in recruiting high 
quality candidates for the position of Director, Office of Drug Safety, 
through traditional mechanisms such as scientific journal 
advertisements and government vacancy announcements. We are committed 
to using all available resources to ensure a systematic, inclusive 
recruitment process for this critically important position. To that 
end, FDA has partnered with the recruitment and staffing professionals 
at the Office of Personnel Management (OPM), Center for Talent 
Services, to develop and manage a recruitment strategy that we are 
confident will yield a sizable number of strong candidates and 
ultimately, a top-notch director. We feel that the additional time and 
resources invested in a thorough analysis of the leadership and 
technical competencies required to successfully manage the drug safety 
program, including input from internal and external subject matter 
experts and stakeholders, will be time well spent.

    Question 5. During your tenure as either Acting Commissioner or 
Deputy Commissioner of the FDA, the agency placed a black box warning 
on antidepressant medications 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 5. As of February 2005, FDA has requested studies on 298 
products under the Best Pharmaceuticals for Children Act (SPCA), has 
received the results of those studies on over 117 products, and has 
added new labeling to 87 products. Most importantly, about 25 percent 
of the time, when these products that were being used in the pediatric 
population were studied, we discovered the following: a need for a 
change of dosing, a new pediatric specific safety concern, or a lack of 
pediatric efficacy. In fact, most of the pediatric studies conducted to 
assess the efficacy and safety of the selective serotonin reuptake 
inhibitors (SSRI) antidepressants were performed utilizing the SPCA 
process. The data collected for these studies allowed FDA to evaluate 
the risk of suicidality (thoughts or attempts) in children who have 
taken these products.
    As you know, in December 2003 the Pediatric Research Equity Act 
(PREA) became law and established FDA's authority to implement the 
principles of the Pediatric Rule. Since PREA was enacted, the Agency 
has required evaluation of the pediatric need for drug and biologic 
product applications that are submitted for an adult indication. 
Through this process, the Agency determines if pediatric studies are 
required, may be deferred, or should be waived for each product for the 
specified indication. Waivers are granted, for example, if the disease 
or condition to be treated does not occur in pediatrics, such as 
prostate cancer or Alzheimer's disease. Once a pediatric need 
determination is made, the sponsor is informed if pediatric studies are 
required, have been deferred, or are waived.
    The BPCA and PREA work together as powerful FDA tools for obtaining 
important safety, efficacy, and dosing information for pediatric 
patients.

    Question 6. 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. If you are 
confirmed as Commissioner, 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 6. FDA is working with manufacturers and its regulatory 
counterparts in anticipation of having an ample supply of influenza 
vaccine for the coming season and annually thereafter.
    FDA is using a dual-track strategy. FDA's first track is to 
facilitate Chiron's effort to correct its manufacturing problems. FDA 
and MHRA, the British regulatory agency, have an agreement with Chiron 
that allows full information sharing. FDA has used that agreement to 
collaboratively review Chiron's remediation plans and activities, and 
the Agency is providing continuing and extensive feedback to both 
Chiron and MHRA. In addition, FDA signed an information sharing 
agreement with MHRA that will, among other things, permit advance 
communication on important issues. The agreement was effective February 
14, 2005.
    FDA is actively communicating on inspection activities. Only after 
passing MHRA and FDA inspections will Chiron be able to provide vaccine 
to the U.S. market. In the spring when critical stages of manufacturing 
are taking place, the Agency plans a comprehensive inspection to verify 
whether Chiron has adequately addressed its problems. While much work 
remains to be done, it appears that Chiron is making progress.
    FDA's second track is to facilitate overall greater capacity and 
diversification in the U.S. influenza vaccine supply. It is important 
to recognize that the demand for vaccine and other economic issues are 
primary factors that determine whether a manufacturer will seek and 
maintain a license in this country.
    CDC and FDA are working to encourage vaccination throughout the flu 
season, including January and February. To increase the total doses 
available, manufacturers can produce vaccine over a longer time period, 
and that becomes available during these months. Because influenza cases 
usually continue well after November and December when most people are 
seeking immunization, later vaccination is beneficial. The Public 
Health Service is working to better communicate this important public 
health message.
    In addition, FDA has been working to stimulate manufacturers not 
licensed in the U.S. to provide or, where needed, develop the safety 
and effectiveness data to obtain U.S. licensure. The Agency has 
actively engaged several interested companies. FDA has informed 
manufacturers that the Agency is willing to consider all approaches to 
licensing, including accelerated approval based on surrogate markers, 
e.g., the patients' immune response to the vaccine. In addition, Sanofi 
Pasteur and MedImmune have indicated their willingness, if needed, to 
do what they can to increase production.
    Very importantly, FDA has challenged itself to identify other 
lessons learned from this year's influenza season and is evaluating how 
this experience could be used to prevent similar events in the future. 
While there are some elements that FDA cannot control, the Agency is 
making significant changes. For example, FDA plans to conduct 
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. In 
addition, FDA has recently engaged in a confidentiality agreement with 
MHRA that covers exchange of information for all inspections.

    Question 7. There are many clinical areas where the synthesis and 
evaluation of existing research, as well as better, more definitive 
research, could improve the quality of care and reduce costs. The 
Agency for Healthcare Research and Quality (AHRQ) has recently begun a 
program of comparative effectiveness studies, for which my colleagues 
and I managed to secure $15 million dollars in funding last year. One 
of the first studies to be initiated under this comparative 
effectiveness program is a systematic review of the Cox-2 drugs, which 
will be completed in August 2005. Could you please comment on the ways 
in which such comparative effectiveness reviews can be used to enhance 
the work of the Office of Drug Safety?
    Answer 7. We are more than willing to use any information that may 
be discovered by the comparative effectiveness studies to assist the 
Office of Drug Safety. Although such studies are not necessarily 
designed to identify unknown safety concerns, it is certainly possible 
that valuable information may be identified. We would want to evaluate 
the results and data before we can comment as to whether such studies 
will enhance the work of the Office of Drug Safety.

    Question 8. Several questions have been raised as to whether the 
FDA has the legislative and regulatory authority it needs to carry out 
its mission. 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 8. FDA is fully capable of carrying out its mission under 
its current statutory and regulatory authority. If we identify gaps in 
our authority as we move to implement our various initiatives, we will 
work with the Administration and the Congress to address those. We have 
worked with Congress on many legislative efforts including MDUFMA, 
generic and pediatric exclusivity provisions, food allergens, minor use 
and minor species for animal drugs, and bioterrorism protections--all 
of which have enhanced our ability to help protect public health.

    Question 9. Do you feel the FDA has adequate access to clinical and 
scientific expertise in the full range of specialties and sub-
specialties? If not, what steps can the agency take to improve this 
access? How can the agency better utilize the scientific and medical 
resources in our Nation in a way that will not raise the conflict of 
interest issues for which the FDA has been criticized in its 
experiences with both the Cox-2 and silicone breast implant advisory 
panels?
    Answer 9. The Food and Drug Administration (FDA) has a 
responsibility to regulate products that comprise approximately one 
fourth of the Nation's consumer expenditures. Within the United States 
there are only a limited number of experts on any given topic; these 
experts usually work together through effective scientific 
collaboration. Most of the Nation's scientists are honored to serve 
their country by becoming members of FDA's advisory committees and, 
consequently, the Agency has little trouble recruiting the foremost 
experts in the field to serve on such advisory committees. Inherent in 
the process of clinical product development and evaluation is the 
competition for the Nation's experts. FDA staff evaluates the potential 
for financial conflict of interest and weighs these facts with the need 
for the Agency to use the most qualified experts to gain the necessary 
scientific information upon which to evaluate decisions that impact the 
public health.

    Question 10. At a hearing of the House Appropriation Committee's 
Subcommittee on Agriculture on March 11, 2004, you stated: ``The FDA is 
overwhelmed by imports, which have increased fivefold since 1994. It's 
difficult for us and we are missing the mark, but we pledge to do 
better.'' The FDA's proposed budget for 2006 includes a 5 percent cut 
for food-safety inspections. How do you plan to ensure the safety of 
FDA-regulated food imports? What percentage of food shipments should 
FDA be inspecting and on what basis do you make that determination?
    Answer 10. The fiscal year 2006 Budget does not reduce field 
examinations of imported food. FDA will continue to examine about 
93,000 import lines in fiscal year 2006 as well as in fiscal year 2005. 
To manage the ever-increasing volume of imported food shipments, FDA is 
using risk management criteria to achieve the greatest food protection 
with our available resources. While we cannot physically inspect every 
shipment, it is important to note that every shipment containing FDA-
regulated products entered through the Bureau of Customs and Border 
Protection (CBP's) automated system is electronically reviewed by FDA's 
system and those FDA-regulated products requiring further investigation 
are identified. FDA's Operational and Administrative System for Import 
Support (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 allows FDA to 
concentrate its limited enforcement resources on high-risk shipments 
while allowing low-risk shipments to proceed into commerce.
    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 provided a significant new tool that enhances 
FDA's ability to electronically review all FDA-regulated imported 
shipments. That law requires that FDA receive prior notice before food 
is imported or offered for import into the United States. Advance 
notice of import shipments, called ``Prior Notice,'' allows FDA, with 
the support of the CBP, to target import inspections more effectively 
and help protect the Nation's food supply against terrorist acts and 
other public health emergencies. With the new prior notice requirement, 
specific information mandated by the Bioterrorism Act must be submitted 
to FDA before the imported food arrives in the United States. This not 
only allows the electronic system to review and screen the shipments 
for potential serious threats to health (intentional or otherwise) 
before food arrives in the United States, but it also allows for FDA 
staff review of prior notices for those products flagged by the systems 
as presenting the most significant risk. FDA worked very closely with 
CBP in developing this screening system. FDA receives approximately 
27,000 prior notice submissions about incoming food shipments every 
day. The Prior Notice Interim Final Rule became effective December 12, 
2003. At the time of the statement you mentioned, FDA had not yet had 
much experience with the new prior notice requirement. Since then, 
FDA's experience with the prior notice system has been that it permits 
FDA to further refine our risk-based targeting and allocate resources 
for inspections more effectively.
    The fiscal year 2006 budget requests an increase of $30 million for 
food defense activities. Twenty million dollars of this increase will 
support a national laboratory network known as the Food Emergency 
Response Network (FERN). A critical component of controlling threats 
from deliberate food-borne contamination is the ability to rapidly test 
large numbers of samples of potentially contaminated foods for a broad 
array of biological, chemical, and radiological agents. FERN will 
increase our laboratory surge capacity through a nationwide network of 
Federal and State laboratories capable of testing the safety of 
thousands of food samples, thereby enhancing the Nation's ability to 
swiftly respond to a terrorist attack. The additional $10 million will 
be used for targeted food defense research, for continued coordination 
and sharing of data with the Department of Homeland Security as part of 
the government-wide Bio-Surveillance Initiative, and for upgrades in 
FDA's crisis management capabilities.

    Question 11. Section 130 of the Food and Drug Administration 
Modernization Act requires sponsors to report annually on the status of 
post-marketing commitments. In what ways has such reporting improved 
the FDA's ability to engage in post-approval safety monitoring? How can 
the system be improved so as to avoid the confusion that arose among 
patients and providers following the recent Cox-2 controversy?
    Answer 11. This authority assisted FDA greatly in considering the 
risk/benefit profile of marketing drugs. For example, FDA recently 
convened a joint meeting of the Arthritis Advisory Committee and the 
Drug Safety and Risk Management Advisory Committees to discuss overall 
benefit to risk considerations for COX-2 selective non-steroidal anti-
inflammatory drugs. The Advisory Committees analyzed all available 
information, much of it post marketing data obtained through this 
authority, from recent studies of Vioxx, Celebrex, Bextra, naproxen, 
and other data for non-selective NSAIDs and COX-2 selective products. 
The Advisory Committee issued recommendations that the Agency is 
promptly and carefully reviewing before taking further action.
    Recently, I joined Secretary Leavitt to announce important efforts 
that we are undertaking with FDA to improve its ability to monitor and 
respond to emerging drug safety information.
    These steps will ensure both a better internal process of 
deliberation on drug safety issues that ensures appropriate and 
independent consideration of all issues, as well as a stronger ability 
to gather data about drug safety issues once a drug has been approved.
    Most importantly, we are moving to encourage more transparency and 
to ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent as possible.
    This is in addition to FDA's Five Point Plan to Improve Drug 
Safety, a major initiative designed to improve the monitoring of drug 
products recently approved for marketing. The major components of this 
initiative include:
     Sponsoring a major study of the Drug Safety System by the 
Institute of Medicine;
     Implement a Program for Adjudicating Differences of 
Professional Opinion;
     Conducting a nationwide search to identify a permanent 
director for the Office of Drug Safety;
     Conducting a series of workshops and meetings on drug 
safety and risk management; and
     Publishing risk management guidance.

    FDA's Office of Drug Safety (ODS), in the Center for Drug 
Evaluation and Research (CDER), is already an independent office 
separate from the Office of New Drugs, the office that reviews new drug 
applications. Both the Office of New Drugs and the Office of Drug 
Safety report directly to the Director of the CDER. ODS has independent 
authority to perform its own research and does so every day. To be 
valuable, this independent research must conform to widely accepted 
scientific standards and normal scientific procedures and peer review 
should not be bypassed. And when drug safety issues are identified, 
they must be factored into the risk-benefit equation so that safe and 
effective drugs remain available to patients who need them.
    FDA has a longstanding commitment to provide a strong resource base 
for its drug safety program. The budget for fiscal year 2006 continues 
this commitment. The President has proposed a 24 percent increase for 
FDA's post-market safety program to help further ensure that America's 
drug product supply is safe and effective, and of the highest quality. 
Under this proposal, CDER's ODS would receive increased funding to 
expand the Agency's ability to rapidly survey, identify and respond to 
potential safety concerns for drugs on the market. ODS will hire 
additional staff to manage and lead safety reviews, will increase the 
number of staff with expertise in critical areas such as risk 
management, risk communication and epidemiology, and will increase 
access to a wide range of clinical, pharmacy and administrative 
databases. Our commitment to increase resources available for post-
market safety will enhance the structural changes we are proposing to 
advance drug safety.

    Question 12. 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 12. FDA has often been in the position of making decisions 
that have strongly motivated interests in favor or opposed to a product 
approval decision. While social factors and economic interests, for 
example, may result in opposing decision preferences, FDA's statute is 
clear that decisions should be based on science, and the requirements 
of the law, not ideology or opinion. Sometimes the science is not 
adequately developed to provide for a clear decision, and decisions 
have to be deferred until the adequate information is available. I am 
committed, if confirmed, to ensuring that, during my tenure as 
commissioner, FDA's decisions will be based on science and the 
requirements of the law and that the basis for FDA's decisions are as 
open and transparent to the public as possible, consistent with the 
law.
    My vision for the future of FDA is one of transformation. 
Internally at FDA, we're transforming from domestic-focused, paper-
based processes, employing yesterday's technologies, to global, 
electronic data-driven decisions that apply the latest science. And 
we're transforming our culture to one of transparency, collaboration, 
and cutting-edge thinking.
    As you know, I have recently appointed new Associate Commissioners 
for the Office of Management and for the Office of Policy and Planning. 
The qualifications that are most important to me as I assemble my 
leadership team are the qualities that support transformation: 
scientific and management ability, innovation and cutting-edge 
thinking, ability to confer and collaborate internally and externally 
and to ensure transparency of our processes, ability to manage 
organizational change effectively, and vision to see leveraging 
opportunities that yield public health protection.
                                 ______
                                 
 Response to Question of Senator Ensign by Lester Crawford, DVM, Ph.D.
    There is currently a major dispute between independent compounding 
pharmacists and the Food and Drug Administration (FDA) regarding the 
very legality of pharmacy compounding.
    The FDA appears to be taking the position that when a pharmacist 
compounds a prescription drug pursuant to a lawful order from a 
physician, veterinarian or medical practitioner, that this is a new 
drug that technically needs to be submitted through the new drug 
approval process. This interpretation, which does not seem to be based 
on existing statutes or recent court decisions, would effectively 
outlaw compounding and would deny patients necessary medical care.
    Recently, the FDA has been aggressive in its enforcement against 
compounded medications for non-food animals, arguing that these 
compounded medications are new drugs that must be submitted to an 
Abbreviated New Drug Application (ANDA) process. Additionally, the FDA 
has asserted that it is illegal to use bulk ingredients when 
compounding for non-food animals. Since the vast majority of drugs 
compounded for use by non-food animals utilize bulk ingredients, this 
would result in the denial of medical care to countless animals.

    Question. Can you please provide the committee with a clear 
statement as to the FDA's current position on pharmacist compounding 
for both human and non-food animals, including actual statutory 
citations for the FDA's position?

    Answer.--I. Statutory Authority: General Overview
    Sections 201(p) and (v) of the Federal Food, Drug, and Cosmetic Act 
(the act) respectively define the terms ``new drug'' and ``new animal 
drug'' as products that are not generally recognized among qualified 
experts as safe and effective for use under the conditions recommended 
in their labeling. With respect to human drugs, section 505(a) 
prohibits the introduction or delivery for introduction into interstate 
commerce of ``new drugs'' that have not been pre-approved by FDA as 
safe and effective for their intended uses. Similarly, new animal drugs 
that have not been pre-approved by FDA are deemed unsafe within the 
meaning of section 512(a)(1) of the act and, therefore, adulterated 
under section 501(a)(5) of the act. Where the compounding is for food 
or non-food animals and is from approved animal or human drugs, it is 
permitted if it complies with sections 512(a)(4) and (5) of the act and 
21 CFR Part 530.
    Sections 301(a)-(d) and (k) of the act prohibit, among other 
things, the introduction, delivery, and receipt for distribution of 
unapproved, adulterated, or misbranded drugs in interstate commerce. 
Because the drugs compounded in pharmacies typically are not 
``generally recognized as safe and effective'' within the meaning of 
sections 201(p) and 201(v), they meet the act's definition of ``new 
drugs'' and ``new animal drugs.'' Accordingly, they are also 
technically subject to the act's pre-approval requirements for ``new 
drugs'' and ``new animal drugs.''

    II. FDA's Current Approach to Human Drug Compounding

    In light of the preceding statutory analysis, Congress attempted to 
legalize certain aspects of traditional pharmacy compounding by 
amending the act in the mid-1990s. Section 127 of the Food and Drug 
Administration Modernization Act of 1997 amended the act by adding 
section 503A, which specified certain conditions under which compounded 
human drugs could be exempt from certain requirements of the act, 
including the aforementioned requirement under section 505 that all new 
drugs be pre-approved by FDA as safe and effective for their intended 
uses before being introduced into interstate commerce. In April 2002, 
however, the United States Supreme Court struck down as 
unconstitutional the commercial speech restrictions that Congress 
included in section 503A of the act. See Thompson v. Western States 
Medical Center, 535 U.S. 357 (2002). The Court left in place the Ninth 
Circuit's holding that the unconstitutional restrictions could not be 
severed from the rest of section 503A, and that the provision 
(including its exemptions) was therefore invalid in its entirety.
    As a result, the agency now uses its longstanding policy of 
exercising its enforcement discretion to permit certain types of 
pharmacy compounding. This policy is articulated in Compliance Policy 
Guide (CPG), section 460.200, issued on June 7, 2002. FDA recognizes 
that pharmacists traditionally have extemporaneously compounded 
reasonable quantities of drugs. This traditional practice follows the 
receipt of a valid prescription for an individually identified patient 
from a licensed practitioner. The compounding is performed at the 
pharmacy site for nearly immediate dispensing or administration to the 
patient. FDA has long expressed the view that such compounding serves 
an important medical purpose, and FDA has no intention of eliminating 
or frustrating this historical practice.
    FDA believes, however, that some pharmacies are engaged in 
practices that fall outside the bounds of traditional pharmacy 
compounding. These pharmacies are engaged in manufacturing and 
distributing unapproved new drugs in violation of the act. Many of 
these pharmacies make large quantities of unapproved drug products in 
advance of receiving a valid prescription for them, and copy 
commercially available drug products when there is no medical need for 
these compounded products. It is appropriate that pharmacies engaged in 
activities analogous to manufacturing drugs for human or animal use be 
held to the same provisions of the act as drug manufacturers.
    FDA's CPG contains factors that the agency considers in deciding 
whether to exercise its enforcement discretion with respect to pharmacy 
compounding. One factor is whether a firm is compounding drugs for 
third parties who resell them to individual patients. Another is 
whether a firm is compounding drugs in anticipation of receiving 
prescriptions, except in very limited quantities. Another is whether a 
firm is compounding a copy, or essentially a copy, of a commercially 
available FDA-approved drug product. In certain circumstances, it may 
be appropriate for a pharmacist to compound a small quantity of a drug 
that is only slightly different than an FDA-approved, commercially 
available drug. In these circumstances, however, FDA may consider 
whether there is documentation of patient-specific medical need for the 
compounded product. Other factors in the CPG include whether a firm is 
compounding drugs from active ingredients that are not components of 
FDA approved drugs, whether a firm is compounding drugs that are like 
drugs that were withdrawn or removed from the market for safety 
reasons, or whether a firm is not in compliance with applicable State 
law regulating the practice of pharmacy.

    III. FDA's Current Approach to Animal Drug Compounding

    As in the case of human drugs, FDA recognizes that some compounded 
animal drugs serve an important purpose in the practice of veterinary 
medicine. Accordingly, FDA continues to evaluate the appropriateness of 
different animal drug compounding and to use its enforcement discretion 
in applying the provisions described above. Under its policy described 
in Compliance Policy Guide (CPG) 7125.40, FDA is most likely to pursue 
enforcement action when the scope and nature of the compounding 
activities raise the kinds of concerns normally associated with a drug 
manufacturer and result in significant violations of the act. As with 
human drug compounding, the CPG contains factors that the agency 
considers in deciding whether to exercise its enforcement discretion 
with respect to animal drug compounding. The 13 factors described in 
the CPG include whether a firm is compounding drugs for third parties 
who resell them; whether a firm is compounding drugs in anticipation of 
receiving prescriptions, except in very limited quantities; whether a 
firm is compounding a copy, or essentially a copy, of a commercially 
available FDA-approved drug product; and whether a firm is compounding 
from bulk active ingredients, except where the use of the bulk active 
ingredient is of low regulatory concern either in general or on a case-
by-case basis.
    FDA is revising the CPG to further explain its enforcement policies 
with respect to the compounding of drugs for food and non-food animals. 
A number of groups, including the International Academy of Compounding 
Pharmacists, the American Veterinary Medical Association, the American 
Association of Equine Practitioners, and other affected groups, have 
met with the Agency to discuss their concerns with the current CPG and 
to suggest changes to it. In revising the CPG, FDA wants to make sure 
that it provides the clarity that the regulated industry believes is 
lacking in the current CPG.
                                 ______
                                 
 Response to Questions of Senator Frist by Lester Crawford, DVM, Ph.D.
    Question 1. Americans have tremendous confidence in the United 
States' prescription drug supply due to our closed regulatory system, 
which includes rigorous safety and efficacy standards enforced by the 
Food and Drug Administration (FDA). Following the worldwide withdrawal 
of Vioxx, some have questioned the FDA's ability to maintain the 
public's trust and confidence, and have argued that the FDA has not 
been sufficiently concerned about the safety of Cox-2 inhibitors and 
other prescription drugs. As Commissioner, what steps would you take to 
strengthen the FDA's drug safety program and better protect public 
health? Are there actions the FDA could take to improve its post-market 
surveillance of prescription drugs?
    Answer 1. I take very seriously the questions that arise concerning 
safety and efficacy of drugs both before and after approval. FDA 
approves a drug only when the demonstrated benefit outweighs its known 
risk for an intended population. However, the Agency cannot anticipate 
all possible effects of a drug during the clinical trials that precede 
approval. Occasionally, FDA identifies serious adverse effects after 
approval either in post-marketing clinical trials or through the 
Agency's strong post-market drug safety program.
    Recently, I joined Secretary Leavitt to announce important efforts 
that we are undertaking with FDA to improve its ability to monitor and 
respond to emerging drug safety information.
    These steps will ensure both a better internal process of 
deliberation on drug safety issues that ensures appropriate and 
independent consideration of all issues, as well as a stronger ability 
to gather data about drug safety issues once a drug has been approved.
    Most importantly, we are moving to encourage more transparency and 
to ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent as possible.
    This is in addition to a major initiative designed to improve the 
monitoring of drug products recently approved for marketing. The major 
components of this initiative include:
     Sponsoring a major study of the Drug Safety System by the 
Institute of Medicine;
     Conducting a nationwide search to identify a permanent 
director for the Office of Drug Safety;
     Conducting a series of workshops and meetings on drug 
safety and risk management; and
     Publishing risk management guidance.

    FDA's Office of Drug Safety (ODS), in the Center for Drug 
Evaluation and Research (CDER), is already an independent office 
separate from the Office of New Drugs, the office that reviews new drug 
applications. Both the Office of New Drugs and the Office of Drug 
Safety report directly to the Director of the CDER. ODS has independent 
authority to perform its own research and does so every day. To be 
valuable, this independent research must conform to widely accepted 
scientific standards and normal scientific procedures and peer review 
should not be bypassed. And when drug safety issues are identified, 
they must be factored into the risk-benefit equation so that safe and 
effective drugs remain available to patients who need them.
    FDA has a longstanding commitment to provide a strong resource base 
for its drug safety program. The budget for fiscal year 2006 continues 
this commitment. The President has proposed a 24 percent increase for 
FDA's post-market safety program to help further ensure that America's 
drug product supply is safe and effective, and of the highest quality. 
Under this proposal, CDER's ODS would receive increased funding to 
expand the Agency's ability to rapidly survey, identify and respond to 
potential safety concerns for drugs on the market. ODS will hire 
additional staff to manage and lead safety reviews, will increase the 
number of staff with expertise in critical areas such as risk 
management, risk communication and epidemiology, and will increase 
access to a wide range of clinical, pharmacy and administrative 
databases. Our commitment to increase resources available for post-
market safety will enhance the structural changes we are proposing to 
advance drug safety.

    Question 2. The National Institute for Health Care Management 
(NIHCM) estimates that spending on direct-to-consumer advertising 
increased to $2.5 billion on 2000, compared to $791 million in 1996. 
What is the FDA's role in regulating prescription drug advertising? In 
particular, has the FDA conducted recent studies or surveys of 
physicians or consumers regarding the impact of direct-to-consumer 
advertising on prescription drug utilization, cost, and quality of 
care? And if so, what have been the results? Based on the results of 
the FDA's own analysis, and the analysis of others, what is your view 
regarding the impact of direct-to-consumer adverting on utilization, 
costs, quality of care, and patient education?
    Answer 2. Section 502(n) of the Federal Food, Drug, and Cosmetic 
(FD&C) Act (or the act) provides the Agency with authority to regulate 
prescription drug advertisements. Implementing regulations (Title 21, 
Code of Federal Regulations [CFR] section 202.1) provide specifics 
about the content of such advertisements. Nothing in the law or 
regulations prohibits direct-to-consumer (DTC) promotion in any 
advertising medium. Also, the advertising provisions of the act do not 
address the issues of pharmaceutical coverage by insurance companies, 
advertising costs, or drug product price.
    FDA believes consumer-directed advertisements can play an important 
role in advancing the public health by encouraging consumers to seek 
treatment of diseases that may be under-treated and diseases for which 
patients may not be aware of treatment options. We have conducted 
research that confirms that DTC advertising, when done correctly, can 
serve positive public health functions, such as increasing patient 
awareness of diseases that can be treated, and prompting thoughtful 
discussions with physicians that result in needed treatments being 
prescribed--often, not the treatment in the DTC advertisement. Results 
of our research shows that many physicians believe that DTC can play a 
positive role in their interactions with patients and that many 
physicians thought that DTC ads made patients more involved in their 
healthcare.
    At FDA, CDER's Division of Drug Marketing, Advertising, and 
Communications (DDMAC) is responsible for regulating prescription drug 
promotion. DDMAC's mission is to protect the public health by helping 
to ensure that prescription drug information is truthful, balanced, and 
accurately communicated. This is accomplished through a comprehensive 
surveillance, enforcement and education program, and by fostering 
optimal communication of labeling and promotional information to both 
health care professionals and consumers.
    In February 2004, we issued three draft guidance documents, 
addressing: (1) consumer-friendly options for presenting risk 
information in consumer-directed print advertisements for prescription 
drugs; (2) criteria FDA uses to distinguish between disease awareness 
communications and promotional materials; and, (3) a manner in which 
restricted device firms can comply with the rules for disclosure of 
risk information in consumer-directed broadcast advertising for their 
products.
    FDA adopted a comprehensive, multi-faceted, and risk-based strategy 
for regulating consumer-directed advertising of medical products, which 
emphasizes the use of warning letters, untitled letters, development of 
guidance that facilitate voluntary compliance, frequent informal 
communications with industry and advertisers, and research on the 
public health effects of consumer-directed promotional materials.
    While we believe the survey results discussed above confirm our 
belief that DTC ads help increase patient awareness about the 
availability of effective treatments for their health problems, we will 
continue to ensure that our DTC policies help prevent potential 
misperceptions about benefits and risks of the advertised treatment and 
promote the importance of prescribing decisions being made with the 
intervention of a health care professional.

    Question 3a. Last year, the British Medicines and Healthcare 
products Regulatory Agency (MHRA) suspended Chiron's license to 
manufacture influenza vaccine, resulting in a loss to the U.S. 
influenza vaccine supply. As we approach the 2005-06 influenza season, 
recent events highlight the pressing need to stabilize, protect, and 
strengthen our vaccine supply. What are the FDA's plans to prevent a 
future potential shortage?
    Answer 3a. Recent experiences, particularly those of the past 7 
months, have taught us important lessons about manufacturing and 
inspectional activities with respect to influenza vaccine. Although FDA 
has always interacted extensively with influenza vaccine manufacturers 
throughout the vaccine production cycle, the annual changes in the flu 
vaccine and the increased dependence on a smaller number of 
manufacturers highlight the risks of unexpected manufacturing 
difficulties. For these reasons, in 2005 and the future, we plan to 
conduct inspections of influenza vaccine manufacturers on an annual 
basis, with additional interactions with manufacturers and, in the case 
of foreign facilities, their regulatory agencies where appropriate, 
based on findings or events that raise concerns.
    FDA is working with manufacturers and its regulatory counterparts 
in anticipation of having an ample supply of influenza vaccine for the 
coming season through a dual-track strategy.
    FDA's first track is to facilitate Chiron's effort to correct its 
manufacturing problems. FDA and MHRA, the British regulatory agency, 
have an agreement with Chiron that allows full information sharing. FDA 
has used that agreement to collaboratively review Chiron's remediation 
plans and activities, and the Agency is providing continuing and 
extensive feedback to both Chiron and MHRA. In addition, FDA signed an 
information sharing agreement with MHRA that will, among other things, 
permit advance communication on important issues. The agreement was 
effective February 14, 2005.
    FDA is actively communicating on inspection activities. Only after 
passing MHRA and FDA inspections will Chiron be able to provide vaccine 
to the U.S. market. In the spring when critical stages of manufacturing 
are taking place, the Agency plans a comprehensive inspection to verify 
whether Chiron has adequately addressed its problems. While much work 
remains to be done, it appears that Chiron is making progress.
    FDA's second track is to facilitate overall greater capacity and 
diversification in the U.S. influenza vaccine supply. It is important 
to recognize that the demand for vaccine and other economic issues are 
the primary factors that determine whether a manufacturer will seek and 
maintain a license in this country.
    CDC and FDA are working to encourage vaccination throughout the flu 
season, including January and February. To increase the total doses 
available, manufacturers can produce vaccine over a longer time period, 
and that becomes available during these months. Because influenza cases 
usually continue well after November and December when most people are 
seeking immunization, later vaccination is beneficial. The Public 
Health Service is working to better communicate this important public 
health message.
    In addition, FDA has been working to stimulate manufacturers not 
licensed in the U.S. to provide or, where needed, develop the safety 
and effectiveness data to obtain U.S. licensure. The Agency has 
actively engaged several interested companies. FDA has informed 
manufacturers that the Agency is willing to consider all approaches to 
licensing, including accelerated approval based on surrogate markers, 
e.g., the patients' immune response to the vaccine. Sanofi Pasteur and 
Med Immune have indicated their willingness, if needed, to do what they 
can to increase production.
    FDA has challenged itself to identify other lessons learned from 
this year's influenza season and is evaluating how this experience 
could be used to prevent similar events in the future. For example, as 
mentioned above, FDA plans to conduct 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.

    Question 3b. What policy proposals are necessary to increase 
domestic production capacity and advance research and development? And, 
what is the status of new technologies such as animal cell culture and 
reverse genetics?
    Answer 3b. HHS has announced that it plans to spend $439 million 
department-wide on influenza related activities in fiscal year 2006. 
This amount is an increase of nearly $400 million over the fiscal year 
2001 level of $41 million, and represents the Administration's 
commitment to addressing this important public health concern.
    The Administration is making the largest investment ever made by 
the Federal Government to protect against influenza. We welcome the 
continued support of Congress for this work, and view influenza 
preparedness as a critical responsibility as well as an important 
opportunity. The Department has announced two Requests for Proposals 
designed to encourage U.S.-based influenza vaccine manufacturers to 
have both the capacity and raw materials necessary to produce large 
quantities of vaccine using current egg-based methods, which are 
efficient and have a long and generally successful history. In November 
2004, HHS awarded a contract to Sanofi Pasteur to help ensure year 
round availability of an increased egg supply in case it is needed for 
a pandemic or for future vaccine shortages. These contracts and other 
research supported by HHS through NIAID will also help us move from 
dependence solely on egg-based production technology to the development 
of U.S. licensed cell-culture based and/or recombinant protein and DNA-
based vaccines. While work remains to obtain sufficient vaccine yields 
and evaluate cell-based vaccines for their safety and effectiveness, 
moving from an egg-based production to a cell-culture production can 
potentially shorten the time needed to produce vaccine as well as 
decrease the risk of contamination inherent in egg-based production.
    In an important new development, HHS is supporting development of 
vaccines against potential pandemic strains. Through this effort we 
hope to obtain experience in the formulation and use of such a vaccine 
and to prepare in the event that these strains become pandemic. As part 
of HHS' efforts to support pandemic preparedness, NIAID contracted for 
the production of pilot lots of potential pandemic vaccines from the 
two licensed U.S. manufacturers of inactivated influenza vaccine. HHS 
contracted for the production of 2 million doses of vaccine against 
H5NI avian flu, the influenza type of current concern in Southeast 
Asia. NIAID is preparing to initiate clinical studies of the first H5N1 
vaccine under INDs that FDA oversees, and both agencies will be working 
together to evaluate the results. While much work remains, these steps 
to produce and evaluate pandemic influenza vaccines are a critical 
component of our preparedness efforts. Reverse genetics is a method 
that can lead to more rapid generation of reference strains needed to 
manufacture influenza vaccines. This methodology was used to 
manufacture the H5N1 investigational vaccine noted above. In addition, 
studies supported by the National Institutes of Health and FDA will try 
to develop vaccine strategies that could lead to longer lived immunity 
and to vaccines that help protect against multiple strains of 
influenza. FDA is actively engaged with sponsors and manufacturers that 
are interested in developing such new technologies and has approved 
cell-based and recombinant vaccines for prevention of other infectious 
diseases such as chicken pox, rubella, polio, and hepatitis.

