[House Hearing, 110 Congress]
[From the U.S. Government Publishing Office]


 
               ASSESSING THE SAFETY OF OUR NATION'S DRUG
                                 SUPPLY

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

                                HEARING

                               BEFORE THE

                         SUBCOMMITTEE ON HEALTH

                                 OF THE

                    COMMITTEE ON ENERGY AND COMMERCE
                        HOUSE OF REPRESENTATIVES

                       ONE HUNDRED TENTH CONGRESS

                             FIRST SESSION

                               __________

                              MAY 9, 2007

                               __________

                           Serial No. 110-43


      Printed for the use of the Committee on Energy and Commerce

                        energycommerce.house.gov


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                    COMMITTEE ON ENERGY AND COMMERCE

    JOHN D. DINGELL, Michigan,       JOE BARTON, Texas
             Chairman                    Ranking Member
HENRY A. WAXMAN, California          RALPH M. HALL, Texas
EDWARD J. MARKEY, Massachusetts      J. DENNIS HASTERT, Illinois
RICK BOUCHER, Virginia               FRED UPTON, Michigan
EDOLPHUS TOWNS, New York             CLIFF STEARNS, Florida
FRANK PALLONE, Jr., New Jersey       NATHAN DEAL, Georgia
BART GORDON, Tennessee               ED WHITFIELD, Kentucky
BOBBY L. RUSH, Illinois              BARBARA CUBIN, Wyoming
ANNA G. ESHOO, California            JOHN SHIMKUS, Illinois
BART STUPAK, Michigan                HEATHER WILSON, New Mexico
ELIOT L. ENGEL, New York             JOHN B. SHADEGG, Arizona
ALBERT R. WYNN, Maryland             CHARLES W. ``CHIP'' PICKERING, 
GENE GREEN, Texas                        Mississippi
DIANA DeGETTE, Colorado              VITO FOSSELLA, New York
    Vice Chairman                    STEVE BUYER, Indiana
LOIS CAPPS, California               GEORGE RADANOVICH, California
MIKE DOYLE, Pennsylvania             JOSEPH R. PITTS, Pennsylvania
JANE HARMAN, California              MARY BONO, California
TOM ALLEN, Maine                     GREG WALDEN, Oregon
JAN SCHAKOWSKY, Illinois             LEE TERRY, Nebraska
HILDA L. SOLIS, California           MIKE FERGUSON, New Jersey
CHARLES A. GONZALEZ, Texas           MIKE ROGERS, Michigan
JAY INSLEE, Washington               SUE WILKINS MYRICK, North Carolina
TAMMY BALDWIN, Wisconsin             JOHN SULLIVAN, Oklahoma
MIKE ROSS, Arkansas                  TIM MURPHY, Pennsylvania
DARLENE HOOLEY, Oregon               MICHAEL C. BURGESS, Texas
ANTHONY D. WEINER, New York          MARSHA BLACKBURN, Tennessee         
JIM MATHESON, Utah                   
G.K. BUTTERFIELD, North Carolina     
CHARLIE MELANCON, Louisiana          
JOHN BARROW, Georgia                 
BARON P. HILL, Indiana               

_________________________________________________________________

                           Professional Staff

 Dennis B. Fitzgibbons, Chief of 
               Staff
Gregg A. Rothschild, Chief Counsel
   Sharon E. Davis, Chief Clerk
   Bud Albright, Minority Staff 
             Director

                                  (ii)
                         Subcommittee on Health

                FRANK PALLONE, Jr., New Jersey, Chairman
HENRY A. WAXMAN, California          NATHAN DEAL, Georgia,
EDOLPHUS TOWNS, New York                 Ranking Member
BART GORDON, Tennessee               RALPH M. HALL, Texas
ANNA G. ESHOO, California            BARBARA CUBIN, Wyoming
GENE GREEN, Texas                    HEATHER WILSON, New Mexico
    Vice Chairman                    JOHN B. SHADEGG, Arizona
DIANA DeGETTE, Colorado              STEVE BUYER, Indiana
LOIS CAPPS, California               JOSEPH R. PITTS, Pennsylvania
TOM ALLEN, Maine                     MIKE FERGUSON, New Jersey
TAMMY BALDWIN, Wisconsin             MIKE ROGERS, Michigan
ELIOT L. ENGEL, New York             SUE WILKINS MYRICK, North Carolina
JAN SCHAKOWSKY, Illinois             JOHN SULLIVAN, Oklahoma
HILDA L. SOLIS, California           TIM MURPHY, Pennsylvania
MIKE ROSS, Arkansas                  MICHAEL C. BURGESS, Texas
DARLENE HOOLEY, Oregon               MARSHA BLACKBURN, Tennessee
ANTHONY D. WEINER, New York          JOE BARTON, Texas (ex officio)
JIM MATHESON, Utah
JOHN D. DINGELL, Michigan (ex 
    officio)
  
                             C O N T E N T S

                              ----------                              
                                                                   Page
Hon. Frank Pallone, Jr., a Representative in Congress from the 
  State of New Jersey, opening statement.........................     1
Hon. Nathan Deal, a Representative in Congress from the State of 
  Georgia, opening statement.....................................     3
Hon. Henry A. Waxman, a Representative in Congress from the State 
  of California, opening statement...............................     3
Hon. Lois Capps, a Representative in Congress from the State of 
  California, opening statement..................................     4
Hon. Diana DeGette, a Representative in Congress from the State 
  of Colorado, opening statement.................................     6
Hon. Joe Barton, a Representative in Congress from the State of 
  Texas, opening statement.......................................     7
Hon. John D. Dingell, a Representative in Congress from the State 
  of Michigan, opening statement.................................     8
Hon. Michael C. Burgess, a Representative in Congress from the 
  State of Texas, opening statement..............................    10
Hon. Hilda L. Solis, a Representative in Congress from the State 
  of California, opening statement...............................    11
Hon. Mike Rogers, a Representative in Congress from the State of 
  Michigan, opening statement....................................    12
Hon. Edolphus Towns, a Representative in Congress from the State 
  of New York, opening statement.................................    13
Hon, Tim Murphy, a Representative in Congress from the 
  Commonwealth of Pennsylvania, opening statement................    13
Hon. Jan Schakowsky, a Representative in Congress from the State 
  of Illinois, opening statement.................................    14
Hon. Marsha Blackburn, a Representative in Congress from the 
  State of Tennessee, opening statement..........................    15
Hon. Gene Green, a Representative in Congress from the State of 
  Texas, opening statement.......................................    16
Hon. Anna G. Eshoo, a Representative in Congress from the State 
  of California, opening statement...............................    17
Hon. Tom Allen, a Representative in Congress from the State of 
  Maine, prepared statement......................................    18
Hon. Barbara Cubin, a Representative in Congress from the State 
  of Wyoming, prepared statement.................................    18

                               Witnesses

Steven K. Galson, M.D., Director, Center for Drug Evaluation and 
  Research, Food and Drug Administration.........................    19
    Prepared statement...........................................    22
    Answers to submitted questions...............................   161
Marcia Crosse, Director, Health Care Issues, U.S. Government 
  Accountability Office..........................................    36
    Prepared statement...........................................    38
Lisa Van Syckel, Flemington, NJ..................................    78
    Prepared statement...........................................    78
Ellen Sigal, chairperson and founder, Friends of Cancer Research.    81
    Prepared statement...........................................    83
Susan Ellenberg, University of Pennsylvania School of Medicine, 
  on behalf of the Coalition for a Stronger FDA..................    87
    Prepared statement...........................................    88
Caroline Loew, senior vice-president, scientific and regulatory 
  affairs, Pharmaceutical Research and Manufacturers of America..    90
    Prepared statement...........................................    92
Diane Thompson, vice-president, public policy and communications, 
  Elizabeth Glaser Pediatric AIDS Foundation, on behalf of the 
  Alliance for Drug Safety and Access............................   122
    Prepared statement...........................................   123
John Theriault, chief security officer and vice president, global 
  security, Pfizer...............................................   125
    Prepared statement...........................................   127
Sharon Levine, M.D., associate executive director, Permanente 
  Medical Group, on behalf of the Kaiser Permanente Medical Care 
  Program........................................................   129
    Prepared statement...........................................   132
John Powers, M.D. assistant professor of medicine, the George 
  Washington University School of Medicine, and University of 
  Maryland School of Medicine....................................   143
    Prepared statement...........................................   144

                           Submitted Material

Drug Safety & Drug Efficacy Two Sides of the Same Coin...........   172


            ASSESSING THE SAFETY OF OUR NATION'S DRUG SUPPLY

                              ----------                              


                         WEDNESDAY, MAY 9, 2007

                  House of Representatives,
                            Subcommittee on Health,
                          Committee on Energy and Commerce,
                                                    Washington, DC.
    The subcommittee met, pursuant to call, at 10:00 a.m., in 
room 2123 of the Rayburn House Office Building, Hon. Frank 
Pallone, Jr. (chairman) presiding.
    Members present: Representatives Waxman, Towns, Eshoo, 
Green, DeGette, Capps, Schakowsky, Solis, Matheson, Dingell, 
Markey, Deal, Buyer, Pitts, Ferguson, Rogers, Murphy, Burgess, 
Blackburn, and Barton.
    Staff present: Ryan Long, Chad Grant, John Ford, Virgil 
Miller, Bobby Clark, Jack Maniko, Melissa Sidman, Lauren 
Bloomberg, and Nandan Kenkeremath.

OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE 
            IN CONGRESS FROM THE STATE OF NEW JERSEY

    Mr. Pallone. Today the subcommittee is holding a hearing to 
assess the safety of our Nation's drug supply, and I feel very 
strongly that today's hearing is long overdue. For far too 
long, the subcommittee has not paid enough attention, I think, 
to the issue of drug safety, despite the growing concerns that 
the health and well-being of millions of Americans may be at 
risk due to a broken and inadequate drug safety system.
    In recent years, there have been a number of revelations 
about drug safety that have shaken public confidence in the 
FDA's ability to ensure that consumers have access to safe and 
effective medications. From Vioxx to Paxil, tens of thousands 
of patients have been placed in harm's way due to the failings 
of our current drug safety system. And as a result, the 
American people have steadily begun to lose faith in the FDA. 
That should change.
    We must restore public confidence in FDA's ability to 
protect people from harmful products and to safeguard the 
public health. But first, the FDA itself must change. There are 
a number of issues we must consider as we move forward. First 
and foremost, FDA is woefully underfunded. This was 
highlighted, as you know, in the hearing that we had a couple 
weeks ago on the reauthorization of PDUFA. More money is 
necessary for FDA to carry out its responsibility to protect 
consumers from harmful drugs.
    However, it is an issue of where that money is going to 
come from. And obviously there is a lot of debate. There is 
growing concern regarding the increasing amount of user fees 
that FDA relies on to fund its budget. And as I have said 
before, if given the option, I think everyone would agree that 
FDA should be funded more, if not entirely, by annual 
appropriations. But realistically speaking, we are not in a 
place where we can't rely on user fees to help support the 
functions of the FDA.
    That is not to say that we should give the drug industry 
carte blanche on how these fees should be applied. FDA should 
have more flexibility about what functions these monies can be 
used for, such as postmarket and surveillance.
    For far too many years, the focus of FDA has been to 
approve the amount of time it takes to improve new drugs. And 
this is, of course, a direct result of previous PDUFA 
agreements in which industry provides a new revenue stream to 
FDA and in exchange establishes benchmarks for a more timely 
drug approval process.
    Unfortunately, however, this has caused an imbalance 
between the pre-approval process and the post-market monitoring 
of drugs. We have to fix this imbalance and focus more of our 
attention on what happens with drugs once they reach the 
marketplace. Assessing the risk of the drug once it is on the 
market is just as important, if not more, than before it is 
approved.
    Now, how are we going to achieve a more robust post-market 
drug safety system? Fortunately, we seem to already have many 
of the answers. First, we need to give the FDA greater 
authority and flexibility to manage the risks associated with a 
new drug once it has been approved. Currently FDA has little 
authority to control how a drug is marketed and how the risks 
and benefits are communicated to consumers.
    FDA should have more options to mitigate the risks 
consumers face from a particular drug other than pulling it off 
the market entirely. Let us give the FDA the ability to require 
label changes, should it deem them necessary. Similarly, FDA 
should have the authority to require, as a condition of 
approval, that manufacturers follow through on their 
commitments to conduct and publish phase-four trials.
    Even more important is ensuring that information about the 
clinical trials, including the results, is made public. It 
makes no sense that we would allow such information to remain 
locked away at the discretion of the industry. If my Republican 
friends are keen on transparency in the health care market, as 
they say, then let us start with full transparency of clinical 
trials. Let the consumers and their doctors decide what they 
think is safe or not based on complete information. The results 
of these clinical trials contain valuable information for 
patients and their physicians, and we should demand that they 
be made available.
    Finally, I want to voice my concern about direct-to-
consumer advertising. I realize that this is a very contentious 
issue, and I appreciate the industry and FDA's willingness to 
work out a compromise, which was included in this year's PDUFA 
proposal. However, as I said a couple of weeks ago, I am not 
certain that the new program outlined in the PDUFA proposal 
will suffice.
    The fact that the program relies on voluntary participation 
from the industry strikes me as a program with no teeth. I am 
skeptical of these advertisers and the alleged value they bring 
to consumers. We will have to look at this program further and 
ensure that consumer's best interests are being served well.
    There are many other issues that need to be discussed as we 
talk about drug safety. That is why today's hearing is an 
important one. And like I said at the beginning of my 
statement, it is long overdue that we have these hearings. I am 
looking forward to hearing from today's witnesses, and I thank 
you all for being with us and now recognize my friend from 
Georgia, Mr. Deal, for an opening.

  OPENING STATEMENT OF HON. NATHAN DEAL, A REPRESENTATIVE IN 
               CONGRESS FROM THE STATE OF GEORGIA

    Mr. Deal. Thank you, Mr. Chairman. Thank you for holding 
this hearing today on an issue that certainly will be a 
component of our discussions on other FDA-related legislation 
that comes before our committee this year. Recent incidences, 
such as the recall of Vioxx that highlighted the importance of 
FDA's role in evaluating the safety of products both pre- and 
post-market, these events undermine consumers' confidence in 
the safety of medications they are taking and remind us that, 
while drugs provide useful life-saving treatment, there are 
risks associated with any medication.
    In February 2005, the FDA announced the creation of a new 
independent drug safety oversight board to oversee the 
management of drug safety issues and provide information to 
help providers and patients about the risks and benefits of 
medicines.
    I hope that our witnesses will be able to tell us about 
some of the work this board has been doing to monitor drug 
safety in addition to the FDA's other drug safety efforts. I 
also look forward to hearing about the role of databases in 
studying drug safety. I believe one of these studies was 
instrumental in highlighting that Vioxx increased the risk of 
heart disease. Studies like these show promise and demonstrate 
some of the possibilities for the FDA make use of existing drug 
data.
    I want to thank our witnesses for their time and attendance 
today, and I look forward to your testimony as we evaluate the 
best means for ensuring patients have access to safe 
medications. Thank you, and I yield back.
    Mr. Pallone. Thank you, Mr. Deal. Mr. Waxman.

OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Mr. Waxman. Thank you, Mr. Chairman. I want to applaud you 
for holding this hearing today, for taking up the issue of drug 
safety at an opportune time. The Prescription Drug User Fee 
Act, or PDUFA, must be reauthorized this year, and everyone 
knows that in the end, it will pass. There is no realistic 
argument that it won't.
    So we have a vehicle that will move, and as recognized in 
the administration's own PDUFA proposal, this vehicle could 
serve as a means to strengthen FDA's oversight of drug safety. 
We need to ensure that FDA not only has the ability to collect 
fees that help to finance its oversight in our drug supply, but 
it also has the authority it needs to do this job well.
    There is recent and mounting evidence that FDA's ability to 
oversee drug safety is a pale shadow of its ability to review 
drugs before they are approved. We are familiar with the series 
of post-market safety problems in the past year with drugs like 
Vioxx and Ketek. They demonstrate beyond a shadow of a doubt 
that FDA's post-market drug safety oversight is in serious need 
of repair.
    The Institute of Medicine, the GAO, have examined this 
situation. Both concluded that FDA cannot protect Americans 
from unsafe drugs unless Congress provides more resources and 
more legal authorities. For example, right now, FDA cannot 
require post-market safety studies, even when FDA believes they 
are necessary to fully understand the drug's risk. FDA's only 
choice is to ask a company to perform these studies and hope 
they will agree. And in the case where the companies do commit 
to doing the studies in advance, if they don't do it, the only 
option is to take the drug off the market completely, which is 
a very serious one called a nuclear option, in fact. It is too 
tough for FDA to actually pursue.
    According to the FDA's own figures in 2006, manufacturers 
submitted only 11 percent of the 1,200 open study commitments. 
71 percent of these studies hadn't even started. The FDA also 
can't compel companies to make labeling changes after approval, 
as the case of Vioxx illustrates. FDA must haggle with 
companies, often for many months on end about the wording that 
should be used to notify the public about what are often very 
serious risks associated with taking their drugs. And 
throughout this process, the American public continues to take 
these drugs without any knowledge of these risks.
    I have my own ideas for drug safety. Congressman Markey and 
I have introduced a bill, which incorporates the 
recommendations of the IOM and GAO. It is a counterpart to the 
drug safety legislation being debated on the floor of the 
Senate this week as part of its consideration of PDUFA. H.R. 
1561 represents the blueprint for what we should be working on 
to fix the FDA's ailing drug safety system. I hope the 
committee will have an opportunity to consider it.
    Thank you, Mr. Chairman.
    Mr. Pallone. Thank you, Mr. Waxman. Mr. Buyer.
    Mr. Buyer. I will waive my time.
    Mr. Pallone. The gentlewoman from California, Mrs. Capps.

   OPENING STATEMENT OF HON. LOIS CAPPS, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Mrs. Capps. Thank you, Mr. Chairman, and thank you for 
having this hearing, as others have said. I thank our witnesses 
for being here. I know the issue of drug safety has to be front 
and center as we discuss ways to go forward with PDUFA 
reauthorization. It is vitally important for the millions of 
people who depend upon pharmaceuticals and reasonably assume 
that they will do no harm.
    FDA is charged with the responsibility to ensure that there 
are safe and effective drugs, and that is the purpose of our 
hearing today, to discuss ways to ensure that this 
responsibility is fulfilled. Drug safety must be addressed 
before clinical trials and continue not only through the 
approval process but extend to post-market activity as well.
    In the pre-approval period, we have to make sure that 
clinical trials are conducted with the highest scientific and 
ethical standards, ensure also that the members of the advisory 
committees, who make such important decisions about drug 
approvals, are free of ties to the industry.
    The FDA has taken a supposed first step in this direction. 
I understand they have proposed a regulation which prohibits 
voting advisory committee members from holding more than 
$50,000 in stock in a drug before being considered or any of 
its competitors.
    But do we really believe that goes far enough? Certainly we 
know that it hasn't yet been implemented. We must have 
confidence that drug approval decisions are based on scientific 
data, not on financial interests. As my colleague has 
mentioned, the high profile cases of Ketek and Vioxx and many 
others were fateful reminders about the importance of post-
marketing studies and data collection.
    I also hope we can discuss direct-to-consumer 
advertisements. It is a great concern to me that so many 
consumers who are patients rely on these ads and that proper 
oversight of their content does not exist. Perhaps most 
importantly, I believe we must equip the Food and Drug 
Administration with adequate resources. User fees have been 
instrumental in reducing drug approval time, but we must make 
sure that fees do not make up such a large proportion of FDA 
funding that it becomes a conflict of interest.
    So I thank you, Mr. Chairman, again for holding this 
hearing. I look forward to ways in which we can work together 
to improve drug safety. I yield back the balance of my time.
    Mr. Pallone. Thank you. Mr. Ferguson.
    Mr. Ferguson. Thank you, Mr. Chairman. I am going to waive 
my opening statement for additional time in questioning, but I 
do just want to welcome constituent and friend Lisa Van Syckel. 
She will beon the second panel today. I am delighted that she 
is here today. I know she has several folks with her, including 
Ellen Liversage and Vera Sheral and Kim Witsack also here with 
her today. And because of the many, many meetings that she and 
I have had talking about drug safety over the course of the 
last several years, I have become very involved in the 
medication guide issue. We have been doing an investigation in 
our office and working with FDA and others. So I am looking 
forward to getting into that today, and I will look forward to 
using my extra time during questioning. I yield back.
    Mr. Pallone. Thank you. Ms. DeGette. I didn't count that. I 
guess I should have. Yes, we are going to have to watch----
    Mr. Ferguson. I think I am owed a little latitude by a 
chairman from my home State.
    Mr. Pallone. I will do better in the monitoring this in the 
future. Ms. DeGette.

 OPENING STATEMENT OF HON. DIANA DEGETTE, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF COLORADO

    Ms. DeGette. Thank you, Mr. Chairman. I think it is 
important that as we prepare to mark up legislation affecting 
regulation of pharmaceuticals and biologics that we put the 
safety of patients as paramount. And so I know these drugs will 
save countless lives, but we have to do what we can to mitigate 
unintended harm.
    I really have three concerns today. The first one has been 
mentioned by several of my colleagues, and that is how we can 
make systemic changes to the FDA to make sure that they are 
really approving drugs that are safe. And our own 
investigations of Vioxx and Ketek as well as a number of other 
drugs over a period of years have shown that we really can't 
have that confidence that the safety is paramount.
    The second issue that I have is that the FDA just really 
doesn't have the resources to adequately address drug safety 
concerns. And the most PDUFA agreement provides a significant 
increase in resources for post-market surveillance, but the 
fact remains that Congress still has to provide additional 
funds.
    Also because of the drug safety problems, the American 
public has lost faith in the FDA and its ability to protect 
them from adverse effect. And this problem has been exacerbated 
by the ambiguous nature of the drug safety process. The general 
lack of transparency to the American public means that they 
don't see how decisions are made, and therefore they don't see 
why the drug companies are accountable to the FDA.
    And finally, the full Senate is currently considering 
legislation to reauthorize PDUFA as well as a seemingly endless 
array of other drugs included in it. Though watered down, the 
Senate bill includes drug reimportation. Those of you who read 
the New York Times this last weekend saw the front page article 
that should make us all think twice about that policy. 
According to that article, counterfeit drugs made in China were 
exported to Panama for sale, and they included a deadly toxin. 
Last year, 365 families reported deaths as the result of the 
tainted cough syrup and fever medication. And they think that 
that number is vastly underreported.
    Mr. Chairman, the dangers from counterfeit and contaminated 
drugs are frighteningly real, even under the current construct. 
Permitting reimportation would significantly increase the risk 
of counterfeit, misbranded and adulterated drugs that would end 
up in my constituents home. I hope we keep this in mind as we 
mark up-
    [Applause.]
    Ms. DeGette. I might have to take that back given the 
response from the other side. But seriously, I hope we keep 
this in mind as we mark up legislation on prescription drugs. 
If we have a problem with drug prices being too high in this 
country, we need to confront that problem head on and not allow 
reimportation policies that may affect the efficacy and safety 
of our drug supply in this country.
    Mr. Pallone. OK, now we have applause. Our ranking member 
of the full committee, Mr. Barton.

   OPENING STATEMENT OF HON. JOE BARTON, A REPRESENTATIVE IN 
                CONGRESS FROM THE STATE OF TEXAS

    Mr. Barton. Thank you, Mr. Chairman. It is good to have 
this hearing. I just got back from the trilateral committee 
hearing in Ways and Means where we had Ways and Means, 
Financial Services, and Energy and Commerce. Their opening 
statements will go on until about 5:00 this afternoon, I guess. 
So it is good to be here with one committee and one 
subcommittee and focus on one subject.
    We do appreciate this hearing today. When I was full 
committee chairman of this august committee, I took the issue 
of drug safety very seriously. I am glad to see that Mr. 
Dingell and Mr. Pallone are continuing this. I requested a 
Government Accountability Office review of how the FDA 
approaches issues related to drug safety. I am looking forward 
to hearing from that agency today about what steps it has taken 
to improve the safety of our drug supply.
    Where action is needed to improve drug safety, I think that 
Congress should be prepared to act. I do hope that we do it 
right instead of just in a hurry. I can testify personally that 
the development of new prescription drugs have revolutionized 
medicine and is saving lives.
    Forty years ago, a person who had a heart attack like I had 
a year and a half ago would have been given nitroglycerin, a 
pat on the back, and sent home. Now, modern pharmaceuticals can 
help prevent attacks from occurring or even reoccurring. I know 
because each morning when I get up, I take six prescription 
drugs before I begin my day.
    We must take steps to ensure that the drugs that we are 
taking are safe when they are approved and remain safe as they 
are put into commercial use. No drug can be 100 percent safe 
for every person who might take it. Even aspirin, the 
ubiquitous miracle drug that does everything from curing 
headaches to stopping heart attacks, has to be avoided by some 
people.
    No responsible authority insists on absolute 100 percent 
safety because that standard would have the reverse effect of 
increasing the likelihood that many people would suffer or even 
die because they didn't have access to that particular drug.
    As a drug used in the general population, less common side 
effects may be evident. Congress could impose Draconian new 
regulations that provide marginal benefits so that we appear to 
address the problem. What we would actually be doing in that 
case, in my opinion, is severely limiting access to life-saving 
drugs for tens of thousands or hundreds of thousands of people, 
lives that might be lost without that particular drug.
    The history of drug regulation in this country reflects a 
conscious weighing of the drug's risks versus the drug's 
benefit. If more needs to be done to bring this balance into 
equilibrium, this Congress and this committee should and must 
explore those options, but we should never lose sight that 
millions of Americans depend on these medications to preserve 
and improve their lives.
    Twenty-first century medicines must come with 21st century 
surveillance. Our health care system produces large quantities 
that can and should be used to monitor drug safety issues. We 
should have systems in place that can link up clinical data 
with prescription drug use. Pre-market clinical trials are 
useful to determine the safety and efficacy profile of a drug, 
but if rare side effects occur, they must not become known 
until after the drug has been taken by a larger population.
    It is my understanding that the FDA has begun to use 
clinical databases as a methodology to monitor safety concerns. 
I believe we should enhance that ability to tap into the 
existing health information. I am pleased that the agreement on 
Reauthorization of Prescription Drug User Fee Act will provide 
the FDA the ability to obtain access to additional drug safety 
information, including population-based epidemiological data 
and other types of observational data resources. I look forward 
to hearing from the FDA on their efforts in this area.
    I also am looking forward to hearing from the testimony of 
Mr. John Theriault who will discuss the issue of prescription 
drug counterfeiting. It is shocking and unacceptable that the 
maximum penalty for counterfeiting a prescription drug in this 
country is 3 years in prison. Three years in prison. Phony 
drugs are the ultimate bad medicine. Impurities in the 
counterfeit drugs pose dangerous consequences for patients, and 
intentionally giving a serious ill person a drug that does not 
contain the active ingredients that they think it does could 
actually be considered to be murder.
    Addressing counterfeit drugs requires public and private 
entities working together. Unfortunately, our anti-
counterfeiting drug problems are not nearly as smart as the 
counterfeiters are. A first step to address the problem would 
be for the House to pass Congressman Rogers' legislation to 
substantially increase the criminal penalties for drug 
counterfeiters.
    Second, we should look at new technologies that will allow 
us to better track these drugs in our supply system. I look 
forward to hearing from the company Pfizer about what steps 
that they are taking in this area.
    Again, Mr. Chairman, thank you for holding this hearing. I 
look forward to participating.
    Mr. Pallone. Thank you, and I will recognize the chairman 
of our full committee, Mr. Dingell.

OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF MICHIGAN

    Mr. Dingell. Mr. Chairman, thank you for holding this 
important hearing. The committee is here today to discuss the 
safety of our Nation's drug supply. And included in that is the 
competence and ability of FDA to carry out its very important 
mission.
    The question here is what does it mean to say that a drug 
is FDA approved. Good government would say that the Food and 
Drug Administration approval should be the gold standard 
throughout the world, that the drugs approved provide needed 
therapies for consumers without causing further medical 
complications or worse, death.
    Unfortunately, Food and Drug approval of pharmaceuticals as 
the gold standards has been called into question. Incidents 
highlighted by the recall of the arthritis drug Vioxx have 
created a crisis of confidence in the Food and Drug 
Administration.
    It should be observed, however, that problems with Food and 
Drug go more broadly than this. It is an agency which has 
inadequate resources, inadequate numbers of personnel, 
inadequate financial support, and inadequate ability to carry 
out its responsibility, over both drugs manufactured and food 
manufactured in this country, and over imports, something which 
has shaken my confidence in a very real way in the agency.
    I publicly express my dissatisfaction with the way in which 
Food and Drug has handled the important issue of drug safety. 
FDA's lack of transparency and recent recalls have greatly 
contributed to the loss of public confidence. The agency must 
aggressively monitor and assess safety and efficacy throughout 
the entire life cycle of a product. Simply stated, FDA must 
ensure that just as much time, resources and energies are 
invested in the aggressive post-market observation as is spent 
in pre-market trials, consultation, and meetings with the 
industry.
    Unfortunately, it appears that there is a singular lack of 
resources at Food and Drug to carry out these responsibilities 
as it is to carry out other important responsibilities of that 
agency. A recent Institute of Medicine report concluded FDA and 
the pharmaceutical industry do not consistently communicate 
safety concerns in a timely and efficient and effective manner.
    In addition to insisting on structural and resource changes 
within the agency, the country must also see to it that FDA 
continues to push for significant improvements in cultural 
changes at that agency. Public health policy is ultimately a 
human enterprise, and all facets of FDA's drug programs must 
work in a coordinated fashion for a common purpose, thereby 
ensuring consumers that the drugs they take are safe and 
effective. Again this will require a cultural change, but more 
importantly, it is going to require adequate funding and 
support for the agency which it currently lacks.
    FDA has taken steps to boost consumer confidence. In 2004, 
they introduced a new drug safety initiative that promised to 
promote a cultural of openness and enhanced oversight within 
the agency. And it has included additional drug safety 
provisions in its recent PDUFA proposal.
    The agency also asked the Institute of Medicine to evaluate 
its current system of drug safety and make recommendations for 
improvement. The Government Accountability Office, GAO, has 
also weighed in, and in 2006, released a report on FDA's 
ability to ensure a safe drug supply. The report included a 
number of recommendations. I am pleased that a representative 
from GAO is here to discuss this report. We will also want to 
discuss it with representatives of FDA and of higher officials 
in the Department of Health and Human Services.
    It is, I think, appropriate that we should appreciate these 
efforts, but it is not clear to me that they, when coupled with 
the budget shortages of the agency, are sufficient. We are here 
today to see what additional steps that Congress may need to 
take so that American citizens are protected and the confidence 
in the agency is restored.
    I appreciate this hearing, and I look forward, Mr. 
Chairman, to the testimony of our witnesses and the input of 
our members as we discuss the safety of the U.S. drug supply 
and the reasons why it is not as safe as it should be and what 
steps we will take to improve it. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you, Chairman Dingell. The gentleman 
from Texas, Mr. Burgess.

OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE 
              IN CONGRESS FROM THE STATE OF TEXAS

    Mr. Burgess. Thank you, Mr. Chairman, and frankly about the 
referenced aspirin, I guess I can't help but wonder if we were 
to send aspirin now through the Food and Drug Administration 
process if it would survive the approval studies or whether it 
would survive the post-market surveillance.
    But this is a good hearing. This is an important panel of 
witnesses. I believe that we must strive to seek a balance 
between the safety measures that we put in place, at the same 
time allowing and facilitating new drugs coming to market. I 
believe that the FDA has done a good job with the resources 
available to it, but we can make it better. And Chairman 
Dingell may be correct about the allocation of resources.
    Senator Mike Enzi from Wyoming has made a reasonable start 
to this discussion over in the other body by introducing his 
bill. His legislation would bring the risk/benefit analysis in 
at the beginning of the drug approval process. It would 
facilitate a lifetime approach to drug evaluation through the 
establishment of a drug safety oversight board.
    Senator Enzi's bill also addresses two topics that are of 
particular interest to me, the critical path initiative and the 
establishment of databases. The critical path initiative 
strikes me as having great potential to fundamentally improve 
the way that we approve new drugs by utilizing the science that 
the research has yielded. If we could make our approval process 
more personalized, more efficient, safer, and faster, than I 
certainly support this.
    In reading the materials supplied by the general 
accountability office, they raise a question what safety action 
that the FDA lacks--or rather they raised the point that the 
FDA lacks the information about what safety actions to take and 
when to take them. I believe that additional databases and data 
mining can help utilize information that is already available 
but needs to be collected properly. This can be helpful 
whatever we are examining, whether we are looking at the 
results from clinical trials or searching for adverse drug 
events through, for example, the Permanente patient population.
    Data mining and rapid learning techniques are tools that 
are available but not being used to their full potential. Mr. 
Chairman, there is lots of information out there. It is a time 
of rapid change in the medical field. Going on 
clinicaltrials.gov Web site this morning, you can see that they 
have had 143 new hits during last week alone. And that is the 
pace at which information is coming into the FDA. This deals 
with illnesses as varied as asthma and appendicitis, pulmonary 
hypertension, and magnetic therapy for depressed adolescents. 
Innovative therapies must reach the clinical applicability 
stage with greater speed, but there also has to be the 
collection of data, the utilization of that data, and the post-
marketing studies. Data collections should be available to 
arrive with greater speed and clarity for the clinician.
    Finally, I do have to agree with my colleague from Colorado 
about reimportation. If the debate is over cost, then let us be 
honest and have that debate. Don't reimport drug price controls 
from countries who refuse to participate in paying for the 
research and development of those products in the first place.
    Thank you, Mr. Chairman. I will yield back my time.
    Mr. Pallone. Thank you. The gentlewoman from California, 
Ms. Solis.

 OPENING STATEMENT OF HON. HILDA L. SOLIS, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Ms. Solis. Thank you, Mr. Chairman, and good morning. I am 
very pleased that you are having this hearing today and have an 
opportunity to talk about this important issue. Hundreds of 
millions of Americans rely on FDA's judgment regarding the 
safety of prescription drugs.
    In 2005, the number of prescriptions purchased was about 
3.6 billion, on an average, about 12.3 prescriptions per 
person. And FDA regulates daily 25 percent of gross domestic 
product and is sometimes called the largest consumer protection 
agency. It is critical that our consumers are actually being 
protected.
    Each decision made by FDA is crucial and has life or death 
consequences for many of our constituents. In the past, drug 
safety may have been taken for granted. Patients have great 
trust and faith in FDA. However, the publicity surrounding many 
several drug recalls in the Institute of Medicine's report 
``The Future of Drug Safety: Promoting and Protecting the 
Health of the Public'' shows that much work is needed to 
improve the safety of our medicines. The Institute of Medicine 
identified serious problems in monitoring drug safety and 
created numerous recommendations.
    FDA has a difficult balancing act indeed. So I am pleased 
that FDA has taken the initiative to strengthen and improve the 
drug safety efforts. We know that FDA has to deal with external 
constraints, including significant funding gaps at the Center 
for Drug Evaluation and Research. However, FDA has a 
responsibility to evaluate and address the safety of 
prescription drugs after they have reached the market.
    We must enable providers and patients to make the best 
possible decision about using medicines to improve their 
health. I have serious concerns regarding the transparency of 
the drug approval process, specifically adverse event reporting 
and the fact that FDA lacks authority to require that a 
manufacturer conduct a rigorous clinical trial to investigate 
post-market safety. Even if FDA requests a trial to be 
conducted, it has no way of enforcing the completion of that 
study. The fact that the completion rate of the post-market 
studies was less than 25 percent between 1991 and 2003 is 
disturbing.
    The Adverse Event Reporting System is not an adequate drug 
surveillance system and does not capture all the adverse drug 
events. We need greater transparency and better communication 
in order to protect American consumers.
    I thank the witnesses for coming today, and I look forward 
to hearing their recommendations, and I yield back the balance 
of my time.
    Mr. Pallone. Thank you. Mr. Rogers.

  OPENING STATEMENT OF HON. MIKE ROGERS, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF MICHIGAN

    Mr. Rogers. Thank you, Mr. Chairman. I have a long 
statement, and I would like to waive it at the end so that I 
can get more time in questions. Just kidding. If you are from 
New Jersey, you think that is funny, Mr. Chairman.
    I want to bring your attention to an article published in 
The New York Times on May 6, 2007. It highlighted an 
investigation into the global and often deadly epidemic of 
counterfeit drugs. The investigation by the Times examined how 
counterfeit glycerin, a product often used in cough syrup, 
fever medication, and injectable drugs made its way via a 
poison pipeline stretching halfway around the world.
    The counterfeit product was diethylene glycol, an 
industrial solvent and prime ingredient in antifreeze. Through 
shipping records and interviews, the counterfeit product from 
Panama was traced back through trading companies in Barcelona, 
Spain, a permitted country, I might add, under the legislation 
currently being considered--and back through Beijing, China.
    Seventy years ago, when medicines laced with diethylene 
glycol killed more than 100 people in the United States. It led 
to the passage of the toughest drug regulations of that era and 
creation of the modern Food and Drug Administration. This 
creates an interesting contrast to the current debate over the 
potential drug safety and reimportation legislation. This has 
to be a component of that discussion, Mr. Chairman.
    Last year, in Panama, 365 deaths were attributed to this 
poisoning with diethylene glycol in cough syrup. The World 
Health Organization estimates that global sales of counterfeit 
drugs were $32 billion in 2003. That is the last best year we 
have information. 10 percent of all those medicines sold 
worldwide, the value seized for counterfeit and diverted drugs 
in the United States alone was almost $200 million in 2003. And 
that was a sevenfold increase from the previous year.
    Authorities have encountered significant difficulty in 
tying deaths to the actual consumptions of fake drugs mainly 
for the reporting system that is in place today. In Canada, it 
is currently investigating the death of a British Columbia 
woman, who died apparently after taking counterfeit pills she 
ordered online from what she believed was a Canadian Internet 
pharmacy. Officials have linked the death to pills purchased 
from this alleged Canadian Internet pharmacy about a month 
before she died. Her toxicology tests revealed that the 
counterfeit pills contained dangerous high levels of heavy 
metals strontium, uranium, and lead.
    The World Health Organization estimates that 50 percent of 
the medicines purchased over the Internet from sites that 
conceal their address are counterfeit. This is a serious and 
growing problem, Mr. Chairman. The five top countries ranked 
for counterfeit incidents to the FDA are: one, China; two, 
Columbia; three, Russia; four, India; and five, the United 
States. So I have introduced H.R. 780, a counterfeit drug 
protection act to strengthen the criminal penalties against 
those who participate in the production, distribution, and sale 
of counterfeit drugs, understanding the prevalence and dangers 
of counterfeit drugs is absolutely necessary, Mr. Chairman, in 
determining the safety of prescription medications in our 
Nation. And would yield back the remainder of my time.
    Mr. Pallone. Thank you. Mr. Towns.

 OPENING STATEMENT OF HON. EDOLPHUS TOWNS, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF NEW YORK

    Mr. Towns. Thank you very much, Mr. Chairman, for having 
this very important hearing today. Making sure that drugs are 
safe means making sure that they are safe for the diverse 
segments of our population as well. That simply is not the 
case. Minority participation in clinical trials has been cut in 
half over the last decade from 12 percent to 6 percent. And 
African-Americans represent less than 8 percent of those 
enrolled in cancer clinical trials, while Hispanics make up 
just 3 percent.
    While pharmaceuticals are largely an effective means for 
addressing a wide range of health care needs, I am concerned 
that minority patients have not been adequately represented in 
many clinical trials. This means that as we seek to reauthorize 
the FDA, that we take into account the needs of diverse 
populations. To do this, we must increase the number of racial 
and ethnic minorities in clinical trials, particularly for 
diseases and conditions where there are health disparities.
    This will increase public confidence in the FDA's ability 
to ensure drug safety. We must also make sure that the FDA 
itself is diverse. In addition, data from diverse populations 
must also be included in both pre- and post-marketing reports 
on safety and effectiveness to ensure that these studies look 
like America. Mr. Chairman, if we are to serve a diverse 
America, we cannot continue a one-size-fits-all approach to the 
development of new drugs and ensuring patient safety. Thank 
you, Mr. Chairman, for bringing this critical subject before us 
today, and I look forward to the testimony coming from the 
witnesses.
    Mr. Pallone. Thank you. Mr. Murphy.

   OPENING STATEMENT OF HON. TIM MURPHY, A REPRESENTATIVE IN 
         CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA

    Mr. Murphy. Thank you, Mr. Chairman. The recent case, the 
tragedy at Virginia Tech, and actually the less publicized but 
equally problematic problems throughout our universities with 
mental health issues remind us that we have a large mental 
health problem nationwide that is not being adequately 
addressed. And when it comes to FDA and drug safety, and given 
my career as a psychologist, I want to emphasize some of the 
problems with this that I hope the FDA will address.
    Today we are scheduled to hear some rather tragic testimony 
from a mother about her daughter, about some of the problems 
she had with antidepressant medication. And I want to emphasize 
this for the FDA. That dealing with safe drugs is not just a 
matter of running clinical trials and posting more news in the 
PDA. It is also making sure that careful trials on adults and 
children and any of the population that will be using the 
medication is done, that research is ongoing, and that 
information is readily available and sent to all those who are 
prescribing the medications.
    In the example of psychiatric medications, I find it 
disturbing to note that 75 percent of psychiatric medications 
are prescribed by non-psychiatrists. Even though we also know 
that a combination of medications with regular psychotherapy 
provided by trained licensed professionals is the most helpful, 
very often what happens with patients, they are given some 
medication and have little or no additional follow-up.
    I believe it is critically important, whenever the FDA 
looks at approving drugs, they also make it absolutely clear 
under what context medication should be used, not only 
providing information on the use and side effects and regular 
and rapid updates to positions, but also making sure that 
information on the full context of treatment under which that 
medication is used is part of the prescribed regimen and not 
just the idea of handing off a pill.
    It is also essential that messages continue to go out to 
the prescribers that clear communication must be ongoing with 
the parents when dealing with the pediatric population. 
Unfortunately we have set up so many barriers where parents are 
not aware of what is happening with their children's medication 
and with treatment, we are actually contributing to the 
problems of these children, and that is wrong.
    Good health care has never been just a matter of taking a 
pill. Our culture, our whole health care system, has too often 
supported this past approach of take a pill and call me in the 
morning. We have to make sure that the FDA, in approving any 
medication, makes it absolutely clear the context that 
medication is prescribed and make sure that all involved are 
part of that communication system. And parents of the pediatric 
population, psychologists, psychiatrists, and others who are 
involved. Failure to do so will mean that more families will be 
harmed, and I hope that is one of the outcomes of what the FDA 
will be working on. Thank you.
    Mr. Pallone. Thank you. The gentlewoman from Illinois, Ms. 
Schakowsky.

 OPENING STATEMENT OF HON. JAN SCHAKOWSKY, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF ILLINOIS

    Ms. Schakowsky. Thank you, Mr. Chairman. I first want to 
associate myself with the remarks of Mr. Towns, the clinical 
trials are to look like America. I know that women weren't 
included in cardiovascular trials until women were present in 
the Congress. And so now that we are a grand number of 72, I 
was surprised to hear at one of our last hearings that still 
the clinical trials, only 25 percent are women that are being 
tested. And yet we know already that there are great 
differences, as we know with African-Americans as well when it 
comes to cardiovascular disease and others.
    I also wanted to talk about the approval process. The fact 
that it has been trimmed down from over 29 months in 1987 to 
cut in half since then is a good thing for many people who are 
facing serious illness or chronic disease. But as we move 
forward with this conversation, it is very important to 
consider the other end of this approval process, the proposed 
approval process, which is essential to the health and safety 
of our constituents. If we accelerate pre-approval procedures, 
then tracking a drug in its post-approval lifespan becomes ever 
more important.
    Relying on the current Adverse Events Reporting System, the 
AER System, is not sufficient. Not all adverse reactions are 
obvious to those who experience them. In cases like Vioxx, they 
only become apparent after months of use. Additionally a person 
won't always make the correct connection between a prescription 
drug and the side effect they are experiencing. Or they will 
fail to make any connection at all.
    Furthermore, one has to consider how often a person or 
doctor will take the time to actually report a serious side 
effect. How many adverse effects are we missing with this 
process? We need to make sure that the right mechanisms are in 
place at the FDA to deal with these adverse events information 
in an efficient, objective, scientifically sound way and that 
the reported data is accessible to those who can use it to help 
avoid further incidents down the road.
    One other concern I want to mention, we are relying on 
patients, many of whom are frail, elderly to understand 
complicated medical advisories, unclear directions issued by 
pharmaceutical manufacturers. Who is making sure that this 
information makes sense to them? Can they understand the 
relevant safety information on the drug inserts that come with 
their prescription medications? Is this information in the 
appropriate language? Are seniors and other relying on 
advertisements in the paper or able to read warnings that may 
be in four-point font? I am concerned with the dependency on 
adverse reporting to recognize post-market problems, troubled 
by the lack of oversight and authority on FDA's part to monitor 
the information on prescription drugs that is received or we 
think is received by those who need them. So I look forward to 
hearing from our witnesses, and I thank each of you for being 
here. I yield back.
    Mr. Pallone. Thank you. The gentlewoman from Tennessee, 
Mrs. Blackburn.

OPENING STATEMENT OF HON. MARSHA BLACKBURN, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF TENNESSEE

    Mrs. Blackburn. Thank you, Mr. Chairman. Thank you for the 
hearing, and I did want to say welcome to our witnesses. We do 
look forward to hearing from you, and we look forward to the 
information you are going to give us.
    According to the GAO, the FDA lacks a clear and effective 
process for decision making about and providing oversight of 
post-market drug safety issues. I have often thought it would 
be interesting if the FDA were a patient to see what kind of 
diagnosis we would provide the agency.
    The situation is exactly what my constituents complain 
about when they reference those bureaucrats in Washington, DC. 
We have two FDA offices functioning without clear guidelines 
and duplicating each other's work. And it is unfortunate that 
the Federal Government both allows and tolerates this kind of 
bureaucracy. And it is amazing that it comes at the risk of 
public safety.
    I would hope that there are some best practices that 
someone is looking at implementing. Any private sector company 
would be out of business if they ran their business like the 
FDA runs the public's business. However, our drug review system 
is not totally broken, as many would believe, and sometimes it 
is as if we are trying to scare people to death by chipping 
away at the public's trust in this drug review process that we 
have. The U.S. has the best pharmaceuticals in the world and 
will continue to ensure that all drugs are properly vetted 
using the highest safety and review standards. And I hope that 
the FDA has the institutional will to reform their process and 
work toward restoring this trust.
    While I understand the need for oversight and increased 
transparency in the FDA's drug review process, Congress should 
work toward a system with appropriate checks and balances. We 
must refrain from tactics, such as imposing a litany of 
needless regulation on the drug review system, which will 
prevent access to lifesaving drugs. Expediency, transparency, 
efficiency should be a big part of the discussion.
    As we continue to learn about drug safety issues, we must 
not forget that it is our duty to protect the public from 
unsafe drug approval and post-market review tactics.
    I am looking forward to hearing from our witnesses. Mr. 
Chairman, I thank you, and I yield back.
    Mr. Pallone. Thank you. I recognize our vice chair, Mr. 
Green.

   OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN 
                CONGRESS FROM THE STATE OF TEXAS

    Mr. Green. Thank you, Mr. Chairman, for holding this 
hearing on the safety of our drug supply. This hearing will 
complement this subcommittee's work on the Reauthorization of 
Prescription Drug User Fee Act as well as the Oversight and 
Investigation Subcommittee work on drug safety lapses at the 
FDA.
    And the O&I subcommittee has uncovered serious problems 
with the FDA's handling of Ketek, antidepressants, and, of 
course, Vioxx. These cases have shed light on the structure and 
cultural and administrative problems at the FDA with regard to 
drug safety. They also have contributed to a decline in the 
American people's confidence in the FDA's ability to ensure the 
safety of our drug supply.
    According to a Harris poll, 58 percent of Americans gave 
the FDA a negative rating when it came to public confidence, a 
number that has increased from 39 percent 2 years ago. To 
improve the public's confidence in the safety of our drug 
supply, there needs to be some big changes in the FDA. Some of 
the drug safety concerns can be addressed administratively at 
the FDA. I know that Dr. von Eshenbach has made significant 
effort to implement many of the Institute of Medicine's 
recommendations.
    To correct other problems, however, the agency needs 
expanded authority from Congress. And it is our job to give the 
FDA the resources it needs to improve drug safety. We need to 
take a serious look at the Adverse Events Recording System and 
its ability to identify adverse drug reactions following the 
drug's approval. The system is plagued with underreporting, and 
the FDA currently has a very high threshold for action. When 
taken together, these two factors unfortunately result in too 
many Americans being subject to harmful drugs for too long 
before the FDA steps in.
    While the high profile cases make the nightly news, we know 
that problems continue beyond Vioxx, Ketek, and 
antidepressants. According to the GAO, 51 percent of all 
approved drugs have had at least one serious adverse drug 
reaction that wasn't caught during the approval process. There 
is no question we should be catching more of these adverse drug 
reactions before approval, but we should also have a robust 
post-market system that is nimble enough to recognize problems 
and act quickly to correct it.
    Unfortunately, the scope that the FDA has authority to 
react is currently severely limited, and I hope that we change 
that in the PFUDA. If we are going to expand the FDA to ensure 
safety of our drug supply, they need to have the authority to 
require changes to drug labels when their scientists determine 
that black box warnings are necessary or that products should 
be restricted.
    The FDA also needs the authority to enforce post-market 
study commitments made by drug manufacturers. With 71 percent 
of post-market study commitments not even begun by drug 
manufacturers, it is clear that the FDA lacks an enforcement 
mechanism with any teeth. Otherwise, the drug sponsor wouldn't 
show such blatant disregard for their post-market commitments 
to the FDA.
    I would like to commend my colleagues, both Mr. Waxman and 
Mr. Markey for addressing many of these issues in their current 
legislation, a good portion of which is currently being 
considered on the Senate floor. I look forward to hearing from 
our witnesses on these issues and many others surrounding drug 
safety, and we appreciate their being here today. And I yield 
back my time, Mr. Chairman.
    Mr. Pallone. Thank you. Ms. Eshoo.

 OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Ms. Eshoo. Thank you, Mr. Chairman, for holding this 
important hearing. I think that the issues that we are dealing 
with in this hearing are amongst the most important for the 
American people because there isn't a person in the country 
that, on their own, on their very own, can guarantee in any 
way, shape, or form that what they are taking, what they are 
ingesting is absolutely safe. They know that they have to 
depend on really the government and its blue chip agency, the 
Food and Drug Administration for it.
    Now, we know that we have a problem, and it lies, I think, 
more in the post-marketing phase of drugs. The FDA actually 
does not have an active drug surveillance system. So I think 
now is the time. We are reauthorizing PDUFA, and we need to 
build in a process by which and an authorization, a direction 
for the FDA to actually have an active drug surveillance 
system.
    The drugs that have caused problems or high profile Vioxx 
and Ketek, first of all, the agency has to have the funding to 
do this. I think that we have gotten to a point now where there 
is an overreliance on user fees. And the Congress has to step 
up to the plate to make sure that the agency has the resources 
it needs to carry out what, I believe, we need to do, and that 
is to set up a post-marketing drug surveillance system.
    So I look forward to what the witnesses are going to inform 
us. I would like to thank publicly the IOM for the work that 
they have done on this. I think it has been useful and 
instructive to us. And I look forward to a reauthorization of 
PDUFA that is going to very clearly define the responsibilities 
for the FDA in this very particular area, as well as our 
recommendation relative to the resources for it. I think if we 
do one without the other, that it simply won't happen, and this 
is just too critical.
    So thank you, Mr. Chairman. This is important, and we have 
had, since you have taken over as the chairman of this 
subcommittee, I think the hearings that we are having are the 
hearings that really matter on the most important things that 
are challenging us in the health arena. Thank you.
    Mr. Pallone. Thank you very much. I believe we are done 
with the opening statements, and any other statements for the 
record will be accepted at this time.
    [The prepared statements of Mr. Allen and Mrs. Cubin 
follow:]

Prepared Statement of Hon. Tom Allen, a Representative in Congress from 
                           the State of Maine

    Mr. Chairman, thank you for calling for this important 
hearing to examine efforts to improve the current drug safety 
system.
    I want to commend Representatives Waxman and Markey for 
their work on this issue and for the introduction of H.R. 1561, 
the Enhancing Drug Safety and Innovation Act, which will make 
the critical changes necessary to improve our current process 
for ensuring the safety and effectiveness of prescription 
drugs.
    A pillar of U.S. policy on prescription drugs is the 
protection of the individuals who use them. Public confidence 
in our Nation's drug supply has been shaken in recent years by 
recalls of heavily marketed and widely prescribed drugs such as 
Vioxx. A new poll by Consumer Reports indicated that the vast 
majority of Americans want stronger drug safety laws and 
believe that more authority should be given to the FDA to 
protect consumers.
    The Institute of Medicine report issued last fall offered 
25 recommendations to improve the FDA's pre-approval processes. 
One of the most important recommendations, in my opinion, is 
the need for continuous safety monitoring throughout the life 
of the drug, including post-marketing surveillance.
    The study found that ``the FDA lacks the clear, unambiguous 
authority needed to enforce compliance with regulatory 
requirements and instead relies on the prospect of productive 
negations with industry.''
    This is troubling, and a clear indication that the system 
is broken.
    I look forward to working with my colleagues to address 
this and other important issues; including improving public 
access to clinical trial results and ensuring that the FDA has 
adequate staff and funding to fulfill their mission to protect 
the public health.
    I look forward to hearing the views of our distinguished 
panelists on ways to improve the current system to protect 
consumers from unsafe prescription drugs and restore their 
confidence in the FDA.
                              ----------                              


Prepared Statement of Hon. Barbara Cubin, a Representative in Congress 
                       from the State of Wyoming

    The Food and Drug Administration's safety activities are 
directly relevant to the everyday lives of every U.S. citizen. 
The 10,000 person agency is charged with monitoring roughly 
124,000 firms that manufacture or process FDA-regulated 
products, which compose roughly one-fifth of our Nation's gross 
domestic product.
    With this in mind, the notion that the public may be losing 
faith in the FDA's drug safety activities is unsettling at 
best. Over the last few years, the heavily publicized removal 
of drugs from the marketplace has cast a shadow of public doubt 
over the FDA's ability to protect the American people from 
harmful products. 64,000 seniors in Wyoming now have access to 
affordable Medicare prescription drug coverage, but this means 
little if our drug supply is not safe.
    In response to public and congressional concern, the FDA 
asked the Institute of Medicine to assess and make 
recommendations for our Nation's drug safety system, in 
addition to their own ongoing drug safety assessment. I am 
hopeful that today's testimony will help our committee 
understand both the extent of the safety reforms the FDA and 
industry have embarked upon, as well as steps that may need to 
be taken by Congress.
    I would urge my colleagues to keep in mind that the FDA is 
charged not only with assessing drug safety, but also drug 
efficacy. These two prongs of the FDA's mission are not 
mutually exclusive, and should not be separated as we consider 
legislative changes to the agency's structure and authorities.
    The agency does not just conduct risk management. It must 
also conduct risk-benefit analysis. Risk-benefit analysis can 
and should vary based on the severity of an illness and the 
availability of alternative therapies. We must consider the 
cancers and neuro-degenerative disorders for which patients 
have few, or even no, existing treatment options.
    The acceptable risk for a drug treating mild arthritis will 
not be the same as for a drug treating Alzheimer's or Lou 
Gehrig's disease. There are seriously ill patients whose access 
to innovative treatments would be jeopardized by regulatory 
overreach, now matter how good intentioned. Their voices 
deserve to heard in this debate.
    While I believe there is no one-size-fits-all regulatory 
solution for drug safety, there is no question that drug safety 
assessment should be based, to the greatest extent possible, on 
sound science.
    Perhaps the greatest room for improvement in drug safety 
lies with post approval monitoring. Rare and serious side 
effects may not emerge until after a drug has been approved 
based on clinical trial data, in particular, drugs that treat 
smaller populations.
    I hope today's panels will have suggestions for the tools 
and resources the FDA needs to conduct science-based, risk/
benefit analysis throughout the market life of a drug. The dire 
need for innovative medicines among the seriously ill does not 
start and stop with the FDA's approval time-line, nor should 
serious efforts to ensure the health and safety of the American 
people.
    Thank you Mr. Chairman. I yield back.
                              ----------                              

    Mr. Pallone.  I will turn to our witnesses and ask the two 
for the first panel would come forward if you would. Now, let 
me introduce the two of you.
    First, we have Dr. Steven Galson, who is Director of the 
Center for Drug Evaluation and Research at the Food and Drug 
Administration. And next is Dr. Marcia Crosse, Director of 
Health Care Issues at the U.S. Government Accountability 
Office. You have 5 minutes each. Your statements will be made 
part of the record, and you may, at the discretion of the 
committee, submit additional brief and pertinent statements in 
writing for inclusion in the record. And I will now recognize 
first Dr. Galson.