    Question 4. In May 2004, the Institute of Medicine's (IOM) 
Immunization Safety Review Committee examined the hypothesis that 
vaccines, specifically the measles-mumps-rubella (MMR) vaccine and 
thimerosal-containing vaccines, are causally associated with autism. 
The committee concluded that the evidence favors a rejection of a 
causal relationship between thimerosal-containing vaccines, or the MMR 
vaccine, and autism.
    In a joint statement in 1999, the U.S. Public Health Service, which 
includes the FDA, and the American Academy of Pediatrics urged vaccine 
manufacturers to reduce or eliminate thimerosal in vaccines. The U.S. 
Public Health Service and the American Academy of Pediatrics noted that 
they ``are working collaboratively to assure that the replacement of 
thimerosal-containing vaccines takes place as expeditiously as possible 
while at the same time ensuring that our high vaccination coverage 
levels and their associated low disease levels throughout our entire 
childhood population are remained.''
    To date, what process has been made in reducing or eliminating 
thimerosal in vaccines? What does scientific evidence show regarding 
the affect of trace amounts of this preservative? What are the FDA's 
current efforts to reduce child exposure to mercury? And, what is your 
view of the current scientific evidence regarding a relationship 
between vaccines and autism?
    Answer 4. FDA actions have resulted in a marked reduction in 
mercury exposure from thimerosal in vaccines. Since 2001, all vaccines 
routinely recommended for children 6 years and under (DTa), hepatitis 
B, Haemophilus b conjugate (Hib), pneumococcal conjugate, IPV, MMR, and 
varicella) manufactured for the U.S. market have contained no 
thimerosal or only trace amounts, with the exception of inactivated 
influenza vaccine.
    In 2004, the Advisory Committee on Immunization Practices 
recommended routine use of influenza virus vaccine in children 6 to 23 
months of age. FDA has approved preservative-free formulations (which 
contain either no or only trace amounts of thimerosal) for each of the 
two licensed inactivated influenza vaccines. These influenza vaccines 
continue to be marketed in both the preservative-free and thimerosal-
preservative-containing formulations. Of the two licensed inactivated 
influenza vaccines, Sanofi Pasteur's (Fluzone) is approved for use in 
children down to 6 month's of age; Chiron's Fluvirin is approved for 
individuals 4 years of age and older. The live attenuated influenza 
vaccine (FluMist, manufactured by MedImmune) contains no thimerosal, 
and is approved for individuals 5-49 years of age. In addition, 
pediatric vaccines such as DT, which are administered only to children 
for whom DTaP is not indicated, are also available in thimerosal-
preservative-free formulations, as are Td vaccines, which are indicated 
for individuals 7 years of age and older.
    In addition to FDA's actions outlined above, the PHS agencies have 
collaborated with various investigators to initiate further studies to 
better understand any possible health effects from exposure to 
thimerosal in vaccines. In 2001, the Institute of Medicine (IOM), at 
the request of CDC and NIH, convened the Immunization Safety Review 
Committee (the committee) to review selected issues related to 
immunization safety. This committee has completed two reviews of 
studies addressing a potential link between thimerosal-containing 
vaccines and autism. In its first review, conducted in 2001, the 
committee concluded that the evidence is inadequate to either accept or 
reject a causal relationship between thimerosal exposure from childhood 
vaccines and the neurodevelopmental disorders of autism, attention 
deficit hyperactivity disorder, and speech or language delay. The 
committee believed that the effort to remove thimerosal from vaccines 
was ``a prudent measure in support of the public health goal to reduce 
mercury exposure of infants and children as much as possible.''
    In 2004, the IOM's Committee reviewed this topic again, including 
new data that had accumulated since its review in 2001. These data 
included several epidemiological studies conducted in the U.S., 
Denmark, Sweden, and the United Kingdom, and studies of biologic 
mechanisms related to vaccines and autism. The committee concluded that 
this body of evidence favors rejection of a causal relationship between 
thimerosal-containing vaccines and autism, and that hypotheses 
generated to date concerning a biological mechanism for such causality 
are theoretical only. Further, the committee stated that the benefits 
of vaccination are proven and the hypothesis of susceptible populations 
is presently speculative, and that widespread rejection of vaccines 
would lead to increases in incidences of serious infectious diseases 
like measles, whooping cough, and Hib bacterial meningitis.
    FDA has succeeded in reducing children's exposure to mercury from 
vaccines during the first 6 months of life and continues to work toward 
reducing everyone's thimerosal exposure through vaccines. With the 
exception of the inactivated influenza vaccine, which was recently 
added to the list of routinely recommended pediatric vaccines, all 
routinely recommended licensed pediatric vaccines that are currently 
being manufactured for the U.S. market contain no thimerosal or only 
trace amounts of thimerosal. FDA, together with our colleagues within 
the other Health and Human Service agencies, will continue to study 
data relating to the incidence and etiology of autism.

    Question 5. This month the World Health Organization (WHO) 
confirmed 10 new cases of human infection with H5N1 avian influenza 
virus, as reported by the Ministry of Health in Viet Nam. Since January 
2004, 69 human cases of H5N1 infection have been reported, 46 cases of 
which have been fatal. Earlier this year, Senator Gregg, myself and 
others unveiled S. 3, the Protecting America in the War on Terror Act 
of 2005, which includes biodefense provisions to better protect and 
strengthen our public health infrastructure in the event of a pandemic 
outbreak. What is the FDA's role in ensuring pandemic preparedness? Are 
there actions the FDA Commissioner could take to improve our 
preparedness and response capabilities?
    Answer 5. FDA's goal is to establish a process to produce pandemic 
influenza vaccine in the shortest amount of time possible and protect 
the largest number of people, using a vaccine that is safe, effective 
and easy to deliver. The full details of the draft Pandemic Influenza 
Preparedness and Response Plan are located on the HHS website at: 
http://www.dhhs.gov/nvpo/pandemicplan/annex5.pdf. Through all these 
efforts, and with enhanced global surveillance by CDC and its partners, 
we have the unique opportunity to effectively intervene and potentially 
blunt a global pandemic, should one occur.
    FDA is actively participating in the HHS efforts for pandemic 
planning as highlighted in our response to Question 3.

    Question 6. Over the past 20 years, the number of people who are 
obese nearly doubled in the United States. An estimated 30 percent of 
U.S. adults are now classified as obese and over 60 percent are 
classified as overweight. The number of obese children between the ages 
of 6 and 11 has tripled over the past 3 decades. During the 108th 
Congress, I introduced two pieces of legislation, the Improved 
Nutrition and Physical Activities (IMPACT) Act and the Childhood 
Obesity Reduction Act. Both were intended to help address this serious 
and significant public health threat.
    Last year, the Department of Health and Human Services (HHS) 
unveiled a strategy to combat obesity. As a part of HHS' comprehensive 
strategy, the FDA's Obesity Working Group released a report which 
proposes a series of recommendations, including developing a national 
education campaign, encouraging the availability of nutritional 
information at restaurants, enhancing the calorie information on food 
labels, and strengthening the coordination of obesity research. Where 
does this FDA initiative stand today? What have been its results? Are 
there additional steps the FDA could take in order to combat the ever-
rising tide of obesity across this Nation?
    Answer 6. There is no simple solution to the problem of obesity. 
Achieving success in reducing and avoiding obesity will occur only as a 
result of efforts over time by individuals as well as various sectors 
of our society. Most associations, agencies, and organizations believe 
that diet and physical activity should be addressed together in the 
fight against overweight and obesity.
    Obesity is a growing and urgent public health problem in the United 
States. Today, almost two-thirds of all Americans are overweight and 
over 30 percent are obese. To help confront the problem of obesity in 
the U.S. and to help consumers lead healthier lives through better 
nutrition, in August 2003, FDA created an Obesity Working Group (OWG), 
which was charged with preparing a report that outlines an action plan 
to cover critical dimensions of the obesity problem from FDA's 
perspective and authorities. FDA's ``Calories Count'' report was 
released on March 12, 2004.
    The OWG report provides a range of short and long-term 
recommendations to address the obesity epidemic. For FDA's actions the 
emphasis is on calories. Progress to date follows:
    We have published two advance notices of proposed rulemaking 
(ANPRMs), in response to the recommendations in the OWG report, seeking 
comments on the following:
     How to give more prominence to calories on the food label, 
for example, increasing the font size for calories, including a column 
in the Nutrition Facts panel of food labels for percent Daily Value for 
total calories, and eliminating the listing for calories from fat. In 
addition, the Agency is seeking comment on the reformulation of the 
foods or redesign of packaging that may occur if any changes are made 
to the food label;
     Whether to amend certain provisions of the nutrition 
labeling regulations concerning serving size, such as for multiple-
serving packages that may reasonably be consumed in a single eating 
occasion.

    We continue to encourage manufacturers to take advantage of the 
flexibility in current regulations on serving sizes to label as a 
single-serving those food packages where the entire contents of the 
package can reasonably be consumed at a single eating occasion. We also 
continue to encourage manufacturers to use appropriate comparative 
labeling statements that make it easier for consumers to make healthy 
substitutions. Since release of the OWG report, the Agency, in meetings 
with industry, has made a point to encourage manufacturers to take 
advantage of the existing flexibility in serving size regulations, and 
companies are responding. For example, Kraft Foods is instituting dual 
column labeling for all its packaged foods containing 2-4 servings per 
package.
    FDA continues to encourage restaurants voluntarily to provide 
point-of-sale nutrition information to customers, including calorie 
information on a nationwide basis.
    FDA is also working to develop educational strategies and 
partnerships to support appropriate messages and teach people, 
particularly children, how to lead healthier lives through better 
nutrition. We are starting work with the Girl Scouts of the USA, under 
terms of a Memorandum of Understanding signed this past fall, to 
provide outreach and education in a science-based initiative to focus 
on improving health, nutrition, and physical activity. In addition, 
FDA's field offices are participating in local partnerships to reach 
and teach children. For example, in Central Florida, FDA's South East 
Region is part of the Seminole County Healthy Kids Partnership to 
promote positive opportunities for school-aged children in Seminole 
County to learn healthy nutrition and the value of increased daily 
physical activity.
    Also, FDA's Center for Drug Evaluation and Research (CDER) will 
continue to work with pharmaceutical sponsors to facilitate development 
of effective therapies to address the important public health issue of 
obesity and its attendant morbidities. An advisory committee meeting 
was held on September 8, 2004 to discuss the draft guidance on Clinical 
Evaluation of Weight-Control Drugs. The Agency is working to finalize 
the guidance.
    We believe that, when implemented, the report's recommendations 
will make a worthy contribution to confronting our Nation's obesity 
epidemic and helping consumers lead healthier lives through better 
nutrition.
                                 ______
                                 
  Response to Questions of Senator Jeffords by Lester Crawford, DVM, 
                                 Ph.D.

Emergency Contraception Questions

    Dr. Crawford, while you have been the Acting Commissioner of the 
FDA the agency has failed to approve Barr Laboratories' application to 
make Plan B emergency contraception available over-the-counter. This is 
despite the recommendations of the FDA's own advisory panels, the 
support of major professional medical associations, and overwhelming 
scientific evidence supporting the move. I have a series of questions I 
would like to ask on this issue:

    Question 1a. Please explain how the FDA failed to approve the 
application when the independent medical and scientific review 
performed by the FDA Advisory Committees overwhelmingly approved the 
application?
    Answer 1a. Advisory committees at the Food and Drug Administration 
(FDA or the Agency) are designed to be only advisory in nature. 
Advisory Committees offer a wide range of views on topics, usually in a 
public forum. FDA seeks and appreciates the recommendations made by the 
committees. The statutory responsibility for making a final decision on 
a drug application, however, remains with the Agency. Although the 
Agency frequently makes final decisions concerning new drug 
applications (NDAs) that are consistent with advisory committee 
recommendations, FDA is not bound to follow their recommendations. 
Ultimately, a final decision is based on FDA's evaluation of the data, 
taking into account all of the views expressed.
    At the joint advisory committee meeting held December 16, 2003, to 
review the Barr/Plan B OTC application, the Chairman of the Advisory 
Committee on Over-the-Counter Drugs as well as other members of the 
joint committee expressed concerns regarding whether the actual use 
data in the application were generalizable to the overall population of 
nonprescription users, chiefly because they felt the data showed 
inadequate sampling of younger age groups. Their concerns were strong 
enough for them to vote against approving the application, and the 
Center Director felt these concerns were important enough to seek 
further information from the sponsor on that issue. It is his job to 
see that the data meet the standards for safe and effective OTC use 
before a final decision is made.

    Question 1b. To better understand how this decision on Plan B was 
reached, can you provide a full account of the decision processes that 
caused the FDA to go against the recommendations of the review panel 
and professional staff?
    Answer 1b. After completing review of the supplemental application, 
FDA concluded that the application could not be approved at this time 
because: (1) adequate data were not provided to support the conclusion 
that young adolescent women can safely use Plan B for emergency 
contraception without the professional supervision of a licensed 
practitioner and (2) a proposal from the sponsor to change the 
requested indication to allow for marketing of Plan B as a 
prescription-only product for women under 16 years of age and a non-
prescription product for women 16 years and older was incomplete and 
inadequate for a full review. The supplemental application that was 
submitted proposed OTC status for both adults and children based 
primarily on an actual-use study in 585 subjects. Only 29 of the 585 
subjects enrolled in the study were 14-16 years of age, and none was 
under 14 years of age. Therefore, FDA concluded that the application 
was not approvable during that review cycle.
    In its letter notifying the sponsor of this decision, the Agency 
stated the following:
    ``Before this application can be approved, you would have to 
provide data demonstrating that Plan B can be used safely by women 
under 16 years of age without the professional supervision of a 
practitioner licensed by law to administer the drug. Alternatively, you 
could supply additional information in support of the revised 
indication to allow for marketing of Plan B as a prescription-only 
product for women under the age of 16 years and a non-prescription 
product for women 16 years and older, including draft product labeling. 
If you take the latter approach, your response to this letter would 
have to include details of how you propose to implement simultaneous 
prescription and non-prescription marketing of Plan B for women of 
different ages in a single packaging configuration while complying with 
all relevant statutory and regulatory requirements for labeling and 
marketing of this product. We will have to assure ourselves that your 
proposed approach is consistent with our statutory authority. If you 
pursue the alternative approach, we also would request details of your 
proposed program to educate consumers, pharmacists, and physicians 
about the dual marketing of Plan B as both a prescription and non-
prescription product, as well as your proposed program to monitor 
implementation of this novel approach.''
    The issuance of the Not Approvable letter in May 2004 did not mean 
that a supplemental application could not be approved in the future. 
The Not Approvable letter described what the applicant would need to do 
to obtain approval for its initial supplemental application. In this 
case, the applicant chose to revise its application and requested to 
market Plan B as prescription-only for women under the age of 16 and as 
nonprescription for women 16 years of age and older. FDA is reviewing 
this latest supplemental application.

    Question 1c. Barr Pharmaceuticals has submitted a revised proposal 
to the FDA, but even though a deadline has passed, they have not been 
notified of any outstanding questions or requests for information. Can 
you tell us what the reason is for the delay at this point, why the 
review was not completed on time and when a decision could be expected?
    Answer 1c. The Prescription Drug User Fee Act (PDUFA) goal date for 
the Barr Laboratories/Plan B OTC supplemental application was January 
22, 2005. Because of the complexities involved, the application is 
under review at the Center.

Use of PDUFA Funding for Drug Safety

    In the past, the Congress has authorized the FDA to accept user 
fees to augment its ability to review drug and medical device products. 
Some have urged that some of those fees should be directed to ensuring 
the safety of these products. Thus far, the Congress has agreed with 
the industries' position that post-market product safety review is the 
responsibility, and should be paid for, through general revenues.

    Question 2. I would like to hear your thoughts on how you plan to 
provide funding for post market product safety. Failing the 
availability of appropriations, would some portion of user fees be a 
reasonable source of funding?
    Answer 2. Under the current system of user fees, a portion of fees 
is used for drug safety activities. Drug safety activities are a 
cornerstone of the drug approval process, and PDUFA user fees support 
these activities. Moreover, under PDUFA III, Congress authorized the 
use of user fees for certain post-market risk management activities. 
Thus, user fees already fund drug safety activities, and the Agency 
supports the use of fees for this essential activity.

Clinical Trials Database

    Dr. Crawford, clinical trials are an important part of the drug 
approval and use process. Information that comes out of clinical trials 
continues to be of vital concern to doctors, patients, manufacturers 
and regulators. To that end, it seems like a good idea to expand the 
amount of information about trials that is available.

    Question 3. What is your response to the idea of creating a 
mandatory clinical trials registry, modeled after clinicaltrials.gov, 
which makes information available about all clinical trials? Would 
having complete information, including results information, available 
publicly help doctors and patients make better decisions about 
medications?
    Answer 3. I believe that patients and health professionals should 
have as much information possible to inform their treatment decisions. 
That is why I joined Secretary Leavitt to announce important efforts 
that we are undertaking with FDA to improve its ability to monitor and 
respond to emerging drug safety information.
    Importantly, we are moving to encourage more transparency and to 
ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent as possible.
    Moreover, clinicaltrials.gov is the world's largest source of 
information about federally- and privately-sponsored clinical trials 
throughout the United States and abroad, making critically important 
public health information available to patients and the healthcare 
community. Working together and in collaboration with our sister 
agencies in the HHS, FDA implemented section 113 with the establishment 
of ClinicalTrials.gov in February 2000. Today, ClinicalTrials.gov 
contains information on more than 11,000 publicly and privately funded 
trials. Recent public attention to the increasing availability of 
clinical trial information has made pharmaceutical companies more aware 
of the responsibility to list clinical trials in ClinicalTrials.gov. 
Moreover, many companies that previously listed ``pharmaceutical 
company'' in the drug sponsor field are now identifying themselves by 
their company name.
    Moreover, the agency has been making information from drug approval 
packages publicly available for some time. Drug approval packages, 
which include medical, chemistry, pharmacology, statistical, and 
clinical pharmacology/biopharmaceutics reviews, are posted on the FDA 
website Drugs@FDA (http://www.accessdata.fda.gov/scripts/cder/
drugsatfda/) and are made available in response to requests under the 
Freedom of Information Act after certain trade secret, confidential 
commercial or other privileged information has been redacted in 
accordance with relevant legal requirements. The Best Pharmaceuticals 
for Children Act (BPCA) requires FDA to make available to the public a 
summary of the medical and clinical pharmacology reviews of the 
pediatric studies conducted for supplements submitted under the BPCA. 
This information can be found at: http://www.fda.gov/cder/pediatric/
Summaryreview.htm. Additional information is also available from 
questions and answers posted on FDA's website and can be found at: 
http://www.fda.qov/cder/drugsaffda/FAQ.htm.

Protecting First Responders

    In order to ensure that first responders are prepared to respond to 
a chemical terrorist attack, the Congress and Department of Homeland 
Security have worked hard to ensure that funding is available and that 
the first responders and the public have the best possible equipment 
and medical countermeasures. The military for decades has used 
effective countermeasures against chemical, biological, radiological or 
nuclear (CBRN) threats. There is concern about how the FDA is 
transitioning use of these products from the battlefield to the 
domestic sector as terrorist threats have expanded.

    Question 4a.Please explain what FDA is currently doing to ensure 
the chemical, biological, radiological or nuclear (CBRN) medical 
countermeasures are reviewed and approved without jeopardizing the 
safety of the general public.
    Answer 4a. FDA is working diligently to speed the development and 
availability of safe and effective medical products to protect 
Americans from the harmful effects of chemical, biological, 
radiological, and nuclear (CBRN) agents. The Agency is coordinating and 
collaborating with the Centers for Disease Control and Prevention 
(CDC), the National Institutes of Health (NIH), the Department of 
Defense (DOD), academia, and industry regarding novel medical 
countermeasures (MCMs) and new (counterterrorism) indications for 
approved medical products for the public and the U.S. military. An 
important part of this effort is FDA's participation in several 
interagency working groups to address scientific and policy issues 
related to medical countermeasure development.
    FDA has a number of mechanisms that may be used to expedite 
approval and access to MCMs. These include the familiar processes for 
fast track, priority review, and accelerated approval, as well as 
innovative new tools, such as the ``Animal Rule.'' Under the Animal 
Rule, animal efficacy data may be used for product approval when human 
efficacy studies are not ethical or practical and when safety is 
established through human studies. FDA continues to play a critical 
role in the design and analysis of animal models that mimic disease 
progression in humans, recognizing that the lack of established animal 
models for the study of CBRN agents and associated medical products is 
a key impediment to future MCM development.
    Though not an approval process, FDA also is implementing new 
authority to allow the use of unapproved medical products and 
unapproved uses of approved medical products to protect the public and 
U.S military forces during a declared emergency involving a heightened 
risk of exposure to a CBRN agent. FDA may issue an Emergency Use 
Authorization (EUA) for a medical product only if certain statutory 
criteria are met, including a requirement that the known and potential 
benefits outweigh the known and potential risks. The Agency may impose 
certain conditions on the EUA and may revoke the authorization if 
appropriate to protect public health or safety.
    FDA's current activities on specific CBRN agents and MCMs include 
the following:
     Ongoing development efforts associated with a new 
preventative anthrax vaccine and therapies to treat anthrax infections; 
a new and safer preventative smallpox vaccine and therapies to treat 
active smallpox infections; a vaccine to protect against botulinum 
toxin; therapies for plague; and treatments for special populations, 
such as children, pregnant women, and those with weakened immune 
systems, when standard therapies are not advised.
     Continuing an Interagency Agreement (IAG) with CDC for 
clinical trials to collect human data on plague in African countries to 
label an antibiotic that would otherwise require an investigational new 
drug application for product deployment.
     Funding, with the National Institute for Allergies and 
Infectious Disease, the development of a non-human primate model of 
pneumonic plague.
     Conducting workshops and meetings to discuss strategies 
for developing therapeutics for certain CBRN agents.
     Drafting guidance on MCMs for anthrax toxins.
     Working on animal model studies for radiation-related 
countermeasures.
     Maintaining a database of approved and investigational 
products that may be candidates for medical countermeasures against 
Category A agents.
    Many of the CBRN threats demand immediate medical treatment, which 
creates substantial medical and first responder logistical challenges.

    Question 4b. Please tell us what FDA's position is regarding the 
expanded availability of existing medical countermeasures, including 
the availability of these countermeasures through prescription for 
individuals, before a terrorist incident occurs.
    Answer 4b. The Department of Health and Human Services (HHS) has a 
lead role in protecting Americans from the effects of terrorist attacks 
by enhancing public health preparedness and response capabilities. 
Within HHS, the CDC works with provider and first responder 
organizations on terrorism prevention and preparedness efforts. FDA's 
role is to speed the availability of new medical countermeasures 
through responsive regulatory review of these medical products.
    Within the scope of the Agency's statutory authority and mission, 
FDA participates in and collaborates with HHS and other Federal 
Agencies on certain public health preparedness and response activities. 
These include working with CDC in the Cities Readiness Initiative 
(CRI), a pilot program to aid cities in increasing the capacity to 
deliver medicines and medical supplies during a large-scale 
catastrophic event. CRI participants include City/State medical, 
bioterrorism, and emergency responders, Health Resources and Services 
Administration (HRSA), Department of Homeland Security Federal 
Emergency Management Agency (DHS-FEMA), Strategic National Stockpile 
(SNS), the Department of Justice (DOJ), the Federal Bureau of 
Investigation (FBI), the Veteran's Administration (VA) and the United 
States Postal Service (USPS).
    FDA also works closely with CDC's SNS, which stockpiles large 
quantities of medicine and medical supplies to protect the American 
public if there is a public health emergency (terrorist attack, flu 
outbreak, earthquake) severe enough to cause local supplies to run out. 
Once Federal and local authorities agree that the SNS is needed, 
medicines will be delivered to any State in the United States within 12 
hours. Each State has plans to receive and distribute SNS medicine and 
medical supplies to local communities.

Post Marketing Study Commitments Under Fast Track

    When Congress passed the Food and Drug Modernization Act in 1997, 
we included new authorities for FDA to provide fast-track approval for 
drugs to treat serious and life threatening diseases. The law was 
intended to ensure that innovative new treatments would be made 
available to patients in a timely manner while at the same time 
ensuring they were both safe and effective. We did that by empowering 
FDA to mandate additional post approval studies on both safety and 
efficacy without delaying the approval process. Instead, FDAMA provided 
the agency with the authority to withdraw approval of a fast-track drug 
if the drug sponsor failed to conduct a required study with due 
diligence.
    The law has clearly been effective in getting new life-saving 
treatments on the market. But I'm concerned about reports concerning 
drug maker compliance with post-approval study commitments those 
studies are an important piece of the safety and efficacy picture. Now 
however, questions are being raised about how many of those fast track 
studies are actually completed.

    Question 5a.Please provide a summary on the status of each fast 
track studycommitment, including the date of the drug's approval and 
the expected date of the study fulfillment. For those that have not yet 
been initiated, please provide an explanation as to why.
    Answer 5a. FDA has approved 38 products under fast track review. 
Nineteen of the approved fast track products were approved under 
accelerated approval. All fast-track products that FDA approved under 
accelerated approval (based on a surrogate endpoint or on a clinical 
endpoint other than survival or irreversible morbidity) must complete 
post-marketing confirmatory studies (refer to 21 CFR 314.510). There 
are 19 such approvals, listed in the answer to question. These products 
are: Alimta (NDA 21677 only), Erbitux, Velcade, Iressa, Fabrazyme, 
Fuzeon, Arimidex, Eloxatin, Zevalin, Viread, Gleevec, Campath, Kaletra 
(NDAs 21226 and 21251), Agenerase (NDAs 21007 and 21039), Ziagen (NDAs 
20977 and 20978), and Sustiva.
    Twenty three percent (18/80) of accelerated approval confirmatory 
studies are proceeding according to or ahead of the original schedule. 
Twenty-six percent (21/80) of accelerated approval confirmatory studies 
are considered ``pending.'' Many older postmarketing study commitments 
(e.g., those established prior to FDAMA 1997) did not have study 
schedules specified at the time of approval. A commitment cannot be 
deemed ``delayed'' unless the progress of the study has fallen behind 
the original study schedule (21 CFR 314.81(b)(2)(vii)). Because some of 
these older commitments do not have an original study schedule on which 
compliance may be based, they cannot be considered ``delayed.'' Studies 
remain ``pending'' for a variety of reasons; typically while a study is 
``pending,'' FDA and the applicant are working together to design a 
study that will adequately address the objective of the commitment.
    Four percent (3/80) of accelerated approval confirmatory studies 
are considered ``delayed.'' Studies are considered ``delayed'' if they 
are proceeding, but not meeting the original study schedule. Studies 
can be considered ``delayed'' for a variety of reasons (e.g., 
enrollment problems, ongoing analysis of study results, or submission 
of the final study report later than the scheduled date). The review 
divisions work proactively with sponsors to design trials that will 
provide the required information and to identify obstacles to 
completing the trials as they are initiated and begin accrual. However, 
when unexpected or unavoidable obstacles are encountered and the study 
becomes ``delayed,'' FDA continues to work with the sponsor to address 
and try to resolve the reasons for the delay. Sometimes when the 
obstacles associated with the original study design cannot be readily 
resolved, new confirmatory studies with defined study schedules are 
established. One percent (1/80) of accelerated approval confirmatory 
studies are considered ``terminated.'' FDA encourages sponsors to 
submit final study reports for ``terminated'' studies as soon as the 
reports are completed.
    Final study reports have been ``submitted'' for 60 percent (48/80) 
of accelerated approval confirmatory studies. Of these 48 PMCs, FDA has 
reviewed 45 (94 percent) of them and determined that the terms of the 
commitment have been met (i.e., ``fulfilled''); a fulfillment letter 
has been issued for these PMCs. Three are currently considered 
``submitted'' while the other 45 are considered ``fulfilled'' according 
to 21 CFR 314.81(b)(2)(vii). All of the studies for which final study 
reports were submitted were completed (i.e., none of the final study 
reports were submitted for ``terminated'' studies).

    Question 5b. Have you ever withdrawn a fast track drug for failure 
to conduct a required study? What factors guide the FDA in making these 
decisions?
    Answer 5b. For drugs approved under accelerated approval or the 
animal efficacy provisions, FDA may withdraw approval (described 
further under 21 CFR 314.530 and 314.620) if:
    A post-marketing clinical study fails to verify clinical benefit;
    The applicant fails to perform the required post-marketing study 
with due diligence;
    Other evidence demonstrates that the drug product is not shown to 
be safe or effective under its conditions of use.
    If a manufacturer fails to submit a supplemental application 
containing the information or request for approval of a pediatric 
formulation within the time specified by FDA (i.e., deferred pediatric 
studies under PREA), the drug product may be considered misbranded or 
an unapproved new drug or unlicensed biologic.
    To date, FDA has not undertaken an enforcement action in any of the 
scenarios described above; however, FDA actively monitors the 
completion of the required post-marketing commitments and works with 
individual sponsors to address factors that may delay timely completion 
of the required studies (e.g., slow enrollment, changes in practice or 
disease patterns).

    Question 5c. Can you tell us what you'll do as Commissioner to 
ensure drug makers make good on fast-track study commitments in a 
timely manner.
    Answer 5c. In addition to the enforceable post-marketing study 
commitments described above, the Food and Drug Administration 
Modernization Act of 1997 (FDAMA) provided FDA with additional 
authority for monitoring the progress of post-marketing studies. 
Section 130(a) of Title I of FDAMA added a new provision (section 506B) 
on post-marketing studies to the Federal Food, Drug, and Cosmetic Act 
356b (``the act'') (21 U.S.C. 356b). This new provision required 
sponsors of approved drugs and biological products to report to FDA 
annually on the progress of their post-marketing study commitments. In 
addition, FDA was required to do the following:
     Develop and publish regulations prescribing the format of 
the reports sponsors are to submit to FDA.
     Report annually in the Federal Register on the performance 
of post-marketing commitment studies.
     Report to Congress on the studies.

    After receiving and considering public comments on its proposed 
rule, FDA published the final rule on October 30, 2000 (65 FR 64607) 
and the regulations, promulgated under 21 CFR 314.81(b)(2)(vii), became 
effective in April 30, 2001. In the preamble to the proposed and final 
rules, FDA announced its intention to make basic information about the 
status of each post-marketing study commitment available to the public 
on the Internet. In May 2003, the Agency launched this website. The 
website is updated quarterly. It includes a searchable database of 
information on post-marketing studies for drugs and biological 
products. The database is maintained internally and tracks the progress 
of all post-marketing study commitments; including those that are 
required and those that are agreed upon by applicants. FDA's Report to 
Congress was delivered to Congress in March 2002, and there have since 
been three annual reports (fiscal year 2002, fiscal year 2003, and 
fiscal year 2004) on the performance of post-marketing commitment 
studies published in the Federal Register.

Publication Bias

    Among the controversies FDA has faced in recent years is the 
question of antidepressants prescribed to children. In one now well-
publicized case, the drug sponsor had results of several pediatric 
studies of its widely prescribed drug an off-label use--only one of 
which demonstrated efficacy in treating major depressive disorder. That 
single study was published and promoted to doctors, while the other 
studies, including some submitted to FDA were not publicized.
    While I understand the importance of ``off label'' use drugs to the 
practice of medicine, I'm equally concerned about cases in which FDA 
has the results of failed efficacy trials for an off-label use and 
knows the drug remains widely prescribed for that use.

    Question 6.What is FDA's obligation to the public and healthcare 
providers to proactively inform them about information the agency has 
that contradicts published studies about the safety or efficacy of off-
label uses?
    Answer 6. FDA makes every effort to keep the public and healthcare 
providers proactively informed about information concerning the safety 
and efficacy of drugs that they use. In fact, under our new safety 
initiative, we plan to release important new information about safe and 
effective product use, and we intend to make information about emerging 
risks regarding drug uses available earlier. This will include 
information such as known and potential safety issues based on reports 
of adverse events, new information that may affect prescribing of the 
drug, and the approved indications and benefits of the drug. Under this 
initiative, we want to make emerging safety information available to 
practitioners and to patients, so they may consider the information 
themselves.
                                 ______
                                 
Response to Questions of Senator Roberts by Lester Crawford, DVM, Ph.D.
    Question 1. Currently, a decision is pending in the commissioner's 
office regarding the use of an FDA approved antimicrobial for the 
treatment of severe respiratory outbreaks in poultry. While I 
understand you cannot comment on this case, many experts in poultry 
science, veterinary medicine, risk assessment and medical epidemiology 
have questioned the validity of FDA's evaluation which has been 
challenged as not being compliant with the Information Quality Act. 
Further, it appears that the potential benefits to food safety and 
human health associated with the use of this product were presented to 
FDA but not considered. As commissioner, will you subject such 
assessments and decisions to unbiased scientific peer review to ensure 
that the best science is used in making decisions that support food 
safety and protect human health, yet not taking away the ability of 
livestock and poultry producers to judiciously use the valuable tools 
that they need?
    Answer 1. FDA is committed to using the best available science in 
its decision-making and has, like other HHS agencies, developed 
guidelines concerning the Data Quality Act. We are also working, as are 
other Federal Agencies, to implement where applicable the OMB's Peer 
Review Bulletin. Moreover, as you know, the formal process for 
withdrawing approval of a new animal drug gives the drug's sponsor the 
opportunity to present evidence and legal arguments in support of 
keeping the drug on the market. In such cases, I review the sponsor's 
evidence and legal arguments before reaching my determination, and I am 
not required to follow the rulings by the Administrative Law Judge.

    Question 2. We appreciate your leadership last year in FDA moving 
forward with the draft guidance for the Early Food Safety Assessment. 
Given the importance of final guidance to assisting USDA in working 
with our trading partners to keep our international grain markets open, 
could you give us an indication on when we could expect to see the FDA 
Early Food Safety Evaluation guidance be published in its final form?
    Answer 2. We are currently analyzing over 2000 comments the Agency 
received on the proposed guidance on the Early Food Safety Evaluation 
of New Proteins Produced by New Plant Varieties, and we intend to 
finalize the guidance by the end of the year. FDA's commitment to 
finalize this document is reflected in the Center for Food Safety and 
Applied Nutrition 2005 Program Priorities list, or yellow book, where 
the guidance is an ``A-list'' goal slated for completion by the end of 
2005.

    Question 3. The Medical Device User Fee and Modernization Act of 
2002 (MDUFMA) required reprocessors of certain types of previously 
cleared reprocessed medical devices originally intended for single use 
only to submit to FDA supplemental cleaning, sterility, and 
functionality data demonstrating that the device functions ``like new'' 
in order for the FDA to provide continued market clearance for the 
device. Approximately 1,800 models of reprocessed SUDs required 
validation data under MDUFMA. The FDA announced toward the close of 
2004 that it had completed its review of supplemental validation data 
submitted by reprocessors and determined that a significant number of 
these devices can no longer be commercially distributed. In light of 
the FDA's determination that at least 33 percent of these submissions 
failed to demonstrate substantial equivalence, would it not be in the 
interest of patient safety to require reprocessors to submit validation 
data for all reprocessed single use devices in order for them to remain 
marketable?
    Answer 3. In the Medical Device User Fee and Modernization Act of 
2003/P.L.107-250 (MDUFMA), Congress specified a detailed process by 
which FDA was to re-evaluate previously-cleared reprocessed single use 
medical devices (SUDs). In accordance with the intent of Congress, FDA 
has expended significant resources to accomplish the following:

Premarket Review

    On April 30, 2003, FDA identified certain reprocessed SUDs for 
which 510(k)s must now include ``validation data . . . regarding 
cleaning and sterilization, and functional performance'' to show that 
the devices remain substantially equivalent to predicate devices after 
all intended reprocessing. FDA issued a guidance document on July 8, 
2003 (revised June 1, 2004), describing the types of validation data 
that would satisfy this MDUFMA requirement.
    For devices in this category that already had cleared 510(k)s, 
validation data (referred to as ``Supplemental Validation Submissions 
(SVSs)'') were required to be submitted to FDA by January 30, 2004. FDA 
received 44 SVSs for reprocessed SUDs for which the 510(k)s had already 
been cleared. This represented approximately 1,800 previously cleared 
reprocessed SUDs. Regulatory decisions on all but two of these SVSs 
were issued by November 1, 2004 as outlined below.
     Fifty-two percent of these devices were determined to be 
substantially equivalent (SE) to a legally-marketed predicate device 
and may continue to be marketed.
     An additional 33 percent of the models were determined to 
be Not Substantially Equivalent (NSE) to a legally marketed predicate 
device based on the failure to submit supplemental data OR the 
submission of inadequate supplemental data to FDA. These devices may no 
longer be legally marketed since they are no longer cleared for 
commercial distribution in the United States at this time. Reprocessors 
of these devices may seek clearance for the subject devices anytime in 
the future by submitting a new 510(k) premarket notification to FDA 
that satisfies the Agency's premarket requirements including 
supplemental validation data.
     Approximately 15 percent of previously cleared reprocessed 
SUD models were withdrawn by the reprocessor. These devices may no 
longer be legally marketed at this time. Also, FDA conducted field 
inspections to verify discontinuance of marketing.
    In November, 2004, FDA posted, on its website, the status of 
previously-cleared, reprocessed SUDs that were subject to supplemental 
validation data requirements described above. This allows hospitals and 
other interested parties to verify the status of reprocessed devices 
for use in their facilities. The website includes lists of devices 
found to be Substantially Equivalent based on a review of the 
supplemental data. These devices appear under the heading of ``Legally 
Available.'' In addition, the website lists those devices which may no 
longer be legally marketed because supplemental data were required but 
not received, subject 510(k)s were withdrawn by the sponsor, or 
supplemental data were determined by FDA to be inadequate. These 
devices are listed as ``No Longer Legally Marketed''.
    On April 30, 2003, FDA also published a list of ``critical'' 
reprocessed SUDs whose exemption from premarket notification 
requirements was terminated. Reprocessors of the devices on this list 
were required to submit 510(k)s, including the types of validation data 
described above, by July 30, 2004. No reprocessors of the critical 
reprocessed SUDs provided any submissions. FDA will conduct follow-up 
inspections to verify that the firms have stopped marketing these 
reprocessed devices.
    On April 13, 2004, FDA published a list of ``semi-critical'' 
reprocessed SUDs whose exemption from premarket notification 
requirements was terminated. Reprocessors of the devices on that list 
are required to submit 510(k)s, including validation data, by July 13, 
2005.
    MDUFMA created a new type of premarket submission, a ``premarket 
report'' (PMR), for reprocessed SUDs that otherwise would have required 
premarket approval applications. Among other items, a PMR must include 
data on reprocessing procedures, such as validation data regarding 
cleaning, sterilization, and functional performance.

Adverse Event Reporting

    In accordance with MDUFMA, FDA revised the mandatory and voluntary 
MedWatch report forms to incorporate the reporting of information on 
incidents related to reprocessed SUDs. FDA posted the revised forms on 
the MedWatch website in October 2003, along with revised instructions 
for mandatory reports, and, in early 2004, published a Federal Register 
notice announcing the availability of the revised MedWatch forms.

Inspections/Enforcement

    Since MDUFMA was enacted, FDA has inspected over 150 third-party 
reprocessors and hospitals engaged in reprocessing. As a result of the 
information collected, CDRH's Office of Compliance has issued two 
Warning Letters (to a hospital and a third-party reprocessor).
    In fiscal year 2004, FDA inspected over 100 U.S. hospitals and 
found none currently reprocessing single use devices. FDA has also 
issued an inspection assignment in fiscal year 2005 for five firms that 
reprocessed SUDs to ensure that they have discontinued marketing of the 
devices that were NSE. The five inspections have just been completed 
and inspection reports are being prepared.

Next Steps

    FDA will continue to review submissions for reprocessed single use 
devices as they are received. FDA has received comments on the lists of 
critical and semi-critical reprocessed SUDs whose exemption from 
premarket notification requirements was terminated, and we are 
currently reviewing these comments. Finally, FDA will continue to 
inspect reprocessors as appropriate and will inspect new hospital or 
third-party reprocessors as they are identified.
 Response to Questions of Senator Gregg by Lester Crawford, DVM, Ph.D.
    Question 1. In response to controversies surrounding FDA's actions 
taken with the popular pain-management drugs Vioxx and Celebrex and 
other medications, FDA recently announced new initiatives to improve 
drug safety monitoring. Among the initiatives is a plan to provide 
emerging safety information to physicians and patients. What will be 
FDA's scientific threshold for determining whether ``emerging'' safety 
information should be communicated? Will FDA consider factors 
surrounding the use of the drug, including risks associated with 
patients avoiding the use of potentially life-saving medicines based on 
the preliminary data and whether there are alternative treatments 
available? Does FDA need any additional authority to ensure the safety 
and efficacy of new and marketed drugs?
    Answer 1. An emerging risk, or emerging safety concern, is a 
possible serious new side effect, potentially related to a drug on the 
market, that has been reported to FDA and that FDA is analyzing. A side 
effect is considered new when, for example, the effect was not seen (or 
the rate or severity of the effect was not seen) during clinical 
testing, but was identified after the drug went on the market. For 
example, sometimes, after a drug is approved, rare but serious side 
effects may emerge as the drug is more widely used. Sometimes drugs are 
prescribed for new uses (off-label uses) with unanticipated results. If 
FDA receives information that a drug interacts with another drug, and 
this interaction may be causing a serious side effect, this information 
would be considered emerging.
    FDA will consider factors surrounding the use of the drug, 
including risks associated with patients avoiding the use of 
potentially lifesaving medicines based on the preliminary data and 
whether there are alternative treatments available.
    I do not believe new statutory authority is needed. We will use all 
existing regulatory authority and enforcement powers when negotiating 
label changes with drug companies or when monitoring or managing drug 
safety issues.

    Question 2. Shortly after the Bioterrorism Act was signed into law, 
the FDA and Customs entered into a Memorandum of Understanding 
concerning increased coordination and communication over the prior 
notice requirement for imported foods. What is the status of the 
implementation of that MOU? To what extent are FDA and Customs and 
Border Protection (CBP) coordinating with the increased inspections and 
reinspections of food products? Can you identify what are the barriers 
to establishing a mechanism for providing prior notice without a 
manufacturer's facility registration number for food products that are 
imported for analytical testing or research and development activities 
that do not involve consumption by humans or animals?
    Answer 2. FDA and Customs and Border Protection (CBP) signed the 
Memorandum of Understanding on December 3, 2003. It allows FDA to 
commission CBP inspectors to assist FDA in the implementation of the 
Prior Notice provisions contained in Section 307 of the Public Health 
Security and Bioterrorism Preparedness and Response Act of 2002 (Public 
Law 107-188.) This assistance includes coordinating examination and 
sampling operations with local FDA personnel. At ports that are not 
staffed by FDA personnel, this assistance includes responding to 
requests from FDA's Prior Notice Center to examine and sample suspect 
shipments arriving at such ports. As of March 2005, FDA has 
commissioned approximately 9,500 CBP inspectors who have received the 
requisite training. Joint FDA and CBP prior notice activities are 
coordinated by FDA's Prior Notice Center, which is co-located at CBP's 
National Targeting Center. This collaboration allows both agencies to 
share each others' data and targeting systems to evaluate high-risk 
shipments.
    With respect to food imported for quality assurance, research or 
analysis purposes, FDA stated, in the November 2004 revision of the 
Compliance Policy Guide for Prior Notice, that it intends to exercise 
broad enforcement discretion if, after a good faith effort, the person 
submitting prior notices does not know the registration number of the 
facility that manufactured the food and instead provides the name and 
full address of the facility that manufactured the food. FDA has had a 
version of this policy in effect since August 2004. FDA is also 
considering this issue, and the comments it has received on it, as it 
develops the final rule on prior notice.

    Question 3. The Federal Food Drug and Cosmetic Act does not include 
provisions to allow for abbreviated biologics license applications 
(otherwise known as generic biologics). Can you identify the steps--
including steps related to scientific knowledge--needed to proceed with 
the approval of follow-on versions of biological drugs? Do you agree 
that any approval requires separate Congressional authorization?
    Answer 3. As you know, FDA is conducting a public process to 
examine the many questions, including scientific and legal issues, that 
must be answered regarding these products and to ensure that all 
interested parties have an opportunity to comment. When this process is 
complete, FDA intends to provide guidance to industry to clarify, 
consistent with its legal authority, the approval pathway and 
principles for review of such products, which will protect the public 
health.
    In recent years--and with increasing frequency--questions about 
generic or follow-on proteins have arisen in response to scientific 
advances, impending patent expirations, and the ability to better 
characterize and understand biological products.
    Acknowledging scientific and legal limitations in this area, yet 
also recognizing the public health need to move forward to assist 
industry and make more products available to the public, FDA is 
conducting a public process to examine the scientific, and related 
issues regarding follow-on biologics. This process will ensure that 
scientific considerations and issues related to Agency authority are 
fully examined and that all interested parties have an opportunity for 
input.

    Question 4. The media has alleged that there exists a conflict of 
interest on the part of many qualified specialists who serve on FDA 
advisory committees. Despite that it is beneficial for both industry 
and FDA to consult with top experts concerning a drug, device or 
biologic, critics allege that because they have received compensation 
by industry during their professional career or because they have used 
a drug, device or biologic in their professional practice, they are 
assumed to have conflicts which affect their professional judgment. 
Would the FDA be able to have an effective advisory committee process 
without the use of experts who have worked with the drug, device or 
biologic of interest? Describe the process that FDA has in place to 
screen and make public potential conflicts of interests before an 
expert serves on an advisory committee.
    Answer 4. It would not be possible for FDA to have an effective 
advisory committee process without the use of experts who are familiar 
with the technology related to new proposed drugs, devices or biologics 
of interest. Due to the scarcity of the specific expertise necessary to 
evaluate complex scientific issues, these experts are often sought 
after for consultation by both the Agency and industry. Utilizing 
junior scientists who are less experienced or less highly qualified in 
order to completely remove any potential conflict from the committee 
would hamper the Agency's ability to protect and advance the public 
health.
    The Agency's process is to evaluate the potential financial 
interests of members and other invited special government employees. 
FDA makes a determination as to whether the participation of an 
individual with some financial ties outweighs the need for the agency 
to understand the science on the topic before the committee. Although 
the Agency has public guidelines for this process, this is not a black 
and white process. It requires careful consideration of all facets of 
the issue in order to evaluate that balance. By permitting waivers for 
conflicts of interest, Congress has ensured the Nation that the Agency 
and the public (through the advisory committee process) has access to 
the most knowledgeable individuals on the meeting topic.
    FDA's process of evaluating potential committee members for 
conflicts is very extensive and transparent. Our methodology is 
articulated in an extensive document that is publicly available on the 
agency's Web site (http://www.fda.00v/oc/advisory/conflictofinterest/
intro.html). At the beginning of each meeting, a conflict of interest 
statement is read into the record, which summarizes the results of the 
conflicts of interest screening. FDA has been commended by the Office 
of Government Ethics (1997) which stated that it was ``impressed with 
FDA's Program for protecting SGEs from COI . . .'' and that FDA is ``a 
model for other Agencies to use in developing their own systems and 
procedures.'' Nonetheless it is always prudent to regularly assess the 
Agency program and determine if any improvements are warranted and in 
the near future, the Agency will review the advisory committee 
conflicts of interest disclosure process and work to make the 
disclosures more easily accessible to the public.

    Question 5. As you know, there are no FDA approved drugs to treat 
some major conditions of companion animals and horses. Despite that 
many species of animals cannot be successfully treated with currently 
available FDA approved drugs, the Center for Veterinary Medicine 
prohibits pharmacists from filling prescriptions for animals by 
compounding the prescribed drug from bulk drugs. Their policy permits 
no exceptions even for non-food animals, such as cats, dogs, and 
horses. Critics of this policy say that, were this ban to be fully 
implemented and enforced, many animals would suffer or die needlessly. 
As Commissioner would you permit licensed veterinarians to prescribe 
drug products which must be compounded and pharmacists to compound such 
prescriptions for non-food animals when medically warranted from bulk?
    Answer 5. FDA has had a longstanding policy of exercising its 
enforcement discretion regarding certain types of pharmacy compounding. 
This policy is articulated in Compliance Policy Guide (CPG), section 
7125.40, issued in July 2003. FDA recognizes that pharmacists 
traditionally have extemporaneously compounded reasonable quantities of 
drugs. This traditional practice follows the receipt of a valid 
prescription for an individually identified patient from a licensed 
practitioner. The compounding is performed at the pharmacy site for 
nearly immediate dispensing for administration to the animal or 
animals. FDA has long expressed the view that such compounding serves 
an important medical purpose, and FDA has no intention of eliminating 
or frustrating this historical practice.
    FDA believes, however, that some pharmacies are engaged in 
practices that fall outside the bounds of traditional pharmacy 
compounding. These pharmacies are engaged in manufacturing and 
distributing unapproved new animal drugs in violation of the act. It is 
appropriate that pharmacies engaged in activities analogous to 
manufacturing drugs for animals be held to the same provisions of the 
act as drug manufacturers.
    FDA's CPG contains factors that the agency considers in deciding 
whether to exercise its enforcement discretion with respect to animal 
drug compounding. The 13 factors described in the CPG include whether a 
firm is compounding drugs for third parties who resell them; whether a 
firm is compounding drugs in anticipation of receiving prescriptions, 
except in very limited quantities; whether a firm is compounding a 
copy, or essentially a copy, of a commercially available FDA-approved 
drug product; and whether a firm is compounding from bulk active 
ingredients, except where the use of the bulk active ingredient is of 
low regulatory concern either in general or on a case-by-case basis. 
Thus, for example, where a pharmacist contemporaneously compounds 
reasonable quantities of drugs from bulk active ingredients for non-
food animals in response to a valid prescription for an individually 
identified patient, FDA has typically not taken enforcement action.
    FDA is revising the CPG to further explain its enforcement policies 
with respect to the compounding of drugs for food and non-food animals. 
A number of groups, including the International Academy of Compounding 
Pharmacists, the American Veterinary Medical Association, the American 
Association of Equine Practitioners, and other affected groups, have 
met with the Agency to discuss their concerns with the current CPG and 
to suggest changes to it. In revising the CPG, FDA wants to make sure 
that it provides the clarity that the regulated industry believes is 
lacking in the current CPG.

    Question 6. On November 16, 2004, I wrote a letter to you 
recommending the establishment of descriptive claims for whole grains 
on food labels. Do you agree that establishing descriptor claims such 
as ``excellent source,'' ``good source,'' and ``made with'' for whole 
grain content can provide information so that consumers can make better 
dietary choices that could lead to the prevention of some diet-related 
diseases? I understand that the FDA is currently considering a petition 
requesting descriptive claims for whole grains on food labels. When 
does FDA expect to act on that petition?
    Answer 6. FDA is committed to the goal of making available to 
consumers more and better information about the health benefits of 
foods. HHS and the U.S. Department of Agriculture developed the 2000 
Dietary Guidelines for Americans and the Food Guide Pyramid, which 
contain guidelines for increased consumption of whole grain foods. On 
May 11, 2004, FDA received a petition asking the Agency to establish 
the descriptive claims ``excellent source'', ``good source'', and 
``made with'' for whole grain content of foods. That petition is under 
review in our Center for Food Safety and Applied Nutrition.

    Question 7. Under the proposed reorganization of CDER, the 
Ophthalmology Sub-Division would be completely absorbed by the Division 
of Anti-Infective drugs. This proposed merger could potentially have a 
harmful impact to the review of ophthalmic drugs. As ophthalmic 
products are merged into anti-infectives, will staff with ophthalmic 
experience maintain management and review of ophthalmology drugs and 
final approval recommendations for such products? If not, how does this 
represent a more efficient structure to ensure the safety and efficacy 
of ophthalmic drugs?
    Answer 7. We expect that individuals with expertise in 
ophthalmology will continue to play a critical role in reviewing new 
ophthalmology products, and the reorganization will not affect the 
timely approval of treatments and drug therapies available to eye care 
practitioners and their patients. All drug review processes for all 
products will continue to be held to existing PDUFA goals and timelines 
during and as a result of the reorganization.

    Question 8. FDA has a key role to play in evaluating and approving 
effective treatments for tobacco dependence, like the nicotine gum, 
lozenge, and patch. However, more can be done within FDA's existing 
authority to help smokers who are trying to quit. Such actions include 
``fast track'' status to applications involving products to treat 
tobacco dependence and considering alternative indications for nicotine 
replacement therapies, including relapse prevention, relief of 
cravings, and extended use for those smokers who wish to gradually wean 
off of tobacco consumption. What steps is FDA taking to expand access 
to these promising therapies?
    Answer 8. The Food and Drug Administration (FDA or the Agency) is 
committed to employing tools to facilitate the development and 
marketing of products that may represent important public health 
advances for smoking cessation. FDA would evaluate for fast track 
designation and/or priority review status novel products that have the 
potential to truly represent a significant advance in the treatment of 
tobacco dependence. This accelerated development/review is a highly 
specialized mechanism for speeding the therapies for serious or life-
threatening illnesses or for illness for which no therapy exists.
    FDA approved Nicorette Gum (nicotine polacrilex), manufactured by 
GlaxoSmithKline, on January 13, 1984, under accelerated review (6 
months). This product received accelerated review because it was a new 
molecular entity with a therapeutic advantage over existing therapies 
for smoking cessation. FDA switched Nicorette Gum to over-the-counter 
status on February 9, 1996. All other approved products underwent 
standard review because they did not demonstrate a significant benefit 
over Nicorette Gum.

    Question 9a. The FDA approval of RU-486 has raised many concerns 
regarding the safety and efficacy of the drug regimen.
    (a) Please describe why RU-486 was approved under Subpart-H, which 
is reserved for drugs in treating serious or life-threatening 
illnesses, such as AIDS and cancer?
    Answer 9a. As you know, Mifeprex (sometimes referred to as RU-486) 
was approved in September 2000 under a previous Commissioner. I am 
therefore unable to fully respond to this question.
    FDA has received reports of serious bacterial infection, bleeding, 
ectopic pregnancies that have ruptured, and death. In response, in 
November 2004, FDA announced new safety changes regarding the labeling 
of Mifeprex. The new warnings to health care providers and consumers 
include changes to the existing black box on the product to add new 
information on the risk of serious bacterial infections, sepsis, and 
bleeding and death that may occur following any termination of 
pregnancy, including use of Mifeprex.
    We will continue to closely monitor the safety of this and all 
drugs on the market.

    Question 9b. Would you also describe why the FDA approved RU-486 
for pediatric patients but waived the pediatric rule?
    Answer 9b. As you know, RU-486 was approved in September 2000 under 
a previous Commissioner. I am therefore unable to fully respond to this 
question. As noted above, the FDA is carefully monitoring adverse 
events related to this and all drugs on the market.

    Question 9c. Please describe information that you have that the 
product is being promoted by the manufacturer, or by providers on 
publicly accessible websites, for ``off-label'' uses. What actions has 
the agency taken in response to such information?
    Answer 9c. The Agency is not aware of the manufacturer promoting 
off label use of Mifeprex on publicly available websites. FDA's 
authority to regulate advertising is directed at advertising by the 
manufacturers, packers or distributors of regulated products.

    Question 10. Aside from Mifeprex, in the past 20 years how many new 
drug applications has FDA approved based solely on data from 
uncontrolled clinical trials? In the past 20 years how many new drug 
applications has FDA approved based solely on data from historically 
controlled trials? For each answer please provide the name of any drugs 
listed, the NDA number, and a brief description of the trials. With 
respect to historically controlled trials, please describe the control 
group used.
    Answer 10. Below is a brief summary of FDA's policy regarding 
control groups for clinical trials intended to support an effectiveness 
claim for a new drug.
    An adequate and well-controlled investigation must be designed to 
distinguish the effect of a drug from other influences, such as 
spontaneous change in the course of the disease, placebo effect, or 
biased observation. Reports of adequate and well-controlled 
investigations provide the primary basis for determining whether there 
is substantial evidence to support the claims of effectiveness for new 
drugs. By definition, an adequate and well-controlled study uses a 
design that permits a valid comparison with a control to provide a 
quantitative assessment of the drug effect. Generally, we recognize the 
following types of controls (21 CFR 314.126(b)(2)):
     Placebo concurrent control
     Dose-comparison concurrent control
     No treatment concurrent control
     Active treatment concurrent control
     Historical control
    ``No treatment concurrent control'' is defined as trials where 
objective measurements of effectiveness are available and placebo 
effect is negligible. In such trials, the test drug is compared with no 
treatment. Such trials usually include randomization. In ``historically 
controlled trials,'' the results of treatment with the test drug are 
compared with experience historically derived from the adequately 
documented natural history of the disease or condition, or from the 
results of active treatment, in comparable patients or populations. 
Examples include studies of diseases with high and predictable 
mortality (for example, certain malignancies) and studies in which the 
effect of the drug is self-evident (general anesthetics, drug 
metabolism).
    In contrast, uncontrolled studies or partially controlled studies 
are not acceptable as the sole basis for the approval of claims of 
effectiveness. However, such studies, if carefully conducted and 
documented may provide corroborative support of well-controlled studies 
regarding efficacy and may yield valuable data regarding safety of the 
test drug. (21 CFR 314.126(e))
    As noted above, uncontrolled studies are not an acceptable basis 
for establishment of a claim of effectiveness, therefore, we cannot 
cite any examples of drugs approved solely based on uncontrolled 
trials. With regard to historical controls, FDA does not capture 
information on the type of control used in clinical investigations to 
support a demonstration of effectiveness in our databases. Therefore, 
we are not able to provide a comprehensive list of applications 
approved based on historical controls in response to your question. 
However, the following are examples to illustrate experience (NOTE: 
This is not intended to be a comprehensive listing of all such 
approvals.):
    Example of a product approved using ``no treatment concurrent 
control'':
    NDA 50-747 Synercid (quinupristin/dalforpristin) for the treatment 
of vancomycin resistant Enterococcus faecium bacteremia. Four non-
comparative studies were conducted. Three of the trials were 
prospective; the fourth consisted of a collection of individual 
emergency-use requests.
    Examples of products approved using historical controls:
     NDA 20-645 Ammunol (sodium benzoate/sodium phenylacetate) 
for the treatment of urea cycle disorders. Efficacy was compared to 
historical data from published literature to evaluate percent survival 
with therapy compared to how these patients fared in other cohorts 
before such therapy was available on an investigational basis.
     NDA 21-227 Cancidas (caspofungin acetate) for the 
treatment of invasive aspergillosis in patients who are refractory to 
or intolerant of other therapies, on the basis of a historically 
controlled trial with the control developed from hospital records by 
the sponsor. The approval was supported by information on safety from 
trials in candida infections.
     BLA STN 103737 Rituxan (rituxumab) and BLA STN 125011.0 
Bexxar (tositumomab plus13'I-labeled tositumomab) for the treatment of 
non-Hodgkin's lymphoma. Approvals for both products were based on 
multicenter, single-arm studies. The historical control is based on 
knowledge of the natural history of untreated non-Hodgkin's lymphoma, a 
disease that does not have spontaneous remissions.

    Question 11. Aside from Mifeprex, how many drugs has FDA approved 
in which an off-label, unapproved use for a second drug is mandated as 
part of an approved regimen? If there are any others, please provide 
the name of the drugs, the NDA numbers in which such use was mandated, 
and any documents from FDA requiring such use.
    Answer 11. We do not track information about references to the use 
of other drugs as part of the approved labeling for drug products. 
Therefore, we are not able to provide a comprehensive response to your 
question. The following examples illustrate FDA's experience: (NOTE: 
This is not intended to be a comprehensive listing of all such 
products.)
    Examples of products approved in combination with another drug for 
a use that was not sought by the sponsor of the second product and for 
which a change in labeling of the second product was not required 
include:
     NDA 20-954 Busulfex (busulfan), in combination with 
cyclophosphamide, for hematopoietic stem cell transplant.
     NDA 20-509 Gemzar (gemcitabine hydrochloride), in 
combination with cisplantin, for treatment of non-small cell lung 
cancer.
     NDA 20-388 Navelbine (vinorelbine tartrate), in 
combination with cisplantin, for treatment of non-small cell lung 
cancer.
     NDA 20-262 Taxol (paclitaxel), in combination with 
cisplantin, for treatment of ovarian cancer and non-small cell lung 
cancer, and for use with Adriamycin (doxorubicin) plus Cytoxan 
(cyclophosphamide) in adjuvant breast cancer.
     NDA 20-638 Vistide (cidofovir), for the treatment of CMV 
retinitis in patients with AIDS, has a boxed warning which states that 
it must be administered with probenecid to reduce nephrotoxicity.
     BLA STN 103792.0 Herceptin (traxtuzumab), in combination 
with paclitaxel, for first-line treatment of metastatic breast cancer.
     NDA 21-462 Alimta (pemetrexed disodium), in combination 
with cisplantin, for the treatment of mesothelioma.
     NDA 21-663 Menopur (menotropins), for use in female 
infertility in which pituitary suppression is required. Dosage 
instructions are given for patients who have received a GnRH agonists; 
however, GnRH agonists are not approved for this use.
                                 ______
                                 
 Response to Questions of Senator Harkin by Lester Crawford, DVM, Ph.D.

Post Market Surveillance

    Question 1. On February 15th, the Food and Drug Administration 
announced the formation of the Independent Drug Safety Oversight Board. 
The purpose of the Board is to get information to doctors and consumers 
about safety concerns with drugs that have already been approved. 
However, the board has no regulatory authority and is only advisory in 
nature. In addition, the Board is not truly separate from the Office of 
New Drugs, the entity responsible for action if a problem is found with 
a drug after market approval. Shouldn't there be a separate entity 
charged with post-market surveillance and evaluation of approved drugs? 
Should this entity have the authority to make label changes or take 
other actions designed to protect the consumer? What actions could FDA 
take to inform physicians and consumers about the risks associated with 
specific drugs after drug approval? What resources would be necessary 
to maintain this advisory role for FDA?
    Answer 1. The make up of the Drug Safety Oversight Board (Board) 
and the vesting of decision-making authority in the Center Director 
ensure that the Board's deliberations will be independent of the drug 
approval process. Representatives of the Office of New Drugs comprise 
only three of the Board's 15 voting members. To the extent possible, we 
will ensure that none of the three voting members has been involved in 
the actual decision-making concerning a particular drug coming to the 
Board. If they have been involved in the actual decision-making 
process, they will not be allowed to vote. The Board will make 
recommendations to the Center Director who will make the final 
decisions on drug safety issues. The Center Director and the Deputy 
Center Director are not normally involved in the approval of new drugs. 
Decisions made by the Center Director, based on recommendations made by 
the Board, will be implemented through the appropriate program office. 
The Center Director retains final authority for Center decisions. A 
dissenting Office Director may appeal the Board's recommendations to 
the Center Director before the Center Director makes a final decision.
    The Office of Drug Safety (ODS) is charged with post-marketing 
surveillance of approved drugs. ODS is already an independent office 
separate from the Office of New Drugs, the office that reviews new drug 
applications. Both offices report directly to the Acting Director of 
CDER. ODS has strong support within both CDER and the Agency and has 
been a vital part of FDA's efforts to ensure drug safety. In addition, 
ODS has independent authority to perform its own research and does so 
every day.
    Regarding the issue of informing physicians and consumers about the 
risks associated with specific drugs after approval, FDA will share 
drug safety information sooner and more broadly, including information 
on potential safety problems even before the Agency has reached 
conclusions that would prompt a regulatory action. The new 
communications include:
     The Proposed Drug Watch ``Web'' Page
    At the direction of the new Drug Safety Oversight Board, this Web 
page will include emerging information about possible serious side 
effects or other safety risks.
     Healthcare Professional Information Sheets
    We have also started developing and making these sheets available 
to better communicate emerging risk information to the medical 
community. We will continue to develop these information sheets, or 
will update existing ones, as we become aware of possible serious new 
side effects for a drug. The sheets will contain an FDA Alert 
describing emerging information.
     Patient Information Sheets
    We have already begun to develop and make available on CDER's 
Website user-friendly information for patients and consumers on drugs 
about which we have identified emerging issues. We will continue to 
develop these sheets, or update existing ones, as we become aware of 
possible serious new side effects for a drug. The sheets will contain 
an FDA Alert describing emerging information.

Mercury Exposure

    Question 2a. Many of my constituents are concerned about the 
apparent rise in the rate of Autism, or Autism spectrum disorders, in 
children. One hypothesis offered to explain the rise is that increased 
exposure to mercury causes autism. Scientists have demonstrated that 
mercury levels are rising in fish common in human consumption. In 
addition, some childhood vaccines contained mercury as a preservative. 
It is my understanding that only some flu vaccine currently uses 
mercury based preservative. Is this correct?
    Answer 2a. Yes, this is correct. The mercury-containing 
preservative referred to above is thimerosal. At this time, there are 
three U.S. licensed influenza vaccine manufacturers, Sanofi Pasteur, 
Chiron and Medlmmune. Both Sanofi Pasteur and Chiron manufacture 
inactivated influenza vaccines, which are available in a thimerosal-
preservative containing formulation and a preservative-free formulation 
that contains no thimerosal or only trace amounts ( 1 microgram 
mercury per 0.5 ml dose;  0.5 micrograms mercury per 0.25 ml dose). 
Medlmmune manufactures a live, intranasally administered influenza 
vaccine that contains no thimerosal. Only Sanofi Pasteur's Fluzone is 
indicated for children as young as 6 months of age (no influenza 
vaccine are approved for children less than 6 months of age). Chiron's 
Fluvirin is indicated for persons 4 years of age and older, and 
Medlmmune's Flumist (a live intranasal vaccine) is indicated for 
persons 5-49 years of age.
    In 2004, the Institute of Medicine considered this topic, including 
new data that had accumulated since its previous review in 2001. These 
data included several epidemiological studies conducted in the United 
States, Denmark, Sweden, and the United Kingdom, and studies of 
biologic mechanisms related to vaccines and autism. The committee 
concluded that this body of evidence favors rejection of a causal 
relationship between thimerosal-containing vaccines and autism, and 
that hypotheses generated to date concerning a biological mechanism for 
such causality are theoretical only. Further, the committee stated that 
the benefits of vaccination are proven and the hypothesis of 
susceptible populations is presently speculative, and that widespread 
rejection of vaccines would lead to increases in incidences of serious 
infectious diseases like measles, whooping cough, and Hib bacterial 
meningitis.

    Question 2b. In existing childhood vaccines are there problems with 
mercury contamination even in trace amounts? If so, in FDA's opinion is 
there a health hazard or does more research need to be conducted?
    Answer 2b. Childhood vaccines, are not contaminated with mercury. 
Thimerosal, an organic mercury compound, has been added as a 
preservative to some vaccines, including pediatric vaccines. The need 
for a preservative can be eliminated to the extent that it is feasible 
to manufacture vaccines in single dose vials or syringes. In those 
instances where thimerosal has been used in earlier stages of 
manufacture to prevent contamination, it can be removed to the extent 
possible before final formulation of vaccines, but trace (0.1 microgram 
mercury per 0.5 ml dose) remains.
    Under the FDA Modernization Act (FDAMA) of 1997, the FDA conducted 
a comprehensive review of the use of thimerosal in childhood vaccines. 
Conducted in 1999, this review found no evidence of harm from the use 
of thimerosal as a vaccine preservative, other than local 
hypersensitivity reactions. However, as a precautionary measure, and 
because the elimination or reduction of mercury in vaccines was a 
feasible means of reducing an infant's total exposure to mercury in a 
world where other environmental sources are challenging to eliminate, 
the Public Health Service (including the FDA, National Institutes of 
Health (NIH), Center for Disease Control and Prevention (CDC) and 
Health Resources and Services Administration (HRSA)) established the 
goal of removing thimerosal as a preservative from vaccines routinely 
administered to infants as soon as possible. The PHS and the American 
Academy of Pediatrics issued two Joint Statements, urging vaccine 
manufacturers to reduce or eliminate thimerosal in vaccines as soon as 
possible (CDC 1999) and (CDC 2000).
    FDA has worked with and continues to work with vaccine 
manufacturers to reduce or eliminate thimerosal from vaccines, and 
significant progress has been made. Since 2001, all vaccines routinely 
recommended for children 6 years of age and under (DTa), hepatitis B, 
Haemophilus b conjugate (Hib), pneumococcal conjugate, IPV, MMR, and 
varicella) manufactured for the U.S. market have contained no 
thimerosal or only trace amounts, with the exception of inactivated 
influenza vaccine. FDA has approved preservative-free formulations 
(which contain no thimerosal or only trace amounts of thimerosal) for 
each of the two licensed inactivated influenza vaccines. FDA is in 
discussions with manufacturers of influenza vaccine regarding their 
capacity to increase the supply of preservative-free vaccine.
    The U.S. Public Health Service agencies have collaborated with 
various investigators to initiate further studies to better understand 
any possible health effects from exposure to thimerosal when used as a 
preservative in vaccines. Available data has been reviewed in several 
public forums including the Workshop on Thimerosal sponsored by the 
National Vaccine Advisory Committee, held in August 1999, two meetings 
of the Advisory Committee on Immunization Practices of the CDC, held in 
October 1999 and June 2000, and the Institute of Medicine's 
Immunization Safety Review Committee in July 2001 and February 2004. 
Through its Vaccine Safety Datalink, the CDC has examined the incidence 
of autism as a function of the amount of thimerosal a child received 
from vaccines. In this study, no significant association was found 
between autism and exposure to thimerosal-preservative-containing 
vaccines. Additional studies are planned in these areas.
    In 2001, the Institute of Medicine (IOM), at the request of CDC and 
NIH, convened the Immunization Safety Review Committee (the committee) 
to review selected issues related to immunization safety. This 
committee has completed two reviews of studies addressing a potential 
link between thimerosal-containing vaccines and autism. In its first 
review, conducted in 2001, the committee concluded that the evidence is 
inadequate to either accept or reject a causal relationship between 
thimerosal exposure from childhood vaccines and the neurodevelopmental 
disorders of autism, attention deficit hyperactivity disorder, and 
speech or language delay. The committee believed that the effort to 
remove thimerosal from vaccines was ``a prudent measure in support of 
the public health goal to reduce mercury exposure of infants and 
children as much as possible.''
    In 2004, the IOM's Committee reviewed this topic again, including 
new data that had accumulated since its review in 2001. These data 
included several epidemiological studies conducted in the United 
States, Denmark, Sweden, and the United Kingdom, and studies of 
biological mechanisms related to vaccines and autism. The committee 
concluded that this body of evidence favors rejection of a causal 
relationship between thimerosal containing vaccines and autism, and 
that hypotheses generated to date concerning a biological mechanism for 
such causality are theoretical only. Further, the committee stated that 
the benefits of vaccination are proven and the hypothesis of 
susceptible populations is presently speculative, and that widespread 
rejection of vaccines would lead to increases in incidences of serious 
infectious diseases like measles, whooping cough, and Hib bacterial 
meningitis.