  STATEMENT OF STEVEN GALSON, M.D., DIRECTOR, CENTER FOR DRUG 
     EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION

    Dr. Galson. Thank you very, very much, Mr. Chairman and 
members of the committee. I am Rear Admiral Steven Galson, 
FDA's director for the Center for Drug Evaluation and Research. 
I am very pleased to be here to talk about FDA's drug safety 
program and to reemphasize our continued commitment to drug 
safety.
    As a physician, I have dedicated my career to serving 
public health. As a career medical officer in the U.S. public 
health service since 1986, I have worked in the Nation's public 
health agencies to assess scientific data and make health 
recommendations and regulatory decisions that protect and 
promote the health of the American people. In my current 
position as director of CDER, I am deeply committed to leading 
an organization that inspires the trust and confidence of the 
people we serve.
    My detailed testimony submitted for the record talks about 
the many initiatives CDER has on the way to strengthen drug 
safety. Modernizing the science of drug regulation, improving 
our internal operations, and enhancing our communications. I 
will focus my brief remarks today on describing my vision for 
the center and our vital role in protecting and promoting the 
public health with an increasingly complex health care system.
    As you know, no drug is risk-free, and FDA plays a key role 
in assuring that a drug's benefits outweigh its risks, 
beginning with our determination whether a drug can be approved 
for marketing. And if so, ensuring that is it truthfully and 
adequately labeled.
    Scientific progress is key to improving drug safety. CDER 
is meeting this challenge in many ways, including partnerships 
with outside groups who can assist us in developing new tools 
to improve safety. One example is an ongoing FDA scientific 
collaboration intended to yield better tests for toxicity than 
our current screening techniques. Such new tests would detect 
toxicity problems earlier in drug development than our current 
approaches.
    Our responsibility continues, as you know, post-marketing 
when our programs identify adverse events not previously 
brought forward. To meet this challenge, CDER has taken a 
number of steps to strengthen the science that underpins these 
regulatory decisions. These scientific activities include 
developing and incorporating new tools to assess benefit and 
risk, upgrading our adverse event reporting system, and 
expanding our database resources. One example of the work we 
are doing to support the science of post-marketing drug safety 
assessment is exploring opportunities for linking private 
sector and public sector post-marketing safety monitoring 
systems to create a nationwide medical product safety network. 
Such a system could enable better safety information about 
medical products to get to health care professionals and 
patients at the point at which they are providing and receiving 
their care.
    Communicating about marketed drugs is one of our key 
responsibilities, and health communications technology is 
rapidly evolving in this century. We too must change as this 
technology changes and improves. In this area, we have recently 
issued final guidance that describes our approach to 
communicating drug safety information, including emerging drug 
safety information to the public quickly, even if, in some 
cases, we are still evaluating this data.
    Another part of improving our approach to drug safety is to 
listen to people outside FDA for ideas. Next month, on June 25 
and 26, we will hold a public workshop to seek input from 
outside experts to discuss how risk management plans are 
working to enhance patient safety. In addition, we plan to 
establish a new advisory committee to obtain input on how to 
improve our external communications.
    Lastly, I would like to address the steps we are taking to 
affect a culture change within CDER to become the kind of 
effective, efficient and integrated center I am committed to 
leading. We are addressing tensions between our pre-approval 
and post-approval staff. We have enlisted the help of external 
experts to help to identify opportunities for improvement and 
assist us with implementation of these steps. We are examining 
ways to improve our handling and resolution of scientific 
disagreements.
    CDER has employed process improvement teams to recommend 
changes to our drug safety program. A number of their 
recommendations have already been implemented, including the 
establishment of new safety-related positions in each of our 
drug review divisions and conducting regular safety meetings 
between groups.
    We are also developing pilot projects to evaluate models of 
integrating our surveillance staff more into our drug review 
process, including having the staff participate in new drug 
reviews. We are firmly committed to ensuring that our 
surveillance staff have a strong voice pre- and post-marketing 
in safety decisions.
    In conclusion, CDER's mission is to ensure that Americans 
have access to safe and effective drugs. Toward that end, our 
regulatory decisions must be based on sound science, applied 
with consistency and integrity. My personal commitment is to 
ensure that these decisions are informed by diverse points of 
view and vigorous academic debate.
    We are committed to creating a comprehensive, systematic 
approach to improving the drug safety system, as quickly and 
efficiently as available resources allow. As always, we value 
input from Congress, the public, and the medical community as 
we develop and refine these drug safety initiatives.
    Thank you for the opportunity to testify in front of the 
committee today, and I am happy to respond to questions after 
the next person. Thank you.
    [The prepared statement of Dr. Galson follows:]

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    Mr. Pallone. Thank you, Doctor. Am I supposed to refer to 
you as Admiral or Doctor?
    Dr. Galson. Either.
    Mr. Pallone. Well, I guess we will stick with Doctor, I 
guess. And, Dr. Crosse, If you would give us your statement, 
thank you.

STATEMENT OF MARCIA CROSSE, DIRECTOR, HEALTH CARE ISSUES, U.S. 
                GOVERNMENT ACCOUNTABILITY OFFICE

    Ms. Crosse. Mr. Chairman and members of the subcommittee, I 
am pleased to be here today as you examine the safety of the 
drug supply. My remarks today are based on GAO's March 2006 
report on FDA's process for decision making regarding post-
market drug safety and on steps FDA has taken that respond to 
the recommendations we made in that report.
    Our work focused on two FDA offices that are involved in 
post-market drug safety: the Office of New Drugs, OND, and the 
Office of Drug Safety, ODS, which has since been renamed the 
Office of Surveillance and Epidemiology. Consistent with our 
report, I am referring to this office as ODS.
    As we reported in March 2006, we found that FDA lacked a 
clear and effective process for making decisions about post-
market drug safety issues. We found a lack of clarity about how 
decisions were made and about organizational roles. There was 
insufficient oversight by management. There were significant 
data constraints, and the agency lacked sufficient resources 
and authority to effectively ensure the safety of marketed 
drugs.
    The decision-making process for post-market drug safety is 
complex, involving input from a variety of FDA staff, drug 
sponsors, the public, and many other information sources. 
Central to the process is the iterative interaction between OND 
and ODS, and many of the problems we identified derived from 
the ways these two offices managed their drug safety 
responsibilities. In particular, there was a lack of criteria 
for determining what safety actions to take and when to take 
them, which contributed to disagreements over decisions about 
post-market safety.
    We found that insufficient communication between ODS and 
OND was an ongoing concern and hindered the decision-making 
process. For example, ODS did not always know how or whether 
OND had responded to safety analyses and recommendations for 
safety actions. ODS management did not systematically track 
information about the recommendations its staff made and OND's 
response. This limited the ability of ODS management to ensure 
that safety concerns were resolved in a timely manner.
    Moreover, FDA faced data constraints that contributed to 
the difficulty in making post-market safety decisions. FDA's 
access to post-market clinical trial and observational data is 
limited. FDA does not have authority to require that a drug 
sponsor conduct a study for the purpose of investigating a 
specific post-market safety concern.
    In the absence of such authority, FDA has relied on drug 
sponsors voluntarily agreeing to conduct these studies. 
However, as we heard, these studies have not consistently been 
completed. FDA was also limited in the resources it had 
available to obtain data from outside sources. Annual funding 
for this program was less than $1 million a year for 2002 
through 2005 and was $1.6 million in 2006, which allowed for 
four data contracts.
    Today, just over a year after our report was issued, FDA 
has begun to take steps that could address the goals of three 
of our four recommendations to the agency. First, we 
recommended that FDA systematically track post-market drug 
safety issues, and the agency is in the process of implementing 
a tracking system.
    Second, we recommended that FDA revise and implement its 
draft policy on the decision-making process for major post-
market safety actions. And FDA has made revisions to, but not 
finalized, its draft policy.
    Third, we recommended that FDA clarify ODS's role in 
scientific advisory committees, and the agency is developing, 
but has not finalized, guidance to clarify their role.
    And fourth, we recommended that FDA improve its process to 
resolve internal disagreements, but FDA has not taken action in 
response to this recommendation.
    In addition, we suggested in our 2006 report that Congress 
consider expanding FDA's authority to require drug sponsors to 
conduct post-market studies as needed to collect additional 
data on drug safety concerns.
    In conclusion, while FDA has taken positive steps, its 
actions are not yet fully implemented, so it is too soon to 
evaluate their effectiveness in addressing these problems. Most 
importantly, the agency needs additional resources and 
authority to be able to fully address the range of post-market 
drug safety concerns.
    Mr. Chairman, this concludes my prepared remarks. I would 
be happy to respond to questions that you or other members of 
the subcommittee may have.
    [The prepared statement of Ms. Crosse follows:]

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    Mr. Pallone. Thank you, Dr. Crosse, and we will start with 
the questions. I will recognize myself for 5 minutes, and I 
wanted to ask these questions of Dr. Galson.
    In your testimony, you talked about all the things that FDA 
is doing in response to the IOM report. For example, you cite 
steps you have taken to improve communications and information 
flows as well as improve operations and management, especially 
between the Office of Surveillance and Epidemiology and the 
Office of New Drug. And I think these are positive steps that 
FDA has taken to reform itself administratively.
    But as you know, there are some recommendations made by the 
IOM report that FDA can't do administratively. And I would like 
to know where the administration might stand on some of these 
recommendations. It is important for us to know where the 
administration stands as we move forward with reforming our 
drug safety system and whatever legislation we are going to put 
forward.
    So I have three questions. Let me begin with the clinical 
trials. Does the administration agree with the IOM report that 
Congress should require industry sponsors to register in a 
timely manner at clinicaltrials.gov, at a minimum, all phase 
two through phase four clinical trials wherever they may have 
been conducted if data from the trials are intended to be 
submitted to the FDA as part a MBA, SMBA or to fulfill a post-
market commitment? This goes on. Why or why not? And if 
Congress were to include this in our drug safety reform 
package, do you know whether or not the administration would 
object? That is my first question.
    Dr. Galson. Yes, as you know, provisions changing the way 
that we register and require registration of clinical trials 
has been part of the debate and the discussions going on in the 
Senate. And we are very actively participating in providing 
technical assistance to those provisions, and it has changed as 
time has gone by. We have supported some and not supported 
others, so we look forward to continuing the work----
    Mr. Pallone. I haven't necessarily followed the Senate. 
Sometimes we take pride in not following the Senate. Do you 
just want to comment, as best you can, on what you have been 
saying over there in this regard?
    Dr. Galson. We are very much in favor with providing as 
much transparency as possible, concerning clinical trials that 
are underway. There has been a huge amount of progress made 
over time in getting more of these trials registered, and I am 
sure you are going to hear more about this from the 
pharmaceutical representatives that are up here. But if you 
look on that Internet site now, there is a lot more information 
on there than it used to be, and we are in favor of that.
    Mr. Pallone. Well, what about the mandate though, the 
mandatory aspect?
    Dr. Galson. With regard to the specific provisions, we will 
continue to discuss that with staff, and the administration 
hasn't taken a firm position on exactly where we stand on each 
one of those provisions.
    Mr. Pallone. OK. Well, let me go to No. 2. The IOM 
recommended that Congress ensure that the FDA has the ability 
to require such post-marketing risk assessment and risk 
management programs as needed to monitor and ensure safe use of 
drug products. They go on to recommend that FDA should have the 
ability to impose these conditions before and after approval of 
a new drug, as well as having increased authority and better 
enforcement tools, such as fines, injunctions, and withdrawal 
of approval to ensure compliance by drug sponsors. Are these 
recommendations something that the administration would 
support, and again why or why not with regard to the risk 
management assessment?
    Dr. Galson. Thank you. As you know, I am sure, there are 
risk management plans that are currently part of approval of a 
number of drugs that are on the market, and we thought them 
through very carefully. And after the drugs are on the market, 
we evaluate those plans to see whether they are working. This 
is another area we have been very active providing technical 
assistance to the Senate and other Members of Congress that are 
interested in talking about this. And we think when there are 
drugs that have special risks, they do require special 
attention and special risk management plans for the drugs to be 
approved and for us to carefully follow up afterwards.
    Mr. Pallone. But again in those cases, you have mentioned 
special cases, would you think the FDA should have the ability 
to require the risk assessment and the risk management in those 
cases?
    Dr. Galson. We don't feel comfortable approving drugs that 
have special risks, unless there is a way to manage that risk. 
And it is very much on a case-by-case basis that we make that 
assessment. We are concerned about a one-size-fits-all approach 
in the discussions that we have had with the Senate on this 
provision because the work is very time consuming for our 
staff. And we want the ability to focus our attention on the 
most pressing public health problems. So, in general, we 
haven't favored a one-size-fits-all approach but our ability to 
make a case-by-case assessment. And that could include, in some 
cases, being able to make sure that some studies get done.
    Mr. Pallone. OK, I have to ask one more question only 
because I didn't get a chance last time. This is about the new 
DTC user fee program that was included in PDUFA Four Proposal. 
That was negotiated between the FDA and industry. I wanted to 
ask this at the PDUFA hearing, but I ran out of time, and again 
I am running out of time. What assurances do we have that drug 
companies would actually participate in this new program, given 
that it remains voluntary? And would the administration support 
a program that requires all advertisements for new drugs be 
reviewed by the FDA?
    Dr. Galson. Again, this is a complex regulatory and legal 
area, and as you may be aware, there are a large number of 
television ads and, of course, even much larger number of 
printed materials that are produced by the pharmaceutical 
industry. And we have a fairly modest staff that is able to 
review those as it is. So again we are concerned that if we are 
asked to review more materials that we have adequate ability to 
do that, and that has been a challenge between the resources 
and the number of products that have come in.
    What this new program does is give us additional staff so 
that we can do a lot more comprehensive job of looking at this 
particular subset as they come in. And we are very, very 
interested in making sure that they are truthful and they are 
not misleading. And I suspect that the industry is interested 
in that as well.
    Mr. Pallone. So it is a question of money as always. All 
right, thank you very much. I yield to the gentleman from 
Georgia, Mr. Deal.
    Mr. Deal. Thank you. One of the issues that has come up 
before this subcommittee on other hearings as it relates to 
approval of products has been the question of where 
intellectual property rights become an impediment to making 
information more available.
    With regard to clinical trials, both pre-approval and post-
approval, one of the discussions has been to make more 
information about those clinical trials available to the 
public. Are intellectual property rights one of the constraints 
that you encounter in those environments? And if so, would you 
elaborate on that?
    Dr. Galson. Absolutely. One of the challenges in all the 
work that we do is having our scientists able to look at all 
the vast information that is available concerning products. We 
digest this. We evaluate it. We sometimes debate it, and in the 
end, we come out with assessments and communication that helps 
both practitioners and patients make the right decisions about 
risk and benefit.
    Putting every single piece of information that may be in 
that drug company application down to the patient level does 
raise intellectual property issues. And we are obligated by our 
laws to protect the intellectual property, and I am not sure 
that it would really benefit patients as well because they 
don't want the undigested data. They want to know what is FDA's 
assessment of this data.
    An additional point on that is that we do think very 
carefully about patients who need new products, patients who 
have cancer and other chronic conditions. And we don't want to 
do anything that is going to stand in the way of getting those 
products through the development process and evaluated by us in 
making those appropriate products available.
    Mr. Deal. One of the tools for post-market determinations 
and safety, of course, is in mining data that may be available. 
To what extent has the FDA utilized whatever resources, if any, 
might exist in mining data collected by CMS, since they have a 
huge bank of data? Has there been any correlation between the 
two agencies in that regard?
    Dr. Galson. Yes, there has. As you know and you have heard, 
some of the statements that you all have made have indicated 
the very, very exciting frontier really in drug safety--our 
ability to look at large data sets as they are being developed 
specifically, electronic medical records, more records from 
these larger payer databases, such as CMS. And as you all are 
very, very aware, the new provisions in Medicare drug benefit 
are going to make a lot more data available in the Medicare 
system that will allow us to link eventually medical outcomes 
with the drugs that are prescribed.
    And to prepare for that very optimistic future of being 
able to use more of this data, we have been engaged in an 
interaction with the Medicare program, looking at the existing 
data to try to see how can we work with that and learn lessons 
with that interaction. We have been working with our sister 
agency, AHRQ as well, and I just got a briefing on this earlier 
in the week. And we are making some good progress and hopefully 
will learn some lessons that will allow us to move forward as 
we get more funds from Congress to be able to use this data and 
hire our staff so we are prepared to mine any available data 
sets that are valuable for patients.
    Mr. Deal. Dr. Crosse, have you had the opportunity to look 
at what other countries are doing on post-market surveillance 
of drugs, and how does that compare with what we are doing in 
the United States?
    Ms. Crosse. Sir, I am afraid we have not done any recent 
work at all looking at drug safety systems in other countries. 
As you know, there are a number of differences in the review 
and approval process in those countries and also in the kinds 
of data that may be available to them because of the national 
health systems they have. But we have not done any recent 
reviews that would help you on that.
    Mr. Deal. Dr. Galson, with regard to imported drugs, does 
the law, as it is currently written, in your opinion, give FDA 
sufficient authority to deal with drugs that are actually 
manufactured in other countries? What are the limitations that 
you incur in dealing with those imported drugs?
    Dr. Galson. Right. I assume you mean the legally imported 
drugs that are part of our current system, and there is a 
significant portion of the drug supply that is currently 
manufactured by some of the same companies that are household 
names, but they happen to be manufactured overseas.
    All of our requirements for drug approval generally apply 
for drugs that are imported, as they do here. So we go 
overseas, and we inspect foreign manufacturing facilities when 
those companies are importing their product to the United 
States. When clinical trials are done overseas and those 
clinical trials are used in our application process, we go 
overseas and inspect them. So we have good authorities to do 
that.
    Mr. Pallone. Thank you. Mr. Waxman.
    Mr. Waxman. Thank you, Mr. Chairman. Dr. Galson, if you 
look at the drugs where there have been problems or drugs that 
have been withdrawn from the market, it looks like a pattern 
where the risks appeared before approval, and the agency got 
caught off guard. To fully address this trend, I think it is 
clear you need some help from Congress. You need more 
resources. You need more authorities. But within the confines 
of FDA's current authorities and resources, what are you going 
to do to fix this problem?
    Dr. Galson. That is a very challenging issue, and I think 
the first thing is we have to be very wary about looking 
backwards and trying to figure out what we may have done wrong 
in the past when the situation was very different back when you 
were looking at data initially, but your point is well taken. 
And I think the real future of improvements in drug safety lie 
in scientific areas, and we are very invested in that and our 
critical path initiative and talking to many of you working on 
projects with not just the industry but also with academic 
groups and non-profit organizations to try to make sure that 
the information that we are getting before approval gives us 
the best possible data so that we do a better job of being able 
to predict which drugs are going to work and which drugs are 
going to cause adverse events in other people. And so that 10 
years down the road, we will be able to stand on our laurels 
and say that these sort of surprises after approval have been 
avoided. Now, we do sometimes get signals before a drug is 
approved, as you said, that there may be a safety issue. And 
each time we see that, based on clinical trial data, we look 
carefully into that, and we try to make an assessment about 
whether that signal is going to result in a problem post-
approval. The way to do a better job of that and to avoid what 
you are pointing out is better techniques, techniques like 
pharmacogenomics that will allow us to understand better 
individual differences between patients.
    Mr. Waxman. In the meantime, there are problems that are 
discovered after the drug has already been approved. FDA asks 
the manufacturer if they would be willing to do a drug 
surveillance after approval. And especially if you have those 
signals, you want the manufacturer to do that because you think 
there may be a problem down the road. When FDA identifies, 
after a post-market survey, a need to change the drug's label, 
including adding a black box warning, can you describe the 
process FDA uses to compel a drug company to make a change? Can 
you compel a drug company to make that change?
    Dr. Galson. We feel pretty strongly that when we need a 
black box, or we feel like a drug has to be labeled better, 
either with a black box or another kind of warning for the drug 
to stay on the market--we have a very good process of sitting 
down with the company and saying look, there is this new 
information that has come out. We are really not comfortable--
--
    Mr. Waxman. When you negotiate in this process with the 
company, that can take a long time, can't it?
    Dr. Galson. We are committed to reducing that time, and it 
has been reduced. And the other thing that we are doing related 
to that is that if there is not agreement there, we will go 
ahead--and we have done this in numerous cases over the last 
couple years. We will go ahead and put that information out 
without discussing it with the company. We will put out patient 
or physician information sheets. We will issue a public health 
advisory.
    Mr. Waxman. But how about that label, even a black box 
label, if the company refuses as you are negotiating, and it 
takes months to negotiate. Meanwhile the public is unaware of 
these problems. If the company refuses to make the labeling 
change that FDA believes is necessary, what are your options? 
Isn't it just simply to take the drug off the market?
    Dr. Galson. We could take the drug off the market, but we 
push the companies, and in general, they respond. It doesn't 
take months, and once we say we are going to go out and put 
this information in the public realm, whether or not you move 
quickly enough, they usually move.
    Mr. Waxman. Dr. Crosse, from what Dr. Galson has told us, 
it seems like he feels comfortable with the situation. Yet you 
made a recommendation that Congress provide FDA with the 
authority to require post-market studies and to be able to put 
these labels on and to insist that these studies be done.
    Ms. Crosse. Yes, sir. The information that we have reviewed 
over a number of years has found that it can be a lengthy 
process. I think it is a very positive step that FDA is now 
taking to more publicly notify physicians and individual 
patients of concerns that have arisen. In the past, that was 
not their general practice. And so I do think that that is a 
positive step that the agency is taking to put the information 
out publicly if the company is not moving expeditiously to make 
these changes.
    But our understanding is that the FDA's options are limited 
if the company is not cooperating. And while I agree that 
pressure can be brought to bear, and making this information 
public helps to bring that pressure, still the options 
available are quite limited if FDA feels that there is a 
positive benefit of this drug and that there are patients who 
need to continue to be able to receive it, and they don't 
therefore want to enforce the withdrawal from the market.
    Mr. Waxman. Just a last comment. I know my time is up, but 
I am in a situation now where I am chairman of the Oversight 
Committee, try to get information to conduct investigations. 
But knowing that I have the authority to issue a subpoena 
doesn't mean I have to issue subpoenas. But it does mean that 
those who have to deal with me are more forthcoming. I would 
rather have FDA be able to deal from a position of strength 
rather than pleading for information, which they need and ought 
to have in order to protect the public health and to make sure 
the public is aware of the problems once they are discovered.
    Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. Mr. Barton.
    Mr. Barton. Thank you, Mr. Chairman. Back in August 2007, 
Mr. Whitfield and I wrote a letter to the Department of 
Justice, asking for them to review current law in terms of FDA 
authority with respect to imports of drugs both legally and 
illegally into this country. And their response back to us was 
this past December. And in that letter, the Assistant Attorney 
General, a Mr. Klinger, said that they, the Department of 
Justice, would support a change in the Food, Drug, and Cosmetic 
Act that would make sure that that Act gave the FDA explicit 
jurisdiction over conduct that occurs outside the United States 
for drug products that are subject to the Food, Drug, and 
Cosmetic Act when they are imported into the United States. I 
would assume that the FDA supports that. Is that correct?
    Dr. Galson. Yes, we do, as well as stiffer fines in those 
circumstances.
    Mr. Barton. And if we did give this authority, this 
explicit authority, how would the FDA and would that give the 
FDA the authority to inspect facilities overseas on a random, 
surprise basis like you have here in the United States? My 
understanding is when you inspect a pharmaceutical factory in 
China, you have to get permission before the fact and they 
actually announce sometimes 2 to 3 months in advance so that 
the day you show up, everything is sparkling clean and smiley-
faced.
    Dr. Galson. I am not an expert at international comparative 
regulatory law; however, it is very important that we are able 
to go into foreign factories. The current situation is we do 
work with foreign countries, governments, when we make these 
visits. Even to get into many countries, they have to be aware 
that FDA officials are coming in.
    On the other hand, we do do a lot of these inspections, and 
we send teams over, and they successfully inspect and identify 
problems. And those problems are addressed or we move forward 
to take the next step.
    Mr. Barton. In the United States, you can just show up and 
flash the badge, so to speak, and do the inspection. Isn't that 
correct?
    Dr. Galson. That is correct.
    Mr. Barton. But overseas, you can't do that. Is there any 
country that you can inspect as you do here in the United 
States? Or do you have to pre-clear it?
    Dr. Galson. I am happy to look into that to see whether 
there are any countries where we have the capacity to do that 
and get back to you.
    Mr. Barton. And on counterfeit drugs, what is the current 
status of trying to prevent the counterfeit drugs in terms of 
number of inspectors and things like that?
    Dr. Galson. We do focus some resources on counterfeit 
drugs, and we are very concerned about this. We work with 
pharmacies, with States, to move forward when we identify 
problems and to make sure that we have an open policy wherein 
people hear about counterfeit drugs. They are reported to us. 
We investigate it. We are concerned about counterfeits that are 
available on the Internet. And of course, if there are more 
drug imports coming in, that would be something we have to 
focus on more.
    Mr. Barton. Dr. Crosse, would you like to comment on any 
suggestions for combating counterfeit drugs?
    Ms. Crosse. Well, we had undertaken a review about 2\1/2\ 
years ago of Internet pharmacies, and we placed a number of 
orders from pharmacies over the Internet, both in the United 
States and in Canada and other foreign countries. We found a 
number of problems including counterfeit drugs. Some of the 
samples that we received were counterfeit medications, and a 
very small sample of drugs we purchased, out of about 63 
purchases, we have four counterfeit drugs. And we had other 
drugs that were provided without any instructions for use, 
without appropriate labels or warning information or directions 
on how many tablets to take and at what interval. There are a 
number of difficulties that we identified in that review in the 
use of foreign pharmacies.
    Mr. Barton. But four of the 63 purchases were counterfeit?
    Ms. Crosse. Yes, sir.
    Mr. Barton. That is pretty amazing. Well, Mr. Chairman, my 
time has expired, but I hope that is something that, as we move 
forward, this whole issue of counterfeiting is, I think, a very 
great concern and based on what Dr. Crosse just said, I was 
assuming it was maybe 1 percent, 1 out of 100. But 4 out of 60 
is--what is that--about 8 percent, something like that. So that 
is non-trivial. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. The gentlewoman from Colorado, Ms. 
DeGette.
    Ms. DeGette. Thank you, Mr. Chairman. Following up a little 
bit on Mr. Barton's question. Dr. Crosse, I think the time is 
now to start looking at these counterfeit drugs because we had 
some hearings in the Oversight Investigation subcommittee in 
the last Congress where customs is just seizing all kinds of 
these drugs coming in, and as Dr. Crosse described, they have 
no description what they are and when they are tested. Some of 
the drugs from South America were actually yellow paint, dyed 
paint. And there is no indication if the proper climate 
controls or other kinds of controls have been established.
    And so I guess my question to you is what mechanisms do we 
currently have in the U.S. to expose counterfeit drugs before 
they reach a U.S. consumer? Do we have enough laws to do that, 
and maybe more importantly do we have enough resources to do 
that?
    Dr. Galson. Let me talk about a couple of the things that 
we have been doing. We have been focusing on this for quite a 
few years, but there is no doubt that this is something that 
probably needs more attention into the future. And you only 
have to open up the newspaper to see some of the problems that 
have occurred.
    One of the things that we did is we were hearing that it 
was cumbersome for people to figure out how to report when they 
found a counterfeit or when they heard about a counterfeit. So 
we modified our standard adverse event reporting form that 
comes in to make it easier for people to explicitly say when 
they find a counterfeit.
    Ms. DeGette. When did you modify that report?
    Dr. Galson. I believe it was 2005.
    Ms. DeGette. And have you noticed an increased number of 
reports coming in?
    Dr. Galson. We haven't, but that probably reflects the fact 
that the adverse reporting system is not that sensitive.
    Ms. DeGette. It has probably been the least effective way, 
waiting until the drug actually gets to the consumer. And then 
they have to make a report.
    Dr. Galson. Absolutely.
    Ms. DeGette. So what else are you doing?
    Dr. Galson. Well, one of the things that does concern us, 
and we are going out with education efforts about this, is the 
increase of number of drugs that have been purchased over the 
Internet and the proliferation of Internet pharmacies and 
people thinking that this is an answer to getting their drugs. 
And clearly that makes it easier for people to get. Even if the 
drug is advertised that it is ``from Canada'' it may come from 
somewhere else.
    Ms. DeGette. I know that, so what are those efforts?
    Dr. Galson. Those efforts are trying to communicate with 
people and with pharmacists and.
    Ms. DeGette. And have those born fruit in finding 
additional counterfeit drugs?
    Dr. Galson. I don't think our detection of counterfeits is 
robust enough to really know whether----
    Ms. DeGette. And so what do we need to do?
    Dr. Galson. Yes. Well, I think one thing is resources, and 
we do expect to be getting more resources under PDUFA that we 
will be able to put out in the field to detect more of these. 
As you know, there is just a sea of drugs coming in through the 
mail and through the borders. And it is a challenge for us to 
open up every single package. But there is more that we could 
do, and we will be focusing----
    Ms. DeGette. Dr. Crosse, do you have any opinions what we 
could do to beef up our detection of counterfeit drugs coming 
in?
    Ms. Crosse. I think it is a very difficult issue for FDA 
alone to face because a lot of the drugs that are coming from 
the Internet pharmacies from overseas are coming directly to 
consumers.
    Ms. DeGette. Right.
    Ms. Crosse. They are not passing through the normal drug 
supply chain in this country. And so, there really is very 
little, short of intercepting packages at the border, that FDA, 
I think, can do beyond these kinds of steps to monitor the 
pharmacies that are on the Internet. We found Web sites popping 
up and closing in a matter of days when we were undertaking our 
work. It is very difficult to track all of the Web sites that 
may be available to sell some of these drugs.
    Ms. DeGette. So really consumer education will be 
important?
    Ms. Crosse. That is one of the steps, and certainly, I 
think there are some technological solutions that are being 
proposed to try to put in some sorts of tracers and other kind 
of tracking information that would allow the drug supply system 
to more adequately monitor when the drugs that are coming in 
are authentic.
    Ms. DeGette. Now, do you think that this problem we have 
got right now would be exacerbated if more reimportation was 
allowed by Congress?
    Ms. Crosse. I am not aware of what the specifics are for 
proposals that are under consideration for the limits that we 
placed on that importation. In the small review that we did, we 
did not find problems with the drugs we purchased from Canadian 
pharmacies. But, as Dr. Galson has indicated, one cannot always 
determine just from looking at a Web site whether a site that 
identifies itself as being Canadian actually is.
    Ms. DeGette. Dr. Galson.
    Dr. Galson. Yes. A couple points. The first is just 
following up on the technological solution. We do think that 
there are some technological steps, and these radio frequency 
identification tags, RFID, is one of the technologies that has 
been identified that can mark packages so they can be tracked 
and traced more efficiently. We have issued guidance on the use 
of this technology, and we are going to be putting more effort 
towards that. So that is a technological solution. On your 
question about importation, I don't think there is any question 
that if there are more drugs coming into the country from other 
places, it is going to be more difficult. And I think about my 
challenge in being responsible for all the currently legally 
imported drugs. If the number of manufacturing facilities and 
companies doubles or triples with drugs coming in from a lot 
more countries or from countries that are difficult for us to 
inspect, there is no question that it is going to be more of a 
challenge to detect these counterfeits and go out and inspect 
the sources.
    Ms. DeGette. Thank you.
    Mr. Pallone. Thank you. The gentleman from Indiana, Mr. 
Buyer.
    Mr. Buyer. I want to thank Ms. DeGette. I welcome her to 
this issue. This is a pretty strong concern of members on this 
committee. We reauthorized PDUFA, and we are now examining the 
post-market review. I don't understand how a manufacturer out 
there can do the very best they can, they are responsive to 
these reports of adverse effects that are being sent on, yet 
their ability to police the counterfeit--it is almost as if we 
have a system--so what do we have in America? We have got this 
system, and we have a leak. And the strength of the policing of 
that leak is going to come from who? Those whom have the most 
at stake. So it is going to come from, first would be the 
manufacturers themselves. They are going to protect because 
they have liability on the line. Second it is you, us, the 
Federal Government because we have given this assurance to the 
American people that we are going to have a closed system with 
regard to our drug supply, and that it is that FDA stamp of 
approval. It has got to mean something. So I think it is pretty 
clear. An unapproved FDA drug lacks your assurances of safety, 
effectiveness, quality, and purity. Now, if the FDA cannot 
assure the safety and efficacy of a drug product line because 
you can't gain access to the manufacturing process, we have 
serious problems.
    So if that drug is manufactured in a foreign country and 
you gain access to that manufacturing process, there is not a 
problem there, and you do that all the time. In the mid 1990's, 
we had this political escalation and the attacks of our 
pharmaceutical manufacturers and as if well, just run off to 
Canada and get your drugs. And this reimportation issue began 
to erupt.
    And then we see this increase in the volume of adverse 
event reports. So my question is do you know of any correlation 
between this increase in adverse reports and the amount of FDA 
unapproved drugs that are finding access into our country. Is 
there a correlation between this? Do you know?
    Dr. Galson. We are not aware of a correlation between those 
two. There are a number of hypothesized explanations for why 
that number is increased. One is there are more drugs out 
there. More people are taking more prescription products. If 
you look over time at the number of prescription drugs taken 
per person in the United States, it has gone up. And similarly 
there is absolutely more awareness of drug adverse events. I am 
not at all trying to say that there is no correlation, but I 
wouldn't want to blame that increase entirely on this issue.
    Mr. Buyer. All right, let us bubbacize this. So last night, 
I picked up the phone and I called an internist, Dr. Lauren 
McClure in Muncie, Indiana, OK. Now, she is dealing with a 
problem because the mayor of Muncie, he is going to reduce the 
drug costs to the city of Muncie, Indiana. So what does he do? 
He instructs the city employees and the workers and the 
retirees to do what? Get their drugs from Canada. Now, as a 
practicing internist, she has a challenge. She will do her 
diagnosis, and in her prognosis, she will prescribe particular 
drugs. And she doesn't know what is working and what is not 
working and why.
    So here we have someone that we as a country have invested 
greatly into this medical expertise, and it is a scratch of the 
head. She doesn't know whether the drugs the person is taking 
are FDA-approved drugs, or are these the counterfeit drugs? And 
so she has been challenged as she continues on. Now, this 
happens to be a doctor that actually knows that a patient is 
gaining access through Canadian pharmacies. How about if the 
docs all across the country, you prescribe a drug, and they 
don't even realize that their patients are out there. Ma'am, 
when you said I don't have a problem with Canadian pharmacies, 
what about these Canadian Internet sites? People think that 
they are approved, and many of them are unapproved, and they 
are the flow, the pathways of these illegal substances.
    Now, our challenge is the person may not get better and die 
if it doesn't get reported. Those who say well, let us go to 
reimportation. People aren't dying from reimportation. You 
never know. So now if we want to make sure that we really 
understand about a drug that is out there, what do we in 
Congress need to do here? Do we have to mandate that doctors 
ask their patients that--I gave you that prescription. When you 
come back and you are not better, we ask them where did you buy 
your drugs? I hate to do something like that. Are we going to 
have to do that? And No. 2, when you talk about tools and 
modernization in the aftermarket, are you going to take into 
account the knowledge that we have about this escalation of the 
counterfeit drugs that are coming into the market? Those are my 
two questions.
    Dr. Galson. Yes. Well, we have identified one of our major 
goals in drug safety is to improve how we communicate to the 
public about drug risks, through the Internet, through other 
types of media, through medical organizations, other 
professional organizations, such as the pharmacists. There are 
other players in this, as you may know. The pharmacy world is 
regulated by and large by the State pharmacy boards, so talking 
to State people. And there is no question that we need to do 
more communication. We have a lot of activities underway in the 
agency focused on this, particularly warning people about 
Internet pharmacies and to get their drugs through a 
traditional source. But there is no question we could do more.
    Mr. Buyer. Here is how you stop the mandate. How about you 
contact the AMA and through the continuing medical education, 
advising counsel with regard about asking that question. Where 
are you getting your drugs?
    Dr. Galson. Yes, we do work with the AMA.
    Mr. Buyer. In medical schools?
    Dr. Galson. Yes.
    Mr. Buyer. In the training? You work with the medical 
schools?
    Dr. Galson. We do some work with medical schools. That is 
an excellent idea.
    Mr. Buyer. Let us do more with our medical schools and 
teaching so that they know it is part of their prognosis is 
what I would recommend, and the continuing medical education 
piece. And you can take that with you.
    Dr. Galson. Thank you.
    Mr. Buyer. The last is on the increase in surveillance. I 
like the fact that you are checking our ports of entry and 
working properly with customs. So in PDUFA, if we want a purity 
with regard to that close market review sample, what in 
resources do we need to put in this bill? Tell me what you want 
and need to get the assurances of clients.
    Dr. Galson. Right, the FDA staff who are out in the field 
who are at the ports working with customs are not part of the 
drug center. It is a different part of the agency. I would be 
happy to go back and ask them exactly to let you know what they 
think is needed to move forward here. We do provide technical 
and other kinds of compliances systems and work together with 
that group. And we are looking very much forward to additional 
resources coming in through the PDUFA program so that we can do 
more of this kind of assistance and participation in our 
compliance efforts.
    Mr. Buyer. What agency is it?
    Dr. Galson. It is part of FDA. It is called the Office of 
Regulatory Affairs.
    Mr. Buyer. All right, thank you. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. Recognize the gentlewoman from 
Illinois, Ms. Schakowsky.
    Ms. Schakowsky. Thank you, Mr. Chairman. I wanted to ask 
Dr. Galson, you may have said this already. Maybe I missed it. 
The GAO suggested that Congress expand or consider expanding 
FDA's ability to require drug sponsors to conduct post-market 
studies, and so what is your view on that?
    Dr. Galson. Well, we have been working, as you know, with 
providing technical assistance to the committees in Congress 
and both sides that are working on issues of authority, so we 
will continue to do that. We do feel like we are able to get a 
lot of information post-marketing, and we are very committed to 
what we have talked about, improved surveillance by getting 
data sets and groups of data about drugs and how they are 
prescribed and the adverse events that may result through them 
that had nothing to do with even requiring drug companies to do 
studies. This is kinds of surveillance data that other groups, 
such as the health care payers--you are going to hear a little 
bit from them in the afternoon--that I think is the future of 
drug safety, looking at the databases that are out there.
    Ms. Schakowsky. I understand you are talking about outside 
groups, but if we maintain a voluntary infrastructure on this 
in general, why would we as members of Congress or the public 
have confidence when we have seen so many problems with failure 
to report things and poor reporting of clinical trials and all 
kinds of things that the pharmaceutical companies have done? I 
mean I am trying to understand the source of your confidence 
when you emphasize this relationship with the private sector 
and pharmaceutical companies.
    Dr. Galson. Yes, a couple points. First is that what many 
people don't realize in the debate is that we can require some 
studies to be done in several different categories. The first 
of those are under the legislation that has promoted the 
development of more information about drugs for children, and 
we are able to require companies to do studies.
    Ms. Schakowsky. How is it that many of them have been 
started but incomplete?
    Dr. Galson. In the pediatric area, I will get to that in a 
second. The other second area is the program that we have under 
our regulations called accelerated approval. When there is 
something that is really needed to fulfill a medical need, such 
as a cancer drug where there isn't another drug out there, we 
can approve the drug and then require a company to do a study 
after approval. And those studies do get done. And the third 
area is in the counter-terrorism area where there is a drug 
that we think needs to be made available in case of a terrorist 
attack, but it wouldn't be ethical to do that study in humans. 
We can approve the drug using animals and then require a later 
study or a later collection of data.
    But with regard to your main question, we are happy to 
continue to discuss it with this committee and with others your 
ideas for requiring more study to be done and give you our 
views on the specifics.
    Ms. Schakowsky. Dr. Crosse, I wondered if you wanted to 
comment on that.
    Ms. Crosse. Yes, we do believe that FDA would benefit from 
having additional tools at hand to be able to take steps when 
they believe they were necessary and they were not getting 
voluntary cooperation. With regard to the pediatric studies, 
that certainly has promoted a number of drugs being studied for 
pediatric uses; however, almost 20 percent of those drugs that 
FDA asked to be studied, the sponsors declined to study for a 
variety of reasons.
    But nevertheless, there still are a number of drugs out on 
the market that FDA had indicated were important for review. 
And it was at the option of the manufacturer whether to pursue 
those. The alternative path that the pediatric--and 
specifically Best Pharmaceuticals for Children Act--have 
provided for the Foundation for the National Institutes of 
Health to pursue the studies has not been effective. None of 
the drugs that have been referred for study by that 
organization have yet been studied.
    Ms. Schakowsky. We have a problem here. I was intrigued 
by--both Dr. Crosse mentioned that there were some problems 
with the pre- and post-marketing divisions of the FDA. You 
called it tensions, Dr. Galson. Do we have to really deal with 
tensions here? I mean can you resolve those problems?
    Dr. Galson. Well, there is tension inherent in drug 
regulation, and I don't think we will ever get away with a 
totally stress-free easy job. And that is really not what I am 
looking for. And the fact is that two people looking at the 
same scientific data may come to different conclusions, and so 
it is not just between offices but even within the staff. And 
again this is normal, and the other regulatory and scientific 
agencies that I have worked in, you have had this same tension.
    I am not meaning to diminish it or anything by calling it 
tension. It is part of the regular scientific debate when we 
make science-based decisions in public health agencies, and we 
have to do our best. And we are working to improve how we 
handle those disagreements to make sure that both sides are 
able to articulate their views and that we document our 
position in relation to those views and move forward and make 
our decisions.
    Ms. Schakowsky. I am out of time. Thank you.
    Mr. Pallone. Thank you. Mr. Ferguson.
    Mr. Ferguson. Thank you, Mr. Chairman. Thank you both for 
being here, and thank you for your testimony. Dr. Galson, I 
have a lot I want to try and get through, and I am just going 
to try and get through it as quickly as I can. I appreciate 
your cooperation as well.
    As you are aware, I have been interested in this issue of 
regulation and distribution of medication guides, med guides, 
for a while now. I want to focus my time today on this alarming 
situation in which young patients and their parents may not be 
receiving the information that they need to make fully informed 
decisions about the treatment of certain medications, 
particularly including antidepressant medications.
    Specifically, it has been brought to my attention by 
constituents in New Jersey that the FDA-required med guides are 
in many instances not distributed when antidepressant 
medications are dispensed, even though such a distribution is 
required under the regulations introduced by the FDA, by your 
agency. In examining this issue, I contacted the FDA 
representative from the National Association of Chain Drug 
Stores, the National Community Pharmacists Association, the New 
Jersey Pharmacists Association, the New Jersey State Board of 
Pharmacy, and four different drug manufacturers of these 
products, of antidepressant medications.
    In fact, I have two letters that I sent to Dr. von 
Eshenbach and the two responses that I received from the FDA. 
Mr. Chairman, I would ask unanimous consent to submit them for 
the record in this hearing. It has appeared to me throughout 
this investigation that a significant breakdown is occurring 
between the FDA and the State regulatory authorities, a 
breakdown that is depriving parents of children for whom 
antidepressant medications are prescribed, that their ability 
to make these fully informed decisions, to have all the 
information they really need. And med guides are so important 
because it gives us information in English that normal people 
can understand.
    For example, it is impossible to determine with certainty 
that the med guides are in fact being distributed with the 
prescribed antidepressant medications because regulatory 
authorities at the Federal and State levels are not enforcing 
the FDA's Stated protocol on medication guides. I am going to 
just read the portion of the statute that is relevant here, and 
I quote,