    Question 2c. Is mercury used at any other stage in the 
manufacturing process? Is FDA conducting or has the FDA conducted any 
research into mercury exposure and its potential linkage to Autism or 
related disorders?
    Answer 2c. FDA has taken seriously reports to the Vaccine Adverse 
Event Reporting System (VAERS) of developmental delay following 
vaccination. CBER conducted a follow-up study of VAERS reports of 
autism. As part of the study, CBER, in conjunction with outside autism 
experts, reviewed available medical records and surveyed parents and 
others who have reported autism after vaccinations. The goal of the 
interviews was to gather information about demographics, clinical 
features, potential risk factors, family history, vaccines 
administered, time interval from vaccination to autism onset, rapidity 
of symptom onset, and interval from diagnosis to submission of reports. 
Another goal was to determine how a parent makes the association 
between a child's autism and vaccination. Because of the limitations of 
VAERS, this study could not be designed to determine whether vaccines 
cause autism. However, the study demonstrated a secular trend in the 
perception that autism might be associated with vaccines. The study 
specifically recommended that when providing guidance about 
immunizations and vaccine-preventable diseases, the risks of 
immunization should be discussed in the context of the risks of 
infection [Woo J., AJPH 94(6):990-995, 2004].
    As noted in the response to the previous question, CDC did conduct 
a study using the Vaccine Safety Datalink that did not show an 
association between thimerosal preservative-containing vaccines and 
autism (Vertraeten T etal, Pediatrics 112:1039-1048, 2003). In 
addition, the IOM was asked by the PHS to do an independent assessment 
of this issue, and their reports (published in 2001 and 2004) are noted 
above as well.

Old Drugs

    Question 3. There are many old drugs on the market that have never 
been approved directly by the Food and Drug Administration. Many are 
very common. However, several drugs have been removed from the market 
after specific manufacturers pursue a New Drug Application on the old 
drug. This process has, in some cases, removed some competitors from 
the market.
    Last year, you testified before the House Agriculture 
Appropriations Committee that a Prescription Drug Monograph System that 
could govern these drugs would be too expensive to implement. But you 
also said that you had another way to bring these drugs under 
regulation without disrupting the market. Have you determined another 
solution?
    Answer 3. FDA believes that the Agency's draft Compliance Policy 
Guide (CPG) on marketed, unapproved drugs, when finalized, will provide 
a means of protecting the public health without imposing undue burdens 
on consumers or disrupting the market unnecessarily. The Compliance 
Policy Guide (CPG) describes how we intend to exercise our enforcement 
discretion with regard to drugs marketed in the United States that do 
not have required FDA approval for marketing. By targeting drugs based 
on health risk, efficacy, and health fraud factors, the CPG will enable 
the Agency to: (1) devote its limited resources to those actions most 
likely to improve public health; (2) proceed against an individual 
product or an entire class of products, as appropriate; (3) preserve 
resources for review and approval of new, innovative drugs; and (4) 
remove potentially unsafe or ineffective products from the market 
without awaiting the resolution of lengthy rulemaking processes. The 
CPG also will create an incentive for manufacturers of marketed, 
unapproved drugs to seek approval of their products, which further 
addresses safety and efficacy concerns while preserving Agency 
resources. We received a number of comments on the draft CPG and we are 
revising the draft in response to the comments.

Emergency Contraception

    Question 4. Last spring, the FDA refused to allow over the counter 
sale of emergency contraception, which prevents pregnancy in almost all 
cases when taken within 48 hours and has been found to be safe and 
effective. In January, the FDA failed to act by its own internal 
deadline on a new request to sell emergency contraception from behind 
the counter. Can you provide assurances that a decision will be made 
within the next 3 months?
    I understand that part of the delay is concern by the FDA about the 
precedent of requiring Plan B be held behind a pharmacy counter as they 
do many places in Europe. However, in Iowa and many other States we are 
going to start requiring that all pseudoephedrine products be held 
behind the pharmacy counter. Do you agree that keeping emergency 
contraception behind the counter is a perfectly workable option?
    The denial of the Plan B application for over the counter status 
despite the vote of the Advisory Board and the internal staff 
recommendation has created the appearance that the Agency caved to 
political pressure. What plans do you have to prevent that sort of 
problem in the future once you are confirmed?
    Answer 4. The Prescription Drug User Fee Act (PDUFA) goal date for 
the Barr Laboratories/Plan B OTC supplemental application was January 
22, 2005. The application is still under review.
    This current cycle review is in response to resubmission of the 
application by the sponsor in July 2004. The resubmission proposes a 
revised indication to allow for marketing Plan B as prescription-only 
for women under the age of 16 and as nonprescription for women 16 years 
of age and older. In addition, they propose an educational program for 
healthcare providers, pharmacists, and patients.
    The issuance of the Not Approvable letter in May 2004 did not mean 
that a supplemental application could not be approved in the future. 
The Not Approvable letter described what the applicant would need to do 
to obtain approval for its initial supplemental application. In this 
case, the applicant chose to revise its application and requested to 
market Plan B as prescription-only for women under the age of 16 and as 
nonprescription for women 16 years of age and older. FDA is currently 
reviewing this application.
    Advisory committees at FDA were established to be only advisory in 
nature. When selecting participants for membership in advisory 
committees, we seek experts with a broad range of experience in their 
field. Such committee meetings offer a wide range of views that are 
discussed in a public forum. FDA seeks and appreciates the 
recommendations made by the committees. The final determination on a 
drug application, however, remains with the Agency. Although the Agency 
frequently makes final decisions concerning a new drug application 
(NDA) that are in accord with an advisory committee's recommendations, 
FDA is not bound to follow their recommendations. It is not unusual for 
there to be occasional differences of opinion among staff at the Agency 
on a particular issue. The scientific interchange of ideas is widely 
encouraged during the review process to ensure a thorough vetting of 
the issues. Decisions on drug reviews, however, cannot be made by 
simple majority vote or with the Agency feeling obligated to rubber 
stamp an advisory committee vote. Ultimately, a final decision is made 
based on FDA's evaluation of the data, taking into account all of the 
views expressed.
    Decisions on this review are being made within FDA's Center for 
Drug Evaluation and Research where the supplemental application is 
still under review.

Restaurant Labeling

    Question 5. Dr. Crawford, in your remarks, you stated some members 
of the chain restaurant industry had adopted some measures to provide 
nutritional information to consumers. Could you provide specific 
information on which chains are meeting the recommendations found in 
``Counting Calories: Report of the Working Group on Obesity.'' What are 
they doing to meet those recommendations? Given the rise in eating 
outside the home, Dr. Crawford, in your opinion do consumers need more 
information, rather than less, to make rational, responsible, and 
personal decisions about their own health? How can this information be 
standardized across restaurants?
    Answer 5. The FDA Report on Obesity, ``Calories Count,'' recommends 
several steps be taken concerning ``away-from-home'' foods. 
Specifically the Agency urged the restaurant industry to launch a 
nationwide, voluntary, and point-of-sale nutrition information campaign 
for consumers, to include information on calories. As a companion to 
that, and in response to input from the restaurant industry that they 
do respond to consumer demands, the report also calls on consumers to 
routinely request calorie and other nutrition information when they eat 
away from home. FDA has been doing this in speeches and meetings since 
release of the report. Further, the report calls on FDA to work with a 
third party facilitator to begin a national policy dialogue to seek 
consensus-based solutions to specific aspects of the obesity problem 
involving food consumed away from home. In June of 2004, FDA signed a 
contract with the Keystone Center, a nationally recognized facilitator 
for policy and scientific issues, to begin the dialogue process on this 
and the pediatric obesity (education) issue. The goal of the away-from-
home foods dialogue will be to consider what can be done, given the 
best available evidence to date, to support consumers' ability to 
manage energy intake with respect to preventing undue weight gain and 
obesity. The dialogue is intended to produce options for a range of 
actions by a diverse range of stakeholders. Keystone will convene its 
first plenary meeting of stakeholders, to include representatives from 
the restaurant industry, academia, consumer groups and government, on 
April 26-27, 2005.
    You are correct that a number of chain restaurants have put in 
place initiatives to address obesity. Some quick service restaurants 
have made nutrition information available to consumers for years, on an 
in-store poster, on tray liners, via the internet, or on request by 
phone or mail. Specific examples of some of the current initiatives we 
are aware of are as follows:
     Over a year ago, the Ruby Tuesday restaurant chain 
introduced menus with full calorie (and other nutrient) information for 
each item offered. We are unaware of how many of their restaurants use 
this menu at the present time.
     Many of the familiar quick service restaurants, including 
McDonald's, Burger King, Wendy's and Yum! Brand Foods chains such as 
Taco Bell, Kentucky Fried Chicken and A&W, continue to introduce 
alternative menu items focused on fruits and vegetables as alternatives 
to the traditional items. Many of these same restaurants have also 
focused on the need to balance calories with physical activity with 
online programs combining nutrition information on their products with 
recommendations for increasing physical activity.
     Subway restaurants have supplied nutrition information, 
including fat and calories with their menu items for some time.
    FDA continues to encourage restaurants voluntarily to provide 
point-of-sale nutrition information to customers, including calorie 
information on a nationwide basis. For those consumers that want 
calorie and other nutrition information at the point of sale, we 
believe the industry should continue to strive for more innovative and 
helpful solutions nationwide. This will be part of FDA's focus in the 
upcoming Keystone dialogue.
                                 ______
                                 
 Response to Questions of Senator Hatch by Lester Crawford, DVM, Ph.D.
    Question 1. Much has been made about a recent Institute of Medicine 
report, Complementary and Alternative Medicine in the United States, 
which recommended amendment of the Dietary Supplement Health and 
Education Act (DSHEA). In its report, the IOM recommended amendment of 
DSHEA and FDAOs current regulatory scheme to address six issue areas: 
(1) seed to shelf quality control; (2) accuracy and comprehensiveness 
in labeling; (3) enforcement efforts against false and misleading 
claims; (4) research into how consumers use supplements; (5) incentives 
for privately funding research into efficacies; and (6) consumer 
protection against all potential hazards.
    Although I do quarrel a bit with terming supplement use 
``alternative medicine,'' I do appreciate the IOM's interest in this 
issue and its identification of areas for discussion. That being said, 
could you comment on whether you believe either the law or FDA 
regulation would need to be amended in order to address the IOM's 
recommendations?
    Answer 1. In November 2004, FDA published a regulatory strategy 
that clearly lays out, for the industry and consumers, the Agencys 
direction in implementing all the provisions of the Dietary Supplement 
Health and Education Act of 1994 (DSHEA). The strategy is designed to 
give consumers a higher level of assurance about the safety of dietary 
supplement products and the reliability of their labeling, as well as 
to improve the transparency, predictability, and consistency of the 
Agencys scientific evaluations and regulatory actions to protect 
consumers against unsafe dietary supplements and dietary supplements 
making unauthorized, false, or misleading claims. Last year, FDA took 
action on dietary supplements containing ephedrine alkaloids because 
they present an unreasonable risk of illness or injury. The Agency will 
continue its ongoing efforts of monitoring and evaluating product 
safety, ingredient safety, and product labeling, as well as ensuring 
product quality.

    Question 2. Dr. Crawford, there is apparently growing concern among 
many dietary supplement consumers that the CODEX Alimentarius 
guidelines on vitamins and minerals, said to be adopted this July, will 
supersede U.S. law and DSHEA specifically, resulting in limits on the 
potency of vitamins and minerals now available in the United States. 
Could you give us your understanding of whether CODEX guidelines 
supersede U.S. law?
    Answer 2. The Codex Alimentarius Commission was created in 1963 by 
the Food and Agriculture Organization of the United Nations (FAO) and 
the World Health Organization (WHO) to develop food standards, 
guidelines and related texts such as codes of practice under the Joint 
FAO/WHO Food Standards Program. The main purposes of this program are 
protecting health of the consumers and ensuring fair trade practices in 
the food trade, and promoting coordination of all food standards work 
undertaken by international governmental and non-governmental 
organizations. The CODEX guidelines will not supersede U.S. law--in 
part because of the statutory provisions of FDAMA that direct FDA to 
try to harmonize its regulatory requirements with those of other 
governments specifically exclude dietary supplements. See section 
410(b) of the Food and Drug Administration Modernization Act of 1997.--
(FDAMA) (Pub. L. 105-115, codified at 21 USC 383(c)).

    Question 3. Doctor, 10 years ago, the Dietary Supplement Health and 
Education Act authorized the Food and Drug Administration to develop 
good manufacturing practice standards (GMPs) specific to dietary 
supplements. I recognize that the law did not require you to do so, but 
it did allow this process to begin. We were greatly heartened that FDA 
did undertake to develop dietary supplement GMPs. That's the good news. 
The bad news is that 10 years ago the Dietary Supplement Health and 
Education Act authorized the FDA to develop GMPs for dietary 
supplements, and we have not yet seen them published. It is my 
understanding that the HHS-approved GMP regs were forwarded to OMB for 
final clearance during the Clinton administration. Shortly after 
President Bush was elected, my office received a call from a senior HHS 
official stating that HHS was going to make certain the GMP regs 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 have had numerous reports that the 
regs were going forward, but they still have not been published. 
Accordingly, I would like to know the following things about the status 
of these regulations:
     Have they been cleared in final by FDA?
     Have they been cleared in final by HHS?
     What specific issues remain outstanding so that these 
regulations may be finalized?
     Please tell the committee when the regulations will be 
published, that is, on what date certain can we be assured the 
regulations will have been finalized?
    Answer 3. I am as disappointed as you are that we have not been 
able to finalize the dietary supplement GMP rule. In the past 4 years, 
I assure you that there has been significant work done on the dietary 
supplement GMPs. The proposed rule was published March 13, 2003, and 
included responses to numerous comments received after publication of 
the ANPRM in 1997. The comment period for the proposed rule was 
extended until August 2003. We held public stakeholder meetings on 
April 29, 2003 in College Park, MD, and on May 6, 2003 in Oakland, CA. 
We also held a public meeting, via satellite downlink, on May 9, 2003, 
with viewing sites at our district and regional offices throughout the 
country. After the comment period closed, we began the process of 
analyzing the comments submitted to the proposed rule. The issues 
raised by the comments are complex, legally and substantively, and in 
some cases, novel. We have expended significant internal resources on 
reviewing and preparing responses to the comments received. In 
addition, we have worked hard to ensure that the goals of DSHEA are 
carried out with careful consideration of the impact on the dietary 
supplement industry.
    Since we are in the rulemaking process, I can only assure you that 
we continue to work hard on the final rule and as I stated during the 
hearing, I believe that the final rule should be published by the end 
of the year. I recognize this has taken longer than it should have and 
longer than anyone likes. But, we have come so far on the rule and 
currently are in the final stages of review--I would hate to see this 
critical work on the final rule lost because of problems introduced in 
a last minute rush to completion. I assure you full attention is being 
given to completing the rule.

    Question 4. We are hopeful that the GMP regulation will include 
dietary supplement, and ingredient manufacturers worldwide. How will 
FDA address the issue of GMP compliance by foreign manufacturers?
    Answer 4. Since we are in the rulemaking process, I can only assure 
you that we continue to work hard on the final rule and as I stated 
during the hearing, I believe that the final rule should be published 
by the end of the year. I cannot however, comment on what will be in 
the final rule. I will note that in the proposed rule, FDA proposed 
applying the final rule equally to both domestic and foreign 
manufacturers of dietary supplements. Also, FDA proposed addressing 
cGMP compliance by dietary supplement manufacturers in the same fashion 
as the Agency handles compliance for foreign and domestic manufacturers 
of conventional food.

    Question 5. Section 9 of DSHEA is explicit that a GMP may not 
impose standards for which there are no current, generally available 
analytical methods. We are aware that a number of organizations are 
working very hard to develop analytical methods. What is FDA doing to 
collaborate with the Office of Dietary Supplements at NIH and industry 
to assure that analytical methods are available for the most important 
dietary ingredients?
    DSHEA is now 10 years old, and yet it is not fully implemented 
although I recognize the substantial work that has been conducted under 
your tenure at FDA to move us toward better implementation. Now that 
the President has sworn in Secretary Leavitt, and your confirmation is 
imminent, would you consider meeting with key industry leaders and the 
Secretary to lay out a plan to fully implement DSHEA as soon as 
possible?
    Answer 5. Since 2001, FDA has had an IAG with ODS/NIH that funds a 
significant portion of a multimillion dollar 5-year contract with AOAC 
International to develop/identify, evaluate and validate analytical 
methods for dietary supplements. Industry also contributes funds and 
participates in the validation studies. Prioritization of the targeted 
dietary ingredients is determined by an Ingredient Ranking Subcommittee 
convened by AOAC stakeholders; the composition of this subcommittee is 
balanced between members from the Federal Government (esp. FDA and 
NIH), the industry, and academia. As such, prioritized dietary 
ingredients for which the validation process is completed include 
several that pose public health concerns (e.g., ephedra alkaloids, St. 
Johns wort, and aristolochic acid). Other dietary supplements of 
concern include aconotine, pennyroyal, sour orange, blue cohosh, 
chapparal, comfrey, germander, mayapple, tansy and wormwood for which 
laboratory studies in CFSAN continue. Twenty-two additional methods of 
particular interest to the dietary supplement industry are in the 
process of validation.
    Because AOAC as changed the way collaborative studies are 
conducted, they are able to validate more methods than originally 
projected for the 5-year contract (20 methods). We are currently in the 
third year of the contract.
    FDA would be glad to meet with industry leaders on DSHEA 
implementation.

    Question 6. Dr. Crawford, I have a general and a specific question 
for you on the issue of ``follow-on'' or ``generic'' biologics, 
something you and I have discussed before.
    First, could you outline for the committee the FDA's current 
activities to develop a policy or pathway so that consumers at some 
point will have available lower cost alternatives to costly biologic 
products? When might FDA's activities in this area conclude:
    Second, in March 2001 the FDA announced that it was working on two 
generic biologic guidances for human growth hormone and insulin, and 
the trade press reported in April 2002 that one guidance had been 
drafted and the other was in process. In May of last year you testified 
that FDA was preparing to release guidance for certain biological 
products. HgG was specifically mentioned but presumably insulin was the 
other product you were referring to.
    Apparently you have blocked the guidances pending the FDADs larger 
consideration of the generic biologics issue. Dr. Crawford, the country 
is spending billions of dollars on products such as insulin and human 
growth hormone. Yet, 4 years after it announced it would issue these 
guidances, FDA still has not done so. When do you plan to release any 
hold on the guidances that have been prepared and allow them to proceed 
through clearance so companies may know what is required to develop 
generic versions of Human Growth Hormone and Insulin?
    Answer 6. As you know, FDA is conducting a public process to 
examine the many questions, including scientific and legal issues, that 
must be answered regarding these products and to ensure that all 
interested parties have an opportunity to comment. When this process is 
complete, FDA intends to provide guidance to industry to clarify, 
consistent with its legal authority, the approval pathway and 
principles for review of such products, which will protect the public 
health.
    In recent years--and with increasing frequency--questions about 
generic or follow-on proteins have arisen in response to scientific 
advances, impending patent expirations, and the ability to better 
characterize and understand biological products.
    Acknowledging scientific and legal limitations in this area, yet 
also recognizing the public health need to move forward to assist 
industry and make more products available to the public, FDA is 
conducting a public process to examine the scientific, and related 
issues regarding follow-on biologics. This process will ensure that 
scientific considerations and issues related to Agency authority are 
fully examined and that all interested parties have an opportunity for 
input.
    The Agency understands the importance of human growth hormone and 
insulin. We are currently re-evaluating guidance documents to assure 
that they are scientifically in-line with current efforts to ensure the 
efficacy of follow-on biologic products.

    Question 7. As you know, I take a great interest in the White Oak 
Facility and am watching its progress closely. Could you provide me 
with a progress report on work done to date, your projected timetable 
for the future, and the cost estimates for remaining work? Is the 
necessary funding to complete work at White Oak contemplated in the 
President's Budget?
    Answer 7. We appreciate your interest and support in the FDA White 
Oak Consolidation Project. The White Oak Consolidation Project 
continues its coordinated efforts to execute the 2000 Master Plan 
design to provide a new state-of-the-art facility for the FDA at White 
Oak.
    On December 11, 2003, a dedication ceremony was held for the Life 
Sciences Laboratory, a state-of-the-art chemistry, bioscience and 
animal research facility. As the first new building to open on the 
site, the laboratory provides approximately 124,000 gross square feet, 
for 120 employees from the Center for Drug Evaluation and Research 
(CDER) and the Center for Devices and Radiological Health (CDRH).
    Construction for the CDER Office Building I began on November 15, 
2002, and has progressed on schedule for occupancy in summer 2005. This 
building provides 560,000 gross square feet of modem office space to 
accommodate the Office of New Drugs, comprised of approximately 1,700 
scientists and support staff. The facility also includes a 60,000 
square foot, efficient document storage center, mail room and support 
space.
    Construction of the Central Shared Use Building began in October 
2004. When complete this facility will provide employees and visitors 
with a cafeteria, conference and training center, credit union, fitness 
center, health unit, central library and R&W store, along with housing 
the Agency security command center, central data center and NTEU 
offices. The first phase of this building, including the cafeteria, 
fitness center and security command center, is scheduled for completion 
in spring 2006.
    The construction contract for the CDRH Engineering/Physics 
Laboratory was awarded in January 2005. This building will provide 
approximately 128,000 square feet of high tech laboratories engaged in 
evaluating electromagnetic and medical devices, radiological 
instruments and consumer appliances generating radiological signals. 
The facility consists of numerous vibration isolation slabs, 
electromagnet shielding, an anechoic chamber and laser devices 
especially dedicated to the program science. This facility is scheduled 
for occupancy in early 2007.
    With design to be complete in spring 2005, the approximately 
291,000 gross square foot CDER Office Building II will accommodate the 
Center Director's office and the balance of the CDER scientific and 
support staffs. This is a uniquely designed office building in that the 
entire building will be equipped with an under-floor ventilation 
system. This design change provides for more offices benefiting from 
indirect outside daylight, taller windows, more efficient distribution 
of air and electrical wiring along with IT/Telecom and security wiring.
    Finally, the design for the first phase of the site's parking 
garages is complete with the finish of construction planned for 2005. 
This concrete parking structure will contribute approximately 800 
spaces to the overall parking for the campus.
    The design and construction of the new buildings at White Oak are 
funded through General Services Administration (GSA) appropriations 
along with the site infrastructure, internal support services and move 
costs that are covered by the FDA. These costs include: internal 
communication needs, including equipment, cabling and audiovisual; 
security, including infrastructure and equipment; information 
technology and telecommunications cabling; modular furniture and other 
equipment to furnish the building for occupancy; and, relocation costs, 
including records management consolidation, relocation coordination and 
moving.
    FDA and GSA are working to update the estimated cost to complete 
this project given that the schedule for some projects has been 
delayed. Estimates developed a year ago suggest that approximately an 
additional $550 million would be needed after fiscal year 2006 to 
complete the headquarters project. Of this, roughly 4/5ths would be GSA 
construction funding, and 1/5th would be FDA move and fit-out funding.

    Question 8. We in Utah have been very concerned with the progress 
of MDUFA. In the first instance our growing small medical device 
companies were very worried that the PDUFA model used for pharma would 
not work for medical devices. There was a great concern that this 
program to advance approvals at a large cost to our small companies 
would not achieve its goals. In fact it seems that our concerns are 
coming true. By our reckoning the costs are going up, the approval 
times are not coming down, and the Federal Government is not fulfilling 
its commitments, both programatic and financial. Do you have any 
assurance for us that this situation with MDUFA can be turned around in 
the near future?
    Answer 8. Many aspects of the Medical Device User Fee and 
Modernization Act (MDUFMA) are working quite well. Chief among them is 
the fact that the agency is meeting the performance goals agreed to in 
conjunction with MDUFMA. Medical device application review has been 
substantially improved by both the additional resources that MDUFMA 
makes available for reviewing applications and by a number of new 
guidance documents issued in response to MDUFMA, which tend to improve 
communication about expectations in the device review process and to 
standardize aspects of the review process. I have high expectations for 
the continuation of these improvements in device review through fiscal 
year 2007, assuming that the MDUFMA program continues.
    Some of the financial aspects of MDUFMA have been disappointing for 
both FDA and the device industry. First, in spite of agency urging, 
financial aspects of MDUFMA were not patterned after PDUFA, which has 
both annual product fees and annual establishment fees to assure fee 
stability and to reduce the size of the application fee. The device 
industry was adamantly opposed to such annual fees, and demanded that 
all revenue come from application fees alone, which can fluctuate 
widely from year to year. FDA initially opposed having only application 
fees, but relented when the device industry assured revenue stability 
for FDA by proposing an annual compensating adjustment in years when 
revenue collected was less than statutory revenue targets. Also, 
industry wanted to phase in its funding target of $35 million over 5 
years. The result of that phase in, and annual inflation increases, 
should have caused fees to increase at the rate of about 13 to 14 
percent each year. Revenue has been less than statutory revenue targets 
in each year. However, fewer application fees and the compensating 
adjustment proposed by industry have caused fees to increase at rates 
higher than the agreed-to 13 to 14 percent.
    Unlike PDUFA, MDUFMA also specified higher annual appropriation 
levels for FDA's device program. These higher levels did not occur in 
fiscal year 2003 and 2004, and if they are not made up by October 1, 
2005, the MDUFMA program will end. In light of this, the Director of 
the Office of Management and Budget assured the Speaker of the House in 
October 2003 that Administration budget requests for fiscal year 2005, 
2006, and 2007 would be sufficient to meet the higher appropriation 
levels specified in MDUFMA, and he asked Congress to waive the MDUFMA 
requirement for make-up appropriations in fiscal year 2003 and 2004. I 
look forward to working with Congress on this proposal in order keep 
the MDUFMA program functional through fiscal year 2007.

    (Second set of questions)

    Question 1. Do you believe that mercury is a toxin that needs 
careful oversight? On other uses of mercury, the FDA has taken a strong 
stance.
    Answer 1. Mercury, and specifically methyl mercury, is known to be 
toxic to a variety of systems in the human body when exposure occurs at 
a high dose and as such is a toxin that requires careful oversight. FDA 
continues to monitor the science around the issues of mercury exposure 
in order to react appropriately to new evidence of the impact of 
mercury on human health. Lower doses of methyl mercury, such as may 
occur through the consumption of certain types of fish, have been 
associated with a variety of developmental delays in young children.
    The mission of the FDA is to protect public health and, in the 
context of methyl mercury exposure through the consumption of fish, 
this requires one to consider both the health risks from exposure to 
methyl mercury as well as the health benefits from consuming fish. The 
FDA believes that it is important for women who may become pregnant, 
pregnant women, nursing mothers and young children to avoid certain 
types of fish (shark, swordfish, tilefish and king mackerel) that 
contain high levels of methyl mercury. FDA recommends that this same 
group eat up to 12 ounces a week of a variety of fish that are lower in 
mercury. This advice was published jointly with EPA in March 2004. 
Currently, the FDA is in the middle of an education campaign designed 
to get this message out to the specific populations noted above.

    Question 2. Why hasn't the FDA issued warnings to pregnant women 
and children under 6 about mercury exposure from dental amalgam? Isn't 
it true that Health Canada has issued warnings to pregnant women and 
children under the age of 6 since 1996? Why hasn't the FDA taken 
similar action?
    Answer 2. FDA has not issued warnings to pregnant women and 
children under 6 about mercury exposure from dental amalgam, as has 
Canada, because while FDA and other agencies of the U.S. Public Health 
Service (USPHS) continue to investigate the safety of dental amalgam, 
no valid scientific evidence has shown that amalgams cause harm to 
patients with dental restorations, except in the rare cases of allergy.
                                 ______
                                 
Response to Questions of Senator Isakson by Lester Crawford, DVM, Ph.D.
    With respect to FDA's recent decision to reorganize the Office of 
New Drugs--Ophthalmologists are particularly concerned about the 
likelihood that final decisions including clinical sign-off for all 
(ophthalmic) products in the Division will no longer be made by the 
Ophthalmology Deputy Director, but instead will be made by the Division 
Director. With respect to ophthalmic drugs, many feel that keeping the 
risk decision closer to the specialty of ophthalmology as part of the 
overall clinical sign-off is the most efficient and fair approach.

    Question 1. If confirmed as commissioner, what steps will you take 
to ensure current and future patients that the advancement of new 
ophthalmic treatments/therapies into the realm of the eye care 
practitioner will continue to take place as expeditiously as possible?
    Answer 1. Individuals with expertise in ophthalmology will continue 
to play a critical role in reviewing new ophthalmology products, and 
the reorganization will not affect the timely approval of treatments 
and drug therapies available to eye care practitioners and their 
patients. All drug review processes for all products will continue to 
be held to existing PDUFA goals and timelines during and as a result of 
the reorganization.

    Question 2. Given the enormous amount of drug research and 
development presently going on in ophthalmology, what steps will you 
take to ensure that new drug approval will not be unnecessarily delayed 
as a result of the pending reorganization?
    Answer 2. As noted above, the reorganization will not affect the 
timely approval of treatments and drug therapies available to eye care 
practitioners and their patients. All drug review processes for all 
products will continue to be held to existing PDUFA goals and timelines 
during and as a result of the reorganization.
                                 ______
                                 
  Response to Questions of Senator Dodd by Lester Crawford, DVM, Ph.D.

Drug Safety

    Question 1. Transparency
    There have been disturbing reports that suggest that the FDA does 
not place enough emphasis on drug safety, and that concerns raised by 
those in the Office of Drug Safety (ODS) are sometimes ignored and even 
suppressed.
    An internal study conducted by the HHS Office of the Inspector 
General in 2002 revealed that approximately one-fifth of drug reviewers 
had been pressured to approve a drug despite concerns about safety, 
efficacy, or quality. In addition, more than one-third said they were 
``not at all'' or only ``somewhat'' confident that final decisions of 
the Center for Drug Evaluation and Research adequately assessed safety.
    This seems to have been the case with Dr. Andrew Mosholder when he 
had data to suggest that certain antidepressants might increase the 
risk of suicide in children and adolescents; as with Dr. David Graham 
when he had data to suggest that Vioxx is connected with cardiovascular 
problems.

    Dr. Crawford, do you believe that mistakes were made in the 
handling of Dr. Mosholder and Dr. Graham? As Commissioner of the FDA, 
what would you do to ensure transparency, so that dissenting opinions 
are seriously considered and never suppressed, especially when they 
have to do with issues so critical to the health and well-being of the 
public?
    Answer 1. Good scientific decisions depend on robust discussion and 
various layers of peer review. In encouraging such discussion, FDA will 
work to ensure that FDA scientists involved in the decision making 
process do not feel pressured or ignored.
    The rigorous scientific review process is critical to sound 
regulatory decision-making. In both Dr. Mosholder and Dr. Graham's 
cases, the Agency sought the best available data upon which to make a 
regulatory decision. For instance, with the SSRIs, FDA initiated the 
Columbia Reclassification Project, which provided sound data upon which 
to make a decision. These data confirmed Dr. Mosholder's findings, 
which were based on weaker data. With the COX-2 inhibitors, FDA again 
insisted on scientific peer-review of Dr. Graham's work, which he 
submitted for publication prior to the standard Agency peer-review. The 
Agency recently held a joint meeting of the Arthritis and Drug Safety 
and Risk Management Advisory Committees to evaluate all available data, 
including the work of Dr. Graham.
    Pursuant to Federal law, the Agency does not retaliate against 
whistleblowers or interfere with their rights to freely express their 
views in public forums, such as investigations of the Congress.
    FDA constantly strives to improve our drug safety process and 
methods, thereby better serving the public health. Recent developments, 
including the work of Dr. Mosholder and Dr. Graham, have prompted us to 
refocus our drug safety efforts and take additional steps to identify 
drugs that may have unacceptable risk profiles.
    Recently, I joined Secretary Leavitt to announce important efforts 
that we are undertaking at FDA to improve the ability to monitor and 
respond to emerging drug safety information.
    These steps will ensure both a better internal process of 
deliberation on drug safety issues that ensures appropriate and 
independent consideration of all issues, as well as a stronger ability 
to gather data about drug safety issues once a drug has been approved.
    Most importantly, we are moving to encourage more transparency and 
to ensure that patients and physicians have the most up-to-date and 
complete information necessary to inform their treatment decisions. 
This new Drug Information Initiative will give patients, healthcare 
professionals, and other consumers quick and easy access to the most 
up-to-date and accurate information on medicines and make FDA's drug 
review, approval, and monitoring programs as transparent as possible.
    This is in addition to FDA's Five Point Plan to Improve Drug 
Safety, a major initiative designed to improve the monitoring of drug 
products recently approved for marketing. The major components of this 
initiative include:
     Sponsoring a major study of the Drug Safety System by the 
Institute of Medicine;
     Implement a Program for Adjudicating Differences of 
Professional Opinion;
     Conducting a nationwide search to identify a permanent 
director for the Office of Drug Safety;
     Conducting a series of workshops and meetings on drug 
safety and risk management; and
     Publishing risk management guidance.
    FDA's Office of Drug Safety (ODS), in the Center for Drug 
Evaluation and Research (CDER), is already an independent office 
separate from the Office of New Drugs, the office that reviews new drug 
applications. Both the Office of New Drugs and the Office of Drug 
Safety report directly to the Director of the CDER. ODS has independent 
authority to perform its own research and does so every day. To be 
valuable, this independent research must conform to widely accepted 
scientific standards and normal scientific procedures and peer review 
should not be bypassed. And when drug safety issues are identified, 
they must be factored into the risk-benefit equation so that safe and 
effective drugs remain available to patients who need them.
    FDA has a longstanding commitment to provide a strong resource base 
for its drug safety program. The budget for fiscal year 2006 continues 
this commitment. The President has proposed a 24-percent increase for 
FDA's post-market safety program to help further ensure that America's 
drug product supply is safe and effective, and of the highest quality. 
Under this proposal, CDER's ODS would receive increased funding to 
expand the Agency's ability to rapidly survey, identify and respond to 
potential safety concerns for drugs on the market. ODS will hire 
additional staff to manage and lead safety reviews, will increase the 
number of staff with expertise in critical areas such as risk 
management, risk communication and epidemiology, and will increase 
access to a wide range of clinical, pharmacy and administrative 
databases. Our commitment to increase resources available for post-
market safety will enhance the structural changes we are proposing to 
advance drug safety.
    In an effort to improve the current process immediately, CDER has 
instituted a program to formally address the opinions of dissenting 
scientific reviewers to ensure that the decision-making process is 
transparent. For more information on this plan, please visit: http://
www.fda.povIbbs/toDics/news/2004INEW01131.html.

FDA Authority

    Question 2. Dr. Crawford, during testimony before this committee 
earlier this month, an FDA witness, Dr. Sandra Kweder, seemed to 
suggest that additional authority to require companies to conduct post-
market studies and to make changes to the drug label would be 
``helpful'' to FDA. Two days later another FDA witness, Dr. Janet 
Woodcock, backed off of those statements.
    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?
    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. Crawford, 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 2. I do not believe new statutory authority is needed. We 
will use all existing regulatory authority and enforcement powers when 
negotiating label changes with drug companies or when monitoring or 
managing drug safety issues. As Dr. Janet Woodcock testified, a key 
factor in labeling changes is that once a label change is made, old 
labels in paper form are still in distribution and it takes time to get 
newer labels in circulation. Dr. Woodcock testified that the new 
strategy of posting drug safety information sooner using the Drug Watch 
mechanism will help alleviate that factor because it will enable the 
FDA to get information directly to the people who need it in a timely 
manner.

Office of Drug Safety

    The Administration's fiscal year 2006 budget includes an additional 
$6.5 million for the Office of Drug Safety (ODS).

    Question 3a. With this budget increase, how many scientists will 
the ODS employ?
    Answer 3a. With the additional funds, we expect to be able to hire 
eight additional FTEs in the Office of Drug Safety to establish 
policies and processes regarding safety reviews and risk management, to 
manage communications with the Office of New Drugs and to support 
patient safety initiatives and external partnerships with CMS, AHRQ, 
and other HHS Agencies.
    We also plan to hire an additional 14 FTEs in the three operating 
divisions of ODS. These employees will handle the increased workload of 
monitoring biologic therapeutics; promote increased communication and 
coordination of safety review activities within the divisions; increase 
focus on medical error signal detection, address the current backlog of 
unaddressed potential safety signals; increase epidemiological 
expertise to explore safety risks and signals in various population 
databases; and manage the increasing workload in ODS for new drug 
consultations and designing post-approval studies for new drug use in 
specific populations.
    Finally, we plan to hire six FTEs to increase staff dedicated to 
evaluating and communicating drug safety risks to the health care 
community and the American public.

    Question 3b. How does the ODS budget and staff compare to that of 
the Office of New Drugs?
    Answer 3b. The table below presents a 3-year budget and staff 
comparison between the Office of New Drugs and the Office of Drug 
Safety. Please note that a side-by-side comparison of the budgets of 
these offices is not meaningful without considering the significant 
pre-approval responsibilities performed by the Office of New Drugs.



    Question 3c. Given that the ODS is charged with tracking every 
single drug that is on the market, does the balance of resources seem 
appropriate?
    Answer 3c. We believe that the balance of resources has 
appropriately reflected ODS's responsibility within the overall post-
marketing safety function. The Office of Drug Safety is not singularly 
responsible for tracking post marketing safety issues of marketed drug 
products. ODS works with the Office of New Drugs to evaluate safety 
issues once drugs are on the market.

    Question 3d. When do you plan to fill the vacant Director position 
within the ODS?
    Answer 3d. The agency has experienced difficulty recruiting high 
quality candidates for the position of Director, Office of Drug Safety 
through traditional mechanisms such as scientific journal 
advertisements and government vacancy announcements. We are committed 
to using all available resources to ensure a systematic, inclusive 
recruitment process for this critically important position. To that 
end, FDA has partnered with the recruitment and staffing professionals 
at the Office of Personnel Management (OPM), Center for Talent Services 
to develop and manage a recruitment strategy that we are confident will 
yield a sizable number of strong candidates and ultimately, a top-notch 
director. We feel that the additional time and resources invested in a 
thorough analysis of the leadership and technical competencies required 
to successfully manage the drug safety program, including input from 
internal and external subject matter experts and stakeholders, will be 
time well spent. The Office of Personnel Management is targeting the 
end of May for the position to be posted on USAJOBS.

    Question 3e. Why has the ODS been without a director for so long?
    Answer 3e. It is very difficult to hire the appropriately skilled 
individual for this position. The Director should be credentialed in 
medicine and have experience and working knowledge of controlled 
clinical trials, epidemiology, research, medicinal products, and drug 
regulations. Any individual who has these qualifications may be 
reluctant to take this position for the salary we can offer. Further, 
we have tried to promote individuals with these qualifications from 
within the Agency. However, we often find that these individuals 
subsequently are recruited heavily by industry.

Drug Safety Oversight Board

    Dr. Crawford, the centerpiece of the Administration's plan to 
address the drug safety crisis is the creation of a drug safety 
oversight board. While I applaud the Administration for taking action, 
I am concerned that this change is not nearly significant enough to 
address the problem.

    Question 4. Will the new board have any decision making or 
regulatory authority of its own? If not, how can patients be sure that 
the FDA will act on problems that it identifies? The FDA has said that 
the Deputy Director of CDER will chair the board. If this is the case, 
in what way is the board independent?
    Answer 4. The new board will have the authority to make 
recommendations to the Center Director on drug safety questions. The 
Center Director oversees all of the offices in CDER, including those 
that review new drug applications as well as the Office of Drug Safety. 
The DSB will include members from the FDA outside of CDER and medical 
experts from other HHS agencies and government departments (e.g., 
Department of Veterans Affairs) who will be appointed by the FDA 
Commissioner. The Board also will consult with other medical experts 
and representatives of patient and consumer groups. The wealth of 
expertise envisioned in the DSB will create an independent voice to 
make recommendations to the Center Director on drug safety issues. The 
Deputy Center Director is also independent of the Office of New Drugs 
and the Office of Drug Safety and can be expected to manage the Board 
in a fair and evenhanded manner, making sure all opinions are heard. 
The Agency looks forward to receiving recommendations from the 
Institute of Medicine (IOM) study that will be evaluating the current 
drug safety system, and will make appropriate adjustments to its 
programs after reviewing those recommendations. FDA would like to 
emphasize our commitment to a culture of transparency and rigorous 
scientific peer review.

Direct to Consumer (DTC) Advertising

    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.

    Question 5. 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 5. We have conducted research that confirms that DTC 
advertising, when done correctly, can serve positive public health 
functions, such as increasing patient awareness of diseases that can be 
treated, and prompting thoughtful discussions with physicians that 
result in needed treatments being prescribed often, not the treatment 
in the DTC advertisement. Results of our research show that many 
physicians believe that DTC can play a positive role in their 
interactions with patients and that many physicians thought that DTC 
ads made their patients more involved in their healthcare.
    In a survey we conducted, only 8 percent of physicians felt very 
pressured to prescribe the specific drug advertised. Physicians agreed 
that the main effect of DTC ads was to help educate patients about 
their health problems, causing them to seek needed care.
    At FDA, CDER's Division of Drug Marketing, Advertising, and 
Communications (DDMAC) is responsible for regulating prescription drug 
promotion. DDMAC's mission is to protect the public health by helping 
to ensure that prescription drug information is truthful, balanced, and 
accurately communicated. This is accomplished through a comprehensive 
surveillance, enforcement and education program, and by fostering 
optimal communication of labeling and promotional information to both 
health care professionals and consumers.
    While we believe the survey results discussed above confirm our 
belief that DTC ads help increase patient awareness about the 
availability of effective treatments for their health problems, we will 
continue to ensure that our DTC policies help prevent potential 
misperceptions about benefits and risks of the advertised treatment and 
promote the importance of prescribing decisions being made with the 
intervention of a health care professional.
    As you know, FDA has extensive authority over drug promotion. To 
summarize the FD&C Act and regulations do not distinguish between 
promotion to professional and consumer audiences. Section 502(n) of the 
FD&C Act specifies that prescription drug advertisements must contain 
``a true statement of . . . information in brief summary relating to 
side effects, contraindications, and effectiveness'' of the advertised 
product. The implementing regulations specify that prescription drug 
advertisements cannot be false or misleading, cannot omit material 
facts, and must present a fair balance between effectiveness and risk 
information. Further, for print advertisements, the regulations specify 
that every risk addressed in the product's approved labeling must also 
be disclosed in the advertisements.
    For broadcast advertisements, however, the regulations require ads 
to disclose the most significant risks that appear in the labeling. The 
regulations further require that the advertisement either contain a 
summary of ``all necessary information related to side effects and 
contraindications'' or provide convenient access to the product's FDA-
approved labeling and the risk information it contains. Finally, the 
FD&C Act specifically prohibits FDA from requiring prior approval of 
prescription drug advertisements, except under extraordinary 
circumstances.
    To encourage more effective regulation of DTC promotion, FDA plans 
to develop additional guidance documents, including one addressing the 
presentation of risk information in print advertisements and one 
addressing outdoor advertising. FDA also will conduct a series of 
studies to examine the format and content of brief summaries in direct-
to-consumer print advertisements. This will assist the agency to 
finalize the draft guidance on consumer-directed print advertisements 
for prescription drugs. FDA also plans to finalize the guidance on 
criteria FDA uses to distinguish between disease awareness 
communications and promotional materials, to encourage manufacturers to 
disseminate educational messages to the public, and the guidance on the 
manner in which restricted device firms can comply with the rules for 
disclosure of risk information in consumer-directed broadcast 
advertising for their products.

Obesity

    Dr. Crawford, the FDA a year ago announced its plan to combat 
obesity. The plan included modernizing guidances for developers of 
drugs to treat obesity, as well as a national education campaign, 
``Calories Count'', enhancing the calorie information on food labels, 
urging the Nation's restaurants to disclose caloric content, and 
expanding research on obesity.

    Question 6.  Where does this FDA initiative stand today and what do 
you see as its results? If confirmed as Commissioner, what additional 
steps would you like to see to combat the ever-rising tide of obesity 
across this nation?
    Answer 6. Obesity is a growing and urgent public health problem in 
the United States. Today, almost two-thirds of all Americans are 
overweight and over 30 percent are obese. To help confront the problem 
of obesity in the U.S. and to help consumers lead healthier lives 
through better nutrition, in August 2003, FDA created an Obesity 
Working Group (OWG), which was charged with preparing a report that 
outlines an action plan to cover critical dimensions of the obesity 
problem from FDA's perspective and authorities. FDA's ``Calories 
Count'' report was released on March 12, 2004.
    The OWG report provides a range of short and long-term 
recommendations to address the obesity epidemic. For FDA's actions the 
emphasis is on calories. Progress to date follows:
     We have published two advance notices of proposed 
rulemaking (ANPRMs), in response to the recommendations in the OWG 
report, seeking comments on the following:
     How to give more prominence to calories on the food label, 
for example, increasing the font size for calories, including a column 
in the Nutrition Facts panel of food labels for percent Daily Value for 
total calories, and eliminating the listing for calories from fat. In 
addition, the Agency is seeking comment on the reformulation of the 
foods or redesign of packaging that may occur if any changes are made 
to the food label;
     Whether to amend certain provisions of the nutrition 
labeling regulations concerning serving size, such as for multiple-
serving packages that may reasonably be consumed in a single eating 
occasion.
     We continue to encourage manufacturers to take advantage 
of the flexibility in current regulations on serving sizes to label as 
a single-serving those food packages where the entire contents of the 
package can reasonably be consumed at a single eating occasion. We also 
continue to encourage manufacturers to use appropriate comparative 
labeling statements that make it easier for consumers to make healthy 
substitutions. Since release of the OWG report, the Agency, in meetings 
with industry, has made a point to encourage manufacturers to take 
advantage of the existing flexibility in serving size regulations, and 
companies are responding. For example, Kraft Foods is instituting dual 
column labeling for all its packaged foods containing 2-4 servings per 
package.
     FDA continues to encourage restaurants voluntarily to 
provide point-of-sale nutrition information to customers, including 
calorie information on a nationwide basis.
     FDA is also working to develop educational strategies and 
partnerships to support appropriate messages and teach people, 
particularly children, how to lead healthier lives through better 
nutrition. We are starting work with the Girl Scouts of the USA, under 
terms of a Memorandum of Understanding signed this past fall, to 
provide outreach and education in a science-based initiative to focus 
on improving health, nutrition, and physical activity. In addition, 
FDA's field offices are participating in local partnerships to reach 
and teach children. For example, in Central Florida, FDA's South East 
Region is part of the Seminole County Healthy Kids Partnership to 
promote positive opportunities for school-aged children in Seminole 
County to learn healthy nutrition and the value of increased daily 
physical activity.
    Regarding your question on what FDA is doing to modernize 
``guidances for developers of drugs to treat obesity,'' FDA's Center 
for Drug Evaluation and Research (CDER) will continue to work with 
pharmaceutical sponsors to facilitate development of effective 
therapies to address the important public health issue of obesity and 
its attendant morbidities. An advisory committee meeting was held on 
September 8, 2004 to discuss the draft guidance on Clinical Evaluation 
of Weight-Control Drugs. The Agency is working to finalize the 
guidance.

Pediatric Drug Testing

    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) and the 
Pediatric Research Equity Act (PREA)--have led to enormous improvements 
in our knowledge about the appropriate use of drugs for children.
    Dr. Crawford, pediatric testing in children is particularly 
relevant in light of the recent questions about drug safety, and 
especially the possible adverse effects of antidepressants (SSRI's) 
when used to treat youth. Several SSRI's had been studied in children, 
but the results of those studies were inconclusive.

    Question 7a. If confirmed as Commissioner, would you continue to 
support efforts to expand pediatric testing?
    Answer 7a. I strongly support efforts to continue pediatric 
therapeutics testing. In response to the need for pediatric use 
information for prescription medications in the United States, Congress 
passed several important legislative initiatives. FDA has found both 
the BPCA and the PREA to be useful regulatory tools to promote 
development of information and studies on therapies that are or will be 
utilized in the pediatric population.
    As a result, the Agency has labeled almost 100 products with new 
pediatric use information and has disseminated this valuable product 
information to the public. In addition, the number of pediatric 
clinical trials has increased dramatically. As of March 31, 2005, under 
BPCA, FDA has issued 298 written requests for pediatric studies, 
granted exclusivity to 110 drugs of the 120 that have been evaluated, 
and approved pediatric labeling changes for 87 products. Over a third 
of these products had new dosing or pediatric specific safety 
information identified and efficacy was not demonstrated in 8 of these 
products.

    Question 7b. 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?
    Answer 7b. The Agency will continue to advance its pediatric 
initiatives throughout FDA Centers. FDA has found both the BPCA and the 
PREA to be useful regulatory tools to promote development of 
information and studies on therapies that are being utilized in the 
pediatric population.
    At present, the FDA is working with the American Academy of 
Pediatrics, academic institutions, sponsors and the Center for Devices 
and Radiological Health to assess the needs for better information on 
use of devices in the pediatric population and to explore mechanisms to 
promote the development of devices specifically for the pediatric 
population.

    Question 7c. Is there additional authority that Congress can 
provide in this area that would be helpful to the FDA?
    Answer 7c. FDA has not identified the need for additional authority 
at this time. Congress has granted FDA significant, new pediatric legal 
authority in recent years and we are aggressively working to implement 
these authorities.

Global HIV/AIDS Affordable Pharmaceuticals

    The President's Emergency Plan for AIDS Relief includes the goal of 
treating 2 million people by 2008. While estimates vary, I understand 
that we can treat at least two to three people with non-branded anti-
retrovirals (ARV) for the same price of treating one individual with 
brand name drugs. While safety and efficacy must remain paramount, the 
success of the President's treatment goals depends on the government's 
ability to procure high quality drugs (both brand name and non-brand 
name) at the most affordable price.
    I was very happy to learn of the recent tentative approval of an 
HIV anti-retroviral product manufactured by Aspen Pharmacare of South 
Africa. I applaud the FDA and Aspen Pharmacare for working together to 
secure the first tentative approval of a non-brand, first-line HIV drug 
regimen. Additionally, it is very positive that the Office of the 
Global AIDS Coordinator has confirmed that these products will be 
available for purchase under the President's Emergency Plan. For large 
numbers of people in Africa and beyond, this could be a true turning 
point for providing low-cost, safe and effective AIDS drugs to those 
who would otherwise face certain death.
    However, while the Administration formalized an expedited process 
for the FDA to review and tentatively approve non-brand drugs to ensure 
their safety and efficacy in May 2004, there are still very few non-
branded drugs, and no triple-drug fixed dose combinations, that have 
been tentatively approved by this process.

    Question 8a. What specific steps is the Administration, and 
specifically the FDA, taking to ensure that safe and effective non-
brand drugs can be purchased with U.S. government dollars for use in 
the President's Emergency Plan?
    Answer 8a. In May 2004, in direct support of the President's 
Emergency Plan for AIDS Relief, the Department of Health and Human 
Services (HHS) Secretary Tommy Thompson announced that FDA would 
implement a new, expedited review program to help ensure that the 
products purchased under the President's Emergency Plan would be safe, 
effective, and manufactured in a quality manner. The central ethical 
premise of this review program is to ensure that we are not asking 
these governments to give their people medicinal products we would not 
give our own people.
    This new program directly supports Ambassador Tobias' 
responsibility to ensure the quality of HIV/AIDS drugs purchased by the 
U.S. under the auspice of the President's Emergency Plan. Subsequent to 
Secretary Thompson's announcement, FDA published guidance for the 
Pharmaceutical Industry encouraging sponsors (manufacturers) to submit 
marketing authorization applications to FDA for approval of fixed dose 
combination (FDC) and co-packaged versions of previously approved 
individual component antiretroviral therapies for the treatment of 
human immunodeficiency virus (HIV).
    On January 25, 2005, FDA granted tentative approval to a generic 
AIDS drug regimen for potential purchase under the President's 
Emergency Plan for AIDS Relief. This is a co-packaged antiretroviral 
drug regimen manufactured by Aspen Pharmacare of South Africa for the 
treatment of HIV-1 infection in adults. The Agency's tentative approval 
means that although existing patents and/or exclusivity prevent U.S. 
marketing of Aspen's product, it meets FDA's quality, safety and 
efficacy standards for U.S. marketing. This action makes this product 
available for potential procurement by President Bush's Emergency Plan 
for AIDS Relief. This action is the first tentative approval of an HIV 
drug regimen manufactured by a non-U.S.-based generic pharmaceutical 
company.
    The guidance outlines four scenarios for review of different FDC 
and co-packaged products. Some of the scenarios could permit review and 
approval in as little as 2 to 6 weeks after submission of a complete, 
high-quality application. For companies making products where another 
firm owns the U.S. patent rights, FDA issues a ``tentative'' approval 
when it finds the product meets the Agency's normal safety, efficacy, 
and quality standards. A tentative approval does not allow marketing in 
the U.S. because of the market protection that the patent or 
exclusivity provides. However, the administrators of the President's 
Emergency Plan have said they will allow manufacturers of products 
``tentatively'' approved by the FDA to submit tenders for consideration 
as suppliers of these products in countries where the product has the 
approval of the local drug regulatory authority and where such 
provision doesn't violate other laws.

    Question 8b. When do you expect additional non-brand drugs, 
including fixed-dose combinations, to be available for purchase as part 
of the President's Emergency Plan?
    Answer 8b. It is difficult to provide exact dates as to the 
submission of these products, because the companies make the decision 
on when/if they will submit. Moreover, we do not know in advance of our 
review whether or not companies will have the data requisite to 
demonstrate the products do indeed meet the standards of products we 
would give our own people. However, FDA has been involved in a very 
vigorous outreach effort to try to engage potential manufacturers in 
this process. Vigorous discussions and other outreach efforts, both 
within the U.S. and outside the U.S., have occurred and are still 
underway.

    Question 8c. Can you confirm that all non-brand drugs; including 
fixed-dose combinations, could be purchased with U.S. government 
dollars as soon as they are tentatively-approved under the FDA 
expedited process?
    Answer 8c. It is our understanding that once a product is either 
fully approved or tentatively approved, the manufacturer is then 
eligible to be considered as a provider of those products under the 
President's Emergency Plan, provided the local drug regulatory 
authority has approved the use of the product in the country where it 
is to be ultimately provided to patients. Please note that FDA does not 
administer the procurement process for this program, and therefore we 
do not have details about procurement activities for the program.

    Question 8d. What are you doing to encourage drug companies, both 
brand and non-brand, to apply to the new expedited approval process?
    Answer 8d. FDA is very proactively working with manufacturers from 
around the world that have come to us with questions about this review 
process as outlined in our guidance. We have met with them here in 
Washington and in several of the countries identified in the 
President's Emergency Plan. We are devoting much time to answering 
questions about the application process and requirements for submission 
to assist especially non-brand companies in submitting a quality 
application for our review. We are committed to investing such time and 
effort ``up front'' to help increase the probability of a quality 
application and to expediting their review when the completed 
application is submitted. We continue to provide requested information 
from interested companies and have several outreach programs for 
industry and drug regulatory authorities that are presently underway. 
We plan to conduct targeted communication of FDA's Expedited review 
guidance to companies in South Africa and India. We conducted a similar 
program in Ethiopia in early December 2004.

Global HIV/AIDS--Pediatric Therapeutics

    As we now start to treat larger numbers of people in resource-poor 
countries, we must focus our attention on the unique medical needs of 
children. With almost 700,000 new pediatric HIV infections last year 
alone, no global agenda for HIV/AIDS care and treatment is complete 
without attention to the unique treatment needs of children.
    Currently, few programs specifically target the treatment of 
children with HIV/AIDS in resource-poor countries. One of the reasons 
for this is the lack of appropriate pharmaceuticals for their use. 
Children are not small adults and treating them that way jeopardizes 
their lives. Children's growing bodies respond differently to drugs 
than adults, and require dosing guidelines specific to certain age 
groups. For many HIV/AIDS medicines, dosing guidelines are completely 
missing for younger age groups, requiring health workers to estimate 
the correct dose by breaking or crushing pills made for adults. 
Effective treatment of HIV requires appropriate and precise levels of 
medicine to inhibit the virus and prevent the development of viral 
resistance.
    With 2.2 million children infected with HIV around the world, it is 
essential that we have appropriate medications to treat them.

    Question 9. How is the Administration ensuring that the HIV/AIDS 
drugs (both generic and brand) being approved by the FDA expedited 
process also include pediatric formulations as well as important dosing 
information needed for treating different age groups?
    Answer 9. On May 17, 2004, FDA published guidance for the 
pharmaceutical industry encouraging manufacturers to submit marketing 
applications for fixed dose combination (FDC) and co-packaged versions 
of previously approved single entity anti-retroviral therapies. The 
guidance encourages the development of pediatric formulations for fixed 
dose and co-packaged antiretroviral combination products. Also, 
subsequent to the publication of the draft guidance, the expedited 
review program was expanded to include single product generic 
applications. Most of the first line antiretroviral agents are 
currently available in pediatric dosage forms, so these pediatric 
formulations can be made available through the generic drug approval 
process.
    Regarding fixed dose and co-packaged combination products, only one 
company thus far has expressed interest to FDA in developing a 
pediatric combination product. This could be explained in part by the 
challenges associated with dosing pediatric patients with fixed dose 
combination products. Such combination products generally do not 
provide the dosing flexibility needed for pediatric HIV therapy. Also, 
many of the pediatric formulations are in the form of oral solutions 
that are not amenable to combination product development. Combination 
therapy in younger pediatric patients might best be accomplished 
through the use of individually formulated antiretroviral products that 
can be made available through the generic approval process. Generally, 
adult combination products can be used in the older pediatric 
population.

Pediatric Medical Devices

    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.

    Question 10. What is the FDA doing to ensure that devices used in 
children are designed and sized for their use? What can Congress, and 
others, do to ensure that kids have access to appropriately sized 
devices?
    Answer 10. Pediatric medical devices treat or diagnose diseases and 
conditions from birth through age 21. Some products are designed 
specifically for children, while others are borrowed from adult 
applications or produced for more general use.
    Bringing pediatric medical devices to market can be challenging for 
a number of reasons: children are often smaller and more active than 
adults, body structures and functions change throughout childhood, and 
children may be long-term device users bringing new concerns about 
device longevity and long-term exposure to implanted materials. In 
addition, modifying an adult device for pediatric use may require 
significant re-designing of the device and re-tooling of the 
manufacturing process. Conducting clinical trials in children can also 
be more difficult due to the small patient population and the variation 
within the population.
    FDA is committed to supporting the development and availability of 
safe and effective pediatric medical devices. Current initiatives 
include:
     Obtaining pediatric expertise for FDA advisory panels 
whenever there is a reasonable likelihood that the device under 
discussion will be used for children.
     Issuing guidance describing the protections that clinical 
trial sponsors should consider when enrolling children in device 
trials.
     Collaborating with the Institute of Medicine on their 
study of the effectiveness of post-market surveillance of pediatric 
medical devices.
     Collecting data on the unmet needs for pediatric medical 
devices and the barriers to the development of new pediatric devices.
    In May 2004, FDA finalized a guidance document to facilitate the 
development of pediatric medical devices. Entitled ``Premarket 
Assessment of Pediatric Medical Devices,'' this guidance defines the 
pediatric population and pediatric use for medical devices, identifies 
the types of information needed to provide reasonable assurance of the 
safety and effectiveness of medical devices intended for use in the 
pediatric population, and defines the guiding principles and 
protections sponsors should consider for pediatric subjects in device 
clinical trials.
    In June 2004, FDA opened a docket requesting comments identifying 
the unmet device needs in the pediatric population, possible barriers 
to the availability of medical devices intended to treat or diagnose 
diseases and conditions that affect children, and potential incentives 
to facilitating the development of such devices. These comments 
assisted the agency in preparing its recent ``Report to Congress: 
Bafflers to the Availability of Medical Devices Intended for the 
Treatment or Diagnosis of Diseases and Conditions that Affect 
Children.''
    In addition to preparing this report, the agency has been working 
with several pediatric professional organizations to better understand 
this important issue. A series of meetings were held this past fall 
that included representatives from academia, medical specialty 
organizations, the device industry, and several government agencies. 
The group determined that further study is warranted to evaluate the 
scope of the unmet needs and the most promising solutions to addressing 
these needs. HHS believes that this is a critical first step and is 
working with interested stakeholders to ensure that a systematic needs 
assessment to promote a better understanding of the unmet needs and the 
barriers to the development of pediatric device development is 
conducted.
    Finally, to help raise awareness of the challenging issues 
surrounding pediatric device development, the Center for Devices and 
Radiological Health has developed a new web page on pediatric medical 
devices at http://www.fda.aov/cdrh/pediatricdevices/. In addition, 
FDA's Office of Pediatric Therapeutics web page can be accessed at 
http://www.fda.gov/oc/opt/default.htm. One of this Office's goals is to 
coordinate and facilitate all activities effecting the pediatric 
population or practice of pediatrics or involving pediatric issues. Our 
Center for Drug Evaluation and Research also has a pediatric web page 
at http://www.fda.aov/cder/pediatric/.

Flu Vaccine

    In 2004, a Liverpool, England plant responsible for providing our 
country with over 100 million doses of the flu vaccine was shut down. 
As a result, we received less than half the expected doses, resulting 
in a crisis for millions of Americans who depend on the flu vaccine 
each year.
    You have said that the FDA had no idea of escalating concerns at 
the plant before British authorities suspended the plant's license in 
October 2004. However, British authorities dispute this and state that 
the FDA had been notified of ongoing problems as early as mid-
September. The FDA inspected this plant in June 2003 and raised 
concerns then about possible contamination problems, and inspectors 
returned again in August. A full inspection was still not conducted. 
The FDA has been accused of inadequate follow up after major problems 
were identified. You stated that the FDA followed standard procedures, 
and you would not change anything the FDA did. You said: ``This is the 
way we've always done it, and it's worked very well in the past.''

    Question 11a. Do you stand by this statement?
    Answer 11a. FDA inspects U.S. licensed vaccine manufacturing 
facilities every 2 years. Based on this schedule, FDA inspected the 
Liverpool, U.K. facility where the Chiron vaccine is produced in 1999, 
2001, and 2003. It should be noted that Chiron acquired the facility in 
July 2003 after FDA conducted the biennial inspection. During the 1999 
inspection, FDA identified various concerns and, as a result, issued a 
warning letter regarding the Liverpool facility. The most significant 
issues identified in 1999 inspection were the lack of validation for 
its manufacturing processes, including establishing proper limits for 
bioburden (including bacteria) and issues related to assuring sterility 
in the manufacturing process. During the 2001 and 2003 inspections, FDA 
found that the company had made improvements but we also made 
observations related to current Good Manufacturing Practices (cGMPs). 
In each case, FDA reviewed the corrective measures and plans in 
response to these deficiencies. If fully implemented, the company's 
plans appeared adequate to correct deficiencies identified at the 
facility.
    On August 25, 2004, FDA inspectors were on site conducting a 
preapproval inspection and were informed of the contamination of the 
vaccine. FDA inspectors met with Chiron's staff and reviewed the 
preliminary findings and the approach that Chiron was taking to its 
investigation and retesting at multiple points in its process. FDA 
inspectors in Liverpool faxed to CBER preliminary data and information 
regarding the scope and plans for the sterility failure investigation 
being conducted by Chiron. The results of these evaluations were needed 
and essential for any regulatory assessment. Chiron's investigation was 
in the earliest stage and, therefore, only preliminary information was 
available. Chiron informed FDA that all results from the retesting were 
negative for all other finished product and that its final 
investigative report, including all product testing data, would be 
submitted to FDA during the week of October 4-8, 2004. FDA would then 
complete an in depth assessment of the report findings, which would 
indicate appropriate next steps for the agency. However, on October 5, 
the week the report was expected by FDA and just hours before FDA 
expected to receive an update from Chiron during a previously scheduled 
morning teleconference, the U.K. Medicines and Healthcare Products 
Regulatory Agency (MHRA) announced their suspension of Chiron's 
license. MHRA's Chief Executive, Professor Kent Woods, indicated that 
MHRA did not have the legal authority to notify FDA about the 
suspension announced on October 5 until after MHRA instituted its 
administrative action. Dr. Woods has also stated that, ``Contrary to 
some reported statements, MHRA, as the responsible regulatory authority 
in the United Kingdom, made the decision to suspend Chiron's license 
after an internal meeting on October 4 and first informed the company 
and the FDA of this decision on October 5. At the same time, we 
informed other drug regulatory authorities via an intergovernmental 
rapid information alert.''
    Upon learning of the MHRA's suspension on October 5, 2004, FDA 
communicated with both Chiron and the MHRA. While Chiron indicated to 
FDA that it believed it had satisfactorily addressed MHRA's 
inspectional findings and provided to FDA a copy of those findings and 
the company's response, MHRA expressed serious concerns about Chiron's 
vaccine stocks and the company's ability to assure the safety of the 
vaccine.
    FDA performed a comprehensive review of the retesting data during 
its October 10-15, 2004, inspection of the Liverpool facility. The 
retesting results were indeed negative; however, FDA's inspection found 
issues related to the adequacy of the statistical sampling plan used 
for the retesting. These findings, coupled with the other issues 
uncovered during the inspection, led FDA to conclude that it could not 
assure the safety of the vaccine.

    Question 11b. How would you prevent this type of incident from 
happening in the future?
    Answer 11b. Recent experiences, particularly those of the past 7 
months, have taught us important lessons about manufacturing and 
inspectional activities with respect to influenza vaccine. Although FDA 
has always interacted extensively with influenza vaccine manufacturers 
throughout the vaccine production cycle, the annual changes in the flu 
vaccine and the increased dependence on a smaller number of 
manufacturers highlight the risks of unexpected manufacturing 
difficulties. For these reasons, in 2005 and the future, we plan to 
conduct inspections of influenza vaccine manufacturers on an annual 
basis, with additional interactions with manufacturers and, in the case 
of foreign facilities, their regulatory agencies where appropriate, 
based on findings or events that raise concerns.
    FDA is working with manufacturers and its regulatory counterparts 
in anticipation of having an ample supply of influenza vaccine for the 
coming season through a dual-track strategy.
    FDA's first track is to facilitate Chiron's effort to correct its 
manufacturing problems. FDA and MHRA, the British regulatory agency, 
have an agreement with Chiron that allows full information sharing. FDA 
has used that agreement to collaboratively review Chiron's remediation 
plans and activities, and the Agency is providing continuing and 
extensive feedback to both Chiron and MHRA. In addition, FDA signed an 
information sharing agreement with MHRA that will, among other things, 
permit advance communication on important issues. The agreement was 
effective February 14, 2005.
    FDA is actively communicating on inspection activities. Only after 
passing MHRA and FDA inspections will Chiron be able to provide vaccine 
to the U.S. market. In the spring when critical stages of manufacturing 
are taking place, the Agency plans a comprehensive inspection to verify 
whether Chiron has adequately addressed its problems. While much work 
remains to be done, it appears that Chiron is making progress.
    FDA's second track is to facilitate overall greater capacity and 
diversification in the U.S. influenza vaccine supply. It is important 
to recognize that the demand for vaccine and other economic issues are 
the primary factors that determine whether a manufacturer will seek and 
maintain a license in this country.
    CDC and FDA are working to encourage vaccination throughout the flu 
season, including January and February. To increase the total doses 
available, manufacturers can produce vaccine over a longer time period, 
and that becomes available during these months. Because influenza cases 
usually continue well after November and December when most people are 
seeking immunization, later vaccination is beneficial. The Public 
Health Service is working to better communicate this important public 
health message.
    In addition, FDA has been working to stimulate manufacturers not 
licensed in the U.S. to provide or, where needed, develop the safety 
and effectiveness data to obtain U.S. licensure. The Agency has 
actively engaged several interested companies. FDA has informed 
manufacturers that the Agency is willing to consider all approaches to 
licensing, including accelerated approval based on surrogate markers, 
e.g., the patients' immune response to the vaccine. Sanofi Pasteur and 
Medlmmune have indicated their willingness, if needed, to do what they 
can to increase production.
    FDA has challenged itself to identify other lessons learned from 
this year's influenza season and is evaluating how this experience 
could be used to prevent similar events in the future. While there are 
some elements that FDA cannot control, the Agency is making significant 
changes. For example, as mentioned above, FDA plans to conduct 
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.

Ophthalmology

    Dr. Crawford, the FDA's Ophthalmology Group represents a unique 
specialty distinct from other clinical areas. Given the unique nature 
of drug therapies and treatments related to eye care, the work of this 
important group is critical to millions of Americans at risk for 
serious eye disease or blindness. Currently under the Division of Anti-
inflammatory, Analgesic and Ophthalmic Drug Products, it is my 
understanding that the FDA is considering integrating the Ophthalmology 
Group into the Division of Anti-Infective Products. Clearly, research 
of new treatments for potentially blinding diseases is extremely 
important.