    Each authorized dispenser of a prescription drug product 
for which a medication guide is required under this part shall, 
when the product is dispensed to a patient or to a patient's 
agent, provide a medication guide directly to each patient or 
to the patient's agent unless an exemption applies under 
208.26.

     Did the FDA issue this regulation?
    Dr. Galson. Yes.
    Mr. Ferguson. Yes. Thank you. Can you or anybody tell me 
with certainty that medication guides are being distributed to 
patients and parents when they ought to be?
    Dr. Galson. Right. I know you are in a hurry. I will be 
quick.
    We have invested a huge amount of time in determining what 
should be in these medication guides. Every word is looked at 
very, very carefully because we want these messages to get to 
patients. So let me make it easier for you and tell you that we 
share your concern and we are not denying this. We know that in 
many cases, these medications are not being given out. The 
challenge, like so many things at FDA, is what is the best 
thing to do about it. They are required to be given out. On the 
other hand, we don't regulate the practice----
    Mr. Ferguson. Right, and we are going to get to that right 
now.
    Dr. Galson. Yes.
    Mr. Ferguson. I appreciate your----
    Dr. Galson. So it is really our interaction with the States 
and the pharmacy organization.
    Mr. Ferguson. That is exactly right. In my investigation, I 
also contacted the New Jersey State Board of Pharmacy, and I 
got this response from Joann Boyer, who is the board's 
executive director in New Jersey, and I quote,

    The board does have the authority to enforce the Federal 
regulation regarding the distribution of these guides. An 
overview of this Federal regulation will be included in the 
Board of Pharmacy newsletter with a statement addressing the 
need to be compliant and the fact that our inspectors will be 
including this item in their normal inspection routines. I will 
provide the inspectors with all necessary information regarding 
medication guidelines and instruct them to ensure compliance 
when they perform their inspections in our retail pharmacies. 
Those pharmacies identified as being noncompliant will be 
brought to the board's attention for review and action, which 
may include financial penalties.