    Question 12. If confirmed as Commissioner, how would you address 
concerns that ophthalmics may receive diminished attention and 
resources if combined within antiinfectives?
    Answer 12. We expect that individuals with expertise in 
ophthalmology will continue to play a critical role in reviewing new 
ophthalmology products, and the reorganization will not affect the 
timely approval of treatments and drug therapies available to eye care 
practitioners and their patients. All drug review processes for all 
products will continue to be held to existing PDUFA goals and timelines 
during and as a result of the reorganization.
                                 ______
                                 
Response to Questions of Senators Kennedy/Mikulski by Lester Crawford, 
                               DVM, Ph.D.
    (First Set of Questions)

    Question 1. When Tommy Thompson resigned in December 2004 he 
expressed ``grave concern'' about the risks of a terrorist attack on 
the U.S. food supply.
    As Commissioner, what steps would you take to protect America's 
food supply as Secretary Thompson warned?
    Answer 1. Ensuring the safety of the food supply is a top priority 
for me and for the Administration. A great deal has been done in the 
past few years to improve food safety and security. FDA has worked with 
food safety agencies at the Federal, State, and local levels to 
significantly strengthen the Nation's food safety system across the 
entire distribution chain (i.e., from farm to table) to better protect 
our food supply against deliberate and accidental threats. This 
cooperation has resulted in greater awareness of such vulnerabilities, 
the creation of more effective prevention programs, new surveillance 
systems, and faster foodborne illness outbreak response capabilities. 
An effective food defense system is built on a strong food safety 
system.
    The fiscal year 2006 budget requests an increase of $30 million for 
food defense activities. Twenty million dollars of this increase will 
support a national laboratory network known as the Food Emergency 
Response Network (FERN). A critical component of controlling threats 
from deliberate food-borne contamination is the ability to rapidly test 
large numbers of samples of potentially contaminated foods for a broad 
array of biological, chemical, and radiological agents. FERN will 
increase our laboratory surge capacity through a nationwide network of 
Federal and State laboratories capable of testing the safety of 
thousands of food samples, thereby enhancing the Nation's ability to 
swiftly respond to a terrorist attack. The additional $10 million will 
be used for targeted food defense research, for continued coordination 
and sharing of data with the Department of Homeland Security as part of 
the governmentwide Bio-Surveillance Initiative, and for upgrades in 
FDA's crisis management capabilities.
    Significant new tools to enhance the safety of the food supply were 
provided by the Public Health Security and Bioterrorism Preparedness 
and Response Act (Bioterrorism Act), which the President signed in 
2002. This landmark legislation represents the most fundamental 
enhancement to FDA's food safety authorities in many years, and FDA has 
been working hard to implement it. In response to the provisions 
included in the Bioterrorism Act, FDA:
     Published a final rule to implement recordkeeping 
requirement on 12/9/04;
     Published a final rule to implement the administrative 
detention provision on 6/4/04;
     Signed a Memorandum of Understanding with Customs and 
Border Protection on 12/3/03 to allow FDA to commission CBP officers in 
ports and other locations to conduct investigations and examinations of 
imported foods; and
     Published Interim Final Rules to implement the requirement 
for domestic and foreign facilities to register with FDA and the 
requirement for prior notice of imported food on 10/10/03.
    In addition to implementing the Bioterrorism Act, FDA has many 
other ongoing counterterrorism activities. For example, since September 
11, 2001, FDA has increased its emergency response capability by 
realigning resources to counterterrorism and by reassessing and 
strengthening its emergency response plans. FDA has also conducted 
numerous emergency response and preparedness exercises to further 
strengthen our response to a terrorist event involving our Nation's 
food supply. These exercises have included Federal, State, and industry 
partners.
    FDA has completed vulnerability assessments focused on specific 
foods, suspect agents, and processing steps where an agent could be 
intentionally introduced. These vulnerability assessments have assisted 
the agency in focusing on those commodities considered to be most at 
risk for intentional contamination. Government and industry have worked 
together on specific and targeted mitigation steps to address the 
vulnerabilities identified in our assessments. These assessments have 
also assisted the agency in focusing intramural and extramural research 
on four major areas: new methods for detection of agents, prevention 
technologies, agent characteristics, and dose response.
    FDA has also issued food security guidance documents to different 
segments of the food industry on the preventive measures they can take 
to minimize the risk that food or cosmetics under their control will be 
subject to tampering or other malicious, criminal, or terrorist 
actions.
    Other Counterterrorism Activities over past 3 years include:
     Increasing laboratory surge capacity by expanding 
participation in the Food Emergency Response Network, constructing BSL-
3 laboratories in the field and supporting the construction and 
deployment of two mobile laboratories;
     Enhancing an early-warning system to identify hazardous 
foods by expanding the number of Federal, State, and local laboratories 
providing data through our Electronic Laboratory Exchange Network 
(eLEXNET).
     Conducting numerous research projects to improve our 
ability to detect contamination, focusing on rapid test methods for use 
in the field;
     Carrying out food defense activities under Homeland 
Security Presidential Directives; the Interagency Security Plan; the 
Secretary's Bioterrorism Strategic Plan; and FDA's Strategic Action 
Plan;
     Enhancing FDA's ability to plan, manage, and respond to 
food emergencies through the Emergency Operations Network (EON), an 
electronic incident management system; and
     Enhancing law enforcement and intelligence gathering/
analysis by, for example, participating in select Joint Terrorism Task 
Forces and establishing a dedicated Counterterrorism Section in FDA's 
Office of Criminal Investigations.

    Question 2. FDA headquarters is currently located in 40 buildings 
at 18 locations--this will change when FDA headquarters moves to White 
Oak. FDA's consolidation of White Oak has been going on for over 10 
years to give FDA state-of-the-art facilities. Each phase of the 
project costs about $200 million; each year of delay costs millions of 
dollars.
    The President's fiscal year 2006 budget requests $128 million for 
continued consolidation at White Oak less than half the level requested 
by FDA and GSA to construct the next phase of the project (about $280 
million). FDA needs these facilities for many reasons; including to 
attract the best and brightest employees to FDA.
    Would consolidation of FDA be a priority for you as FDA 
commissioner? As FDA commissioner would you advocate for the completion 
of the consolidation project at White Oak? If so, do you have a 
projected time line that you would like to implement for completion of 
the project? What steps would you take to make sure that the 
Administration understands the importance of this project, and the need 
for a strong Federal funding commitment to complete the consolidation 
project?
    Answer 2. The consolidation of FDA Headquarters is a priority for 
the FDA, which upon completion will house over 7,700 staff in 2.3 
million square feet of space. By the end of fiscal year 2005, the 
campus will have almost 700,000 square feet completed with 1,850 staff 
on site. The new buildings will eventually replace all 40 of the 
existing facilities in 18 locations that support the Office of the 
Commissioner, and all of our Centers and Field headquarters, except the 
Center for Food Safety and Applied Nutrition in College Park and the 
National Center for Toxicological Research in Jefferson, Arkansas. This 
project will allow FDA to work towards many of the President's 
Management Agenda goals by standardizing and modernizing document 
handling, providing shared use facilities such as libraries and 
conference areas, further reducing redundancies in administrative tasks 
and allowing conversion to a single computer network. This will help 
create a stronger FDA by reducing operating costs, reducing travel time 
between organizations, increasing collaboration between centers and 
increasing the convenience of access to FDA by the public.
    This Administration has and continues to strongly support the White 
Oak project. Currently, the Project is on track for GSA funding of the 
Office of the Commissioner and ORA buildings in fiscal year 2008. With 
funding on schedule, the move in date for these buildings would be in 
fiscal year 2010. The anticipated move in schedule is provided below:

                          FDA Move in Timeline for the White Oak Consolidation Project
----------------------------------------------------------------------------------------------------------------
                                                                                            Total Employees at
                Phase                         Completion           Employees In Phase           White Oak
----------------------------------------------------------------------------------------------------------------
Life Sciences Laboratory(includes      COMPLETED December 2003  125....................  125
 CDER Labs & CDRH Chemistry &
 Biological Sciences).
CDER Office Building I...............  2005...................  1,725..................  1,850
Central Shared Use I.................  2006...................  150....................  2,000
Engineering Physics Laboratory.......  2007...................  160....................  2,160
CDER Office Building II..............  2007...................  1,076..................  3,236
CDRH Offices.........................  2008...................  1,298..................  4,534
Central Shared Use II................  2008...................  140....................  4,674
CBER Labs............................  2008...................  300....................  4,974
CBER Offices.........................  2009...................  900....................  5,874
CVM Offices..........................  2009...................  426....................  6,300
OC & ORA HQ Offices..................  2010...................  1,420..................  7,720
----------------------------------------------------------------------------------------------------------------


    Question 3a. While mammograms are imperfect, they are the best tool 
we have today to screen for breast cancer. However, mammography should 
not be the only tool. There must be better tools. In 2001, a report 
from the Institute of Medicine on developing technologies for the early 
detection of breast cancer made some recommendations for FDA such as:
     FDA developing and using consistent criteria for approval 
of screening and diagnostic devices and tools.
     FDA approval for new screening technologies should depend 
on evidence of improved clinical outcome.
    Has FDA implemented any recommendations from this report? If so, 
what is the status? If not, why not?
    Answer 3a. New screening and diagnostic processes often are new 
technology, and each technology presents unique questions. The agency 
has tried to reduce inconsistency in the review process wherever 
possible. Note the following examples.
     The agency developed a guidance document for Digital 
Mammographic submissions.
     CDRH is currently working on a guidance for Computer 
Assisted Detection (and Diagnosis) (CAD and CADx).
     A policy is in place to meet with sponsors early in the 
product development cycle to allow them and us to understand the new 
product and its path to market.
     We are developing a guidance on the performance assessment 
of imaging products. We are also training staff on these techniques.
     There is a process for determining whether a new product 
will follow a 510(k) or PMA marketing approval route.
     CDRH follows a least-burdensome process in reviewing 
device submissions.
     There is strong collaboration amongst multiple CDRH 
offices in the review of submissions for new devices, especially PMAs.
     Review of submissions for new novel devices is expedited 
according to Center policy.
    A recent example of a new device approval in this area is the Kodak 
Mammography CAD (computer-aided design) ENGINE. The Kodak Mammography 
CAD ENGINE uses software that helps radiologists who read mammograms to 
highlight areas that might be suspicious for breast cancer and might 
otherwise have been missed.

    Question 3b. Since its creation in 1994, the FDA Office of Women's 
Health has sponsored research, conducted public education campaigns, 
encouraged the participation of women in clinical trials, and served as 
an advocate for women's health in agency decisions. Senator Olympia 
Snowe and I recently introduced the Women's Health Office Act of 2005. 
This bill would statutorily authorize the Office of Women's Health at 
FDA. As Commissioner, will you support legislative efforts to authorize 
this Office? When appropriate, will you seek the advice and 
recommendations of the Office of Women's Health?
    Answer 3b. I strongly support the FDA Office of Women's Health 
(OWH). The OWH has proven to be a valuable source of information both 
inside and outside of the Agency. Its leadership has served the agency 
well on issues of sex and gender differences regarding therapeutic 
interventions. In addition, its national award-winning public 
information campaigns have made it an essential part of FDA. I have 
routinely sought their advice on issues of importance to women and will 
continue to do so during my tenure.

    Question 4. On February 25, 2005, an article in the New York Times 
revealed that 10 of the 32 government drug advisers who voted in favor 
of keeping Vioxx and Bextra on the market had consulted in recent years 
for the drugs' makers. If those who had consulted for the applicants 
had not voted for the companies' products, they would have been 
rejected by the panel.
    Back in 2003, 6 of the 15 voting panel members on the general and 
plastic surgery devices panel were plastic surgeons. All voted in favor 
of approving silicone breast implants for general use and could profit 
from allowing silicone breast implants.
    A majority of the scientists on the panel voted against approval, 
based on failure of the manufacturers to produce long-term data on the 
safety of the product. But, because all the plastic surgeons voted in 
favor, the advisory panel voted to approve silicone implants.
    Following that October 2003 panel, Dr. Thomas Whalen, chair of the 
advisory panel, took the highly unusual step of writing a public letter 
to the FDA commissioner which stated that ``it serves the reputation of 
the FDA in general, and the standing of the panel process in 
particular, exceedingly poorly to have had all of the plastic surgeons 
vote the PMA as approvable on such a close vote. Even in academic 
settings, plastic surgeons may stand to increase their own income with 
the use of these devices.''
    FDA needs to restore public confidence and show its ability to 
protect the public health and safety of the American people.
    What is the FDA's justification for its failure to publicly 
disclose the financial conflicts of interest of the panel participants?
    Answer 4. Although 18 U.S.C. Section 208 provides that a copy of 
any waiver determination is available to the public upon request, the 
Agency may withhold from disclosure information that would be exempt 
under the Freedom of Information Act, 5 U.S.C. Section 522(b). Under 
this provision, all of the information concerning conflicts of interest 
may be withheld as exempt pursuant to 5 U.S.C. Section 522(b)(3) 
because the Ethics in Government Act prohibits release of the 
information. Nevertheless, in order to provide meaningful disclosure of 
conflicts of interest information, the Office of Government Ethics has 
concluded that, under section 208, Federal Agencies have discretion to 
disclose information concerning the waived conflict of interest absent 
a foreseeable harm to be caused by the disclosure. The Office of Legal 
Counsel, United States Department of Justice (OLC), concluded that FDA 
may exercise its discretion in making disclosure to avoid making the 
disclosure requirement so intrusive or onerous as to make outside 
experts unwilling to serve on advisory committees.
    In January 2002, the FDA issued draft guidance on ``Disclosure of 
Conflicts of Interest for Special Government Employees Participating in 
FDA Product Specific Advisory Committee.'' The guidance provides 
information on the type and amount of information that will be 
disclosed to the public when a member is granted a conflict of interest 
waiver with the topic to be discussed by the committee. The guidance 
applies only to those advisory committee meetings at which a particular 
matter relating to a particular product is discussed (product specific 
meetings). The guidance does not apply to advisory committee meetings 
that provide advice on topics of general applicability (i.e., those 
meetings that could affect a class of products and their sponsors) even 
if the members on the committee received general matters waivers 
covering their participation on the committee.
    The disclosure for particular matters identifies whether the 
interest is related to the sponsor or competitor that markets a product 
competing with the product at issue (without naming the competitor), 
the type of interest (stock, consulting, contracts/grants, patents/
royalties/trademarks, expert witness, teaching, speaking, or writing), 
and the magnitude of the interest is described as a range.

    Question 5. What conflict of interest screening measures does the 
FDA currently have in place for advisory panels?
    Answer 5. Because it is imperative to obtain the best scientific 
information available, it is very difficult to obtain qualified 
advisory committee members who are also totally free from all potential 
financial conflicts of interest. The Nation's experts (and in some 
cases, there are only a few experts on a particular topic) are sought 
after for consultation by both the Agency and industry because of the 
scarcity, and therefore the value, of their expertise. Utilizing 
scientists who are less experienced or less highly qualified in order 
to completely remove any potential financial conflict from the 
committee would hamper the Agency's ability to protect and advance the 
public health.
    The Agency's staff examines all potential financial interests. The 
Agency's process is to evaluate the potential financial interests of 
members and other invited special government employees. FDA makes a 
determination as to whether the participation of an individual with 
some financial ties outweighs the need for the agency to understand the 
science on the topic before the committee. Although the Agency has 
guidelines for this process (see Waiver Criteria Document 2000 on the 
FDA web page), this is not a black and white process. It requires 
careful consideration of all facets of the issue in order to evaluate 
that balance. Congress, by permitting waivers for potential conflicts 
of interest, has ensured that the Agency and the public (through the 
advisory committee process) have access to the most knowledgeable 
individuals on the meeting topic.

    Question 6. What steps as FDA Administrator you would take to limit 
conflicts-of-interest in future drug advisory panels?
    Answer 6. FDA's process of evaluating potential committee members 
for conflicts is very extensive and transparent. Our methodology is 
articulated in a comprehensive document on the agency's website (http:/
/www.fda.uov/oc/advisory/conflictofinterest/intro.html). At the 
beginning of each meeting, a conflict of interest statement is read 
into the record, which summarizes the results of the conflicts of 
interest screening. Nonetheless it is always prudent to regularly 
assess the Agency program and determine if any improvements are 
warranted. In the near future, the Agency will review the advisory 
committee conflicts of interest disclosure process and consider if 
further improvements are necessary to make the disclosures more easily 
accessible to the public.

    Question 7. Given that plastic surgeons stand to befit financially 
from the approval of silicone breast implants, do you think that it's 
appropriate for plastic surgeons to serve on the Advisory panel, let 
alone make up its plurality?
    Answer 7. FDA expects this panel to include a number of plastic 
surgeons, as did the October 2003 panel. Please note that plastic 
surgeons comprised only four of the 16 voting panel members for that 
meeting. We believe it is appropriate that the medical specialty most 
likely to implant silicone breast implants be represented during 
deliberations on the device. Their experience with the product and 
insights into issues that impact its safety and effectiveness are 
critical to the agency's evaluation.

    Question 8. What do you intend to do about these conflicts before 
the upcoming April advisory panel to reintroduce silicone breast 
implants for general use?
    Answer 8. The individuals that comprise the General and Plastic 
Surgery panel for the upcoming April meeting will have been screened 
according to the Agency's existing conflict of interest rules. All 
panel members, new and standing, must be cleared through a formal 
process prior to serving as a panel member for a specific PMA. The 
final roster will be posted on FDA's website a week or two prior to the 
meeting when all panel members are cleared to serve on this panel for 
these PMAs.
 Response to Questions of Senator Kennedy by Lester Crawford, DVM, Ph.D
    (Second Set of Questions)

    I understand that just 9 days before he was scheduled to testify 
before the Senate Finance Committee, you offered Dr. David Graham a 
newly created job in your office to lead the agency's effort to enhance 
its monitoring and surveillance of approved drugs. Dr. Graham declined 
the offer, and went on to testify.
    Following that testimony, one senior FDA official called Dr. 
Graham's work ``junk science'' and accused him of scientific misconduct 
to The Lancet. Managers in the center for drugs called Dr. Graham's 
lawyer posing as whistleblowers and tried to discredit Dr. Graham.

    Question 1a. Why did you offer Dr. Graham a prestigious job, then 
only days later allow an FDA official to label his work ``junk 
science''? If his science was junk, why did you offer him the job?
    Answer 1a. Your question relates to a statement made by an FDA 
employee. Dr. Graham and all other FDA employees enjoy freedom of 
expression as guaranteed under the Constitution. That said, it is my 
understanding that this quote comes from a conversation with a 
Washington Post reporter that was taken out of context. The FDA 
official interviewed was asked to respond to the reporter's question 
about whether it was accurate to state that a certain number of 
individuals in particular Congressional districts could be said to have 
died of cardiovascular events because of Vioxx. It is not possible to 
derive from risk estimates the cause of a particular individual's 
death. This concept is complicated to explain, and the FDA official 
reacted to it by characterizing the particular statement regarding 
deaths of individuals in a Congressional district as ``junk science.'' 
The characterization was not made with regard to all of Dr. Graham's 
work. I am not aware of any FDA official accusing Dr. Graham of 
scientific misconduct.

    Question 1b. Some might question whether you were simply kicking 
Dr. Graham upstairs to keep him quiet. Did you look for a different 
candidate when Dr. Graham declined the job? Did you contact any of the 
people whom Dr. Graham recommended for the job? When did you create the 
new position? When did you find out that Dr. Graham was testifying 
before the Senate Finance Committee? Who holds the position now, and 
when was that person hired?
    Answer 1b. My discussion with Dr. Graham focused on the IOM review 
of drug safety and not Congressional hearings. Dr. Janet Woodcock, 
Acting Deputy Commissioner for Operations, was eventually assigned the 
task of designing FDA's drug safety program, including liaison with the 
IOM on the study.

    Question 1c. FDA managers called Dr. Graham's attorney, made 
misleading statements about their own identities, and tried to 
discredit him. What have you done to try to find out who made these 
calls, and what disciplinary action have you taken?
    Answer 1c. There is an Inspector General (IG) investigation of this 
issue underway, therefore, the Agency cannot comment further on this 
matter at this time.

    Question 1d. An FDA manager called Dr. Graham's work ``junk 
science'' and accused Dr. Graham of scientific misconduct. What have 
you done to reprimand this individual, and to clarify to all agency 
employees that this behavior is not appropriate?
    Answer 1d. As noted above, the ``junk science'' quote comes from a 
conversation with a Washington Post reporter that was taken out of 
context and I am not aware of any FDA official accusing Dr. Graham of 
scientific misconduct.

[NOTE.--There was no ``Q2'' in--original document]

    [NOTE.--As revised by Kennedy staff 3/24] In January 2004, FDA 
rejected an application for approval of silicone breast implants and 
issued guidance about the information needed to win approval. Two 
applications for approval of these products have now been submitted, 
less than a year later. I understand FDA did not follow the 
recommendation of its own reviewers who recommended that the 
information in the applications was not sufficient to change the 
decision from last year. Instead, the agency has convened an advisory 
committee to review the applications, and is reportedly hand-picking 
its members to see that they grant the implants swift approval. 
Reportedly there's even an email on which you were copied from your 
special science advisor, Susan Bond, to Dan Schultz, the head of the 
center for devices, specifying in advance the conclusion the review 
should reach.

    Question 3a. On breast implants, why has FDA not accepted the 
conclusion of its own scientific review that the data in these 
submissions are not sufficient?
    Answer 3a. FDA continues to evaluate the science with regard to 
breast implants. No final conclusion has been reached.

    Question 3b. Is it true that you were copied on an e-mail to the 
head of the center for devices specifying in advance the conclusions he 
was to reach regarding the safety of breast implants? How did you 
respond?
    Answer 3b. No, I was copied on an e-mail transmitting a preprint of 
the views of an individual regarding breast implants. The document 
contains a bibliography of recent scientific papers on the subject. 
These papers are all publicly available and therefore already known to 
CDRH. The bibliography was incomplete. In evaluating the safety of 
breast implants, CDRH will consider the entirety of the scientific 
literature.

    Question 3c. Please provide me all the e-mails or other 
correspondence, with all attachments, you received, were copied on, or 
sent that have had to do with breast implants.
    Answer 3c. Enclosed are e-mails that respond to your question.

    Question 4a. On August 26, 2004, the public learned that Chiron, 
one of two manufacturers of the Nation's flu vaccine, had produced 
contaminated lots of vaccine at a plant in Liverpool, England.
    Between that date and October 5, 2005, when the British regulatory 
agency, the MHRA, suspended Chiron's license, the FDA did not inspect 
the Liverpool plant. By contrast, the British carried out two full 
inspections during September 2004, once on September 13th and 14th, and 
again from September 29th to October 1st. British inspectors were 
physically present at the plant and they required Chiron to respond to 
their inspectors' report. FDA never inspected the plant before the 
license was suspended.
    In your testimony to the House Government Reform Committee in 
November 2004, you said that after MHRA suspended Chiron's license, you 
contacted Chiron and the British, but that ``Chiron indicated that it 
believed it had satisfactorily addressed MHRA's inspectional 
findings.'' Why did FDA trust Chiron's assurances rather than verifying 
the safety of half of our vaccine supply the way the British regulators 
did?
    Answer 4a. In our interactions with Chiron, FDA consistently worked 
to verify the safety of their vaccine product. On August 25, 2004, FDA 
inspectors were onsite conducting a preapproval inspection and were 
informed of the contamination of the vaccine. FDA inspectors met with 
Chiron's staff and reviewed the preliminary findings and the approach 
that Chiron was taking to its investigation and retesting at multiple 
points in its process. FDA inspectors in Liverpool faxed to FDA's 
Center for Biologics Evaluation and Research (CBER) preliminary data 
and information regarding the scope and plans for the sterility failure 
investigation being conducted by Chiron. The results of these 
evaluations were needed and essential for any regulatory assessment. 
Chiron's investigation was in the earliest stage and, therefore, only 
preliminary information was available. Chiron informed FDA that all 
results from the retesting were negative for all other finished product 
and that its final investigative report, including all product testing 
data, would be submitted to FDA during the week of October 4-8, 2004. 
FDA would then complete an indepth assessment of the report findings, 
which would indicate appropriate next steps for the agency. However, on 
October 5, the week the report was expected by FDA and just hours 
before FDA expected to receive an update from Chiron during a 
previously scheduled morning teleconference, the U.K. Medicines and 
Healthcare Products Regulatory Agency (MHRA) announced to Chiron, the 
FDA and the world their suspension of Chiron's license.
    FDA performed a comprehensive review of the retesting data during 
its October 10-15, 2004, inspection of the Liverpool facility. The 
retesting results were indeed negative; however, FDA's inspection found 
issues related to the adequacy of the statistical sampling plan used 
for the retesting. These findings, coupled with the other issues 
uncovered during the inspection, led FDA to conclude that it could not 
assure the safety of the vaccine.

    Question 4b. Once the Chiron vaccine was unavailable, the 
Administration began to identify manufacturers of vaccine for other 
countries that it might be able to acquire and make available to the 
public, and it reprioritized who should receive vaccine. Please assess 
the difference beginning these endeavors in late August 2004 would have 
made?
    Answer 4b. The loss of Chiron's planned contribution to the U.S. 
influenza vaccine supply posed serious challenges. FDA worked with 
urgency, aggressiveness and in close coordination with CDC and other 
components of HHS and the private sector to explore all viable options 
to secure additional doses of influenza vaccine. FDA worked with Sanofi 
Pasteur and Medlmmune to secure approximately 5 million additional 
doses of U.S. licensed vaccine. Sanofi Pasteur increased production to 
58 million doses of Fluzone, and Medlmmune scaled up to produce 3 
million doses of FluMist. FluMist is currently recommended for healthy 
individuals 5 to 49 years of age, and therefore provides an option for 
those who would not receive vaccine under CDC's priority guidelines, 
such as the U.S. military. Therefore, to expand further the supply of 
vaccine to those with the greatest need, Secretary Thompson, in 
cooperation with the Department of Defense, announced that the military 
would maximize its use of FluMist as a substitute to the inactivated 
vaccine, making an additional 200,000 doses of injectable vaccine 
available to HHS for high-risk civilian populations. Because Sanofi 
Pasteur produces pediatric dosage forms of vaccine for the U.S. market, 
the supply of vaccine available for high-risk children was, 
fortunately, not reduced. Through these collaborative efforts, 
manufacturers increased the available supply of licensed influenza 
vaccine for the U.S. population to 61 million doses for this influenza 
season, compared with approximately 83 million doses distributed in 
2003-04 and in 2002-03, 77 million doses in 2001-02 and 70 million 
doses in 2000-01.
    Because there was a concern that the need and demand could still 
outstrip supply, particularly if we face a severe influenza season, we 
sought additional doses of vaccine that could be safely used in an 
emergency. Thus, in addition to enhancing the supplies of vaccine 
approved for use in the U.S., we were able to rapidly identify 
suppliers of approximately 5 million doses of additional vaccine, 
licensed in other countries, that could potentially be made available 
under an FDA investigational new drug (IND) application. With 
remarkable cooperation from several companies and from other regulatory 
agencies (including the Paul Ehrlich Institute, Germany; Therapeutic 
Goods Administration, Australia; Swiss Medic and Health Canada) FDA 
immediately sent inspectors and scientists to the manufacturing 
facilities of potential IND sponsors to evaluate their manufacturing 
processes. Coupled with these efforts, we also reviewed a large volume 
of manufacturing and clinical data, all within in a few weeks. These 
efforts resulted in FDA approving INDs that permitted the potential use 
of approximately 4 million doses from GlaxoSmithKline (GSK) and 1 
million doses from Berna Biotech, if needed. Of the 5 million doses 
potentially available under an IND, FDA understands that CDC has 
purchased approximately 1.5 million doses. HHS and FDA's coordinated 
interactions with these and other influenza vaccine manufacturers and 
regulatory agencies also provided valuable information and strengthened 
relationships that we hope will help stimulate interest by additional 
influenza vaccine manufacturers and potentially lead to successful U.S. 
licensure.

    Question 5. Last year Merck withdrew Vioxx from the market, because 
the drug doubled the risk of heart attack or stroke but that was more 
than 5 years after the FDA approved the drug, and after 20 million 
Americans had used it. As a result, tens of thousands of Americans 
needlessly suffered heart attack or stroke, and many died. This is the 
single largest drug safety failure the Nation has ever faced. It simply 
should not take that long, nor should so many people use a drug, before 
such a significant safety risk is discovered. Dr. Sandra Kweder 
testified earlier this month that authority to order both drug labeling 
and drug safety studies after approval would be helpful. Do you agree?
    Answer 5a. I do not believe new statutory authority is needed. We 
will use all existing regulatory authority and enforcement powers when 
negotiating label changes with drug companies or when monitoring or 
managing drug safety issues. As Dr. Janet Woodcock testified, a key 
factor in labeling changes is that once a label change is made, old 
labels in paper form are still in distribution and it takes time to get 
newer labels in circulation. Dr. Woodcock testified that the new 
strategy of posting drug safety information sooner using the Drug Watch 
mechanism will help alleviate that factor because it will enable the 
FDA to get information directly to the people who need it in a timely 
manner.

    Question 5b. At our second hearing, Dr. Janet Woodcock testified 
that the practices of the drug companies promoting their drugs to 
doctors caused the overuse of new drugs. Do you see any drug company 
promotional activities as a problem? Do you think that patients are 
ever prescribed pills that aren't right for them because of advertising 
or high-pressure sales tactics to doctors? Isn't that a particular 
concern for newly approved drugs that may have safety concerns not 
detected in the initial trials?
    Answer 5b. We have conducted research that confirms that DTC 
advertising, when done correctly, can serve positive public health 
functions, such as increasing patient awareness of diseases that can be 
treated, and prompting thoughtful discussions with physicians that 
result in needed treatments being prescribed often, not the treatment 
in the DTC advertisement. Results of our research show that many 
physicians believe DTC can play a positive role in their interactions 
with patients and that many physicians thought DTC ads made patients 
more involved in their healthcare.
    In a survey we conducted, while 75 percent of physicians believed 
that DTC advertising causes patients to think the drug works better 
than it actually does and many physicians felt some pressure to 
prescribe something when patients mentioned DTC ads, only 8 percent 
felt very pressured to prescribe the specific drug advertised. 
Physicians agreed that the main effect of DTC ads was to help educate 
patients about their health problems, causing them to seek needed care.
    While I believe these results confirm our belief that DTC ads help 
increase patient awareness about the availability of effective 
treatments for their health problems, I will continue to ensure that 
our DTC policies help prevent potential misperceptions about benefits 
and risks of advertised treatments and promote the importance of 
prescribing decisions being made with the intervention of a health care 
professional.

    Question 6. In Antibiotic Resistance: Federal Agencies Need to 
Better Focus Efforts to Address Risk to Humans from Antibiotic Use in 
Animals, the GAO lists ``the use of antibiotics in animals raised for 
human consumption as contributing to antibiotic resistance in humans.'' 
They explain that FDA's Guidance No. 152 ``outlines a framework for 
determining the likelihood that an antibiotic used to treat an animal 
would cause an antibiotic resistance problem in humans,'' but note that 
implementation of the Guidance for antibiotics already on the market 
``may take years.'' As Commissioner, what actions would you take to 
reduce, in a timely fashion, agricultural overuse of antibiotics, 
particularly those that are ranked as ``important,'' ``highly 
important,'' or ``critically important'' in Guidance No. 152? How long 
has it taken, and how much FDA staff time and resources have been 
spent, to withdraw Baytril from the market? Has the process been 
efficient and effective? What will you do to make the process of 
limiting the veterinary uses of important drugs more efficient?
    Answer 6. FDA is concerned about antimicrobial resistance and the 
use of antimicrobial drugs in food-producing animals causing an 
unintentional adverse health impact on humans. FDA agrees with the 
Government Accountability Office's recommendation that it is important 
to review the currently approved animal drugs that are critical to 
human health and to collect antibiotic use data. Guidance for Industry 
No. 152, ``Evaluating the Safety of Antimicrobial New Drugs with Regard 
to their Microbiological Effects on Bacteria of Human Health Concern,'' 
sets out the agency's recommendations for the pre-approval safety 
assessment for new antimicrobial drugs intended for use in food-
producing animals. This guidance also is used for re-evaluating 
currently approved veterinary antimicrobial drugs. FDA's Center for 
Veterinary Medicine (CVM) has finished the assessment for the growth-
promoting uses of penicillin-containing antimicrobial drugs. CVM is 
currently in the process of re-assessing the growth-promotion uses of 
tetracycline-containing antimicrobial drugs.
    In addition, CVM has re-evaluated the use of virginiamycin, a 
streptogramin used in five species of food-producing animals, for its 
potential to cause Synercid-resistant Enterococcus faecium in humans. 
Synercid is a streptogramin recently approved to treat vancomycin-
resistant Enterococcus infections, a serious disease in humans. FDA has 
posted the draft risk assessment on its CVM website. In addition, FDA 
published an announcement in the Federal Register on November 23, 2004, 
that the risk assessment was available and that FDA would accept 
comments for 60 days. FDA subsequently extended the comment period an 
additional 30 days to February 23, 2005. The draft risk assessment is 
available at:
    http.//www.fda.gov/cvm/antimicrobial/SREF RA FinalDraft.pdf. FDA 
intends to evaluate all comments received, revise the risk assessment 
accordingly, and then determine appropriate steps that need to be taken 
to address any identified risks to humans.
    FDA intends to continue to review the currently approved 
antimicrobials for food-producing animals for microbial safety using 
GFI 152. FDA intends to begin with antimicrobials considered as 
critically important for human medical therapy. This process is slow 
because it is resource intensive to review each approved new animal 
drug. CVM's experience in connection with its proposal to withdraw the 
approval for Baytril was that the process was expensive and resource 
intensive, with an estimate in excess of 10.0 FTEs for approximately 3 
years and about one-quarter that for an additional 2 years plus 
approximately $500,000 in expert witness fees and travel expenses. CVM 
initially published the Notice of Opportunity for a Hearing (NOOH) on 
its proposal to withdrawal approval of the fluoroquinolones for use in 
poultry on October 31, 2000. This NOOH procedure is required to ensure 
due process for the respondent. The matter is currently under review by 
the FDA Commissioner's team. Additional FDA staff members are now 
expending resources on the review. The agency handles these withdrawal 
proceedings as expeditiously as possible in light of other matters that 
also require the Agency's resources.
    After the initial assessment of the currently approved 
antimicrobials with respect to microbial safety, if safety issues are 
identified, CVM is hopeful that the relevant animal pharmaceutical 
companies will cooperate with the agency in addressing those issues.

    Question 7. That same GAO report strongly recommended that the FDA 
collect, compile and publish data on antibiotic use in agriculture, so 
that researchers might better ``study the linkages between antibiotic 
use in animals and the human risk from antibiotic resistance and to 
develop and evaluate strategies for mitigating resistance.'' I 
understand that the FDA has drafted a rule on data collection that has 
been stalled for some reason. What is the status of the FDA's draft 
rule? Will you move forward with it this year? If not, do you have 
other plans to implement the GAO recommendation?
    Answer 7. The FDA Center for Veterinary Medicine recognizes the 
importance of the monitoring of drug use data as a component of an 
effective surveillance system. The Center currently collects certain 
animal drug sales information under 21 CFR 514. However, as mentioned 
in the GAO Report, more detailed data would assist us in interpreting 
results from the National Antimicrobial Resistance Monitoring System 
(NARMS) on changing resistance levels. Data on the amounts of drugs 
used would be helpful on many levels, for example:
     in analyzing associations between resistance levels in 
animals and humans,
     in risk assessments designed to quantify the human health 
impact attributable to antimicrobial drug use in food-producing 
animals,
     in identifying where mitigation strategies may be 
beneficial, and
     in assessing the success of prudent drug use initiatives.
    Also, the WHO Global Strategy for Containment of Antimicrobial 
Resistance recommends the creation of national systems to monitor 
antimicrobial usage in food animals and several countries have 
developed drug use monitoring systems or are in the process of doing 
so. In order to change the way the current drug marketing information 
is reported, FDA has determined that it must promulgate a proposed 
regulation with a notice and comment process, including an economic 
impact assessment of the regulation. The Agency is considering how to 
best meet these data needs, taking into account the burden on industry 
and the Agency's data collection authority.