    Before my inquiries, States like New Jersey were not using 
their authority to monitor pharmacists and their distribution 
of medication guides. Does the FDA have the authority to 
contact and instruct State board of pharmacy to follow New 
Jersey's example?
    Dr. Galson. We certainly don't need any special authority 
to contact the board of pharmacy and encourage them to action. 
What we have heard from some of the people that we have 
contacted is that they consider the regulations that we have 
onerous, that there is a lot of paper, that they don't have the 
capacity to store all the paper that is required to be given 
out, and that there are some real logistic issues.
    Mr. Ferguson. Right.
    Dr. Galson. And it is because of this that we have 
organized and announced a public meeting coming up this spring 
so we can get the views of all the constituents involved with 
pharmacies and States, hopefully the patients.
    Mr. Ferguson. That is where I am going next.
    Dr. Galson. They will come with suggestions----
    Mr. Ferguson. We didn't even coordinate this, but that is 
where I am going next.
    Dr. Galson. Absolutely, yes. We agree this is a problem.
    Mr. Ferguson. I would urge you to use the authority that 
you say you don't even need, I would urge you to take those 
actions to contact State boards of pharmacy because there are 
actions that they could be taking to make sure that parents and 
patients get these very important information.
    Moving on, I have heard from pharmacists in our district 
and elsewhere that they encounter problems getting the med 
guides, as you were just saying, from manufacturers and storing 
the adequate numbers of the med guides in their stores. Shelf 
space can become an issue. Under the FDA's rule, medication 
guides must be generated by manufacturers, then sent to the 
pharmacists, in most instances via a wholesaler and then given 
to the patient when the drug is dispensed.
    Is the FDA monitoring whether manufacturers are actively 
providing these med guides to pharmacists so they can dispense 
them to patients? Is that something FDA does?
    Dr. Galson. We certainly could do that. I would have to get 
back to you. I don't know for sure whether there have been any 
compliance or inspectional kind of activities specifically 
focused on that.
    Mr. Ferguson. If it not going on, I would urge the FDA to 
take that step. That is another potential breakdown, and in 
some cases I am sure has been a breakdown in the system. Does 
the agency also monitor whether manufacturers of generic 
versions of brand name drugs are distributing these as well?
    Dr. Galson. They are required to give out the same forms as 
the brand names.
    Mr. Ferguson. OK, so they would be included in this 
oversight as well? In our investigation, the National 
Association of Chain Drugstores told me that they delivered a 
proposal to the FDA 2 years ago, asking if they could 
distribute med guides electronically, thereby greatly 
simplifying the lengthy and unreliable distribution chain. Can 
you tell me if the agency will allow pharmacists to print these 
electronically, just sort of print them off the computer rather 
than having to store reams and reams of paper in their 
pharmacy?
    Dr. Galson. Yes, this is one of the issues that we are 
going to take comment on and talk about at this public meeting. 
I am not certain whether the electronic provision of an 
identical medication guide to the one that we require companies 
to put out, I suspect there is no problem with that. The 
problem is that the format sometimes changes. It is different, 
and we have to look at those issues.
    Mr. Ferguson. My time is almost up. I understand in my 
letter from the FDA that you will be holding a public meeting 
soon to discuss the distribution of medication guides. I am 
delighted. That is a very important part of the process. I am 
pleased the FDA has taken that important step.
    My last question. In the last week, the FDA has drafted 
many changes to the med guide for antidepressants, and I have 
copies of each of the two. Most strikingly, the title of these 
med guides was changed. The previous one said ``Medication 
Guide about Using Antidepressants in Children and Teenagers.'' 
That title has changed, and I would like to submit both of 
these for the record under unanimous consent, Mr. Chairman. It 
was changed to ``Medication Guide: Antidepressant Medicines, 
Depression, and Other Serious Mental Illnesses, and Suicidal 
Thoughts or Actions.'' Just seems to me that the old version of 
the medication guide was more thorough and sort of concentrated 
exclusively on the potential adverse reactions that could occur 
when taking antidepressants. The new version seems to sort of 
delve into a whole discussion on depression. Can you tell me 
why? Do you have any idea why these changes were made in that 
way?
    Dr. Galson. Yes, I have a very good idea, and it is not 
easy to explain. If you could give me just a few minutes to do 
it. This has been one of the most contentious and difficult 
areas of drug regulation over the past few years in FDA but not 
atypical in that new information has been developed about 
potential risks related to these products since they have been 
on the market, and those are the risks that are discussed in 
the med guide with suicidality.
    Now, we have taken steps going back a number of years to 
add information to the labels and to the med guides, making 
sure that patients and physicians are aware of this new 
information and what it may mean to patients. And what we have 
heard is some people think that this is great. Other people 
think it is bad.
    The psychiatric community, the American Psychiatric 
Association has been very, very angry at the FDA because they 
think that telling people about these risks is dissuading 
people who really need these drugs for depression from taking 
them and therefore contributing to the number of people that 
are expressing suicidal activity. And this is, of course, 
something that worries us a lot.
    What we try to achieve in our communications products is to 
balance benefit and risk, which is what is absolutely critical 
in explaining the risks and the benefits of drugs so that 
people can make the decisions. So what we have attempted to do 
with these latest changes in the med guide is not to 
excessively focus on the risk but also talk about the balance 
of what these drugs are for, the risks obviously of feeling 
suicidal, and to make sure that people understand.
    And I know that it is a more complex task, but this isn't 
an easy goal to communicate. We are working. We continue to 
work with experts on how to communicate with patients and with 
physicians, and we hope to continue to improve the messages 
that we are getting across, the points we want to.
    Mr. Pallone. Thank you. The gentleman from Texas, Mr. 
Green.
    Mr. Green. Dr. Galson, thank you for being here and 
listening to all our opening statements before we could 
actually ask questions.
    It is correct that the FDA currently does not have the 
authority to grant conditional approval for a new drug 
application. Is that correct?
    Dr. Galson. Yes.
    Mr. Green. Can you comment on how the extension of your 
authority to implement a conditional approval process would 
offer the FDA additional tools to ensure that drug's safety.
    Dr. Galson. Well, that is something that would have to come 
from you all from Congress to do that. We are implementing a 
new pilot program, in the center to look back at drugs a year 
or 18 months after they are approved to see whether new 
information that has been developed about them changes the way 
that we balance benefit and risk and may require us to 
communicate about changes.
    Mr. Green. So would this stand in the place of a post-
market study, or would it just be implemented a second way----
    Dr. Galson. What this pilot project does is it takes the 
information that is available from the reports that have been 
submitted by companies from adverse event reports from any 
information that has been developed in literature, and it has 
us do an additional benefit/risk assessment to see whether 
there has been any change and to see whether there are changes 
that are required and how we communicate. If there is a post-
marketing study that has to happen, it wouldn't influence that 
one way or another.
    Mr. Green. OK, in your testimony, you indicated that the 
responsibility for correcting many of the organizational 
problems has fallen on you and your position. Can you expand on 
your efforts to focus on the drug safety within the center, 
particularly what protections as the FDA put in place to ensure 
that any analysis of post-market data by the Office of Drug 
Safety is accepted and acted upon in a timely manner? Is there 
a process going on now?
    Dr. Galson. Yes, there is a process going on now, but as 
you have heard before, there is a challenge to making sure that 
the decisions that we come out with at the end of the day 
reflect the best possible input that we receive from people 
across the center. And what I have heard is that some people in 
the process sometimes feel undervalued. And my goal is to make 
sure that that doesn't happen, that we improve that situation, 
and that the people from all the different perspectives in the 
center have those perspectives considered. If there is a 
disagreement, it comes to light so that we can make sure that 
the more senior people are the people that have to make those 
decisions, can weigh the evidence on each side and come out 
with the right decision.
    Mr. Green. I think from our hearings in the Oversight and 
Investigations Subcommittee, that is what we are hearing, that 
there has been a discrepancy, and some of the FDA employees 
feel like that their statements or status wasn't considered. So 
I appreciate that.
    Let me ask you a specific issue. I am concerned about the 
safety of signing both the approval process and the post-market 
surveillance. On the approval side, there is an issue that has 
come up about safety issues and particularly surrounding RHLF, 
recombine human lacto-ferin, which has been widely studied for 
treatment of serious illnesses, including cancer. On the drug 
safety side, I think that is on the drug side, but I also 
understand there is a potential for using that as a food 
additive. And I have some concerns because the food additives 
are not as rigidly controlled as a pharmaceutical. Can you 
speak to that issue?
    Dr. Galson. Well, in general--and I don't want to refer to 
a specific product that is under review--but in general, of 
course, we don't want drugs to be put in food. And that would 
concern me a lot. This particular product is a natural product 
and, as you may recall a number of weeks ago, that the deputy 
commissioner, Dr. Woodcock, came and testified to you about 
follow on protein products.
    We have to make sure that if there are products entering 
the marketplace, they get the appropriate types of medical and 
other testing that are necessary to make sure that we 
understand well what the impacts are going to be. This sounds 
like it is a very complex regulatory matter between the food 
side and the drug side, and we will have to have our legal 
experts look into that and follow through on it.
    Mr. Green. But the concern is that using it as a food 
additive, the regulation and the oversight is much less as 
making that an actually prescription drug.
    Dr. Galson. Yes. Well, we have to follow our procedures, 
but just in general, as I said, the idea of a drug being in the 
food supply doesn't strike me as a great idea.
    Mr. Green. I agree, and that is my concern. Thank you, Mr. 
Chairman. I yield back my 6 seconds.
    Mr. Pallone. Thank you, and we have the other gentleman 
from Texas, Mr. Burgess.
    Mr. Burgess. Great, I will take the extra 6 seconds. Dr. 
Galson, Dr. Crosse, thank you both for being here with us. Dr. 
Galson, let me ask you, you mentioned in your testimony the 
importance about communicating and drug safety and the emerging 
data on drug safety. Do you get an annual report from a 
manufacturer every year on the anniversary date of introducing 
a new product?
    Dr. Galson. Yes, we do.
    Mr. Burgess. So we consider that post-marketing 
information?
    Dr. Galson. We get a huge amount of post-marketing 
information.
    Mr. Burgess. But that report on the anniversary date, would 
that be fair to call that post-marketing information?
    Dr. Galson. Of course.
    Mr. Burgess. So how do you utilize that?
    Dr. Galson. Well, we look at those reports. There is a 
specific requirement that companies let us know about any 
serious and unexpected adverse events. And those are the ones 
that we spend the most time looking at very carefully to make 
sure that what we aren't seeing is a new emerging kind of risk 
with the product that we wouldn't see before.
    So we look at those. We combine it with almost half a 
million adverse events reports that we get that come into our 
spontaneous reporting system, separately from that. And we have 
safety evaluators look at those data and then meet with other 
staff if there is a concern that is developing.
    Mr. Burgess. So you would regard this information as 
helpful?
    Dr. Galson. Yes.
    Mr. Burgess. And you have developed the computer algorithms 
and protocols to help you sift through all that voluminous 
information?
    Dr. Galson. We need to do a lot more in that regard, and we 
are moving forward but it is--yes.
    Mr. Burgess. Let us come back to that thought if we have 
time, but there is also a lot of information that is just out 
there in the--we might call open source information that is not 
necessarily the purview of the FDA or even necessarily the--
well, we could reference the CMS database, and I am sure NIH 
has their own databases and their private databases. Do you 
peruse those sources for information about products, 
particularly when something has come to your attention?
    Dr. Galson. We look at any available data. I do want to 
emphasize though that the number of staff that we have been 
able to devote to this activity traditionally has been limited 
by our resources, and that is why we have been working through 
the user fee program with Members of Congress to beef up in 
particular that part of our operations so----
    Mr. Burgess. Since you brought that up, so how many FTEs do 
you devote to that? Can you tell us?
    Dr. Galson. Well, it is difficult to say but----
    Mr. Burgess. Perhaps you can provide it after the fact--the 
number of people who are actively working on that and in an 
ideal perfect world what that number would be so this committee 
could perhaps deal with that----
    Dr. Galson. We will get it to you.
    Mr. Burgess. The stuff that is it the open source, do you 
ever go out and purchase information from private sources?
    Dr. Galson. Yes, we do.
    Mr. Burgess. And is that important?
    Dr. Galson. Extremely important and will be more important 
in the future.
    Mr. Burgess. And does funding play a role there? Is price 
important? Is price a benefit for purchase of that private 
source information?
    Dr. Galson. Price has been important, so that is another 
way that I am looking forward to more progress.
    Mr. Burgess. Could you possibly again provide us with some 
actual data on the specifics of what we are talking about so we 
perhaps could make informed decisions?
    Dr. Galson. Yes.
    Mr. Burgess. And I know in the past, you brought up the 
question of tension. The folks that do the pre-market and the 
post-market testing and the tension that exists between them. 
Is any of this--and I worked in offices. I am well aware of the 
front office/back office tension that is going to occur. But is 
any of the tension related to any perceived financial impetus 
that is placed on either hastening the approval or 
strengthening the post-market surveillance? Does that enter 
into the equation at all? Is that something this committee 
needs to be concerned about?
    Dr. Galson. Well, I haven't seen any evidence----
    Mr. Burgess. Well, let me change the context a little bit 
because it keeps coming up, and I think that it is a good idea. 
And I think it is something that we should continue to do, but 
this concept keeps coming up. It is fair to ask the question is 
this a problem? Is this entering into the tension equation that 
you referenced? And if so, could you help us quantify it? And 
could you help us by providing areas where--if that is an 
issue, and I don't know that it is--but if it is, how can it be 
mitigated? How can it be qualified?
    Dr. Galson. Yes, I may have misunderstood you. You mean the 
disparity in funding issue, but that is a factor if that is 
what you mean. I am not sure what you mean by financial.
    Mr. Burgess. The theme keeps recurring that there is a 
problem with how the FDA does its work because of undue 
influences that are placed on it by outside industry because of 
the funding mechanism, and I don't know. Is that the situation 
or not?
    Dr. Galson. I wanted to make sure I understood what you 
were saying.
    Mr. Burgess. Is that a source of the tension that you 
alluded to?
    Dr. Galson. I don't think so. There are 2,300 people in the 
drug center, and no matter which office they are in, they are 
very, very dedicated to doing the right thing for public health 
regardless of where their source of funding is. Individual drug 
reviewers don't know if their salary is coming from user fees 
or from appropriations. I haven't seen any evidence that that 
is a factor.
    Mr. Burgess. Thank you. That is a very direct answer, and I 
appreciate that. Mr. Chairman, I will yield back.
    Mr. Pallone. Thank you. Ms. Eshoo.
    Ms. Eshoo. Thank you, Mr. Chairman, and thank you, Drs. 
Galson and Crosse for your testimony and the answers that you 
have given to the questions that have been posed by my 
colleagues. I want to make a couple of comments before I ask my 
questions. Number 1, the whole issue of advertising, of drugs. 
I can't help but think it is kind of in the middle of this. I 
mean the heavier something is marketed, the more pressure there 
is to buy, and obviously, this pipeline to examine and for 
efficacy and then the pressure that I think justifiably is 
brought on the Congress and the agency for post-market 
surveillance.
    For the life of me, I really don't know what good 
advertising has done except for, I mean for corporate reasons 
to market. And I can't help but think that we should revisit 
this. We should take a look at this and not only examine, in my 
view, the genesis but all the issues that surround it. To see 
someone skipping through a meadow, and the tagline being buy 
such and such a product. I remember my mother used to say, 
``what is it that they are advertising here?'' So I think that 
we should take a look at that.
    It is curious to me of the whole issue of reimportation 
being raised by Members here. I have always thought that it was 
a very important issue, and there is the bastardization of 
drugs by others and the attempt to bring them into the country. 
But I also think it is a political curiosity about what the 
Congress did in the name of trying to save money to bring other 
drugs into the country. I never thought that was a good policy. 
I didn't support it. I don't support it now, and I think that 
we have our hands full because there is more and more coming 
into the country. And we have to take a look at what to do with 
it.
    Now, my questions. In your testimony, Dr. Crosse, you found 
that FDA's access to post-market clinical trial and 
observational data is limited by both resources and by 
authority. This is a softball issue, but do you think that the 
FDA should have such an authority?
    Ms. Crosse. Yes, we do. We have recommended to Congress to 
do that.
    Ms. Eshoo. Right. Now, would the administration's PDUFA for 
a proposal include this authority, and specifically what types 
of post-market observational and clinical studies will FDA be 
permitted to exercise under the administration's plan?
    Dr. Galson. Right, in our PDUFA proposal and in the 
legislation that is on the Hill, we will get important new 
sources of resources----
    Ms. Eshoo. Does the Waxman-Markey legislation match what 
the administration has proposed?
    Dr. Galson. I don't believe it does.
    Ms. Eshoo. It doesn't?
    Dr. Galson. Yes, I am not an expert.
    Ms. Eshoo. OK. One, I think, is stronger than the other?
    Dr. Galson. I believe so, yes.
    Ms. Eshoo. OK, so it is Waxman-Markey that is the stronger 
of the two. I think we should know that. I mean in my view it 
is. Do you agree?
    Dr. Galson. It depends which provision specifically you are 
talking about here.
    Ms. Eshoo. Well, overall, is it weaker or is it stronger?
    Dr. Galson. I don't like that characterization.
    Ms. Eshoo. OK, I think we know what the answer is here. All 
right. Now, thank you. I want to go to something that I feel 
strongly about, and that is health information technology. Your 
testimony, Dr. Galson, indicates that an additional $4 million 
is adequate to upgrade FDA's current drug review system. Is it 
really? I mean what is an additional $4 million going to buy?
     And how long will it take to go to full implementation? 
This is about, my colleagues, I think this is about expeditious 
review. I mean I don't know. Someone is sitting in a back room 
and going through this sheet by sheet. Or is it all part of a 
technology system? First of all, what is the $4 million going 
to buy? Is it really enough, and how soon does that get the 
agency to full implementation?
    Dr. Galson. We are in the middle of a very rapid 
transformation from a paper environment to--there are some 
areas, depending on what you are talking about, where the 
technology is there.
    Ms. Eshoo. Help us. We want to help you accomplish this.
     So what is the $4 million going to buy?
    Dr. Galson. The $4 million is helping us move from a paper 
system to an electronic system.
    Ms. Eshoo. How much of the system is still paper, using 
percentages?
    Dr. Galson. A lot of it is still paper.
    Ms. Eshoo. But give me--come on.
    Dr. Galson. I think we are getting about half of all our 
applications in by paper, but again that is from the 
pharmaceutical industry. We need to get there faster.
    Ms. Eshoo. I think we need to revisit this, and I think 
that you are tremendously low balling the amount of money that 
needs to be invested in this. We should really take a look at 
it. You tell us what you need to move to full implementation 
and over what period of time. $4 million, my sense is, 
represents snail's pace.
    Dr. Galson. We will be happy to get you there.
    Ms. Eshoo. OK, good. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. Mr. Murphy.
    Mr. Murphy. Thank you, Mr. Chairman. Doctor and Doctor, I 
don't know if you heard some of my opening comments about my 
concerns about the breadth of the kind of warnings and comments 
made when FDA approves a product. That currently it is one that 
focuses, I think, a lot of the other reactions and things, but 
part of my concern as a psychologist, at least when it comes to 
psychiatric medications, particularly pediatric ones, that I am 
concerned that 75 percent of drugs are prescribed by non-
psychiatrists and that oftentimes there may not be coordination 
with other people providing consultation with the family and 
therapy, et cetera. What kind of actions does and can the FDA 
do to make sure that the proper use of the medications and not 
just prescribing them is part of the plan?
    Dr. Galson. Right. We, as you know, we don't regulate the 
practice of medicine. So what goes on in the prescribing room 
and all sorts of other questions having to do with the way 
physicians work is not under our purview. But what we do do and 
what we are very, very committed in is making sure that 
physicians have the best possible information as quickly as 
possible when we develop new recommendations or new views about 
safety and efficacy, the benefit and risk of products.
    And we see our role here in making sure that the 
information accompanying products, the information that is 
available to the public, is as accurate as possible. We also 
work with professional organizations, the people who provide 
different, some specialty organizations. When there are issues, 
we bring them in. We talk to them, so that is the way that we 
work with the medical community, but we don't actually have 
regulatory authority over that operation.
    Mr. Murphy. Dr. Crosse, do you have some comments on that?
    Ms. Crosse. No, we are well aware that this is an issue for 
the FDA and that many of the problems that have arisen with 
drugs and some of the post-marketing safety concerns that have 
arisen have been in instances where medications have been 
prescribed that are not in accordance with the label 
indications or for populations for whom they are not indicated. 
And FDA, in a number of instances, has taken additional steps 
to try to add warnings to the labels of those drugs to try to 
put out information to the public and to try to put on some 
other kinds of controls on who can prescribe these medications. 
But it remains a problem of great concern.
    Mr. Murphy. Certainly, Dr. Crosse, you are involved with 
some of the labels and some of the information that goes to 
physicians on things even though you can't regulate them and 
tell them who has to do it. When it comes to some of these 
psychotropic medications, however, what kind of commentary goes 
into the warnings, et cetera, with regard to, I guess, the pool 
of knowledge someone should have or that medications should be 
used in conjunction with other types of treatment.
    Dr. Galson. Well, we have a team of people who are experts 
and psychiatrists who look specifically at the labeling and the 
information that we provide to the public about that kind of 
medication, as we do oncologists for cancer drugs. And we get 
together, and for a new drug, we look at the information that 
is available from the clinical trials.
    And we determine the best way to communicate about that, 
having to do with the dose, having to do with 
contraindications, other types of warnings or precautions, 
concomitant diseases that may affect the use of the drug. And 
we endeavor to make sure that all that information is put 
together in the drug label, and if there are special ways that 
that has to be communicated, we will get together and discuss 
that as well.
    Mr. Murphy. But is it done, again the psychotropic 
medications, where it is described that the medication--the 
volumes of research indicate it should be done, provided, in 
the context of a sort of structurally trained psychotherapy and 
monitoring these cases, No. 1. The second issue is that in many 
cases, I don't know if these drugs are really evaluated on a 
pediatric population.
    What is done to communicate those issues of the full 
spectrum of treatment under which these medications seem to 
work best?
    Dr. Galson. Our authority doesn't, in most cases, extend to 
some of the things that you are mentioning. When we do think 
that there is a drug that has such severe risks that we think 
that only a physician with a certain kind of training should 
give it. Or there is a drug, for example, that has risks that 
we think it should only be administered in a hospital, we can 
require that.
    Mr. Murphy. Well, I am not saying just in terms of who 
prescribed it, but also other components of therapy that go 
with that. Many medications may have other side effects. Take 
insulin for diabetics. It is not enough just to say here is the 
insulin, but it should be used in accordance with a strict 
dietary and exercise information.
    Dr. Galson. We can put that information in our labels, and 
we do all the time.
    Mr. Murphy. I am not sure that is done adequately when it 
comes to psychiatric medications, especially when it comes to 
recognizing a lot of these medications have not really run 
through proper trials on a pediatric population.
    Dr. Galson. Right. We have under our authorities to require 
and to urge that studies be done in pediatric populations. We 
have succeeded in having more of the studies looked at for 
younger age groups, but there is no question this is a 
challenge.
    Mr. Murphy. I would hope, Mr. Chairman, as we pursue this 
because our culture is becoming so much giving kids drugs, and 
it is amazing how many youth are given drugs for psychiatric 
reasons to quiet them down, to stabilize them. And the almost 
explosion of diagnosing these things. I really hope this is an 
area that you continue to investigate. Thank you very much.
    Mr. Pallone. I appreciate your comments. I agree with you. 
I recognize the gentleman from Massachusetts, Mr. Markey.
    Mr. Markey. Thank you, Mr. Chairman, and again I appreciate 
your giving me this opportunity. Mr. Galson, Mr. Waxman and I 
have introduced the House counterpart to the Kennedy-Enzi drug 
safety legislation, which includes many of the recommendations 
of the Institute of Medicine and GAO. And we are hopeful that 
it will be included as part of PDUFA reauthorization on the 
House side. So Dr. Galson, if I may, my wife is a doctor. So I 
apologize for calling you mister.
    Dr. Galson. I am a doctor.
    Mr. Markey. Doctor, yes, I apologize. Let me begin with 
you. In response to Chairman Pallone's questions about clinical 
trials, you stated that there has been tremendous improvement 
in registration of clinical trials. However, companies aren't 
in 100 percent compliance with registration of required trials. 
Is that correct?
    Dr. Galson. I am not sure that is exactly what--you are 
quoting my response from just a few minutes ago?
    Mr. Markey. Yes, they are not in 100 percent compliance.
    Dr. Galson. I would have to look specifically at the rules. 
What I believe I was trying to convey is that not all the 
detailed information that some people think should be put on 
public databases, going down to patient-level data, is on 
there. I am not aware of compliance issues.
    Mr. Markey. OK, would you agree that if registration is not 
mandatory and the FDA does not have any enforcement mechanisms 
to require registration, that we will never get 100 percent 
compliance?
    Dr. Galson. I don't know really and wouldn't want to 
speculate.
    Mr. Markey. And I appreciate that.
    Dr. Galson. Yes.
    Mr. Markey. If we are trying to ensure that we know about 
all of the trials that have been conducted on a product after 
phase one and eliminate the problem of selective disclosure of 
trial results, which can give the public a distorted view of 
the risk of benefits of the drug getting most of the trials 
doesn't really fix the problem because the trials the companies 
are registering may be the most important for the public to 
know about. By only selecting the answers that you want to 
give, the public might be denied information that could be 
useful, or the physicians could be denied the information. Do 
you agree with that?
    Dr. Galson. I agree that it is very, very important when 
there is a marketed product, if there is a clinical trial that 
is done that is relevant to patient care and drug safety, that 
it is important that the information that could have an impact 
on whether patients and physicians want to use a drug, that 
that be available.
    Mr. Markey. OK. And, Dr. Galson, some people have raised 
the concern that emphasizing post-market safety could slow down 
the approval process. However, it would seem to me that if FDA 
is confident in its ability to detect and manage problems after 
approval, then the FDA should actually be able to approve the 
drugs faster even if there are some lingering questions about 
the safety preapproval because there will be a strong system to 
monitor and invest those issues, if necessary, after the drug 
is on the market.
    Do you agree that having a stronger post-market safety 
system, a safety net if you will, is important to giving the 
FDA the confidence that they don't have to catch everything 
pre-approval because the approval is not the last chance to 
address the safety issues.
    Dr. Galson. That is a complex, multi-part question. Let me 
just say starting that it is not possible to catch everything 
with the current state of knowledge. If we want new products 
for patients who need them, we are going to sometimes find out 
things after approval that we didn't know when the drugs were 
approved.
    Mr. Markey. So the point I am making is don't you think a 
stronger post-market safety system would give people more 
confidence?
    Dr. Galson. Yes, I am a very strong supporter of a stronger 
post-market safety system.
    Mr. Markey. OK, Dr. Crosse, in your testimony, you 
described some major gaps that currently exists in the FDA's 
post-market safety net system. In his statement, Dr. Galson 
testified that the FDA's PDUFA proposals will transform the 
drug safety system at FDA. Do you believe that additional 
resources for post-market safety without additional authority 
to require post-market studies and changes is enough to 
transform the post-market drug safety program in FDA?
    Ms. Crosse. We believe that additional authority is 
warranted for FDA to give them all the tools that they need to 
be able to effectively oversee this process.
    Mr. Markey. How does FDA's current lack of authority to 
require post-market studies affect the FDA's ability to assess 
safety problems after a drug is on the market?
    Ms. Crosse. I think it complicates and slows the 
availability of information that is needed to be able to fully 
understand certain types of problems. Absent certain types of 
information, the agency often cannot make a determination 
quickly or possibly even at all about what kind of action ought 
to be taken.
    Mr. Markey. I thank you. I think of it as a trainer for 
tightrope walkers. Before the walker steps off the platform, 
the FDA is in a strong position to make sure the walker will 
succeed by requiring a harness, if necessary. But once the drug 
is approved and the walker leaves the platform, the FDA can do 
little to require protections if companies don't want to accept 
them.
    Knowing this, the FDA is unlikely to let products go if 
felt a little wobbly. However, if the FDA had a strong safety 
net in place to catch problems and prevent a major crash, the 
FDA is more likely to feel comfortable in getting products to 
patients who need them. That is what the Waxman-Markey safety 
bill would do. It would create a strong but flexible drug 
safety net, and it is something that, I believe, at the end of 
the day is actually essential to having a good drug approval 
system. I thank the chairman for allowing me that little extra 
time.
    Mr. Pallone. Thank you, Mr. Markey. That concludes our 
questions, and thank you both for being here today. I thought 
it was a very good questions-and-answers series. Let me just 
say though that we are going to take a break before the second 
panel goes in. We have 11 minutes left on one vote, and then 
there will be three 5-minute votes after that. So figure about 
half an hour we will be back and start with the second panel. 
But we are now in recess. Thank you.
    [Recess.]
    Mr. Pallone. The subcommittee hearing will reconvene, and I 
will ask the panelists to come forward and sit down. Welcome to 
all of you. Let me introduce each of you actually. We have a 
pretty large panel here today.
    We will start on my left with someone from New Jersey, Lisa 
Van Syckel, who is from Flemington, New Jersey. We are going to 
have a video that she has brought us. And then we have Dr. 
Ellen Sigal, who is chairperson and founder of the Friends of 
Cancer Research. And Dr. Susan Ellenberg from the University of 
Pennsylvania School of Medicine. She is speaking at the request 
for the Coalition for a Stronger FDA. Dr. Caroline Loew, who is 
senior vice-president for scientific and regulatory affairs of 
the Pharmaceutical Research and Manufacturers of America. Diane 
Thompson, who is vice-president for Public Policy and 
Communications at the Elizabeth Glaser Pediatric AIDS 
Foundation. She is speaking on behalf of the Alliance for Drug 
Safety and Access. John Theriault, chief security officer and 
vice president, global security at Pfizer. Dr. Sharon Levine, 
associate executive director for the Permanente Medical Group, 
speaking on behalf of the Kaiser Permanente Medical Care 
Program. And Dr. John Powers, who is assistant professor of 
medicine at George Washington University School of Medicine, 
and I guess also at the University of Maryland School of 
Medicine. So thank you all for being here today. We are going 
to start with Ms. Van Syckel, and does the video go first, or 
how does that work? We will do the video first? Now, we were 
going to try to put it on the big screen, but it didn't work. 
So we are using the TV. Thank you.
    [Video shown.]
    Mr. Pallone. First of all, let me thank you for being here 
and for bringing us the video and relating your own story of 
your daughter. I know it has got to be tough, but we really 
appreciate your being here.

          STATEMENT OF LISA VAN SYCKEL, FLEMINGTON, NJ

    Ms. Van Syckel. Yes, it is very tough, and I just want to 
make sure that no family ever has to endure what our family 
endured. The FDA and pharmaceutical industry continues to 
downplay the risks of antidepressants in children. They have 
gone from causal low to increased risk and to most recently the 
Johns study, saying that the benefits of antidepressants 
outweigh the risks.
    When we hear about increased suicide within the media, they 
think that it is something that is very quiet. And that is why 
I thought it was important to come and play the tape so 
Congress can actually see it for themselves, hear about it, 
because it is a violent suicide. It is not something quiet, and 
I think it is very disturbing for this FDA to allow the 
pharmaceutical industry to negotiate the labels that are placed 
on antidepressant medications.
    They should never be allowed to negotiate the lives of our 
children, and I think that is what the very important issue 
here is. And, Mr. Chairman, we have another serious concern, 
especially in the State of New Jersey where infants are being 
given antidepressant medications, not only antidepressants but 
antipsychotics to medicate children as young as infants, 12 
months. And we need to ask why.
    So with the FDA and their failure to provide the medication 
guides, which is an issue I have been speaking with Mr. 
Ferguson, it is quite clear that the FDA is incapable of doing 
their job and notifying the public of severe side effects. And 
I am begging you, as parents from the State of New Jersey, from 
district 6 and district 7, because I represent all of New 
Jersey, we need an independent office of drug safety.
    We need better control of direct consumer marketing, and we 
need a better med watch program. I want to give you an example. 
My brother had a severe condition and was critical, and a nurse 
had stated to me--I said ``well, what about the side effects.'' 
And it was the particular drug Zocor. And she says you can 
actually get the side effects from the television, from the 
commercial. And I said to the nurse you are telling me, as a 
caregiver, that I should look to the television, to a 
commercial for side effects. That was ridiculous, and I said I 
think you are saying that to the wrong person.
    So I am really concerned as to the direct consumer 
marketing. I realize they have a right to free speech, but 
medical professionals should not be telling patients to watch 
it on TV.
    [The prepared statement of Ms. Van Syckel follows:]

                      Statement of Lisa Van Syckel

    Mr. Chairman, members of the committee, thank you very much 
for inviting me to testify at today's important hearing.
    I would like you to hear how corporate greed, our woefully 
inadequate mental health system and over-reliance on pharma-
psychiatry, and the little pink pill, Paxil, have forever 
altered the life of my most precious gift from God, my daughter 
Michelle.
    Michelle was raised in a loving, stable home in the small 
town of Dunellen where she participated in many community 
events and was proud to be a girl scout.
    In 1995 American Standard transferred my husband to their 
European Division in Brussels, Belgium.
    Michelle, who had always been an honor roll student, 
attended St. John's International School in Waterloo. Michelle 
traveled and explored many European countries. She became 
fluent in the French language.
    Our family returned to the United States in the summer of 
1999. Our life, as we once knew it, would change dramatically. 
Michelle began complaining of ill health and missed her friends 
in Belgium. She was also upset over the declining health of her 
grandmother.
    In April 2000 Michelle continued to complain of ill health, 
she was losing weight and had stopped eating. She was admitted 
to Somerset (New Jersey) Medical Center's eating disorder unit, 
where she was diagnosed with depression and anorexia nervosa 
and was prescribed the antidepressant Zoloft. Within hours of 
digesting Zoloft, she reported to hospital staff that she had 
the urge to hurt and cut herself and two days later, again 
reported she was uncomfortable taking the medication. Her 
complaints were dismissed. Several weeks later, Zoloft was 
discontinued due to dramatic orthostatic changes and 
bradycardia. (very slow heart beat). Michelle became very 
hyperactive and was diagnosed with a personality disorder. No 
one apprised me of what was happening to her. She was fourteen; 
I should have been informed.
    In June 2000 Michelle was placed on Paxil. Within a few 
weeks she began to self-mutilate with knives, razors and broken 
plastic CD cases. She became verbally abusive and was 
displaying extreme oppositional behavior, along with severe 
insomnia, diarrhea, chest pain, weak muscles, and on a few 
occasions vomited blood and had rectal bleeding.
    In August 2000 the Paxil was increased to 40 mg along with 
a diagnosis of major depressive disorder with psychotic 
features.
    In September Michelle's self mutilating behavior was 
increasing. During one episode, she had inflicted over 23 
wounds and cut the word ``die'' onto her abdomen. She became 
violent and suicidal and was hospitalized because she was 
deemed to be a danger to herself and others. Her Paxil was 
reduced from 40 to 20 mg and Depakote was prescribed.
    On October 6, 2000 my daughter Michelle attempted suicide 
and became extremely violent. She assaulted her brother as he 
was desperately trying to keep her from killing herself. He was 
just 4 days shy of his 12th birthday. She then viciously 
attacked three police officers and managed to escape from her 
handcuffs twice. She was kicking, spitting and screaming 
obscenities. She even attempted to kick out the rear window of 
the patrol car. When they arrived at the hospital, it took five 
men to place her in leather humane restraints. The next day 
Michelle awoke dystonic and unaware of her surroundings. Again, 
she became violent and had to be restrained.
    Michelle was transferred to UMDNJ Behavioral Health. Paxil 
was discontinued, but she was then prescribed Celexa and 
Risperdal (what I didn't know then, but have since learned, was 
that Michelle was placed in a clinical trial of these drugs 
without my knowledge or consent). Within 36 hours, Michelle 
again became violent and self mutilated. She was injected with 
Thorazine for her out-of-control behavior.
    Approximately two weeks later, she was released from UMDNJ 
with a 3-day supply of medication (what I know now and didn't 
know then, was that this was a very dangerous thing to do). In 
an abrupt withdrawal, Michelle again became violent and 
threatened to kill me. She thought I was the devil and told me 
I was evil.
    In April 2001 Michelle was removed from all psychotropic 
medication. Recovery was a long, tedious process. Everything 
Michelle endured while on the drugs was suffered through the 
withdrawal process.
    Michelle's Paxil-induced psychosis, self-mutilation, 
violent, and suicidal behavior are gone now. What remains 
upsetting is that the physical scars of her self mutilation 
will be with her forever.
    Michelle's beautiful smile and sweet disposition were 
returned. Michelle never had violent and suicidal behavior 
prior to taking antidepressants, nor displayed this behavior 
after recovering from withdrawal.
    I believe, without question, drug companies and their 
apologists are putting a great deal of pressure on the FDA. 
Despite all of the controversy and exposed failures surrounding 
the FDA in the last few years, it appears that the FDA simply 
cannot muster the guts to act without industry influence. 
Absent this influence, there would be no reason why the FDA 
wouldn't insist on label warnings for all ages on anti-
depressants. No doubt drug companies are a formidable force, 
but the FDA must remember whose interests it is supposed to 
protect. If it does not, the representatives of the people, 
Congress, will have to step in and do it for them.
    I would like to show you about a minute and half of a video 
of Michelle and other families' children who have suffered 
because the FDA failed to better warn the public about 
dangerous side effects.

                        Legislative Suggestions

    So that other families are saved from the tragedy and 
heartbreak that my family and other families in this hearing 
room have endured, I urge you to approve--as part of the must-
pass user fee legislation--the strongest possible FDA drug 
safety reform legislation.
    PDUFA: Break the ties that are distorting the FDA's 
mission. First, on the extension of the Prescription Drug User 
Fee Act (PDUFA IV), I know that the FDA needs the resources, 
and more, that the user fees bring. The user fees need to be 
continued, and expanded to provide more resources for safety.
    But under the current law, the industry's user fee money 
comes with a huge cost. It comes with detailed requirements to 
serve the drug industry--and that is a cancer that is eating at 
the culture and integrity, both real and perceived, of the FDA. 
If anyone doubts that the user fees are having a corrupting 
influence on the culture of the FDA, I urge them to read last 
summer's poll by the Union of Concerned Scientists, to which 
about 1000 of the FDA's medical scientists responded. Many 
poured out their frustration at being pressured to approve 
drugs on which they had serious safety concerns, and a number 
cited PDUFA as an inherent conflict of interest. A recent study 
by a group of Harvard researchers has found that drugs approved 
just in time to meet the PDUFA time goals have many more post-
market safety problems than drugs which receive more review 
time. An earlier study by Harvard Professor Daniel Carpenter 
pointed out that the FDA's time-to-approve drugs was declining 
in the years before PDUFA's first passage in 1992; the study 
found that the FDA staff was being increased through regular 
appropriations, and that every 100 person increase in staff was 
resulting in a 3.3 month decline in approval times. I think 
this study shows that while the FDA does need more resources, 
it does not need the rigid framework of PDUFA.
    This committee is famous for its tough oversight. I am sure 
that you can make sure that the user fee money is well spent 
and that the FDA continues to give priority, timely attention 
to truly life-saving drugs. Therefore, I urge you to break the 
entangling webs of obligations that come with the user fees and 
just let the FDA use the fee money to do its job. Congressman 
Hinchey has previously introduced legislation that would 
achieve this reform.
    Kennedy-Enzi (S. 1082), and Waxman-Markey (H.R. 1561)
    The bill the Senate is passing makes important improvements 
for safety. And in many ways, the bill by Representatives 
Waxman and Markey is even better, because it

     requires a warning signal for the first 2 years a 
drug is on the market (an important fact for consumers, since 
the real test of a drug's safety comes once it is mass marketed 
and used by the general population);
     requires a review of a drug's safety history after 
7 years (important because only about half of a drug's side 
effects and labeling changes are detected in the first 7 years 
it is on the market);
     provides much more meaningful civil monetary 
penalties than the Senate bill;
     protects the public from overuse of particularly 
dangerous drugs by limiting direct-to-consumer ads for up to 
three years; the First Amendment does not give the drug 
companies the right to kill Americans, and moderation of ads on 
a new drug with serious warning signs of danger should be one 
of the FDA's tools;
     ensures that the results of all clinical trials 
(other than phase 1 trials) will be made publicly available in 
a timely manner.

    To save other families from future drug safety disasters, I 
urge you to take this best opportunity in the next five years 
to pass this kind of legislation, and I urge that it be made 
even stronger.
    We need a better Adverse Event/MedWatch Reporting system. 
The Senate bill includes a major new monitoring of huge medical 
databases to detect quickly problems with drugs. It is said 
that the problems with Vioxx might have been detected in about 
3 months under such a system.
    But I believe we also need to educate and involve the 
American consumer more in reporting adverse events. Today, the 
average citizen has no idea how or where to report a problem 
with a drug. I urge you to require all drug ads to prominently 
display a 1-800 number where problems can be reported. The FDA 
should also start using the tools of the Internet and e-mail 
to, with patients' permission, periodically query people who 
are taking a new drug whether they notice any adverse 
reactions. Instead of passively waiting for reports of trouble, 
a modern FDA should be seeking out the areas of danger.
    We need someone responsible and accountable for safety at 
the FDA. I support a separate Office of Drug Safety in the FDA, 
one that will be free of the control and overwhelming presence 
of the Office of New Drugs.
    The FDA Commissioner and many others have said that a 
separate office would be duplicative, expensive, and hold up 
approvals. If that is a problem, the same goal of 
accountability for safety could be achieved by giving the head 
of the Office of Drug Safety the power to call for a safety 
action (a REMS adjustment in HR 1561). If the head of the 
Office of New Drugs disagreed, the Commissioner would decide 
between them, all within a week or so (so that there can be no 
charge that we are delaying the approval of vital new drugs). 
There needs to be a locus of safety accountability in the FDA. 
This proposal, or a wholly separate office, would achieve that 
goal.
    No Conflicts of Interest (COI) in FDA Advisory Committees. 
The FDA recently announced guidance that makes major 
improvements in the Advisory Committee (AC) process: no 
participation in an AC if one has over $50,000 in conflicts, 
and participation in the AC, but no vote if one has any 
conflict. I hope you will codify the FDA's action, but go 
beyond it by requiring the active recruitment of COI-free 
experts, and prohibiting those with conflicts from sitting with 
the AC (they can testify, but they should not be part of the 
camaraderie-building AC process where they can influence 
outcomes even though they can not vote).
    Thank you for your consideration of these legislative 
ideas. If enacted, you could give the American people the FDA 
they need and deserve.
                              ----------                              

    Mr. Pallone. Thank you. And we are going to ask you some 
questions later, but thank you for being here today. I 
appreciate it. Dr. Sigal.

 STATEMENT OF ELLEN SIGAL, CHAIRPERSON AND FOUNDER, FRIENDS OF 
                        CANCER RESEARCH

    Ms. Sigal. Thank you, Mr. Chairman, members of the 
committee. Thank you for the opportunity to testify today about 
drug safety. It is an extremely important issue.
    My name is Ellen Sigal. I am chair of Friends for Cancer 
Research. Friends is a coalition of all of the major groups in 
cancer research. Our mission is the importance of cancer 
research. We represent patients, scientists, clinicians, cancer 
center directors, and we care deeply about research.
    The issue of drug safety is very personal to me. My own 
sister died 21 years ago of toxicity of a drug for breast 
cancer. So I know personally what this means. She left a 4-
year-old child. So this is a very important issue to me and to 
all of us.
    My testimony will cover four major points today that are 
extremely important to the patient community and the science 
community. Patients needs for life-improving therapies and a 
crucial pipeline and access to drugs, providing additional 
resources for FDA--you have heard that before, and you have 
heard it here again--establishing a systematic routine and 
easily accessible safety monitoring system, and finally 
integrating science into the regulatory process, the critical 
path initiative and the proposed FDA foundation. I also do want 
to point out that the president of Friends, Molly Mallick, is 
here today, and I thank her for coming here and supporting us.
    Millions of other people have shared my experience and care 
deeply about this issue of drug safety, just as Ms. Van Syckel 
and others that you will hear today. So this is a concern that 
the patient community cares about deeply. I am going to read a 
quote from Meryl Wineberg, who is the chair of the National 
Health Counsel. ``Speaking on behalf of 100 million Americans 
with chronic conditions and disabilities, it is equally 
important that patients whose quality of life or indeed life 
itself are not deprived of the medications they need.'' I did 
have other testimony for the record from the American Cancer 
Society and other patient groups.
    When the issue of drug safety was surfacing and it was 
clear there were going to be hearings and legislation about 
it--we are very research oriented at Friends of Cancer 
Research, and we convened a group of experts in cancer and 
outside of cancer, clinicians, scientists, epidemiologists, 
patients, to look at the issue because we wanted to have an 
informed position on this. And we wanted to make sure that we 
looked at the position from a scientific point of view. We are 
science oriented, and we thought it was important to have 
clinicians, people that actually treat patients, weighing in on 
this issue.
    Our major recommendations--the White Paper is drug safety 
and drug efficacy. I would like it to be submitted to the 
record. Thank you. The paper highlights three major areas: 
active surveillance, systems of the life cycle of a drug. We 
don't have all the information up front in preclincal 
environment. We really find most of it in post-surveillance. 
Resources for the FDA and training, training for FDA personnel. 
That is absolutely critical. The integration of science through 
critical path, and the public/private partnerships. We can't, 
as much as we need to fund FDA, and we support substantial 
increased funding, partnerships through this critical path 
initiative and this hopefully relief from foundation will be 
critical to it.
    We also think that we have to use existing networks, such 
as the VA, Kaiser, Blue Cross and others. The database and the 
information they have are critical. I want to read a quote from 
the recent IOM report. The recent IOM report on drug safety 
states ``to expect a pre-market studies or FDA review of these 
studies can reveal all the information about the risks and 
benefits of new drugs that is needed to make optimal treatment 
decisions with occasion and reasonable delay in approval.''
    Authority is fine for the FDA. We support additional 
authorities. We do not support those authorities without the 
resources crucial to make these informed decisions. FDA is a 
chronically underfunded agency that is continually assigned 
more responsibilities without matching resources. It is 
unreasonable to starve an agency of the resources it needs yet 
hold it solely accountable for protecting the health of 
Americans.
    One thousand five hundred people a day die of cancer. Four 
thousand will be diagnosed today. They cannot afford to wait. 
They need new treatments. Other patients with chronic diseases 
need treatments too. They deserve better treatments and more 
informed treatments. They should be safe, and they should be 
effective.
    The pipeline for these new patients is critical. They must 
be informed and must have choices, and allow them to 
participate in the process. Patients are crucial to the 
process. Patient needs are not monolithic, nor do all patients 
respond the same to a particular treatment. Only science and 
evaluation of patients will really make us understand that and 
why that happens.
    In conclusion, we remain extremely supportive of the goal 
to improve our drug safety system, and we believe that we can 
best achieve this goal through a science-based approach, taking 
into full account the voice and perspective of patients. We 
applaud the committee for holding these hearings, and we 
welcome further thoughtful policy discussions. Thank you.
    [The prepare statement of Ms. Sigal follows:]

                      Statement of Ellen V. Sigal

    Mr. Chairman and distinguished members of the committee, I 
thank you for the opportunity to discuss the important topics 
of drug safety and efficacy as the committee begins to take 
important steps to strengthen FDA as part of the upcoming 
reauthorization of the Prescription Drug User Fee Act.
    My name is Ellen Sigal, and I am the Chair and founder of 
Friends of Cancer Research. Friends is a non-profit 
organization that over the past 10 years has pioneered 
innovative public-private partnerships, organized critical 
policy forums, educated the public, and brought together key 
communities to develop collaborative strategies in the field of 
cancer research. We are a coalition of major cancer groups 
representing patients, researchers, physicians, and survivors. 
It is our belief that a science-guided approach will best 
enable us to improve drug safety and efficacy in this country.
    We urge this committee and Congress to pursue a legislative 
course that provides FDA with the resources it needs to conduct 
systematic risk assessment across a drug's lifespan while 
protecting patients' access to needed treatments. Specifically, 
we believe that any legislative approach to strengthening FDA 
must give priority consideration to:

     Patient need for life-improving therapies
     Providing additional resources for FDA
     Establishing a systematic, routine and easily 
accessible safety monitoring system
     Integrating science into the regulatory process 
through the Critical Path Initiative and the proposed FDA 
Foundation

    We all want the safest possible drugs. But we recognize 
that no drug is 100 percent safe or 100 percent effective. We 
also realize that each patient responds differently to 
medication. Like the patients I speak on behalf of, and many of 
you in this room today, I have encountered this reality in a 
very personal way.
    Twenty years ago, my own sister died of toxicity associated 
with a bone marrow transplant to treat metastastic breast 
cancer. She was 40 years old and left behind a 4-year-old 
daughter. This was a tragic event that clearly changed my life. 
While I hope that no one would have to go through such an event 
themselves or with their loved ones, this was a risk that we 
knowingly accepted based upon what was best for my sister at 
the time.
    As emotional as my experience was, I recognize that 
emotions cannot be the guiding force behind decisions about 
what treatments should and should not be available to patients. 
We believe that a science-driven approach to drug development 
and approval will help to ensure that each person receives the 
treatment that is most likely to be effective and safe for 
them.
    In examining treatment options, all patients must weigh the 
benefits and risks when determining their own course of 
treatment. Legislation aimed at strengthening drug safety must 
take care to preserve patients' access to a wide array of 
treatment options while not impinging on the development of new 
treatment options or removing existing options for patients in 
need--bearing in mind that for many diseases, including many 
cancers--patients still have few or no treatment options 
available to them at all.
    We are confident that increased funding for FDA and policy 
that is grounded in science can achieve an optimal balance 
between protecting patients and expanding treatment options. A 
benefit-risk approach conducted across a product life cycle--
guided by sound and systematic data collection and careful, 
regular assessment of a drug's safety and efficacy across 
subpopulations, dosage levels, and other factors--is the 
cornerstone of drug development and should be the foundation of 
drug regulation.
    In any treatment decision, consideration must be given to 
the condition the drug is meant to treat as well as to the 
extent of the patient's disease, its duration and its impact on 
the patient's functional status and quality of life. Depending 
on the particular illness, drugs can potentially be designed 
for and used at a specific point in the continuum of disease 
from prevention to terminal illness. Patients' needs are not 
monolithic, nor do all patients respond the same to a 
particular treatment.
    Legislation should acknowledge the great variability across 
diseases, patient preferences, and individual circumstances and 
facilitate continued access to a wide array of treatment 
options accordingly. Indeed, across the board, one need stands 
paramount for patients--it is the need for more and better 
options to fight disease and improve disability. We believe 
that any legislative initiative that limits patient choice and 
access to treatments in the name of safety would be 
counterproductive and not achieve the goal of improving patient 
outcomes.
    As this committee considers ways to enhance the FDA's 
ability to monitor drug safety to help patients make the most 
informed decisions about their treatment options, it is of the 
utmost importance that patient needs and voices be at the 
forefront of discussions and that all decisions pertaining to 
drug safety be driven by sound scientific data.
    Dr. Jerry Yates, National Vice President of Research for 
the American Cancer Society, describes a scientific foundation 
for FDA:
    ``Based on the course of cancer--from prevention to 
terminal illness--improving the science of safety will help 
identify the proper balance between risk and benefit for each 
stage of the disease and assure optimal investments in both 
cancer research and the care of patients.''
    This issue, of course, impacts not only the cancer 
community, but the entire patient community as well. For 
example, Myrl Weinberg, president of the National Health 
Council, expresses her community's needs:
    ``Of course, prescription drug safety is of paramount 
importance, and--appropriate measures should be taken to ensure 
the public is not unnecessarily exposed to--potential harm. 
However, speaking on behalf of 100 million Americans with 
chronic conditions and disabilities, it is equally important 
that patients--whose quality of life,--or indeed life itself--
are not deprived of the medications they need.''
    Lauren Roberts, a multiple sclerosis (MS) patient who was 
directly affected by the temporary removal of Tysabri from the 
market, described her experience by saying:
    ``MS progresses on its own timetable, not the FDA's. In the 
course of 90 days, there will be, on average, 2,160 more people 
who hear the words, ``You have multiple sclerosis.'' My own MS 
continues to ravage my body--Tysabri was the first and only 
therapy that helped me--the small risk from Tysabri pales in 
comparison to the risks created by not having Tysabri available 
to us as a choice--As for me, I am willing to take that risk, 
in exchange for having an improved quality of life, my life, 
back.\1\
---------------------------------------------------------------------------
    1 Roberts, Lauren. Multiple Sclerosis Patients v. FDA Over-Caution. 
Washington Legal Foundation. May 19, 2006
---------------------------------------------------------------------------
    FDA must have the best tools to make these important 
assessments and effectively communicate with physicians and 
patients as they together make individual treatment decisions. 
New policy to expand the authority of FDA alone will not 
sufficiently strengthen the agency. Simply put, FDA needs more 
dollars from Congress. This is a chronically under funded 
agency that is continually assigned more responsibilities 
without matching resources. It is unreasonable to starve an 
agency of the resources it needs, yet hold it solely 
accountable for protecting the health of Americans.
    Now, in a time when public perception is declining, user 
fees are not the best answer. Due to the current budget 
climate, user fees are a reality, but a strong FDA is an 
investment in patient and public health. Congress should find 
the money to invest.

        Drug Safety & Drug Efficacy: Two Sides of the Same Coin

    Several months ago, we convened an independent committee of 
expert academic scientists and clinicians, research advocates, 
and representatives of the patient community to examine and 
recommend ways to further strengthen the agency and its product 
evaluation process.
    It is extremely important that the patient voice be heard 
along with the perspective of expert clinicians experienced in 
clinical trial design and translational research. The members 
of this committee are distinguished experts in diseases such as 
cancer, infectious disease, and diabetes. They are experts in 
drug development but also have first hand knowledge in patient 
care and patient needs. This is a vital perspective that cannot 
be excluded from the drug safety debate.
    I would like to thank Dr. Robert Young, president of the 
Fox Chase Cancer Center in Philadelphia and chairman of the 
board of Scientific Advisors of the National Cancer Institute, 
for his leadership of the authoring committee. The resulting 
document, entitled, ``Drug Safety & Drug Efficacy: Two Sides of 
the Same Coin'' is a proposal for improving drug safety, 
ensuring new drug access, and strengthening the FDA. I would 
like to ask that a copy of the full report be submitted to the 
record as an addendum to my testimony, and I would like to 
briefly discuss some of the recommendations.

              A Systematic Approach to Safety Surveillance

    It is most important for patients that FDA continuously 
evaluate both safety and efficacy when determining public 
access to new products. At the level of medical practice, 
safety and efficacy are always considered together by the 
treating healthcare professional in the context of a patient's 
specific circumstances and preferences. The regulatory process 
should reflect this essential balance that is fundamental to 
all medical decision-making.
    Because it is impossible to know everything about a drug at 
the time of approval, it is important to monitor the safety and 
effectiveness of drugs as they are used in the general 
population. To strengthen the effectiveness of the current 
post-market system, the agency needs to develop and implement a 
more systematic and automated approach to safety surveillance.
    By utilizing drug safety and efficacy information from a 
variety of sources, such as established healthcare networks 
like Kaiser or UnitedHealth Group, the FDA could actively 
identify, evaluate and respond to signals more efficiently. New 
policy should shift the emphasis of drug safety away from 
solely risk management, and instead focus upon systematic 
benefit-risk assessment based on comprehensive and valid 
information provided by the healthcare community.
    Currently, a great deal of drug safety evaluation is based 
upon the limited data available in the New Drug Application. A 
locked focus on safety at this early point in a drug's life 
cycle would increase the amount of pre-market data required, 
with the likely result of stifling or unnecessarily slowing 
patients' access to potentially beneficial medicine. The recent 
IOM report on drug safety states, ``to expect that pre-market 
studies or FDA review of these studies can reveal all the 
information about the risks and benefits of new drugs that is 
needed to make optimal treatment decisions would occasion 
unreasonable delay in approval.'' \2\
---------------------------------------------------------------------------
    2 Institute of Medicine of the National Academies. ``The Future of 
Drug Safety: Promoting and Protecting the Health of the Public'' Sept. 
26, 2006.
---------------------------------------------------------------------------
    It would be far better to utilize available data mining 
techniques and other potential new information sources to 
identify unanticipated adverse events sooner following product 
launch and adoption in medical practice.
    New policy should focus on efficiently and accurately 
identifying unexpected serious adverse events in a 
scientifically rigorous manner. Once a serious signal has been 
identified, FDA should have the tools to react in a proper 
manner that will protect the public while ensuring responsible 
access for patients who may depend on a particular drug. Such 
an approach would benefit all stakeholders.

                   Enhanced Technology Infrastructure

    With the proper resources to improve the technology 
infrastructure, FDA could routinely and systematically evaluate 
data from completed and ongoing clinical trials and registry 
studies, perform useful epidemiological studies, and 
characterize population subtypes and their response to 
treatments.
    In addition, greater ability to compare and combine data 
across different sources would result in greater flexibility 
and improved efficiency and the potential to generate novel 
insights about vulnerable populations. This includes the 
ability to share information regularly with the Center for 
Medicare and Medicaid Services and with sister agencies within 
the Public Health Service, including the National Institutes of 
Health and the Centers for Disease Control and Prevention.

                    Increase Training and Personnel

    Just as FDA needs enhanced infrastructure and information 
systems, it also needs adequate personnel training to meet 
emerging technology advances. Increasing the number of IT 
trained staff is essential for the overall advancement of the 
bioinformatics systems. As the agency strives to monitor and 
evaluate the treatments of the future, it is imperative that 
FDA have the resources to effectively manage and interpret the 
wealth of information currently available.
    FDA needs to attract and retain a greater number of 
professional staff with the training required to perform 
accurate benefit-risk assessment, evaluate new therapies and 
implement scientific initiatives. As the FDA workload grows, so 
too must the resources to recruit and increase staff with 
critical competencies. Increased training of FDA personnel will 
also enhance agency effectiveness and standards.
    FDA experts could play an integral role in the development 
of advanced clinical trial designs that achieve greater 
efficiency and permit definitive conclusions to be obtained 
more quickly. Such advancements to the current clinical trial 
system could result in improved pre-market product evaluation, 
smaller trial sizes, more efficient dosing determinations, and 
ultimately, safer products reaching patients faster.

      Integrating New Science through the Critical Path Initiative

    As science progresses and new treatments emerge from 
laboratories and clinics around the world, FDA must be equipped 
to perform accurate and efficient evaluation and continue its 
science-based tradition. It is imperative that resources be 
devoted to increase the support for the Critical Path 
Initiative to modernize FDA.
    A central goal of the Critical Path Initiative is to 
provide tools to identify patients who will most likely respond 
to particular treatments, thereby improving the risk to benefit 
ratio. As this is accomplished, there will be new ways to 
diagnose, treat, cure or prevent disease and allow life-saving 
therapies to reach patients faster while reducing the overall 
cost of healthcare in the country.
    Legislation introduced by Senators Kennedy and Enzi, and 
recently considered by the Senate, would create the Regan--
Udall Foundation for the Food and Drug Administration. This 
will establish a leading organization for the advancement of 
the Critical Path Initiative and foster the advancement of the 
science of drug safety through public-private partnership.
    NIH initiatives and collaborative research partnerships 
should place high priority upon the identification and use of 
biomarkers to (1) determine the role of genetic polymorphisms 
in causing drug toxicities; (2) establish effective strategies 
for selecting patients for treatment with specific drugs and 
(3) identify early biomarkers of drug benefit. The sub-
populations most susceptible to an adverse event could be 
identified by detecting the presence or absence of a biological 
indicator.
    Further integrating science into the regulatory process 
will aid researchers who design drugs, experts who evaluate 
their safety and efficacy, health care providers who prescribe 
medicine, and most importantly patients who will benefit from 
continued medical discovery and more effective application of 
new treatments.
    Conclusions
    In conclusion, we remain extremely supportive of the goal 
to improve our drug safety system and we believe that we can 
best achieve this goal through a science-based approach, taking 
into full account the voice and perspective of patients. 
Scientific advancements have led to better methods of disease 
treatment, early detection and prevention, and such 
technological advancements can translate to identifying safety 
signals more accurately and efficiently.
    Increased funding for the FDA will help the agency access 
and utilize these tools to assess the benefits and risks of 
medical therapies and, in turn, help patients make the most 
informed decisions about the treatment options available to 
them.
    A wide range of treatment options should and must remain 
available to patients. While we, of course, want safer drugs, 
we caution against unintentional consequences that could remove 
or slow access to valuable therapies without actually improving 
their safety. Of even greater detriment would be discouraging 
the future innovation of potentially life-saving new products 
altogether.
    We applaud the committee for holding this important hearing 
and we welcome further, thoughtful policy discussions toward 
ensuring that FDA has the resources and tools it needs to 
advance the science of drug safety while it continues its 
important work to evaluate and approve new therapies for 
patients in need.
    We look forward to continuing to work with all of you to 
ensure that the lives and hopes of patients continue to improve 
through sound, science-based, and patient-focused FDA policy. 
Thank you for the opportunity to speak to you today. I look 
forward to answering any questions you may have.
                              ----------                              

    Mr. Pallone. Thank you. Dr. Ellenberg.

STATEMENT OF SUSAN ELLENBERG, UNIVERSITY OF PENNSYLVANIA SCHOOL 
 OF MEDICINE, SPEAKING AT THE REQUEST FOR THE COALITION FOR A 
                          STRONGER FDA

    Ms. Ellenberg. Mr. Chairman and members of the committee, I 
am Susan Ellenberg, professor of biostatistics and associate 
dean for clinical research at the University of Pennsylvania 
School of Medicine.
    Prior to my current appointment, I directed the 
biostatistics and post-market surveillance programs at the 
FDA's Center for Biologics Evaluation Research from 1993 to 
2004. I also recently served on the Institute of Medicine 
committee on the assessment of the U.S. drug safety system.
    During my career with the FDA, I was deeply involved in one 
of FDA's most important functions, monitoring the safety of 
medical therapies after they had been approved for marketing. 
As such, I want to thank the committee for inviting me here 
today to testify on the important issue of drug safety.
    Although there are many aspects of drug safety that the 
committee is looking at, I am going to speak particularly from 
my own knowledge and experience about one aspect of FDA's drug 
safety program that I feel most strongly about, and that is its 
resource needs to carry out its congressionally-mandated 
responsibilities.
    As you know and as others have said today, there is no such 
thing as a totally safe drug. All drugs pose some risk to 
patients. Drugs are deemed safe when it appears that their 
benefits outweigh their risks in a given population, safe 
enough.
    The approval for marketing a new drug or vaccine is only 
the beginning of a drug's lifecycle. It is critical drugs be 
monitored once on the market. Drug manufacturers', physicians 
and the FDA continuously watch for signals that a drug poses 
greater risks than originally believed or it may be unsafe in 
certain patient populations, or require special restrictions to 
control hazards that would otherwise cause FDA to remove it 
from the market.
    For some years now, FDA scientists have recognized a 
growing resource imbalance between the agency's pre-market drug 
review program and its post-marketing safety surveillance 
capabilities. This imbalance has resulted from enactment of 
Congress of the Prescription Drug User Fee Act, which has 
greatly enhanced and enlarged FDA's pre-market drug review 
program and a parallel lack of increased funding for FDA's 
post-market drug safety program.
    The recent Institute of Medicine report, ``The Future of 
Drug Safety: Promoting and Protecting the Public Health,'' 
which I am sure many or all of you have seen, noted this 
resource imbalance and concluded that our drug safety system 
was severely underfunded. The User Fee Act has required the 
drug review staff at FDA to grow steadily larger to allow much 
more rapid review and approval of drugs than ever before. That 
has been a great boon to the citizens of this country, 
resulting in more new drugs to prevent and treat illness. But 
the drug safety programs at FDA have received only very limited 
increases in staff and funding, and thus these programs have 
continually lost ground in their ability to monitor the rapidly 
increasing number of new drugs on the market.
    Further, the volume of adverse event reports submitted to 
the FDA has increased steadily. As you can see on the monitor, 
the numbers of reports of adverse events submitted to the FDA 
has climbed so rapidly that they threaten the ability of drug 
safety staff to review and process them effectively. And we 
discussed this earlier, the various reasons. But in any case, 
the numbers have gone up quite dramatically.
    One of the initiatives of which I was most proud during my 
tenure at FDA was a thorough reevaluation of FDA safety 
monitoring systems, an effort commissioned by then Commissioner 
Jane Henney. That assessment, which was completed in 1999, 
resulted in a series of recommendations for major changes in 
our post-marketing safety programs including, among other 
things, intense monitoring of newly marketed products during 
the initial period on the market, obtaining access to health 
care databases, such as those of Medicare and the VA that we 
have talked about today, developing a new active surveillance 
capacity to complement existing passive surveillance system, 
which also need to be improved, funding for research to improve 
FDA's tools for monitoring the study of medical product risks, 
more intense intervention such as stronger warning labels or 
restricted distribution of higher-risk products, and funding to 
conduct focus safety studies when needed.
    Commissioner Henney's request for a substantial boost in 
FDA appropriations to fund these recommendations unfortunately 
were not successful. But these recommendations made by FDA 
staff 8 years ago are very similar to the drug safety 
provisions of the current Senate and House bills that are 
currently being considered, and are entirely consistent with 
the recommendations of the recent IOM report. If the necessary 
funding had been provided at that time, the proposed programs 
would be up and running today and might have permitted much 
more rapid identification of many, if not all, of the recent 
drug safety problems that we have been experiencing, meaning 
far fewer individuals would have been exposed to excess risk.
    And so, Mr. Chairman, I urge you to set as one of your 
highest priorities this year provision of the necessary 
resources to FDA's drug safety programs. I thank you very much 
for inviting me to present my views.
    [The prepared statement of Ms. Ellenberg follows:]

                    Statement of Susan S. Ellenberg

    Mr. Chairman and members of the committee. I am Susan S. 
Ellenberg. Prior to my current appointment as professor of 
biostatistics and associate dean for clinical research at the 
University of Pennsylvania, I directed the biostatistics and 
postmarket surveillance programs at the Food and Drug 
Administration's Center for Biologics Evaluation and Research 
from 1993 through 2004. That Center, as you may know, is 
charged with assuring the safety of biological drugs, blood and 
blood products, and vaccines, and works closely with FDA's 
other programs for approving and monitoring pharmaceuticals. I 
also served on the recent Institute of Medicine Committee on 
the Assessment of the U.S. Drug Safety System, and am associate 
editor of Clinical Trials (the official journal of the Society 
for Clinical Trials) and of JNCI (Journal of the National 
Cancer Institute).
    During my career at the FDA, I was deeply involved in one 
of FDA's most important functions--monitoring the safety of 
medical therapies after they have been approved for marketing. 
As such, I wish to thank the Committee for inviting me here 
today to testify on the important issue of drug safety, an 
issue that the Committee will be considering this year as part 
of its effort to reauthorize the Prescription Drug User Fee 
Act. Although there are many aspects of drug safety that the 
Committee is examining, I have been requested by the Coalition 
for a Stronger FDA to speak in particular, from my knowledge 
and experience, about one aspect of FDA's drug safety program--
its resource needs to carry out its Congressionally-mandated 
responsibilities.