    Question 8. I am concerned that you intend to replace Dr. Marlene 
Haffner, who now leads the Office of Orphan Products Development. 
Please explain why you intend to replace her and how you intend to 
search for a successor with comparable expertise in human orphan 
diseases. The work of this office is extremely important to me and to 
the tens of thousands of patients with rare diseases. What is your 
vision for the office?
    Answer 8. All FDA offices are required to have succession plans. 
The incumbent in the Office of Orphan Drugs has been in that position 
for 17 years. Traditionally, FDA leaders have rotated into other 
positions following lengthy periods in one position. This is the best 
for the institution and for the individual. No current Center Director, 
Associate Commissioner, or Deputy Commissioner has served for 17 years 
in one position. Finally, whenever FDA conducts recruitments for 
vacancies, we strive to identify individuals that have the relevant 
management and subject matter expertise for the position.

    Question 9. 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/enqlish/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? Please explain.
    Answer 9. FDA agrees with Health Canada's statement that current 
evidence does not indicate that dental amalgam is causing illness in 
the general population and that neither a ban nor removal of existing 
sound amalgam fillings is justified. The agency also agrees with Health 
Canada's recommendation that dental amalgam should not be used in 
people allergic to mercury.
    FDA has not issued warnings to pregnant women and children under 6 
about mercury exposure from dental amalgam, as has Canada, because 
while FDA and other agencies of the U.S. Public Health Service (USPHS) 
continue to investigate the safety of dental amalgam, no valid 
scientific evidence has shown that amalgams cause harm to patients with 
dental restorations, except in the rare cases of allergy.
    FDA, together with the Centers for Disease Control and Prevention 
and the National Institute for Dental and Cranio-facial Reseach, 
periodically has reassessed available information on the safety of 
dental amalgam in order to evaluate potential risk and potential 
action. In 1993 and 1997, the United States Public Health Service 
(USPHS) issued comprehensive scientific reports about the safety and 
use of dental amalgam and other materials used to fill dental caries/
lesions.
    The most recent review was completed in 2004 by an independent 
panel of experts under the auspices of the Life Sciences Research 
Office (LSRO), an independent non-profit organization, under contract 
to the National Institutes of Health (NIH). LSRO undertook a 
comprehensive review of the scientific literature published since the 
1997 USPHS report. To help ensure an independent review, LSRO selected 
experts from outside the dental research community, including experts 
in immunotoxicology, neurodevelopment, reproductive toxicology, 
epidemiology and pediatrics. LSRO posted an Executive Summary of its 
report on its website in December 2004 and the report is also available 
for purchase by the public.
    The LSRO report concludes that ``there is little evidence to 
support a causal relationship between mercury fillings and human health 
problems.'' The authors noted, however, that there were research gaps, 
which, if addressed, might settle the dental amalgam controversy once 
and for all. FDA is currently reviewing the full report.
    Dental mercury is currently classified as class I (21 CFR 872.3700) 
and the amalgam alloy is class II (21 CFR 872.3050). An additional 
encapsulated form of mercury, titrated by dentists in the office, was 
never classified. In February 2002, FDA proposed a rule to bring all 
amalgam products into Class II and increase the Agency's regulatory 
oversight by requiring ingredient labeling and proposing conformance to 
international standards. FDA has reviewed more than 750 comments 
submitted to the docket. Continued work is on hold pending the 
evaluation of the LSRO report.
    In conjunction with the proposed rule, in February 2002, FDA 
published a draft special control guidance addressing labeling for 
restorative materials. The proposed labeling has the potential to 
reduce allergic reactions to restorative materials. Final guidance 
would recommend that the product's labeling list the ingredients in 
descending order of weight by percentage and include lot numbers, 
appropriate warnings and precautions, handling instructions, and 
expiration dating. The guidance is also on hold (along with the related 
classification rule) until the LSRO report can be evaluated.
    FDA will continue its review of the LSRO report and its 
consultation with its sister agencies in the Public Health Service on 
this issue. FDA will then determine how to proceed on the proposed rule 
for classification and reclassification of the amalgam products and the 
associated guidance.

    Question 10. 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?
    Answer 10. Bioengineered foods and food ingredients must adhere to 
the same standards of safety under the Federal Food, Drug, and Cosmetic 
(FD&C) Act that apply to their conventionally bred counterparts. This 
means that these products must be as safe as the traditional foods on 
the market. FDA has broad authority to initiate regulatory action if a 
product fails to meet the requirements of the FD&C Act.
    FDA established a consultative process to help companies comply 
with the FD&C Act's requirements for bioengineered foods prior to 
marketing. The Agency has reviewed the data on more than 60 
bioengineered food products under its jurisdiction, ranging from 
herbicide resistant soybeans to modified canola oil. To date, the 
evidence shows that these foods are as safe as their conventional 
counterparts. A list of submissions that have been reviewed by the 
Agency is posted on our website at: www.cfsan.fda.gov/-Ird/biocon.htm/. 
To our knowledge, all developers intending to market a bioengineered 
plant food subject to FDA's jurisdiction have first participated in 
FDA's current consultation process.
    FDA believes that the current voluntary premarket consultation 
process is working well and fully protects public health.

    Question 11. 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 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 11. The Agency has been evaluating its legal and regulatory 
options for regulating transgenic animals to determine the best 
approach possible. As part of its review of its regulatory approach, 
the agency has:
     participated in executive branch deliberations to evaluate 
the role of genetically engineered animals in the Coordinated Framework 
for the Regulation of Biotechnology;
     prepared case studies on animal biotechnology products to 
serve as a basis for legal and policy deliberations; and,
     participated in listening sessions sponsored by the Office 
of Science and Technology Policy with stakeholders from industry, the 
research community, and non-government organizations.
    These deliberations are still underway.
    In addition, the Agency has previously issued some guidances and 
Points to Consider Documents for products from transgenic animals:
     Points to Consider in the Manufacture and Testing of 
Therapeutic Products for Human Use Derived from Transgenic Animals 
(1995);
     Public Health Issues Posed by the Use of Non-Human Primate 
Xenografts in Humans (1999); and
     Source Animal Product, Preclinical, and Clinical Issues 
Concerning the Use of Xenotransplantation Products in Humans (2003) 
working with the Center for Biologics Evaluation and Research.

    Question 12. 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 12. FDA is requiring the declaration of trans fat amounts 
directly under the saturated fat line on the nutrition facts panel 
(without a %DV). This requirement goes into effect January 1, 2006. 
(The trans fat labeling rule that was issued on July 11, 2003 in the 
Federal Register can be found here http://www.cfsan.fda.gov/-acrobat/
fr03711a.pdf).
    FDA is very proud of this regulation because we believe that this 
information will allow consumers to lower their intake of trans fat. We 
estimate that 3 years after the January 1, 2006 effective date, trans 
fat labeling will lower the risk of approximately 600 to 1,200 cases of 
coronary heart disease and 240-480 deaths each year, saving $900 
million to $1.8 billion per year in medical costs, lost productivity, 
and pain and suffering.
    FDA understands the important public health concern associated with 
the consumption of products that contain trans fat. We encourage 
consumers to choose alternative fats by replacing saturated and trans 
fats with mono- and polyunsaturated fats. These latter fats do not 
raise LDL (or ``bad'') cholesterol levels and have health benefits when 
eaten in moderation.
    Fostering the development of healthier food products for American 
consumers is an important aspect of public health. FDA is aware of the 
impact labeling trans fat has on the manufacturer (i.e., potential 
reformulation, consumer demand, etc.) and the alternative ingredients 
or processing techniques under consideration for reducing trans fat. 
FDA is monitoring industry progress in this effort.

    Question 13. How do you intend to implement the 2004 
recommendations of the Institute of Medicine with respect to sugars and 
added sugars in foods?
    Answer 13. The 2005 Dietary Guidelines for Americans recommends 
that consumers limit consumption of added sugars in foods and 
beverages. The Guidelines present the concept of ``discretionary 
calories'' as a way for consumers to understand the amount of added 
sugars that could be incorporated into a healthful diet, and also the 
concept of nutrient dense foods as a way to choose products that are 
good sources of nutrients compared to their calorie content. The 
Nutrition Facts panel of food labels provides consumers with 
information on the total sugars in a product, and the ingredient list 
provides information on what is in a product, including ingredients 
that are sources of added sugars. FDA can help consumers respond to the 
recommendations in the IOM report as well as the Dietary Guidelines by 
educating consumers on how to use the Nutrition Facts panel and 
ingredient list to determine which foods are high in added sugars.
    We are in the early stages of issuing an Advanced Notice of 
Proposed Rulemaking to solicit comments on revising the Daily Values 
used on the nutrition label. This effort is a top priority for the 
Center for Food Safety and Applied Nutrition. This process will 
consider the recommendations from the IOM (Daily Reference Intakes) and 
other scientific reports (e.g., 2005 Dietary Guidelines). It will be a 
comprehensive effort that will include a review of the Reference Daily 
Intakes (RDIs), which include vitamins and minerals as well as the 
Daily Reference Values (DRVs), which include macronutrients (such as 
sugar).

    Question 14a. I understand that the FDA announced that its consumer 
research on qualified health claims was completed nearly a year ago, 
and that the International Food Information Council has completed a 
similar study. Please provide me with the raw data from each of these 
studies.
    Answer 14a. FDA has a copy of slides from an International Food 
Information Council's (IFIC) presentation, but not a copy of the study 
or the raw data. We can make a copy of the slides available, but a 
complete discussion of the study, with slides, can be found on IFIC's 
website: www.ific.org/researchlqualhealthclaimsres.cfm.

    Question 14b. Please summarize the results of these studies.
    Answer 14b. IFCA has summarized its research and this summary 
appears on the web site listed above. FDA is working to finalize our 
study. Therefore, we do not have definitive information to summarize at 
this time.

    Question 14c. I understand that the studies suggest that consumers 
do not understand qualified health claims. 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.
    Answer 14c. FDA issued the Consumer Health Information for Better 
Nutrition Task Force Report on July 10, 2003. The report contained 
interim procedures to implement this initiative to make available more 
and better information about foods and dietary supplements, to help 
Americans improve their health and decrease the risk of certain 
diseases by making sound dietary decisions. One of the goals of the 
Consumer Health Information for Better Nutrition Initiative is to 
encourage makers of conventional foods and dietary supplements to make 
truthful and non-misleading, up-to-date, science-based claims about the 
health benefits of their products. Two guidance documents pertaining to 
procedures to evaluate petitions for qualified health claims were 
issued in the Task Force's Report: (1) Interim Procedures for Qualified 
Health Claims in the Labeling of Conventional Human Food and Human 
Dietary Supplements; and (2) Interim Evidence-based Ranking System for 
Scientific Data.
    In addition, FDA published an Advance Notice of Proposed Rulemaking 
(ANPRM) in November 2003, soliciting public comment on the issues 
identified in the Task Force Report, including alternatives for 
regulating qualified health claims in the labeling of conventional 
human foods and dietary supplements. The consumer research conducted by 
FDA is currently being analyzed. Using the consumer research and other 
available information, including comments to the ANPRM, FDA will decide 
how to proceed with regard to qualified health claims in food labeling.

    Question 15a. I understand that the Administration's proposed 
budget for 2006 cuts inspections of imported food by 5 percent. The FDA 
already inspects a very small percentage of imported foods. Given the 
risk of a bioterrorist attack using food identified by Secretary 
Thompson, please explain why a reduction in imported food inspections 
is prudent.
    Answer 15a. The fiscal year 2006 Budget does not reduce field 
examinations of imported food. FDA will continue to examine about 
93,000 import lines in fiscal year 2006 as well as in fiscal year 2005. 
To manage the ever-increasing volume of imported food shipments, FDA is 
using risk management criteria to achieve the greatest food protection 
with our available resources. While we cannot physically inspect every 
shipment, it is important to note that every shipment containing FDA-
regulated products entered through the Bureau of Customs and Border 
Protection (CBP's) automated system is electronically reviewed by FDA's 
system and those FDA-regulated products requiring further investigation 
are identified. FDA's Operational and Administrative System for Import 
Support (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 allows FDA to 
concentrate its limited enforcement resources on high-risk shipments 
while allowing low-risk shipments to proceed into commerce.
    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 provided a significant new tool that enhances 
FDA's ability to electronically review all FDA-regulated imported 
shipments. That law requires that FDA receive prior notice before food 
is imported or offered for import into the United States. Advance 
notice of import shipments, called ``Prior Notice,'' allows FDA, with 
the support of the CBP, to target import inspections more effectively 
and help protect the Nation's food supply against terrorist acts and 
other public health emergencies. With the new prior notice requirement, 
specific information mandated by the Bioterrorism Act must be submitted 
to FDA before the imported food arrives in the United States. This not 
only allows the electronic system to review and screen the shipments 
for potential serious threats to health (intentional or otherwise) 
before food arrives in the United States, but it also allows for FDA 
staff review of prior notices for those products flagged by the systems 
as presenting the most significant risk. FDA worked very closely with 
CBP in developing this screening system. FDA receives approximately 
27,000 prior notice submissions about incoming food shipments every 
day. The Prior Notice Interim Final Rule became effective December 12, 
2003. FDA's experience with the prior notice system has been that it 
permits FDA to further refine our risk-based targeting and allocate 
resources for inspections more effectively.
    The fiscal year 2006 Budget requests an increase of $30 million for 
food defense activities. Twenty million dollars of this increase will 
support a national laboratory network known as the Food Emergency 
Response Network (FERN). A critical component of controlling threats 
from deliberate food-borne contamination is the ability to rapidly test 
large numbers of samples of potentially contaminated foods for a broad 
array of biological, chemical, and radiological agents. FERN will 
increase our laboratory surge capacity through a nationwide network of 
Federal and State laboratories capable of testing the safety of 
thousands of food samples, thereby enhancing the Nation's ability to 
swiftly respond to a terrorist attack. The additional $10 million will 
be used for targeted food defense research, for continued coordination 
and sharing of data with the Department of Homeland Security as part of 
the governmentwide Bio-Surveillance Initiative, and for upgrades in 
FDA's crisis management capabilities.

    Question 15b. How do you intend to ensure the safety of the 
American public from both intended and unintended contamination of the 
food supply?
    Answer 15b. Ensuring the safety of the food supply is a top 
priority for me and for the Administration. Please see our response to 
one of your previous questions about the steps we are taking to protect 
the food supply. That response describes some of FDA's many food safety 
and defense activities to protect the food supply against intended and 
unintended contamination.
                                 ______
                                 
  Response to Questions of Senator Enzi by Lester Crawford, DVM, Ph.D.
    Question 1. Dr. Crawford, several months ago, you announced several 
changes at the FDA to improve the agency's ability to identify drug 
safety concerns. Among the things you announced last year was a study 
by the Institute of Medicine of FDA drug safety activities. Would you 
please discuss this in more detail? I'd like to know how far along the 
study is, how the IOM is involving all the stakeholders, and when you 
expect to receive the report.
    Answer 1. At our request, an IOM committee will be convened to 
examine the current U.S. system for evaluating and ensuring drug safety 
post-marketing and to make recommendations to improve risk assessment, 
surveillance, and the safe use of drugs. In their proposal to us, IOM 
characterized the scope of their study as including the following:
     An examination of FDA's current role and the role of other 
actors (e.g., health professionals, hospitals, patients, other public 
agencies) in ensuring drug safety as part of the U.S. health care 
delivery system;
     An examination of current efforts for the ongoing safety 
evaluation of marketed drug products at the FDA and by the 
pharmaceutical industry, the medical community, and the public health 
authorities;
     An evaluation of the analytical and methodological tools 
employed by FDA to identify and manage drug safety problems and make 
recommendations for enhancements; An evaluation of FDA's internal 
organizational structure and operations around drug safety (including 
continuing post-market assessment of risk vs. benefit);
     A consideration of FDA's legal authorities for identifying 
and responding to drug safety issues and current resources (financial 
and human) dedicated to post-marketing safety activities;
     An identification of strengths, weaknesses, and 
limitations of the current system; and
     Recommendations in the areas of organization, legislation, 
regulation, and resources to improve risk assessment, surveillance, and 
the safe use of drugs.
    According to their proposal, IOM will assemble a study committee of 
15 experts to develop a consensus report that examines the current U.S. 
drug safety system. The lead study committee will draw upon a broader 
pool of experts/volunteers through the establishment of two 
subcommittees. Subcommittees will conduct data gathering activities to 
support the activities of the lead committee. The committee chair and 
the IOM staff will determine the focus of expertise of the 
subcommittees.
    The IOM expects to announce the committee members very soon and is 
targeting the first meeting of the committee for April 2005. After the 
first meeting, there will be six subsequent meetings of the committee 
at 2-month intervals. The IOM has targeted production and release of 
their report as 19-20 months from inception of the effort.

    Question 2. Dr. Crawford, some have expressed concern about the 
authority of FDA to require drug product labeling to include important 
information. One of the concerns is that FDA is not able to convince 
manufacturers to change their labels in a timely manner. But my 
understanding is that if FDA believes a label is false or misleading, 
and a company isn't willing to make the necessary changes, FDA can 
remove the product from the market. That seems to me to be a 
considerable amount of authority. Is it sufficient, and if not, what 
additional authority would be needed?
    Answer 2. FDA has authority to determine that a drug is misbranded 
if its labeling is false or misleading and can seek judicial relief to 
mandate changes to the label or take action to remove the product from 
the market. The process would normally begin with a warning letter to 
the company expressing FDA's position, and the company would have a 
chance to respond. Unless the company voluntarily made the changes, FDA 
would then pursue judicial relief. Alternatively, for FDA to remove the 
product from the market over a sponsor's objections, FDA would consider 
whether the risks of marketing the product with false or misleading 
labeling outweighed the benefits for the population of patients that 
use the product. The risks may not outweigh the benefits for many 
drugs. The procedures for removing a drug from the market if the 
sponsor does not agree to stop marketing require publication of a 
notice and of an opportunity for hearing in the Federal Register, and a 
possible administrative hearing if the sponsor demonstrates that there 
is a genuine issue of material fact to be decided in a hearing.

    Question 3. Dr. Crawford, would you highlight in the President's 
Budget the areas where additional resources will be dedicated to drug 
safety activities? Specifically what will the additional funds be used 
for, in terms of personnel as well as other activities?
    Answer 3. In fiscal year 2006, FDA has requested an increase of 
$6,500,000 and 28 full time employees (FTE) for the Office of Drug 
Safety (ODS). $5,000,000 and 20 FTE of the proposed increase is in 
budget authority, and $1,500,000 and eight FTE is in user fees. With 
the proposed $6,500,000 increase, FDA will (1) hire eight FTE to 
establish policies and processes regarding safety reviews and risk 
management; manage communications with the Office of New Drugs; and; 
support patient safety initiatives and external partnerships with CMS, 
AHRQ, and other HHS Agencies; (2) hire 14 FTE in the 3 operating 
divisions of ODS to handle the increased workload of monitoring 
biologic therapeutics; increase communication and coordination of 
safety review activities within the divisions; and, increase focus on 
medical error signal detection and address current backlog of 
unaddressed potential signals; (3) hire six FTE to increase staff 
dedicated to evaluating and communicating drug safety risks to the 
healthcare community and the American Public; and (4) apply funding to 
increase access to a wide range of clinical, pharmacy and 
administrative databases. As each drug has its own indication(s) that 
may result in its differential use in different populations, it is 
essential that the CDER have access to a wide range of databases to 
assess adequately drug safety. FDA will also increase transparency by 
sharing drug safety information sooner and more broadly to enhance 
public knowledge and understanding of drug safety issues.

    Question 4. Obesity has increased dramatically in this country. 
Nearly two-thirds of Americans are overweight, and one-third are obese. 
FDA is responsible for regulating the labeling of most packaged foods. 
Could you discuss FDA's plans and actions to use that authority to 
fight obesity, particularly in children?
    Answer 4. There is no simple solution to the problem of obesity. 
Achieving success in reducing and avoiding obesity will occur only as a 
result of efforts over time by individuals as well as various sectors 
of our society. Most associations, agencies, and organizations believe 
that diet and physical activity should be addressed together in the 
fight against overweight and obesity.
    Obesity is a growing and urgent public health problem in the United 
States. Today, almost two-thirds of all Americans are overweight and 
over 30 percent are obese. To help confront the problem of obesity in 
the U.S. and to help consumers lead healthier lives through better 
nutrition, in August 2003, FDA created an Obesity Working Group (OWG), 
which was charged with preparing a report that outlines an action plan 
to cover critical dimensions of the obesity problem from FDA's 
perspective and authorities. FDA's ``Calories Count'' report was 
released on March 12, 2004.
    The OWG report provides a range of short and long-term 
recommendations to address the obesity epidemic. For FDA's actions the 
emphasis is on calories. Progress to date follows:
     We have published two advance notices of proposed 
rulemaking (ANPRMs), in response to the recommendations in the OWG 
report, seeking comments on the following:
     How to give more prominence to calories on the food label, 
for example, increasing the font size for calories, including a column 
in the Nutrition Facts panel of food labels for percent Daily Value for 
total calories, and eliminating the listing for calories from fat. In 
addition, the Agency is seeking comment on the reformulation of the 
foods or redesign of packaging that may occur if any changes are made 
to the food label;
     Whether to amend certain provisions of the nutrition 
labeling regulations concerning serving size, such as for multiple-
serving packages that may reasonably be consumed in a single eating 
occasion.
     We continue to encourage manufacturers to take advantage 
of the flexibility in current regulations on serving sizes to label as 
a single-serving those food packages where the entire contents of the 
package can reasonably be consumed at a single eating occasion. We also 
continue to encourage manufacturers to use appropriate comparative 
labeling statements that make it easier for consumers to make healthy 
substitutions. Since release of the OWG report, the Agency, in meetings 
with industry, has made a point to encourage manufacturers to take 
advantage of the existing flexibility in serving size regulations, and 
companies are responding. For example, Kraft Foods is instituting dual 
column labeling for all its packaged foods containing 2-4 servings per 
package.
     FDA continues to encourage restaurants voluntarily to 
provide point-of-sale nutrition information to customers, including 
calorie information on a nationwide basis.
     FDA is also working to develop educational strategies and 
partnerships to support appropriate messages and teach people, 
particularly children, how to lead healthier lives through better 
nutrition. We are starting work with the Girl Scouts of the USA, under 
terms of a Memorandum of Understanding signed this past fall, to 
provide outreach and education in a science-based initiative to focus 
on improving health, nutrition, and physical activity. In addition, 
FDA's field offices are participating in local partnerships to reach 
and teach children. For example, in Central Florida, FDA's South East 
Region is part of the Seminole County Healthy Kids Partnership to 
promote positive opportunities for school-aged children in Seminole 
County to learn healthy nutrition and the value of increased daily 
physical activity.
    Also, FDA's Center for Drug Evaluation and Research (CDER) will 
continue to work with pharmaceutical sponsors to facilitate development 
of effective therapies to address the important public health issue of 
obesity and its attendant morbidities. An advisory committee meeting 
was held on September 8, 2004 to discuss the draft guidance on Clinical 
Evaluation of Weight-Control Drugs. The Agency is working to finalize 
the guidance.
    We believe that, when implemented, the report's recommendations 
will make a worthy contribution to confronting our Nation's obesity 
epidemic and helping consumers lead healthier lives through better 
nutrition.

    Question 5. The Critical Path Initiative is a framework for 
bringing together academia, patient groups, industry and government 
agencies to create a new generation of performance standards and 
predictive tools that will provide faster and more certain answers 
about the safety and effectiveness of products in development. In the 
FDA Critical Path report issued 1 year ago, it was noted that the 
mission of the FDA is not only to protect the public health, but also 
to advance the public health by helping to speed innovations that make 
medicines more effective, safer, and more affordable.
    As Acting FDA Commissioner, Dr. Crawford, you strongly endorsed 
this initiative and publicly confirmed FDA's commitment to moving the 
initiative forward. What role do you see for the Critical Path 
Initiative in successfully addressing the safety issues FDA is 
currently facing? Do you have sufficient resources available to 
aggressively pursue this initiative?
    Answer 5. As you suggest, there is significant synergy between our 
efforts to improve drug safety and the Critical Path Initiative. While 
it is important that we increase our post-market surveillance of 
adverse events, the real goal is to prevent adverse events from 
occurring. Safety should be built into medical products from the ground 
up. This requires two things. First; we need better predictive science 
and tools for product development, so we can identify compounds likely 
to be too risky very early in development. Second, we need better tools 
for predicting a patient's likely response to a product, so we can 
select for treatment only those patients for whom the risks of the 
product are likely to be outweighed by its benefits. These are 
precisely the kinds of applied science tools that the Critical Path 
sciences produce.
    For example, new biomarkers that predict toxicity could guide 
product sponsors in making better decisions about which potential 
products, and which doses, to test in humans. The same biomarkers could 
also improve treatment choices after the drug is approved, by helping 
identify patients likely to respond adversely to the drug. In short, 
many FDA investments in Critical Path efforts will also be investments 
in improving drug safety.

    Question 6. The reuse of medical devices intended for single use 
has grown in frequency over the last decade as hospitals and doctors 
attempt to cut costs. I'm concerned that FDA isn't receiving the 
critical data necessary to establish whether reprocessed single-use 
devices are still safe and effective for further use. What steps do you 
plan to take to assure that the FDA collects the necessary scientific 
information and enforces the law fully when it comes to reviewing 
marketing applications from device reprocessing companies?
    Answer 6. In the Medical Device User Fee and Modernization Act of 
2003/P.L.107-250 (MDUFMA), Congress specified a detailed process by 
which FDA was to re-evaluate previously-cleared reprocessed single use 
medical devices (SUDs). In accordance with the intent of Congress, FDA 
has expended significant resources to accomplish the following:

Premarket Review

    On April 30, 2003, FDA identified certain reprocessed SUDs for 
which 510(k)s must now include ``validation data . . . regarding 
cleaning and sterilization, and functional performance'' to show that 
the devices remain substantially equivalent to predicate devices after 
all intended reprocessing. FDA issued a guidance document on July 8, 
2003 (revised June 1, 2004), describing the types of validation data 
that would satisfy this MDUFMA requirement.
    For devices in this category that already had cleared 510(k)s, 
validation data (referred to as ``Supplemental Validation Submissions 
(SVSs)'') were required to be submitted to FDA by January 30, 2004. FDA 
received 44 SVSs for reprocessed SUDs for which the 510(k)s had already 
been cleared. This represented approximately 1,800 previously cleared 
reprocessed SUDs. Regulatory decisions on all but two of these SVSs 
were issued by November 1, 2004 as outlined below.
     Fifty-two percent of these devices were determined to be 
substantially equivalent (SE) to a legally-marketed predicate device 
and may continue to be marketed.
     An additional 33 percent of the models were determined to 
be Not Substantially Equivalent (NSE) to a legally marketed predicate 
device based on the failure to submit supplemental data OR the 
submission of inadequate supplemental data to FDA. These devices may no 
longer be legally marketed since they are no longer cleared for 
commercial distribution in the United States at this time. Reprocessors 
of these devices may seek clearance for the subject devices anytime in 
the future by submitting a new 510(k) premarket notification to FDA 
that satisfies the Agency's premarket requirements including 
supplemental validation data.
     Approximately 15 percent of previously cleared reprocessed 
SUD models were withdrawn by the reprocessor. These devices may no 
longer be legally marketed at this time. Also, FDA conducted field 
inspections to verify discontinuance of marketing.
    In November, 2004, FDA posted, on its website, the status of 
previously-cleared, reprocessed SUDs that were subject to supplemental 
validation data requirements described above. This allows hospitals and 
other interested parties to verify the status of reprocessed devices 
for use in their facilities. The website includes lists of devices 
found to be Substantially Equivalent based on a review of the 
supplemental data. These devices appear under the heading of ``Legally 
Available.'' In addition, the website lists those devices which may no 
longer be legally marketed because supplemental data were required but 
not received, subject 510(k)s were withdrawn by the sponsor, or 
supplemental data were determined by FDA to be inadequate. These 
devices are listed as ``No Longer Legally Marketed.''
    On April 30, 2003, FDA also published a list of ``critical'' 
reprocessed SUDs whose exemption from premarket notification 
requirements was terminated. Reprocessors of the devices on this list 
were required to submit 510(k)s, including the types of validation data 
described above, by July 30, 2004. No reprocessors of the critical 
reprocessed SUDs provided any submissions. FDA will conduct follow-up 
inspections to verify that the firms have stopped marketing these 
reprocessed devices.
    On April 13, 2004, FDA published a list of ``semi-critical'' 
reprocessed SUDs whose exemption from premarket notification 
requirements was terminated. Reprocessors of the devices on that list 
are required to submit 510(k)s, including validation data, by July 13, 
2005.
    MDUFMA created a new type of premarket submission, a ``premarket 
report'' (PMR), for reprocessed SUDs that otherwise would have required 
premarket approval applications. Among other items, a PMR must include 
data on reprocessing procedures, such as validation data regarding 
cleaning, sterilization, and functional performance.

Adverse Event Reporting

    In accordance with MDUFMA, FDA revised the mandatory and voluntary 
MedWatch report forms to incorporate the reporting of information on 
incidents related to reprocessed SUDs. FDA posted the revised forms on 
the MedWatch website in October 2003, along with revised instructions 
for mandatory reports, and, in early 2004, published a Federal Register 
notice announcing the availability of the revised MedWatch forms.

Inspections/Enforcement

    Since MDUFMA was enacted, FDA has inspected over 150 third-party 
reprocessors and hospitals engaged in reprocessing. As a result of the 
information collected, CDRH's Office of Compliance has issued two 
Warning Letters (to a hospital and a third-party reprocessor).
    In fiscal year 2004, FDA inspected over 100 U.S. hospitals and 
found none currently reprocessing single use devices. FDA has also 
issued an inspection assignment in fiscal year 2005 for five firms that 
reprocessed SUDs to ensure that they have discontinued marketing of the 
devices that were NSE. The five inspections have just been completed 
and inspection reports are being prepared.

Next Steps

    FDA will continue to review submissions for reprocessed single use 
devices as they are received. FDA has received comments on the lists of 
critical and semi-critical reprocessed SUDs whose exemption from 
premarket notification requirements was terminated, and we are 
currently reviewing these comments. Finally, FDA will continue to 
inspect reprocessors as appropriate and will inspect new hospital or 
third-party reprocessors as they are identified.

    Question 7a. Please update us on the steps FDA has taken to improve 
the situation with regard to vaccine supply, especially in light of 
last year's flu vaccine shortage. Specifically, what changes are you 
making in terms of inspections of foreign facilities, communication 
with foreign regulatory authorities, etc.?
    Answer 7a. Recent experiences, particularly those of the past 7 
months, have taught us important lessons about manufacturing and 
inspectional activities with respect to influenza vaccine. Although FDA 
has always interacted extensively with influenza vaccine manufacturers 
throughout the vaccine production cycle, the annual changes in the flu 
vaccine and the increased dependence on a smaller number of 
manufacturers highlight the risks of unexpected manufacturing 
difficulties. For these reasons, in 2005 and the future, we plan to 
conduct inspections of influenza vaccine manufacturers on an annual 
basis, with additional interactions with manufacturers and, in the case 
of foreign facilities, their regulatory agencies where appropriate, 
based on findings or events that raise concerns.
    FDA is working with manufacturers and its regulatory counterparts 
in anticipation of having an ample supply of influenza vaccine for the 
coming season through a dual-track strategy.
    FDA's first track is to facilitate Chiron's effort to correct its 
manufacturing problems. FDA and MHRA, the British regulatory agency, 
have an agreement with Chiron that allows full information sharing. FDA 
has used that agreement to collaboratively review Chiron's remediation 
plans and activities, and the Agency is providing continuing and 
extensive feedback to both Chiron and MHRA. In addition, FDA signed an 
information sharing agreement with MHRA that will, among other things, 
permit advance communication on important issues. The agreement was 
effective February 14, 2005.
    FDA is actively communicating on inspection activities. Only after 
passing MHRA and FDA inspections will Chiron be able to provide vaccine 
to the U.S. market. In the spring when critical stages of manufacturing 
are taking place, the Agency plans a comprehensive inspection to verify 
whether Chiron has adequately addressed its problems. While much work 
remains to be done, it appears that Chiron is making progress.
    FDA's second track is to facilitate overall greater capacity and 
diversification in the U.S. influenza vaccine supply. It is important 
to recognize that the demand for vaccine and other economic issues are 
the primary factors that determine whether a manufacturer will seek and 
maintain a license in this country.
    CDC and FDA are working to encourage vaccination throughout the flu 
season, including January and February. To increase the total doses 
available, manufacturers can produce vaccine over a longer time period, 
and that becomes available during these months. Because influenza cases 
usually continue well after November and December when most people are 
seeking immunization, later vaccination is beneficial. The Public 
Health Service is working to better communicate this important public 
health message.
    In addition, FDA has been working to stimulate manufacturers not 
licensed in the U.S. to provide or, where needed, develop the safety 
and effectiveness data to obtain U.S. licensure. The Agency has 
actively engaged several interested companies. FDA has informed 
manufacturers that the Agency is willing to consider all approaches to 
licensing, including accelerated approval based on surrogate markers, 
e.g., the patients' immune response to the vaccine. Sanofi Pasteur and 
Medlmmune have indicated their willingness, if needed, to do what they 
can to increase production.
    FDA has challenged itself to identify other lessons learned from 
this year's influenza season and is evaluating how this experience 
could be used to prevent similar events in the future. While there are 
some elements that FDA cannot control, the Agency is making significant 
changes. For example, as mentioned above, FDA plans to conduct 
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.

    Question 7b. Please describe what you are doing to ensure that we 
won't have a major shortage situation on an important vaccine again 
this year.
    Answer 7b. FDA is working with manufacturers and our regulatory 
counterparts in anticipation of having an ample supply of influenza 
vaccine for the coming season. Details on FDA's approach to assuring 
adequate supply are in the response above.

    Question 8. I understand that the FDA relies on advisory panels in 
making important decisions about new drugs and medical devices. 
Although the panels' recommendations are not binding, FDA typically 
follows advisory panels' recommendations an extremely high percentage 
of the time.
    What is the standard FDA uses to determine whether to accept or 
reject the recommendations of advisory committees? Does the failure by 
the agency to follow a recommendation undermine the advisory committee 
process?
    Answer 8. Advisory committees at the Food and Drug Administration 
(FDA or the Agency) are designed to offer a wide range of views on 
topics that are discussed in a public forum and to be advisory in 
nature. FDA seeks and appreciates the recommendations made by the 
committees. The final determination on a drug application, however, 
remains by law with the Agency. Although the Agency frequently makes 
final decisions concerning a new drug application (NDA) that are 
consistent with an advisory committee's recommendations, FDA is not 
bound to follow their recommendations. Ultimately, a final decision is 
based on FDA's evaluation of the data, taking into account all of the 
views expressed.
    The agency poses questions to its advisory committee members to 
obtain expert scientific advice. Often, the committee is used to obtain 
highly technical information that is not available in-house. At other 
times, the committee is asked to consider a scientific question that 
has opposing views in the scientific world. The committee discusses the 
issue in a public forum. Based on the data and/or advice presented, the 
Agency scientists evaluate the advice in the context of the rest of the 
product application (some aspects of which may not be publicly 
disclosed due to confidentiality requirements). Non-acceptance of an 
advisory committee recommendation does not undermine the agency 
process, but rather supports it. The value of the advisory committee 
process is not limited to the final recommendation of the panel. The 
process itself, in which the Agency obtains additional scientific 
information and comment by the Nation's experts and the public in a 
open forum provides the Agency with invaluable scientific information 
and increases credibility in the Agency's decision making process.

    Question 9. I am sure you would agree with me that it is essential 
that the Agency's advisory panels be free of conflicts of interest and 
that any potential conflicts of interest be disclosed. What does FDA do 
now to ensure against conflicts of interest on its advisory committees? 
And, in light of recent criticism about potential conflicts of 
interest, what will you do as Commissioner to further ensure that 
decisions made by advisory committees are not influenced by committee 
members' outside activities?
    Answer 9. It is very difficult to obtain qualified advisory 
committee panel members who are totally free from all potential 
financial conflicts of interest. The Nation's experts (and in some 
cases, there are only a few experts on a particular topic) are sought 
after for consultation by both the Agency and industry because of the 
scarcity, and therefore the value, of their expertise. Utilizing less 
experienced or less highly qualified scientists in order to completely 
remove any potential conflict from the committee would hamper the 
Agency's ability to protect and advance the public health.
    The Agency's staff examines all potential financial interests. The 
Agency's process is to evaluate the potential financial interests of 
members and other invited special government employees. FDA makes a 
determination as to whether the participation of an individual with 
some financial ties outweighs the need for the agency to understand the 
science on the topic before the committee. Although the Agency has 
guidelines for this process (see Waiver Criteria Document 2000 on the 
FDA web page), this is not a black and white process. It requires 
careful consideration of all facets of the issue in order to evaluate 
that balance. Congress, by permitting waivers for potential conflicts 
of interest, has ensured that the Agency and the public (through the 
advisory committee process) have access to the most knowledgeable 
individuals on the meeting topic.
    FDA's process of evaluating potential committee members for 
conflicts is very extensive and transparent. Our methodology is 
articulated in an extensive document on the agency's website (http://
www.fda.gov/oc/advisory/conflictofinterest/intro.html). At the 
beginning of each meeting, a conflict of interest statement is read 
into the record, which summarizes the results of the conflicts of 
interest screening. FDA has been commended by the Office of Government 
Ethics (1997) for serving as ``a model for other Agencies to use in 
developing their own systems and procedures.'' Nonetheless it is always 
prudent to regularly assess the Agency program and determine if any 
improvements are warranted. In the near future, the Agency will review 
the advisory committee conflicts of interest disclosure process and 
consider if further improvements are necessary to make the disclosures 
more easily accessible to the public.

    Question 10. Dr. Crawford, I understand that FDA has recently begun 
a review of its citizen petition process. The FDA proposed changes in 
1999 to make the process more efficient and responsive, partly in 
response to an HHS Inspector General audit. However, FDA withdrew the 
proposed changes in 2003, saying that FDA had improved its handling of 
citizen petitions over the past several years and that the 1999 
proposed rule was no longer necessary. 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?
    Would you provide the committee with an assessment of how many 
petitions were pending at FDA as of September 30, 2004; how many of 
these petitions had been pending for more than 180 days without a 
tentative response; how many of these petitions had been pending for 
more than 180 days without a final response; and how these figures 
compare to those from the 5 previous years?
    Answer 10. FDA receives several different types of citizen 
petitions. Some statutory/regulatory mechanisms contemplate the 
submission of citizen petitions to initiate an action by the Agency. As 
a consequence, petitions may be tracked and handled by the Agency 
through different mechanisms. For example, FDA's Center for Drug 
Evaluation and Research (CDER) receives petitions relating to over-the-
counter drugs or ``suitability'' petitions in which a person wants to 
submit an abbreviated new drug application (ANDA) for a drug product 
that will differ from the reference listed drug in route of 
administration, dosage form, or strength, or to substitute an active 
ingredient (see 21 CFR 314.93). As of September 30, 2004, excluding 
these two categories of petitions, CDER had 126 pending citizen 
petitions. Thirty-nine of these 126 petitions raised regulatory or 
scientific issues related to approval of a generic drug. Of the 126 
pending petitions, 93 were pending for longer than 180 days. Of the 39 
petitions related to a generic drug approval, 21 were pending for more 
than 180 days. We believe virtually all of the petitions that were 
pending more than 180 days received an interim response. Many of the 
petitions pending for more than 180 days involved complex scientific 
questions. Petition responses almost always require review and input 
from scientists in at least one program division; these scientists are 
also responsible for reviewing new drug applications.
    Citizen petition submissions to some of our Centers have increased 
in recent years. For example, CDER has experienced approximately a 50 
percent increase in the number of citizen petitions received in CY 2004 
over CY 2003. For fiscal year 2004 CDER received a total of 62 citizen 
petitions (of which 27 raised issues related to generic drug 
approvals). Although we issued final response letters for 55 citizen 
petitions (of which 19 concerned issues raised about generic drug 
approvals) in fiscal year 2004, we did not keep up with the increasing 
number of citizen petitions filed. As a result, our backlog of pending 
petitions increased. We are currently examining ways to improve the 
citizen petition process and to reduce the backlog.
    In an effort to provide as responsive a reply as possible given the 
exigencies of time, we have focused our answer on citizen petitions 
relating to drugs. If you are interested in additional data regarding 
citizen petitions more generally or a specific type of citizen 
petition, we would be happy to provide additional information. Our 
records on petitions are not kept in a manner that allows for rapid 
generation of comparisons over a 5-year period; but we will work with 
your staff to provide responsive data by the end of the month.

    Question 11. In the past, the Food and Drug Administration has 
expressed concern about the importation of prescription drugs from 
foreign countries. Agency officials have also reported that many drugs 
obtained from other countries that appear to be U.S. approved are of 
unknown quality. Could you describe some of the activities FDA would 
need to conduct to ensure the safety of the drug supply and the kinds 
of resources and personnel it would need if importation is legalized? 
What amount of additional funding and/or personnel would the FDA need 
to insure the safe commercial importation of drugs, and would personal 
importation require more or fewer resources?
    Answer 11. Reimported and imported foreign medications are 
currently outside the regulatory system overseen by FDA and State 
Pharmacy Boards. Therefore, it is very difficult for a consumer to tell 
if they are getting a medication that meets FDA's strength, quality and 
purity standards. We have confiscated a significant amount of 
suspicious packages from foreign sources, many which have contained 
drugs that don't meet FDA standards. As the government agency 
responsible for the safety and efficacy of medications, we are greatly 
alarmed that these drugs are bypassing established safeguards and 
finding their way into the system.
    The drug distribution network for legal prescription drugs in the 
U.S. is a ``closed'' system that involves several entities (e.g., 
manufacturers, wholesalers, pharmacies) that move drug products from 
the point of manufacture to the end user, and helps safeguard against 
receiving unsafe, ineffective, or poor quality medications. All of 
these entities are known and subject to Federal and State regulatory 
and legislative oversight. This system evolved as a result of 
legislative requirements that drugs be treated as potentially dangerous 
consumer goods that require professional oversight to protect the 
public health. The result has been a level of safety and efficacy for 
drug products that is widely recognized as the world's ``gold 
standard.''
    In February 2004, HHS announced the creation of a Task Force to 
study the importation of drugs. In December 2004, HHS released the 
results of this study and the Task Force's findings that concluded:
     It would be extraordinarily difficult and costly to ensure 
that personally imported drugs are safe and effective;
     Commercial importation could be feasible, but would 
require, among other things, additional safety protections and 
substantial resources;
     National savings from a legalized commercial importation 
program will likely be a small percentage of total drug spending;
     Importation would reduce the development of new medicines. 
The forgone benefits to consumers from not having access to new 
medicines could significantly offset the savings from legalized 
commercial importation.
    To maintain current levels of safety, the standards that currently 
exist in the United States (or some equivalent) would need to apply to 
all foreign drug suppliers under a commercial importation program. 
Legalized importation of drugs in such a way that creates an opening in 
the ``closed'' system will likely result in some increase in risk, as 
the evidence shows that weaknesses in the oversight of drug regulation 
and the distribution system have been exploited. Furthermore, the 
volume of packages entering the United States today has been increasing 
at a steady rate. Under a personal importation program, it would be 
very difficult to distinguish which of these millions of packages are 
from ``permitted'' internet pharmacies and which are from rogue 
websites, increasing the potential safety risks associated with 
imported drugs.
    It would take significant resources and new authority to enhance 
current FDA procedures to ensure that imported and reimported drugs are 
both safe and effective. The amount of resources needed would vary 
greatly depending on the specifics of the authorizing legislation.

    Question 12a. We have been talking a lot about how to ensure drug 
safety over the last few months, but some of the people affected by FDA 
decisions tell us there is a real and perhaps even more lethal danger 
if we over-react in ways that slow the development, approval and 
availability of new treatments for diseases like cancer, Parkinson's 
Disease, Alzheimer's, Multiple Sclerosis and a host of more rare, very 
serious and often terminal diseases. The COX-2 inhibitor drugs, for 
example, are primarily approved for pain relief and to reduce 
inflammation, conditions that can be life-limiting but that are not 
usually life threatening. There also are treatment alternatives to COX-
2 inhibitors, so they should be held to a rigorous safety standard for 
marketing, have accurate and up to date labeling, and be prescribed 
only to those who need them based on consideration of a reaasonable 
evaluation of risk versus benefit. However, it seems obvious that 
patients with advanced lung cancer, colon cancer or Parkinson's Disease 
face much more serious and certain risks from disease than does, for 
example, a middle-aged golfer dealing with arthitis who is trying to 
get in a pain-free round of weekend golf?
    Could you share with us your thoughts on how we can best weigh 
risks and benefits to serve these very different patients--one who 
seeks medical care to relieve the limiting but comparatively minor 
symptoms of a non-life-threatening condition like arthritis or 
tendonitis, and another who is trapped in a life and death struggle 
against a disease that has failed to adequately respond to approved 
therapies?
    Answer 12a. Benefit-risk considerations always take into account 
the severity of the disease involved, the alternative treatment 
available, and the nature and magnitude of the benefit of the new drug 
compared to alternatives. Historically, cytotoxis drugs for cancer 
treatment, for example, have been uniformly more toxic than would be 
tolerated in other theraputic areas, with toxicity to bone marrow, 
neurologic toxicities, candiac toxicities, ability to promote life-
threatening infection, and a wide range of other serious toxicities 
that are at best debilitaing and at worst lethal. These are acceptable 
if the drug provides benefit to patients with cancer because there are 
in many cases no alternative and the disease being treated is lethal. 
Other areas where significant toxicity is accepted include, but are not 
limited to, treatment for AIDS, serious fungal infections, organ 
rejection, sepsis, acute respiratory distress syndrome, and other 
severe, chronic degenerative diseases.
    On the other hand, with many well tolerated drugs to lower 
cholesterol or blood pressure, a new drug for these purposes that was 
more toxic than the available drugs would ordinarily not be approved 
(or could be withdrawn) unless it could treat a resistant population 
(whose risk of death would make the extra risk of the drug acceptable). 
Some years ago, a new drug for Alzheimer's Disease that was no more 
effective than available drugs but caused a high rate of severe 
vomiting was rejected because on risk-benefit considerations it was 
clearly worse than available alternatives. Had a study shown that it 
was effective in people who could not respond to alternatives, a 
different conclusion might have been reached. Newly available drugs can 
make a previously acceptable drug unacceptable. The hepatotoxicity of 
troglitizone was considered (by FDA and an advisory committee) 
acceptable for certain diabetic patients until two pharmacologically 
similar drugs (rosiglitizone and pioglitizone) without this toxicity 
became available. Troglitizone was then withdrawn.
    FDA reviewers are very conscious of the need for treatments for 
conditions with no therapy and for disease that fails to respond to 
available treatments and regularly weigh the benefits of treatment 
against even significant toxicity. These considerations are in some 
ways easiest if the diseases are lethal, but they are also critical if 
diseases are life-damaging in other ways--crippling arthritis, 
neurologic diseases, or mental illness, for example. Reviewers 
recognize that patients with such diseases may be willing to accept 
significant risks. It is critical to be sure the risks have been well 
studied and described, and that drug labeling describes the risks and 
benefits candidly. Even in these cases, however, there is a judgment to 
be made, deciding whether the desirability of more safety data 
outweighs the need for a new effective treatment. It is cases like 
these that are regularly brought before outside advisory committees, 
especially where the acceptability of the risk is a close judgment.

    Question 12b. Among your 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. 
You identified it as a priority in several of your speeches. These 
programs are sometimes called compassionate use or expanded access, and 
in this new regulation they are going to be called ``Treatment Use'' 
programs. Patients dying from terminal diseases think this regulation 
should be among the FDA's highest priorities. What is the status of the 
Treatment Use regulation and when will the draft regulation be 
published in the Federal Register?
    Answer 12b. The draft regulation is currently in the Agency 
clearance process. Once it has received Department and OMB clearance, 
we will publish it in the Federal Register.

    Question 13. What are your thoughts on the potential for 
cooperation between the FDA, NIH, CDC and CMS in moving the entire drug 
development, approval and delivery of new therapies to patients 
forward? For example, should there be some kind of a joint chiefs of 
staff in the war on cancer and coordination at other levels between 
those organizations? How can FDA, for example, participate and 
contribute to NCI Director Dr. Andrew Eschenbach's goal of eliminating 
suffering and death from cancer by 2015. What can we do right now to 
make that coordination happen?
    Answer 13. FDA and NIH recently announced the first major program 
stemming from our two Agencies' collaboration in the Interagency 
Oncology Task Force (IOTF). Staff from both Agencies continue to work 
jointly in other major areas under the IOTF umbrella that will be 
crucial to fostering the new age of medical products to conquer cancer, 
including nanotechnology, surrogate markers of clinical benefit, and 
chemoprevention.
    Though FDA and the National Cancer Institute (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 and FDA's mission is 
to assure the safety, efficacy, and quality of manufacturing of new 
medical products prior to marketing. Part of FDA's responsibility is to 
ensure that basic discoveries turn into new and better medical 
treatments. Our close collaboration with NCI through the IOTF is an 
important step in joining the mission of the two agencies to produce a 
seamless process for speeding new technologies to cancer patients. FDA 
and NCI are implementing a Research and Regulatory Review Fellowship 
Program as a critical first step in developing 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.
    There is no better way of learning about the problems inherent in 
developing innovative products than to participate actively in the 
regulatory review process. Clinicians and scientists who are selected 
for these fellowships have a unique opportunity to spend from 1-3 years 
at the FDA to work with, and be mentored by, experienced FDA reviewers 
and researchers. They will be able to watch product development 
programs succeed and fail and, in the process, to learn to recognize 
the characteristics of successful product development. They will then 
be able to take this knowledge of regulatory requirements back to their 
home institutions and incorporate it into their research on new cancer 
treatments from the earliest stages thus enhancing the likelihood of 
success.
    FDA looks forward to our close collaboration with NCI in this 
important training initiative, and believes that this investment will 
benefit the fellows, the partnered agencies, and the American public 
through more efficient use of public resources.

    Question 14. In March 2004, the FDA issued a major report 
``Innovation or Stagnation? Challenge and Opportunity on the Critical 
Path to New Products.'' This report led to the Critical Path 
Initiative, which has been embraced by patients, industry and doctors. 
Identification of biomarkers and creation of new surrogate endpoints 
offer the promise of increasing the sensitivity of clinical trials both 
for efficacy and occurrence of adverse events. Could you describe the 
FDA's efforts to work with industry to identify relevant biomarkers and 
validate surrogate endpoints? Could you describe collaborations that 
you anticipate the FDA will participate in with other government 
agencies and academia to identify biomarkers and surrogate markers?
    Answer 14. A key step in FDA's efforts to facilitate development of 
a robust biomarker infrastructure for product development will be 
publication this spring of the 2005 National Critical Path Challenges 
List. The list will include a description of the science needed to 
speed biomarker identification and validation, as identified by our 
stakeholders (industry, patient groups, academic researchers, and 
others) through our outreach efforts over the past 12 months.
    FDA's role in the work called for in this National List will vary. 
In some cases, no FDA involvement will be needed. In other cases, FDA's 
most important role will be to clarify regulatory expectations for the 
new science. For example, FDA clarification of the level of scientific 
evidence necessary to qualify biomarkers for a particular purpose could 
free innovators to undertake the science needed to validate biomarkers 
in their product areas. In other cases, FDA will need to be a partner 
in undertaking the necessary science. Modernizing the Critical Path is 
a national challenge. It will take the combined efforts of industry, 
government, patients, and academia to create the robust biomarker 
infrastructure we need for efficient development of safe medical 
products.
    We are exploring potential collaborations with several government 
agencies (where our missions converge) and academic institutions to 
work on modernizing the Critical Path sciences. Some of these may 
involve biomarker development, but to date specific projects have not 
been identified. It is not yet clear which potential partnerships will 
come to fruition.
    Some work in this area is already underway. For example, we are 
already working with the National Institutes of Health on developing 
new imaging techniques for identifying, validating, and measuring 
biomarkers for certain cancers.

    Question 15. Manufacturers that commercialize diagnostic laboratory 
tests must comply with FDA regulations, including those on 
manufacturing practices, quality systems regulations, and adverse event 
reporting. However, diagnostic tests developed in-house by laboratories 
(``homebrew'' tests) have not been required to comply with FDA 
regulations. There has been a proliferation of homebrew tests 
(particularly in the area of genetic tests) that have little regulatory 
oversight. How will you address the potential public health concerns 
raised by this growing number of non-FDA regulated tests?
    Answer 15. Most genetic tests are currently offered commercially as 
laboratory testing services (so-called ``in-house'' or ``home brew'' 
tests). FDA does not directly regulate these testing services. The 
laboratories that conduct the tests are subject to oversight under the 
Clinical Laboratory Improvement Amendments of 1998 (CLIA). Commercially 
marketed reagents used by laboratories to create in-house tests are 
subject to FDA regulation as analyte specific reagents (ASRs) to ensure 
that they are made consistently over time according to the quality 
system regulations and to ensure proper labeling.
    In 1997, FDA published a rule setting forth its approach to 
regulating ASRs. This rule provided incremental regulation of ``in 
house'' tests by placing requirements on the building blocks (the 
analyte specific reagents) used to make these tests. These include 
requirements to register and list with FDA, make reagents following the 
quality system regulation, report adverse events, and restrict use of 
reagents to labs holding certificates that permit them to perform high-
complexity tests under CLIA.
    Although the ASR rule has provided a level of complementary 
oversight to that provided by CLIA, FDA has become aware of increased 
instances in which manufacturers appear to circumvent the ASR rule by 
marketing ASR kits that are really complete tests rather than building 
blocks to be validated in laboratory developed tests.
    CDRH's Office of In Vitro Diagnostics (OIVD) continues to foster 
new genetic technology through development of collaborative guidance 
with CDER and CBER, and to work with the Clinical and Laboratory 
Standards Institute on developing standards for these tests. OIVD is 
actively encouraging companies and laboratories that are developing 
genetic tests to consult with the Agency about appropriate FDA 
oversight for those that will be marketed to health care providers and 
lay users.
    On December 23, 2004, FDA cleared the AmpliChip Cytochrome P450 for 
marketing. This new laboratory test system is the first to use the 
patient's own genetic information to help physicians better determine 
which drugs and doses to prescribe for the patient for a wide variety 
of common conditions such as cardiac disease, psychiatric disease, and 
cancer. This test is the first DNA microarray test to be cleared by the 
FDA, and its clearance paves the way for similar microarray-based 
diagnostic tests to be developed in the future. FDA cleared the test 
and the scanner based on results of a study conducted by the 
manufacturers of hundreds of DNA samples as well as on a broad range of 
supporting peer-reviewed literature. FDA's review of this test provides 
independent evaluation of its clinical validity, which is the goal of 
many proposals seeking greater oversight of genetic testing.

    Question 16. The scientific and medical community, as well as 
regulatory authorities, acknowledges there are many scientific and 
legal issues impacting the regulation of follow-on or ``generic'' 
biologics. Some say the science is not yet ready to allow for a safe 
approval process for generic biologics, and others are concerned about 
what such a policy would mean for the intellectual property interests 
of innovator companies. In light of these concerns, what are your views 
on the legal and scientific appropriateness of approving follow-on 
biologics? What would be a suitable level of evidence required for 
establishing safety and effectiveness? Do you think FDA has the legal 
authority to regulate follow-on biologics, either under 505(b)(2) of 
the Food Drug & Cosmetic Act or under the Public Health Service (PHS) 
Act?
    Answer 16. As you know, FDA is conducting a public process to 
examine the many questions, including scientific and legal issues, that 
must be answered regarding these products and to ensure that all 
interested parties have an opportunity to comment. When this process is 
complete, FDA intends to provide guidance to industry to clarify, 
consistent with its legal authority, the approval pathway and 
principles for review of such products, which will protect the public 
health.
    In recent years--and with increasing frequency--questions about 
generic or follow-on proteins have arisen in response to scientific 
advances, impending patent expirations, and the ability to better 
characterize and understand biological products.
    Acknowledging scientific and legal limitations in this area, yet 
also recognizing the public health need to move forward to assist 
industry and make more products available to the public, FDA is 
conducting a public process to examine the scientific, and related 
issues regarding follow-on biologics. This process will ensure that 
scientific considerations and issues related to Agency authority are 
fully examined and that all interested parties have an opportunity for 
input.

    Question 17. Dr. Crawford, some have suggested a kind of 
``isolation'' of drug safety evaluations from medical review and drug 
approval activities. We heard from Dr. Woodcock in testimony a couple 
of weeks ago that complete isolation of the two functions is not a good 
idea, because the people who know the most about a product are the 
medical reviewers who recommended its approval. As you establish a new 
drug safety board outside of the drug review function, how are you 
going to ensure that there is appropriate consultation with the medical 
reviewers who are experts about a product when this board is looking at 
safety questions about that product?
    Answer 17. The Drug Safety Oversight Board is being established to 
provide independent oversight and advice to the 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. Individuals on the Board who 
have been involved in the primary review of the data for a particular 
drug or who were the signatory for a regulatory action under 
consideration will be recused from the Board's evaluation and decision-
making for that drug. This does not mean that they will be excluded 
from participation in Board meetings. The medical reviewers most 
familiar with the issues will routinely present information to the 
Board because they are most knowledgeable about the specific drugs.

    Question 18. Dr. Crawford, as you are aware there has been 
tremendous growth in broadcast Direct-to-Consumer advertising of 
prescription drugs since 1997. This growth is due in large measure to 
the FDA having issued draft guidance in 1997 clarifying its regulation 
regarding the way in which risk information could be communicated to 
consumers. The guidance issued described an approach whereby consumers 
could have the benefit of television and radio prescription drug 
advertising while also ensuring consumer access to the advertised 
product's approved labeling through a toll-free telephone number, a 
website address, a concurrently running print advertisement, and health 
care professionals. Despite my concern about the usefulness of some of 
the DTC ads I have seen of late; on balance, I believe the guidance 
issued was appropriate.
    I am concerned, however, 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, and/or to educate patients about various treatment options 
and the risks associated with those options. Rather, consumers are all 
too often bombarded with ads that make light of a disease and/or 
minimize the therapy risks. Responsible direct to consumer advertising, 
I believe, should inform and educate patients about treatable 
conditions and available therapies.
    Do you generally believe in the merits of DTC advertising and in 
its role in educating and empowering patients? And if so, the question 
then becomes how to ensure consumers get the best of DTC advertising?
    Answer 18. FDA believes consumer-directed advertisements can play 
an important role in advancing the public health by encouraging 
consumers to seek treatment of diseases that may be under-treated and 
diseases for which patients may not be aware of treatment options. We 
have conducted research that confirms that DTC advertising, when done 
correctly, can serve positive public health functions, such as 
increasing patient awareness of diseases that can be treated, and 
prompting thoughtful discussions with physicians that result in needed 
treatments being prescribed often, not the treatment in the DTC 
advertisement. Results of our research shows that many physicians 
believe that DTC can play a positive role in their interactions with 
patients and that many physicians thought that DTC ads made patients 
more involved in their healthcare.
    In February 2004, we issued three draft guidance documents, 
addressing: (1) consumer-friendly options for presenting risk 
information in consumer-directed print advertisements for prescription 
drugs; (2) criteria FDA uses to distinguish between disease awareness 
communications and promotional materials; and, (3) a manner in which 
restricted device firms can comply with the rules for disclosure of 
risk information in consumer-directed broadcast advertising for their 
products.
    FDA adopted a comprehensive, multi-faceted, and risk-based strategy 
for regulating consumer-directed advertising of medical products, which 
emphasizes the use of warning letters, untitled letters, development of 
guidance that facilitate voluntary compliance, frequent informal 
communications with industry and advertisers, and research on the 
public health effects of consumer-directed promotional materials.
    At FDA, CDER's Division of Drug Marketing, Advertising, and 
Communications (DDMAC) is responsible for regulating prescription drug 
promotion. DDMAC's mission is to protect the public health by helping 
to ensure that prescription drug information is truthful, balanced, and 
accurately communicated. This is accomplished through a comprehensive 
surveillance, enforcement and education program, and by fostering 
optimal communication of labeling and promotional information to both 
health care professionals and consumers.
    While we believe the survey results discussed above confirm our 
belief that DTC ads help increase patient awareness about the 
availability of effective treatments for their health problems, we will 
continue to ensure that, consistent with the law, our DTC policies help 
prevent potential misperceptions about benefits and risks of the 
advertised treatment and promote the importance of prescribing 
decisions being made with the intervention of a health care 
professional.

    Question 19. The label (or package insert) is an important part of 
the FDA regulatory process. It is used to provide important information 
to patients and providers about drug action, indications for use, 
contraindications and side effects and drug dosing. Physicians have 
expressed concern that the label does not perform its intended function 
very well and have advocated for new guidance. Is the current package 
insert format adequate to convey risks and benefits to patients and 
providers? Is the information contained in the package insert the most 
useful to patients or providers? When will FDA issue new guidance on 
the package insert?
    Answer 19. FDA agrees that the current package insert format is 
inadequate and has embarked on a major initiative to improve it. In 
recent years, there has been an increase in the length, detail and 
complexity of prescription drug labeling, making it harder for health 
care practitioners to find specific information and to discern the most 
critical information in product labeling. In the Federal Register of 
December 22, 2000 (65 FR 81082), FDA issued a proposed rule to revise 
its regulations governing the content and format of labeling for human 
prescription drug products. Prior to issuing the proposal, the Agency 
evaluated the usefulness of prescription drug labeling for its 
principal audience to determine whether, and how, its content and 
format could be improved. The Agency used focus groups, a national 
physician survey, a public meeting and written comments to develop 
multiple prototypes and to ascertain how prescription drug labeling is 
used by health care practitioners, what labeling information 
practitioners consider most important, and how practitioners believed 
labeling could be improved. The Agency developed a prototype based on 
this accumulated information as the model for the proposed rule. FDA 
received many comments on the proposed rule and is working to finalize 
it. Publication of this rule will be accompanied by publication of four 
implementing guidance documents.

    Question 20a. The FDA currently has a two-part warning system to 
identify adverse drug events resulting from the use of drugs already 
approved for marketing: post-market studies; and the AERS system of 
voluntary reporting. Some feel that this system is too expensive, 
cumbersome and slow to protect the public health.
    Answer 20a. The warning system actually has three parts. First, 
there is the AERS system that is excellent at picking up rare adverse 
events rapidly. The principal burden and costs of collecting and 
reporting data included in this system are assumed by drug companies, 
but the considerable cost of maintaining the system, receipt and triage 
of reports, coding, data entry, quality control, and distribution of 
information is borne by FDA. Second, there is the current Office of 
Drug Safety cooperative agreement program of population-based resources 
for conducting observational epidemiology studies. These are generally 
used to validate and quantify safety signals found in AERS or to 
examine the impact of regulatory efforts to improve safety; they have 
hardly any application in detecting safety problems de novo. Population 
based studies can inform suspected drug safety problems, but only if 
the product has had extensive use. Third, there are post-marketing 
studies done by manufacturers, either as a condition of approval for 
products approved under 21 CFR 314 Subpart H, or under 21 CFR 601 
Subpart E, or voluntarily at the request of FDA or by the company's 
choice. In general, if FDA suspects that there may be a significant 
safety problem with a drug product, FDA will take immediate action 
rather than wait for a post-marketing study to be designed and 
completed. In the case of Vioxx, Celebrex, and Bextra, FDA guided the 
companies' pursuit of new efficacy indications in a way to clarify 
safety concerns that were either in product labeling or uncharacterized 
for other members of the product class.

    Question 20b. Is there any evidence that drug manufacturers have 
been less than forthcoming in informing FDA in a timely fashion of 
adverse drug events?
    Answer 20b. The vast majority of pharmaceutical firms comply with 
the regulations at 21 CFR sections 310.305, 314.80, 314.98, and 
314.540, which require reporting of serious and unexpected adverse 
events within 15 days of initial receipt of the information and the 
submission of periodic adverse (drug) experience reports quarterly for 
the first 3 years after the application is approved or the license is 
granted and annually thereafter. Compliance with these regulations is 
assessed during field inspections conducted by the Office of Regulatory 
Affairs.

    Question 20c. Do you believe new types of post-marketing studies, 
Phase IV randomized, controlled clinical trial, are indicated to 
identify adverse events and improve safety?
    Answer 20c. What you describe are not technically ``new types'' of 
post-marketing studies, but the third category described at the 
beginning of our response. As part of its approval of an initial 
NDAIBIA application or supplement under 21 CFR 314 Subpart H or 21 CFR 
601 Subpart E, FDA can require pharmaceutical firms to conduct 
additional studies during Phase IV. FDA can otherwise encourage 
companies to conduct additional studies on a case-by-case basis, but 
these requests are infrequent and again, not the primary mechanism by 
which FDA addresses safety problems. These requests reflect the need 
for additional information post approval as well as the current state 
of clinical trial science. These studies might be requested to clarify 
the product's stability under specialized conditions, its metabolism by 
special populations, and other topics. If there is a significant or 
likely safety concern at the time of an approval decision that FDA 
thinks is incompletely characterized, FDA ordinarily will not approve 
the product until that study is done.

    Question 20d. Would we be better off with a mandatory, active 
reporting system? If so, what are the barriers to the implementation of 
such a system?
    Answer 20d. If by an active reporting system, you are referring to 
what is called active surveillance systems, there are some limited 
applications for such systems. Active surveillance systems collect data 
in a deliberate and systematic fashion to see if there are health or 
safety problems. Active surveillance is done for example by CDC for 
influenza and is very useful for tracking influenza patterns across the 
Nation. The downside or barrier to implementing active surveillance 
systems is that they are much more expensive in terms of the cost of 
the data, and they are very inefficient unless you are looking for a 
specific problem, as is the case with flu. They have limited detection 
power and will likely result in many false leads. The United Kingdom's 
Drug Safety Research Unit does active surveillance of the first 10,000 
users of a new drug, where they ask but do not require the prescribers 
to report on all the side effects that their patients have after taking 
the new drug. Most of the side effects they find are the common ones 
that were known prior to marketing authorization, e.g., headache, upset 
stomach, etc.
    Besides high cost, inefficiency, and poor detection power for novel 
adverse events, there are other barriers to mandatory, active systems 
of reporting. Experience with mandatory reporting requirements for 
vaccines and medical devices shows that these do not improve either the 
quality or number of reports and may even discourage reporting. FDA 
does not have the authority to require physician or pharmacist 
reporting, though the Joint Commission on the Accreditation of 
Healthcare Organizations, State, and professional licensing authorities 
do have some role in encouraging adverse event reporting.
    In the area of active surveillance, FDA has worked with CDC to 
expand the National Electronic Injury Surveillance System in emergency 
departments to detect adverse drug events that show up in emergency 
rooms. This system appears to have value in picking up easily-
recognized and already known adverse drug events, like allergic 
reactions to drugs and low blood sugar from taking too much insulin. It 
adds to but does not replace the spontaneous adverse event reporting 
system, which is the workhorse of the FDA post-marketing safety program 
and the most common source of information used by FDA in deciding 
whether withdrawal or marketing restriction of a product is necessary.
    There are numerous barriers to the implementation of active and 
mandatory reporting systems. These include, but are not limited to, (1) 
the decentralized nature of primary health care in the United States 
(patients are seen by multiple physicians/health care providers who may 
not communicate with one another and thus may not be aware of all 
factors that have the potential to affect their patient's overall 
health); (2) the lack of a centralized, computerized health information 
system in the United States; and (3) the lack of FDA jurisdiction over 
patients and physicians, two key potential sources of adverse event 
reports. Existing disease and injury surveillance systems are all 
state-based.

    Question 21. I believe that modern health information technology is 
key to improving the FDA regulatory process. Certainly, there is 
strong, bipartisan support on the committee for introducing this 
technology into the healthcare arena, where it will afford many of the 
same advantages as it does to the business community. Dr. Crawford, 
what is your vision for information technology at the FDA? How can 
information technology improve drug safety? What additional resources 
would it take to modernize FDA's information technology systems?
    Answer 21. My vision for the future of FDA is one of 
transformation. Information technology will play a crucial role in 
helping us realize our vision for advancing the public health and 
improving FDA operations in the 215 Century. We are working to 
transform the way FDA accomplishes its vital public health mission, 
moving away from paper-based processes, toward electronic information 
systems that provide the right information to the right people at the 
right time to support rigorous analysis and well-informed decisions 
that meet the highest standards of scientific excellence and 
professional practice. We are actively engaged in developing and 
adopting international consensus standards for clinical data and e-
health records, structured product labeling, remote automated 
monitoring of regulated product manufacturing and distribution 
processes, and other technologies that will help usher in a new 
``golden age'' of food and medical product safety, security, quality, 
and innovation. Information technology will enable business process 
improvements that yield marked jumps in productivity, allowing us to 
keep pace with rising demand for services in an era of limited public 
resources. With modern information technology, FDA can continue setting 
the gold standard for food and drug regulation throughout the world.
    FDA is currently working on an agency-wide long-term plan that 
communicates our vision and some important interim milestones, and we 
hope to share with you the results of this effort this summer. We are 
also developing an FDA information technology strategic plan that will 
provide more detailed planning tools and criteria for making resource 
allocation and investment decisions in the coming years, as we move 
toward our vision. As we progress through this modernization planning 
process, we will work collaboratively with our public health partners 
in HHS and other agencies to ensure that our plans are coordinated and 
efficient. Our future requests for information technology investments 
will be driven by these long-term strategic plans.
    In the near term, our fiscal year 2006 budget request identifies 
several important information technology investments. As part of our 
requested $5 million increase for the Office of Drug Safety, we hope to 
provide increased access to a wider range of clinical, pharmacy, and 
administrative databases that will improve our post-market surveillance 
capabilities. This strategic investment would continue to strengthen 
the FDA review staff's ability to examine more effectively safety data 
that historically have been stored in separate program level 
information silos. They would then gain a more integrated perspective 
into emerging and existing regulated products that cross traditional 
and organizational boundaries. Another strategic investment is the 
consolidated data center at FDA's White Oak campus. This shared-use 
facility will serve as a catalyst to modernize our aging information 
technology systems and thereby give FDA scientists and reviewers better 
access to information that was previously stored on paper or in 
different systems.
    With the previously stated vision and our planned investments in 
information technology, FDA is focusing our current resource requests 
on the highest priorities in the near term, and we are working 
diligently on long-term plans that will provide a more comprehensive 
view of our information technology resource needs over the coming 
years.

    [Whereupon, at 11:23 a.m., the committee was adjourned.]

                                    
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