                               Background

    As you know, there is no such thing as a totally ``safe'' 
drug--all drugs pose some risk to patients. Drugs are deemed 
``safe'' when it appears that their benefit outweighs their 
risks in a given population. The approval for marketing of a 
new drug or vaccine is only the beginning of a drug's ``life 
cycle.'' It is critical that drugs be monitored once on the 
market--drug manufacturers, physicians and the FDA continuously 
watch for signals that a drug poses greater risk than 
originally believed, may be unsafe in certain patient 
populations, or requires special restrictions that must be 
imposed so as to control hazards that would otherwise cause FDA 
to remove it from the market.

                        A Resource for Imbalance

    For several years now, FDA scientists have recognized that 
there has been a growing resource imbalance between the 
agency's premarket review program for drugs and its postmarket 
surveillance capabilities. This imbalance has been occasioned 
by two developments: the enactment by Congress of the 
Prescription Drug User Fee Act, which has greatly enhanced and 
enlarged FDA's pre-market drug review program, and a parallel 
lack of increased funding for FDA's postmarket drug safety 
program.
    The recent Institute of Medicine Report, The Future of Drug 
Safety: Promoting and Protecting the Health of the Public, of 
which I was a co-author, confirmed those internal FDA concerns 
by concluding that our drug safety system was ``severely 
underfunded.'' As the IOM report noted, the user fee act has 
required the drug review staff at FDA to grow steadily larger, 
which has allowed much more rapid review and approval of new 
drugs than ever before. That has been a great boon to our 
citizens, resulting in more new therapies that can prevent or 
treat illness. But the drug safety programs in FDA have 
received only very limited increases in staff or funding, and 
in fact have been largely held to their pre-PDUFA levels. Thus, 
FDA's postmarketing safety programs have continually lost 
ground in their ability to monitor the rapidly increasing 
number of new drugs on the market. Further, the volume of 
adverse event reports submitted to the FDA has increased 
steadily. As you can see from the attached FDA graphic, the 
number of required reports from drug sponsors of adverse events 
they received from physicians has climbed so rapidly that they 
threaten the ability of drug safety staff to review and process 
those reports effectively.

           Resource Limitations Greatly Affect FDA'S Capacity

    One of the efforts of which I was most proud during my 
tenure at the Food and Drug Administration was a study 
commissioned by then-Commissioner Jane Henney, in which she 
charged senior drug, device and biologics officials with a 
thorough re-evaluation of FDA's safety monitoring systems. That 
assessment, completed in 1999, resulted in a series of 
recommendations for major changes in our post-market safety 
programs, including:

     Closer monitoring of newly marketed products, 
particularly those for which safety ``signals'' suggest greater 
risk
     Obtaining access to health care databases, such as 
those of the Medicare program and the Veterans Administration
     Development of a new active surveillance capacity, 
to complement the existing passive surveillance systems (which 
would also be improved)
     Funding for epidemiological and methodological 
research to improve FDA's tools for understanding medical 
product risks
     More intense intervention in higher risk products 
identified by postmarket surveillance as needing special 
attention, such as stronger warning labels or restricted 
distribution, and
     Funding to conduct focused safety studies when 
needed
    Commissioner Henney requested a substantial boost in FDA 
appropriations to fund these recommendations, the 
implementation of which would clearly have required a 
substantial increase in FDA's safety surveillance staff, but 
these requests unfortunately did not yield any additional 
funding .

    Ironically, those recommendations are very similar to the 
drug safety provisions of the current Senate and House bills 
that are being considered along with the Prescription Drug User 
Fee Act. I ask you to imagine, Mr. Chairman, the frustration of 
the FDA drug safety staff who were denied the capacity to make 
those improvements, only to see the very same concepts emerge 
years later in Congressional legislation. One can also imagine 
that we as a nation would be in a far better place if the 
necessary funding had been provided by Congress in those years 
past, as the proposed programs could be up and running today, 
and might well have permitted much more rapid identification of 
many, if not all, of the recent drug safety problems that we 
have experienced, meaning that far fewer individuals would have 
been exposed to excess risk.
    In conclusion, Mr. Chairman, while there are many, many 
issues that the Committee must grapple with in considering drug 
safety legislation this year, I urge you to make resourcing the 
drug safety programs at FDA one of your highest priorities. The 
agency's scientists very much want to make the kinds of 
improvements you are contemplating, and will do so with 
intensity and enthusiasm if you provide to them the staff and 
resources to carry out your mandate.
    Thank you for inviting me to present my views on this 
important matter.
                              ----------                              

    Mr. Pallone. Thank you. Dr. Loew.

 STATEMENT OF CAROLINE LOEW, SENIOR VICE-PRESIDENT, SCIENTIFIC 
   AND REGULATORY AFFAIRS OF THE PHARMACEUTICAL RESEARCH AND 
                    MANUFACTURERS OF AMERICA

    Ms. Loew. Thank you. Mr. Chairman, Ranking Member Deal, and 
members of the subcommittee, I want to thank you for the 
opportunity to testify today about the vitally important issue 
of maintaining the safety of Americans' medicine supply. My 
name is Dr. Caroline Loew, and I am the senior vice president 
of scientific and regulatory affairs at the Pharmaceutical 
Research and Manufacturers of America, or PhRMA.
    PhRMA shares the view of the importance of drug safety. It 
is also a top priority for all our member companies. PhRMA is 
committed to working with the Food and Drug Administration and 
all other stakeholders to continually improve our drug safety 
system in a way that preserves innovation and patient access to 
medicine.
    As we address this critical topic, however, it is important 
to remember that drug safety fundamentally involves a balance 
between benefit and risk. Neither can be considered in 
isolation. Firstly and most importantly, we support the FDA's 
proposal to reauthorize the Prescription Drug User Fee Act, 
also known as PDUFA, because it most effectively addresses the 
issues that are critical in improving drug safety in America 
today.
    The PDUFA proposal will make a good system even better by 
addressing FDA's most pressing drug safety needs: additional 
resources and access to the latest scientific tools and 
technologies. The current drug safety is stronger but could be 
made even stronger by the passage of PDUFA. The agency already 
has robust and effective systems in place for drug approval and 
monitoring of medicines once they are on the market. Drug 
safety is an extensive ongoing process that starts long before 
a medicine enters the market and continues long after it has 
been made available. It does not begin with or end when the new 
medicine is approved.
    Before patients can receive new medicines, they undergo 
rigorous safety and effectiveness testing and evaluation. It 
often spans 10 to 15 years. Drug safety, or more precisely the 
benefit/risk balance, is only determined after extensive 
testing in laboratories, animals, patients, and after FDA 
regulators have studied tens of thousands of pages of 
scientific data for each drug.
    In fact, fully one-half of FDA's drug review project is 
devoted to drug safety. Agency officials also have broad 
statutory authority to monitor and ensure the safety of drugs 
after they are approved. There are extensive adverse event 
reporting requirements, annual reports filed by companies, and 
for the vast majority of approvals, post marketing studies are 
conducted.
    The impact of this systems is undeniable. Over the last two 
decades, only about 3 percent of the medicines approved for the 
American market have been withdrawn for safety reasons. That is 
an enviable record by any estimation. It is also important to 
note that drug safety assessments today are more effective than 
ever before, thanks to new scientific tools and technologies.
    What we need to do now to improve drug safety is to 
continue developing and better utilizing these new modern 
techniques, and we need more resources devoted to drug safety. 
The PDUFA proposal that FDA has put forward would help advance 
these crucial goals. It would provide about $150 million over 5 
years to hire 82 additional staffers for post-market drug 
safety activities, and it would increase the use of large 
medical databases, which contain a wealth of drug safety 
information.
    The proposal put forward by the FDA also addresses all of 
the Institute of Medicine's most important recommendations for 
more agency resources and improvements in the science of drug 
safety. Any additional drug safety reforms considered by 
Congress should strengthen FDA's product oversight capabilities 
without harming innovation or access to medicines.
    PhRMA would support very targeted legislative revisions 
that clarify FDA authority in the areas of clinical drug 
exposure, post-market studies, labeling and distribution 
restrictions. For their part, PhRMA and its member companies 
have contributed to the drug safety improvement effort in 
recent years by initiating a number of major programs from 
clinical trial disclosure to biomarket research to research 
studies on new drug safety tools and methodologies to training 
programs for better adverse event detection and reporting.
    In the end, we all want the same thing: the timely delivery 
of safe and effective medicines to patients suffering from a 
wide range of medical conditions and diseases. We have a system 
that is accomplishing that critical goal. FDA does need more 
resources to increase the use of today's modern technology. And 
that is what the FDA's PDUFA proposal would provide, and we 
urge Congress to reauthorize the PDUFA proposal as quickly as 
possible.
    Thank you for this opportunity to inform the subcommittee 
about PhRMA's perspectives in this critical public health 
arena. Thank you.
    [The prepared statement of Ms. Loew follows:]

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    Mr. Pallone. Thank you. Ms. Thompson.

STATEMENT OF DIANE THOMPSON, VICE-PRESIDENT, PUBLIC POLICY AND 
  COMMUNICATIONS, ELIZABETH GLASER PEDIATRIC AIDS FOUNDATION, 
 SPEAKING ON BEHALF OF THE ALLIANCE FOR DRUG SAFETY AND ACCESS

    Ms. Thompson. Good afternoon, Mr. Chairman, Ranking Member 
Deal, and members of the committee. Thank you for the 
opportunity to participate in today's hearing. I am Diane 
Thompson, vice president for public policy and communications 
at the Elizabeth Glaser Pediatric AIDS Foundation. Today I am 
testifying on behalf of the Alliance for Drug Safety and 
Access, a coalition of 11 patient and provider organizations, 
whose members advocate on behalf of over 30 million patients, 
suffering from hundreds of serious and life-threatening and 
rare diseases. Alliance members also represent over 100,000 
providers of care to children and individuals with mental 
illnesses.
    The Elizabeth Glaser Pediatric AIDS Foundation has been 
focused on speeding patient access to safe medicine since its 
inception in 1988. The foundation's creation was sparked by 
Elizabeth Glaser's outrage over the lack of safe and effective 
options for treating her two HIV-infected children. We know 
this committee shares our goals of ensuring that patients 
continue to have timely access to new therapies while 
strengthening and improving the drug safety system. Simply put, 
we do not accept that patients should have to choose between 
safety and speedy access to new medications. The history of our 
foundation, of the HIV/AIDS community and that of many in our 
coalition is the story of the power of patients' contributions 
to regulatory and scientific decision-making.
    One mom's determination to fight for her child's survival 
helped transform drug development for children. No one stands 
to benefit or lose more than patients in drug safety decisions, 
and patients must have a strong voice in decisions about safety 
and risk management.
    In its September 2006 report on drug safety, the Institute 
of Medicine proposed a fundamental paradigm shift in this 
country's approach to drug safety. We agree. Attention to 
safety must be integrated throughout the life cycle of every 
drug, and it must be recognized that continuous assessment of 
benefit and risk is every bit as important once a product is on 
the market and in the hands of patients as it is during the 
drug review phase.
    FDA must be given the authority to require drug 
manufacturers to continue to study the safety of products after 
approval, to force changes to drug labels when safety issues 
are uncovered, and to require that the results of clinical 
trials be shared with patients who, after all, are the people 
who make the clinical trials possible.
    Giving the FDA adequate authorities and flexible tools to 
enforce them, including civil money penalties, will benefit 
both patients and the industry. By providing FDA the 
flexibility to impose fines for noncompliance, we can avoid the 
worst possible outcome for everyone: having to pull a drug from 
the market that still holds some benefit for some group of 
patients.
    We also agree with the IOM's recommendation that FDA safety 
staff must have a greater formal role in drug review and in 
risk management decisions. Finally, safety-related performance 
goals must be added to PDUFA. The IOM report notes that a 
recent study found that 21 percent of prescriptions are written 
for off-label uses. Any effort to reform the drug safety system 
that fails to address one-fifth of the use of drugs in real 
world settings would leave a significant safety gap, a safety 
gap that would particularly affect children since still far too 
few drugs are ever tested in children before they are allowed 
on the market.
    The FDA's authority to require post-market safety studies 
must clearly and unequivocally extend to both on-label and off-
label uses. We ask that the subcommittee make the public 
dissemination of trial results a cornerstone of its drug safety 
efforts by establishing a clinical trials results database. By 
linking the registration of new trials with final outcomes, the 
database would provide patients and providers with additional 
information with which to assess benefits and risks and could 
help prevent selective reporting of positive results and the 
problems that have resulted from the withholding of negative 
trial results. Given that clinical trials would not exist 
without patients' willingness to give of their time and health, 
such a mechanism could help restore patients' trust in the 
integrity of the clinical trials process.
    For FDA to succeed in implementing these reforms, it is 
essential that new and expanded safety activities be explicitly 
paired with increased resources, both in user fees targeted to 
drug safety activities and in appropriations. The need for new 
authorities and for the increased funding are inextricably 
linked, and we strongly urge the subcommittee to consider these 
issues along with legislation to improve the safety and access 
of pediatric drugs and devices as a part of a single package.
    Mr. Chairman, members of the committee, the committee has 
before it an historic opportunity to finally match our Nation's 
success in speeding new therapies to patients with a system 
that can better ensure the safety of those products once they 
are on the market. We appreciate your interest in the patients' 
perspectives on these critical issues and look forward to 
working with you to accomplish these goals. Thank you again for 
the opportunity to share our views.
    [The prepared statement of Ms. Thompson follows:]

                     Statement of Diane E. Thompson

    Mr. Chairman, Mr. Deal, and members of the subcommittee, 
thank you for the opportunity to participate in today's 
hearing. I am Diane Thompson, vice president for public policy 
and communications at the Elizabeth Glaser Pediatric AIDS 
Foundation. Today, I will be testifying on behalf of the 
Alliance for Drug Safety and Access (ADSA), a coalition of 11 
patient and provider organizations. Collectively, members of 
ADSA advocate on behalf of over 30 million patients, including 
those suffering from HIV/AIDS, Parkinson's disease, spinal cord 
injuries, paralysis, multiple sclerosis, leukodystrophies, 
Tourette Syndrome, and over 6,000 known rare diseases. In 
addition, our members represent over 100,000 providers of care 
to children and individuals with mental illnesses.
    As a representative of the Elizabeth Glaser Pediatric AIDS 
Foundation, I am also proud to offer the perspective of an 
organization that has been focused on speeding patient access 
to safe medicines since its inception in 1988. This issue is at 
the heart of our mission--the Foundation's creation was sparked 
by Elizabeth Glaser's outrage over the lack of safe and 
effective options for treating her two HIV-infected children. 
Although Elizabeth's efforts were too late to save her 
daughter, Ariel, who died from AIDS at the age of 7, her legacy 
includes her son Jake, now 22 years old, and the thousands of 
HIV-infected children around the world who now have the chance 
to grow up healthy and even start families of their own, thanks 
to the search for lifesaving pediatric medicines that Elizabeth 
Glaser and the Foundation championed.
    I would like to thank the chairman, the ranking member, Mr. 
Waxman, Mr. Markey, and other members of the subcommittee for 
your leadership on this issue, for moving beyond the headlines 
to examine our nation's current drug safety system and discuss 
meaningful solutions to ensure that the Food and Drug 
Administration (FDA) remains the world's gold standard for 
public health protection. Your task is not an easy one and we 
appreciate the historic nature of this undertaking.
    We have the opportunity before us to both maintain timely 
access of patients to new therapies, while strengthening 
oversight of drugs already on the market. We believe that with 
sufficient resources both goals are achievable. Simply put, we 
do not accept that patients should have to choose between 
safety and speedy access to new medications.
    Patients with serious illnesses understand that bringing 
drugs to market in a timely way means that not every risk can 
be identified in advance. What they also demand, however, is 
sufficient information for themselves and their providers to 
assess risks and benefits on an ongoing basis--which often 
means further testing of the drug after approval. Yet, the FDA 
has virtually no authority to compel drug manufacturers to 
continue to study the safety of products after they have been 
approved, force changes to drug labels if dangerous side 
effects are uncovered, or require that the results of clinical 
trials be shared with the patients who make them possible.
    Giving FDA these authorities and flexible tools to enforce 
them, including civil money penalties, as legislation pending 
before the Committee would do, ultimately benefits both 
patients and drug manufacturers. Allowing FDA to require 
additional testing of drugs postmarket could actually allow the 
FDA to approve drugs more quickly, knowing it will have the 
ability to act if there are new safety concerns once the drug 
is in the hands of patients. Also, by giving FDA the 
flexibility to impose fines for non-compliance, we can avoid 
the worst possible outcome for everyone: pulling a drug from 
the market that still holds some benefit for some group of 
patients.
    We believe that the core of any effort to improve drug 
access and safety must be a shift to a ``life-cycle'' paradigm, 
with an emphasis on the continuing pursuit of knowledge about a 
drug's risk-benefit profile and timely communication of that 
information to patients and providers. This approach, which is 
recommended by the Institute of Medicine (IOM), has been 
included in drug safety legislation introduced by Mr. Waxman 
and Mr. Markey. In our view, individualized risk evaluation and 
mitigation strategies, rather than a one-size-fits-all approach 
to patient safety, will be key to the appropriate balancing of 
drug risks and benefits that is so critical to patients with 
life-threatening illnesses.
    To further improve the depth and breadth of input into drug 
safety decision making, we ask the Committee also to adopt the 
IOM's recommendation that the Office of Surveillance and 
Epidemiology (OSE) be given a greater role in drug review and 
the development of safety plans. The lack of communication and 
cooperation between that office and the Office of New Drugs, 
highlighted in both the IOM report and a March 2006 report by 
the Government Accountability Office, is deeply troubling. At 
minimum, we recommend that the Committee formally assign OSE 
staff a role in the review of new drugs applications and post 
approval regulatory actions, as the IOM recommends.
    We ask the subcommittee also to ensure that any drug safety 
legislation includes mechanisms for greater public input and 
transparency. The history of our Foundation and of the broader 
HIV/AIDS community is the story of the power of patients' 
contributions to scientific decision making. Although they 
began as three mothers around a kitchen table with no formal 
training in science and medicine, Elizabeth Glaser and the 
other founders of the Foundation ultimately changed the 
accepted thinking of both the National Institutes of Health and 
FDA about the risks of not studying AIDS drugs in children--a 
success story that is repeated throughout the histories of 
patient organizations. Given that no one stands to benefit or 
lose more than patients in drug safety decisions, we ask that 
you consider a significant role for patients in the assessment 
and management of drug risks.
    We also urge the committee to clarify that any new 
authority of FDA to require studies of post-market safety 
concerns is not confined to on-label uses of the drug. In our 
efforts to improve the drug safety system, we need to pay 
particular attention to not only what happens inside the FDA, 
but also what goes on in the real world. A recent study found 
that 21 percent of prescriptions written in 2001 were for off-
label uses. Any effort to reform the drug safety system that 
fails to address one-fifth of the use of drugs in real-world 
settings leaves a significant safety gap.
    Children would be left at particular risk by the failure to 
clarify this authority, since as much as three-quarters 
pediatric prescribing is off-label. Thanks to the efforts of 
many on this Subcommittee, there are mechanisms available to 
both encourage and require manufacturers to study their 
products for children. However, there are gaps in those 
mechanisms. The existing pediatric study requirement does not 
apply to off-label uses. While the existing incentives can be 
applied to off-label studies, they are voluntary--and we are 
seeing that manufacturers are increasingly opting not to 
conduct the studies FDA requests. Unambiguous authority to 
require such studies when the off-label use is significant will 
help ensure that children too can reap the benefits of an 
improved drug safety system.
    In our view the subcommittee must make the public 
dissemination of trial results a cornerstone of its drug safety 
efforts. The establishment of a results database would be a 
significant step forward in giving patients and providers 
additional information with which to assess benefits and risks. 
By linking the registration of new trials with final outcomes, 
this database also could help prevent selective reporting of 
positive results and the problems that have resulted from the 
withholding of negative trial results. And, not incidentally, 
given that clinical trials could not exist without patients' 
willingness to give of their time and health, such a mechanism 
could help restore patients' trust in the integrity of the 
clinical trials process.
    While we work toward providing the FDA additional 
authorities and enforcement tools, we must acknowledge that 
chronic under-funding is severely straining the ability of the 
Agency to perform even its current functions. Years of 
essentially flat funding, coupled with new challenges such as 
increasingly global markets, the threat of bioterrorism, and 
the promise of personalized medicine, have left the Agency 
struggling to meet its obligation to protect the public health. 
We--Congress, the Administration and patients--must work 
together to give the FDA the resources it needs to accomplish 
its critical mission. We suggest the combination of an increase 
in user fees targeted to drug safety activities and an increase 
in appropriations. Because we believe that the need for new 
authorities and for increased funding are so inextricably 
linked, we strongly recommend the subcommittee consider these 
issues, along with legislation to improve the safety and 
availability of pediatric drugs and devices, as part of a 
single legislative package.
    Mr. Chairman, you have before you a historic opportunity to 
finally match our nation's success in speeding new therapies to 
patients with a system that can better ensure the safety of 
those products once on the market. We appreciate your interest 
in patients' and providers' perspectives on these critical 
issues and look forward to working with you to accomplish these 
goals.
    Thank you again for the opportunity to share our views.
                              ----------                              

    Mr. Pallone. Thank you. Thanks a lot. Mr. Theriault.

 STATEMENT OF JOHN THERIAULT, CHIEF SECURITY OFFICER AND VICE 
               PRESIDENT, GLOBAL SECURITY, PFIZER

    Mr. Theriault. Thank you, Chairman Pallone and Ranking 
Member Deal and members of the subcommittee. My name is John 
Theriault. I am the vice president of global security at 
Pfizer. Prior to joining Pfizer, I was a special agent with the 
FBI for 25 years, retiring in 1995 as a member of the Bureau's 
Senior Executive Service. It is a pleasure to appear before you 
today to talk about a critical issue: drug safety and efforts 
to protect the U.S. pharmaceutical supply from counterfeit 
medicines.
    When I joined Pfizer in 1996, the company did not have an 
anti-counterfeiting program, frankly because there were no 
indications that any of our products were being counterfeited. 
That changed in 1998 when we launched Viagra, and I think that 
understanding what happened with that product at that time will 
help in understanding the counterfeit medicines industry that 
has evolved since then.
    Viagra was a unique product in 1998, and it was in great 
demand all over the world. But because of regulatory 
requirements, it was not legally available in many countries. 
So what we saw immediately was a global demand that was filled 
by entrepreneurs who purchased the product in a country where 
it was available and resold it sometimes at 10, 20 times what 
they had paid for it in countries where it was not available.
    Very soon thereafter, we saw our first counterfeiting case. 
It involved a UK organized crime figure who was convicted of 
conspiring to import counterfeit Viagra from a legitimate 
Indian company. Now, over the next few years, we conducted 
several investigations to identify Viagra counterfeiters and 
distributors. But in doing so, what we discovered was that they 
were counterfeiting and distributing other counterfeit 
medicines that we were not aware of. The Viagra investigations 
actually opened a door for us to look into a very robust 
counterfeiting industry that we didn't know existed.
    Since the inception of our anti-counterfeiting program, we 
have discovered counterfeit versions of our medicines in more 
than 60 countries. The medicines span a wide range of 
therapeutic areas, and they include Aricept, Lipitor, Norvasc, 
Diflucan, Ponstan, Cabaser Celebrex, Dilantin, Vibramycin and 
Zoloft. This is an issue that goes well beyond erectile 
dysfunction drugs. It is a counterfeiting issue that affects 
virtually every therapeutic area you can think of.
    Now, it is Pfizer's goal to make sure that every patient 
who buys a Pfizer product receives an authentic Pfizer product, 
and we consider the counterfeiting problem to be so serious 
today that our program to investigate and deal with it has 
increased from one security professional in New York in 1999 to 
17 security professionals based in the United States, Mexico, 
the United Kingdom, Germany, Turkey, mainland China, Hong Kong, 
India, Thailand, and Malaysia.
    To give you some idea of the scope of the problem, in 2006 
alone, law enforcement and customs authorities, with whom our 
investigators are working, conducted 238 raids, made 501 
arrests, seized over 8.1 million units of counterfeit Pfizer 
products and enough active pharmaceutical ingredient to 
manufacture more than 15 million counterfeit Viagra tablets and 
more than 20 million counterfeit Norvasc tablets.
    During those raids, counterfeit versions of other 
companies' medicines were discovered as well. Counterfeiting is 
a serious crime, and as you can see from this display, 
counterfeiters take great care in replicating the appearance of 
genuine product. The counterfeit product there is on the left. 
The authentic is on the right, and it is virtually impossible 
to differentiate those by visual inspection.
    But what you can see from the next display is that the 
counterfeiters don't really take quite as much care in the 
manufacturing process. Counterfeits are inherently dangerous. 
They are manufactured in unknown locations using unknown 
ingredients. We have seen counterfeits that contain no active 
pharmaceutical ingredient and therefore did not deliver the 
therapeutic benefits for which they were prescribed. Some 
contain super potent amounts of active ingredient, which 
increase the risks of adverse events, and yet others contain 
toxic ingredients that are harmful in themselves.
    Our experience indicates that the counterfeit medicines 
problem is growing, and it is being facilitated by the 
Internet, which provides both business-to-business distribution 
capabilities as well as retail opportunities, via bogus online 
pharmacies.
    Counterfeiters are also exploiting a loose distribution 
channel to get their bad medicine into the hands of patients. 
The evidence clearly reveals that the more times medicines 
change hands in the distribution system, the more opportunities 
there are to introduce counterfeits.
    Now, I said the problem is growing, and the reason for that 
is simple. This is a very, very high-profit, low-risk criminal 
enterprise, and we shouldn't lose sight of the criminal nature 
of this as we debate drug safety. How profitable is this for 
counterfeiters? That graphic shows that if you were to invest 
$20,000 in a kilo of cocaine--not that anybody would do that, 
but that is about what it costs these days. $20,000 for a kilo 
of cocaine would yield $60,000 in sales. Subtract the cost, and 
you have got a $40,000 profit. You can buy from any Indian 
company on the Internet the active ingredient for Viagra, $64. 
That would produce 14,000 50-milligram Viagra tablets at $10 
apiece, $140,000 in revenue. Subtract the $64, and you have got 
a much greater profit margin doing counterfeit drugs. This is a 
crime that attracts serious criminals.
    Now, the facts here are irrefutable. The importation of 
counterfeit, infringing, misbranded, non-approved, 
pharmaceutical products in the United States is increasing 
exponentially. Those products, by definition, pose a risk to 
public health and safety. The response by regulatory and law 
enforcement agencies to this growing crisis has to be reviewed, 
analyzed and modified at all levels.
    To sum up quickly, instead of discussing ways to deregulate 
the current safety system, we think that we ought to be 
discussing ways in which the current system could be improved 
to mitigate these threats to patients. Mr. Chairman, Ranking 
Member, members of the committee, thank you for the opportunity 
to share this with you.
    [The prepared statement of Mr. Theriault follows:]

                      Statement of John Theriault

     Chairman Pallone, Ranking Member Deal, and members of the 
subcommittee, my name is John Theriault. I am the chief 
security officer and vice president of global security at 
Pfizer Inc, the world's largest pharmaceutical company. It is a 
pleasure to appear before you today to discuss an issue of 
critical importance: drug safety and efforts to protect the 
United States pharmaceutical supply from contamination with 
counterfeit products.
     Prior to joining Pfizer, I spent more than 25 years as a 
Special Agent of the Federal Bureau of Investigation. During my 
FBI career I had substantial experience in international law 
enforcement and served for a number of years as the Legal 
Attache in Ottawa, Canada and London, England.
     Mr. Chairman, while my testimony today focuses on our 
experience with counterfeit Pfizer products, I wish to impress 
upon the subcommittee that these problems are not limited to 
Pfizer. They threaten the entire pharmaceutical industry and 
most importantly, the U.S. patients who depend upon that 
industry.
     As the subcommittee is well aware, there is already 
importation of counterfeit and diverted medicines into the 
United States through the mail, courier services, and some 
unethical re-packagers and wholesalers. Millions of Americans 
who assume that the prescription medicines they buy online are 
safe and effective are at risk. Regardless of the method of 
obtaining drugs from Canada or other countries, there is a real 
potential for fraud or harm. I would emphasize that every time 
a medicine changes hands represents--an additional opportunity 
for counterfeit products to be introduced into distribution.

 Counterfeit Pharmaceutical Products: What is the Scope of the Problem?

     The problem of counterfeit medicines, once thought to be 
limited to developing countries with weak regulatory systems, 
is now recognized as a global problem from which no country is 
immune. The manufacture of counterfeits is not limited to China 
and India. They are produced in at least twenty-four countries, 
including Canada, the United Kingdom, and four other members of 
the European Union--Belgium, the Netherlands, Poland, and 
Portugal.
     Since 1998, when the first counterfeit Viagra tablets were 
discovered in the United Kingdom, Pfizer has developed a 
focused anti-counterfeiting program to protect the integrity of 
our products and supply chain. Staffing for that program has 
increased from one security professional based in New York, to 
seventeen security professionals based in the United States, 
Mexico, the United Kingdom, Germany, Turkey, China, Hong Kong, 
India, Thailand, and Malaysia. Our Product Integrity Steering 
Committee has set as Pfizer's goal ensuring that every patient 
who buys a Pfizer product receives an authentic Pfizer product.
     We are waging a fierce battle against these 
counterfeiters. Pfizer products targeted by counterfeiters now 
include Aricept (Alzheimer's disease), Lipitor (cholesterol), 
Norvasc (hypertension), Diflucan (antifungal), Ponstan (anti-
inflammatory) and Viagra (erectile dysfunction), Cabaser 
(Parkinson's disease), Celebrex (pain), Dilantin (epilepsy), 
Vibramycin (antibiotic), and Zoloft (depression).
     Although it is difficult to measure the true scope of the 
counterfeiting problem, the number of reported seizures by law 
enforcement of Pfizer products serves as a useful baseline. 
During 2006, authorities from 36 countries reported seizing 
more than 8.1 million counterfeit tablets, a 20.8 percent 
increase over 2005. That increase was most significant in 
Europe, the Middle East and Africa, where seizures increased by 
more than 332 percent

        A Case in Point: Deadly Poison Masquerading as Medicine

    Fake medicines are costing lives. In March 2007, we heard 
of a tragic story of a woman's death which, according to press 
reports, was caused by drugs she ordered online from a bogus 
Canadian pharmacy. Instead of treatment for her arthritis and 
allergies, Ms. Marcia Bergeron was slowly poisoned by products 
that contained dangerously high levels of strontium, uranium, 
and lead, heavy metals that had apparently been used as a cheap 
filler. Ms. Bergeron started losing her hair and had blurred 
vision and died a few days after Christmas in 2006.
    We fear that there may be more terrible stories like this 
one. I'm sure you all have read the story from Sunday's New 
York Times about the hundreds of deaths in Panama from cough 
syrup from China that contained diethylene glycol.
    It is virtually impossible to see differences between 
counterfeit and genuine medications. If you visited the 
manufacturing facilities, the differences would be shockingly 
obvious. Drug counterfeiters do not care about safety or 
sanitation. They only care about profits, and counterfeiting is 
highly lucrative. The profitability of drug counterfeiting far 
exceeds that of the illicit drug trade. However, there is a 
lower chance that these counterfeiters will get caught, and if 
they do, the penalties are less punitive.

                    RxNorth: Profits before Patients

    Another case involves the Internet pharmacy RxNorth. A 
company whistleblower told a Canadian Television (CTV) news 
program that customers had received expired drugs, and that the 
expiry dates had been covered up on packages. In addition, the 
drugs were not Canadian. In fact, RxNorth was filling 
prescriptions for US citizens with counterfeit versions of 
Lipitor, Celebrex and other products. The CTV news program 
reported that many of the drugs RxNorth sold came from sources 
in the UK or Australia and were shipped to a dispensing 
facility in Freeport, the Bahamas, where Internet orders were 
filled and shipped to US customers.
    Counterfeiters often use a convoluted shipping path to 
evade the authorities and trick customers. For example, on May 
22, 2006, UK Customs intercepted a four-pallet shipment of 
pharmaceuticals, which had come to the UK from the United Arab 
Emirates (UAE). The shipment consisted of eight products 
manufactured by five major pharmaceutical companies: Pfizer, 
AstraZeneca, Novartis, Merck, and Proctor & Gamble. The shipper 
was the Oyster Corporation, of Sharjah, UAE. The intended 
recipient was Missouri-Bain Thomson, of the Personal Touch 
Pharmacy, in Freeport, the Bahamas. Investigation by the 
authorities determined that Personal Touch Pharmacy computers 
were connected to Rx North's servers. This is commonplace: 
according to a 2005 FDA study, fewer than two percent of the 
thousands of Web sites advertising cheap Canadian drugs are 
actually based in Canada.
    Our infrared spectral analysis of the seized Lipitor 
tablets showed that the Lipitor was counterfeit, and contained 
about 82 percent-86 percent of the claimed concentration of 
active pharmaceutical ingredient (API). The lot number printed 
on the packaging of the counterfeit Lipitor' was legitimate for 
a product produced for the Middle East market, and the 
counterfeit packaging was elegant. Pfizer analysts examined the 
packaging and determined that the ``i'' in the word 
``atorvastatin'' on the blister foil was placed differently, 
indicating a difference in font size; and the breakage-line 
between the single cavities showed that the authentic blister 
has a tighter punching line than the sample. The counterfeit 
packaging also contained a patient information leaflet, 
although it was smaller than a genuine leaflet, and missing a 
page. The fact that the counterfeiters are using legitimate lot 
numbers is concerning, since it demonstrates a level of 
sophistication in their deception that makes the counterfeits 
that much harder to detect.
    On June 1, 2006, Pfizer investigators notified the Bahamian 
authorities of the facts in this case, and on June 9th the 
Bahamian authorities raided the Personal Touch Pharmacy in 
Freeport. There they seized $3.7 million worth of products, 
spanning numerous different brands from 13 different 
manufacturers. The total amount of product seized amounted to 
3.025 million dosage units of products. The Bahamian 
investigation determined that approximately $8 million worth of 
business was conducted at Personal Touch Pharmacy on a yearly 
basis. The investigation is ongoing.
    We remain concerned that there are thousands of similar 
situations that remain undetected, and that consumers like Ms. 
Bergeron will be victims to this fraud and greed. As Congress 
develops drug safety legislation, it is essential that you 
carefully consider this very dangerous situation that has yet 
to be adequately addressed.
    The facts are irrefutable. The importation of counterfeit, 
infringing, misbranded, and unapproved pharmaceutical products 
into the United States is increasing exponentially, and those 
products, by definition, pose a risk to public health and 
safety. The response by regulatory and law enforcement agencies 
to this growing crisis must be reviewed, analyzed, and modified 
at all levels. The public health and safety depend upon the 
FDA's vigilance. The FDA and Customs must receive the 
additional resources necessary to fulfill their current 
mandate. Regulations currently in existence must be fully 
funded and fully enforced. The notion that somehow importation 
can be done safely by implementing so-called anti-counterfeit 
technology is to ignore everything we know about counterfeiting 
and counterfeiters. Similarly, the notion that importation on 
any scale will be as safe as the current system is to ignore 
all of the available evidence. Again, any time a medicine 
changes hands presents a new opportunity for the introduction 
of counterfeits into distribution. Instead of discussing ways 
to ``de-regulate'' the current safety system, we ought to be 
discussing ways in which the current system can be improved to 
mitigate these threats to patients.
     Mr. Chairman, Ranking Member Deal, and distinguished 
members of the subcommittee, thank you for this opportunity to 
express our concerns about this critical issue. I would be 
happy to answer your questions.
                              ----------                              

    Mr. Pallone. Thank you. I recognize Dr. Levine.

STATEMENT OF SHARON LEVINE, M.D., ASSOCIATE EXECUTIVE DIRECTOR, 
  PERMANENTE MEDICAL GROUP, SPEAKING ON BEHALF OF THE KAISER 
                PERMANENTE MEDICAL CARE PROGRAM

    Dr. Levine. Mr. Chairman, distinguished committee members, 
I am a physician with Kaiser Permanente in northern California, 
and I oversee the Permanente Medical Groups' efforts on drug 
use management in partnership with my Kaiser pharmacist 
colleagues.
    Our shared goal is the delivery of high-quality, safe and 
effective drug therapy and pharmaceutical services to our 
members. In order to do this, our physicians and pharmacists 
need the best available information on the safety and 
effectiveness of the drugs we prescribe and dispense. The 
importance of this issue is increasing every year. New, more 
powerful drugs are being approved and released to the market, 
and prescription drug therapy is playing an ever-increasing 
role in therapy.
    An important benefit of our efforts to fully integrate 
pharmacy services with health care delivery is that we are able 
to capture detailed and very complete information about the 
drugs we prescribe and dispense since almost 98 percent of 
prescriptions written for Kaiser members are filled in our 
pharmacies at our facilities, and we are able to match that 
information with robust clinical and demographic data that is 
captured in our delivery system and our health plan.
    Because of our large and stable population, we have the 
ability to generate enormous statistical power in research 
studies that we do. We have begun in earnest to utilize these 
data to learn more about the safety and effectiveness of 
specific prescription drugs and to answer questions which, when 
applied clinical practice, will protect consumers from drugs 
that pose an unacceptable risk compared to the benefits the 
drugs provide.
    We believe strongly that there is a need for an 
intentional, careful, and systematic data collection and review 
of a drug's use, which begins with its introduction into the 
market. This will enable faster identification of safety 
problems that result from the use of the drug outside the 
carefully controlled circumstances of phase one through three 
trials--ideally before rapid uptake of the drugs in the market 
exposes more people than necessary to unanticipated risks.
    Our researchers have access to and analyze data from 
multiple sources; membership records, hospital discharge 
records, outpatient and inpatient prescription data, outpatient 
clinic data, and laboratory and x-ray results. My written 
testimony provides detailed information on these data sources 
and how they are used. And I want to share with you today two 
examples.
    The Vioxx story is obviously very well known to this 
committee. Almost everyone has mentioned it, and it has become 
the poster child for the call to protect the public from 
unacceptable risk. A relatively limited population of Kaiser 
Permanente members were exposed to this drug. We had in place a 
Web-based tool to enable physicians to identify the small 
subset of patients who actually stood to benefit from the 
theoretical advantage that the drug provided, that of avoiding 
serious gastrointestinal side effects Yet millions and millions 
of patients in the general population received this drug. 
Almost 107 million prescriptions for Vioxx were filled before 
the drug was pulled from the market.
    In collaboration with the FDA, Kaiser Permanente 
researchers and clinicians were able to confirm that Vioxx 
increased significantly the risk of coronary events, 5 years 
after introduction of the drug into the market and 5 years 
after the VIGOR trial which first raised the issue of vascular 
events.
    Equally important, the same prescription drug and clinical 
data can be used to erase safety concerns that are raised by 
spontaneous reports of adverse events. In March 2005, the FDA 
issued an advisory to physicians urging caution in prescribing 
topical tachrolinus and pimecrolimus, two topical agents used 
to treat eczema and other skin conditions, because of concerns 
raised by animal studies and isolated case reports in a small 
number of patients. Matching up our pharmacy database with our 
cancer registry, we were able to identify those patients who 
had received those two drugs and were also diagnosed with 
cancer. Our researchers actually found no increase in the 
overall cancer rates but did find an increase in cutaneous T-
cell lymphoma, a skin malignancy, among the drug users.
    By examining the medical records of these patients, and 
excluding those that the physicians suspected of having cancer 
prior to the drugs, our researchers were able to find no 
increased risk either of cancer in general or of cutaneous T-
cell lymphoma.
    These are just two examples of what is possible using 
existing data, and my written testimony contains many more 
examples. In systems like Kaiser Permanente and the Veterans 
Administration today, the rapidly approaching future of 
complete clinical data capture with electronic medical record 
systems will significantly enhance the ability of researchers 
to identify and quantify problems and assess associated risk, 
which will inform better risk/benefit analysis.
    I want to thank the committee for taking these issues under 
consideration and for your interest in this, and I look forward 
to answering your questions.
    [The prepared statement of Dr. Levine follows:]

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    Mr. Pallone. Thank you, Doctor. Dr. Powers.

STATEMENT OF JOHN POWERS, M.D. ASSISTANT PROFESSOR OF MEDICINE, 
   THE GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE, AND 
           UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE

    Dr. Powers. Thank you, Mr. Chairman and members of the 
committee. My name is John Powers, and I am a physician 
scientist who worked at the Food and Drug Administration for 
the last 8 years. My background is that of a practicing 
clinician and academic investigator and researcher, a scientist 
in the field of drug development, a consultant for several drug 
sponsors, and most importantly, I have been a patient myself. I 
would like to thank you for the opportunity to discuss with you 
today my perspective on the issues of evaluating the risks and 
benefits of medical intervention.
    The Institute of Medicine report on drug safety points out 
that the current reauthorization of the Prescription Drug User 
Fee Act is a golden opportunity to address long overdue 
improvements needed in our system of evaluating drug safety. 
The GAO report points out that there have been at least five 
separate reports since 1971 related to these issues. Therefore 
PDUFA should not be reauthorized without simultaneously 
addressing the important public health issues related to drug 
safety that have persisted for some time.
    Previous drug legislation addressed the issues of pre-
approval safety in 1938 and pre-approval effectiveness in 1962. 
But it is now clear that we need more focus on continuously 
evaluating drugs even after approval.
    For instance, the example of the inevitable emergence of 
antibiotic resistance points out how the assessment of both 
safety and effectiveness of drugs can change over time. The 
standard we should use to judge proposed changes in drug safety 
should be would these changes prevent another safety episode 
like Vioxx of Ketek? Tying pre-approval review that brings 
medical interventions to patients and appropriate post-approval 
evaluations of those same interventions are not mutually 
exclusive goals, and we can do both.
    I would like to divide the issues related to addressing 
drug safety into three categories. First, inputs of resources 
in authority into FDA. Second, internal use of science 
resources and processes inside FDA. And third, outputs of 
decisions and communications with the public from FDA.
    In terms of inputs into FDA, Congress should authorize 
adequate funding for general appropriations, and any PDUFA fees 
should have no strings attached, and their use should not be 
negotiated with regulatory industry. FDA needs the authority to 
require post-approval studies, to mandate labeling changes, and 
to assess simple monetary penalties for not fulfilling risk 
management activities.
    The legislation proposed by Mr. Markey and Mr. Waxman is a 
start in this direction by providing more meaningful penalties. 
FDA needs access to modern databases and active surveillance to 
more efficiently gather information on drug use and potential 
adverse events.
    Any organization is only as strong as the people who work 
there, so FDA needs to hire adequately trained staff and ensure 
the staff remain engaged as a part of the scientific community. 
This leads to issues involving science and process inside of 
FDA. FDA scientists should be free to participate as members of 
the scientific community by having the right to publish and 
share their information and participate in scientific meetings.
    There needs to be a culture of professionalism at FDA. And 
if, on rare occasions, after attempting to reach internal 
agreement, FDA staffers need to seek help outside of FDA in 
order to protect the public's health, there needs to be 
enhanced whistle-blower protections, such as those outlined in 
Mr. Markey's Swift Approval Full Evaluation Act.
    There also needs to be accountability for FDA staff who 
attempt to retaliate against their colleagues or who do not 
uphold the laws and regulations. For instance, in cases where 
drugs have been knowingly approved without substantial evidence 
of effectiveness.
    Any system should have checks and balances, and the Office 
of New Drugs and the Office of Surveillance and Epidemiology 
should have joint decision-making authority regarding post-
approval decisions. FDA needs to define what they mean by best 
use of science and define the criteria used for making risk/
benefit decisions in general.
    In terms of outputs from the FDA, we need transparency of 
decision making in the form of summary bases of approval 
published on the FDA Web site in a timely fashion, which 
explain the scientific rationale for regulatory decisions. This 
would be helpful for both regulated industry and for patients. 
All clinical trials and their results should be included in a 
registry.
    It is FDA's job to communicate with the public, and FDA 
needs the resources to evaluate the effectiveness of all of the 
methodologies used to try to accomplish this goal, as it is 
well known that changes in labeling alone have little effect on 
prescribing behavior.
    The IOM report reinforces that now is the time to address 
sorely needed improvements in evaluating drug safety. Congress 
should include provisions for strengthening drug safety in any 
reauthorization of PDUFA. We can address issues in evaluating 
drug safety in an efficient way without hindering access to 
important medical advances for patients.
    Making these changes today will help us to avoid another 
Vioxx or Ketek tomorrow. Congress can help FDA start down the 
road of being the foremost authority on pharmacoepidemiology, 
to help them work closely with the scientific community, and to 
develop scientifically-based approaches to evaluating the 
balance of risk and benefits for drugs.
    This will help FDA achieve its stated mission of protecting 
and advancing the public health. Most FDA staffers are 
incredibly hard workers and courageous public health servants. 
Please give them the tools they need to do their jobs for all 
of us. Thank you.
    [The prepared statement of Dr. Powers follows:]

                   Statement of John H. Powers, M.D.

    Good morning Mr. Chairman and members of the committee. My 
name is John Powers. I am a physician-scientist who worked at 
the Food and Drug Administration for the last 8 years. My 
background is that of a clinician in internal medicine and 
infectious diseases, an investigator and researcher in clinical 
trials, a scientist in the field of drug development, and a 
consultant for several drug sponsors. Perhaps most importantly, 
I have been a patient myself. I would like thank you for the 
opportunity to discuss with you today my perspective on the 
issues of evaluating the risks and benefits of medical 
interventions.
    As the Institute of Medicine report on drug safety points 
out, the current reauthorization of the Prescription Drug User 
Fee Act is a golden opportunity to address long-overdue 
improvements with drug safety in order to adequately protect 
the public's health. PDUFA should not be reauthorized without 
simultaneously addressing the important public health issues 
related to drug safety. The standard we should use to judge 
proposed changes to the evaluation of drug safety should be: 
Would these changes prevent another drug safety episode like 
Vioxx or Ketek? Bringing medical interventions to patients in a 
timely way and appropriate post-approval evaluations of those 
same interventions are not mutually exclusive goals, and 
addressing post-approval drug safety need not slow bringing new 
medications to patients. Indeed, the FDA Critical Path 
initiative points out that better tools for pre-approval 
evaluation of potential safety issues may allow more efficient 
drug development, earlier cessation of drug development 
programs of drugs with toxicities before spending precious 
resources, and more focused evaluation of drug toxicities post-
approval.
    The passage of the Food, Drug and Cosmetic Act (FD&C) in 
1938 shifted the burden of the evaluation of pre-approval 
safety of drugs from the government to drug sponsors. From that 
time forward there was no assumption that a drug was safe, and 
sponsors had to provide evidence of the potential adverse 
events associated with drug use. This reflected a notion that 
is clear today; no drug is completely safe in that all drugs 
are associated with some adverse events. In 1962, Congress 
amended the FD&C Act to require substantial evidence of 
effectiveness based on adequate and well-controlled trials, 
codifying the logic that there must be evidence of benefit in 
order to justify any risks of drugs, no matter how rare.
    Both these provisions focused on the pre-approval 
evaluation of medical interventions, which was appropriate for 
that time. However, it is now clear that we need to focus on 
the entire life-cycle of medicines with a greater focus on 
post-approval evaluations. This is eminently sensible as we 
cannot learn all we need to know about medical interventions 
given the limited number and types of patients and the short 
time span in which drugs are studied pre-approval. The vast 
majority the life-cycle of a drug is spent post-approval, and 
it follows we can learn much about a drug during this time. FDA 
must play a crucial role in continuing to evaluate drugs once 
they are approved.
    The need for regulation is two fold: first, regulation is 
needed when market forces tend to guide businesses in a way 
that may be contrary to public interest, and second, regulation 
provides a uniform standard for public health and consistency 
and fairness for the regulated industry. In regards to the 
first point, there is little incentive for drug sponsors to 
rigorously evaluate potential safety issues with a drug once it 
is approved since from a business perspective this evaluation 
has the potential to decrease sales. This is in contrast to 
providing evidence of drug effectiveness prior to approval 
which is necessary both for FDA approval for marketing and to 
convince clinicians to use the drug. Many drug sponsors 
certainly do include protecting the public's health in their 
decision making. But as James Madison stated in the Federalist 
#51 in 1788, if all men were angels no government would be 
necessary. Even one sponsor who decides that profits trump 
public health is one too many and it is the FDA's job to ensure 
all sponsors are held to the same standard. This relates to the 
second point, which is that FDA is supposed to ensure a 
scientifically based and consistent standard of public health 
both for the sake of the public health, and out of fairness to 
drug sponsors so that every sponsor is subject to the same 
rules. This allows less uncertainty in drug development, and 
allows sponsors to plan their studies accordingly. The only way 
to ensure both protecting and advancing the public health and 
fairness to drug sponsors is to base laws and regulation upon 
the best science. Since science changes over time as we learn 
new things, regulations need to adapt as well. The prior focus 
on pre-approval evaluations is still needed, but we now need to 
focus our attention of post-approval evaluations as well.
    One can view the issues related to addressing drug safety 
as divided into three categories: inputs of resources and 
authority into FDA, internal use of resources, science and 
functioning inside FDA, and outputs of decisions and 
communications with the public from FDA.

                           I. Inputs into FDA

    FDA staff need the resources in terms of funding, manpower, 
knowledge, data and authority to do its job properly.
     Congress should authorize adequate funding for FDA from 
general appropriations and PDUFA fees should have ``no strings 
attached'' and not be negotiated with regulated industry: FDA 
has been severely under-funded for some time, even to do the 
job it already has to do. Indeed, the original intent of PDUFA 
in 1992 was to bring greater funding to FDA to provide it the 
resources it needed at that time. To address the larger issues 
of post-approval evaluations of drugs it will need greater 
funding. It seems logical that regulated industry should pay 
for a fee for licensing of drugs to defray the costs to the 
government, similar to how drivers pay a fee for their drivers' 
license of doctors pay a fee to State medical boards for a 
license to practice medicine. However, drivers and doctors do 
not negotiate the uses to which those fees are put with 
Division of Motor Vehicles or the State Medical Board. In 
addition to the obvious appearance of conflict of interest of 
allowing the regulated to help decide where the regulator 
appropriates funds, the long time frame between PDUFA 
negotiations--done only once every 5 years--does not allow FDA 
to adapt and shift resources to where they are most needed. 
Again, there is a need for regulation when there is no 
incentive for the regulated to address issues of public health, 
and previous negotiations of PDUFA in which FDA was barred from 
applying fees to post-approval safety evaluations are evidence 
of a desire by some to avoid performing these evaluations.
     FDA needs adequate authority to ensure the public health 
including ability to assess sufficiently stringent civil 
monetary penalties for non-adherence and sufficient authority 
to ensure device effectiveness--FDA needs the authority to 
require post-approval studies and ensure sponsors complete 
those studies. As noted previously, there is an obvious 
incentive for drug sponsors to submit data in support of drug 
effectiveness. Since there is less incentive to perform post-
approval studies, FDA needs the ability to require studies and 
impose meaningful penalties on drug sponsors who do not fulfill 
their stated commitments. The Enhancing Drug Safety and 
Innovation Act (H.R. 1561) is a start in this direction by 
providing for more meaningful penalties beyond those that 
sponsors could just write off as the cost of doing business. 
Penalties need to be appropriate in order to provide an 
incentive to comply. In addition, the current legally mandated 
standards for effectiveness of devices are quite different for 
those from drugs. It is not clear from a scientific point of 
view why this should be so, as patients who receive devices 
should receive the same protection under the law as those who 
receive drugs. Recent approvals of some devices have left 
outstanding questions regarding their effectiveness, such as 
the vagal nerve stimulator for depression. This seems to 
contradict the basic principle that there needs to be 
substantial evidence of effectiveness in order to justify the 
risks of any intervention. Congress should address this by 
changing the law to hold devices to the same standard of 
substantial evidence of effectiveness from adequate and well 
controlled trials as for drugs.
     FDA needs adequate data upon which to base decisions--The 
use of modern databases to more efficiently gather information 
on drug use and potential adverse events is desperately needed. 
FDA cannot rely on the good graces of busy clinicians for 
spontaneous reports of adverse events. Many medical schools do 
not teach their trainees about the need to report adverse 
events, so there is a need for education as well. FDA always 
needs to stay in touch with practicing clinicians, but they 
cannot be the only source of information in evaluating medical 
interventions post-approval. In addition, for reasons discussed 
previously drug sponsors cannot be the sole source of 
information. There is little incentive for them to report 
adverse events and there are recent unfortunate examples in 
which important information was withheld from FDA. If FDA had 
independent sources of information this would be less of a 
concern.
     FDA needs to hire adequately trained staff--It is 
important that FDA hire, train and keep staff who have a 
background and training in drug development and evaluation. It 
is sad to say that many in academic medicine view a career at 
FDA for their trainees as ``a waste of time'' and 
``unscientific''. FDA needs to be on the same scientific par as 
the National Institutes of Health and the Centers for Disease 
Control and Prevention in terms of scientific reputation and in 
terms of appropriately applying science. The only way to 
accomplish this goal is if the scientific community has 
positive interactions with FDA staff, instead of the current 
``black box'' that clinicians see as the current FDA.
     FDA needs close contact with the scientific community--FDA 
has to have a symbiotic relationship with clinicians and 
scientists. As science is ever-changing, FDA staff need to keep 
abreast of the latest scientific developments. In addition, FDA 
staff have much to teach the scientific community about 
clinical trials and the pharmacoepidemiology, and much of the 
view that FDA is ``unscientific'' comes from a lack of 
understanding of the scientific principles upon which 
appropriate drug evaluation is based. This means that FDA staff 
need to be able to interact with scientist in their fields, an 
issue I will address in terms of outputs from FDA as well.

                   II. Science and Process Inside FDA

    FDA has become too focused on ``process'' to the exclusion 
of the reason for why process is needed. The process as FDA 
should serve good science which in turn protects and advances 
the public health. Science should not serve process. 
Appropriate processes are needed in order to drug sponsors to 
submit data and for FDA staff to review this data in an orderly 
way. However, on the Center for Drug Evaluation and Research 
guidance page there are 53 guidances under the heading of 
``process'' and 3 under the heading of ``drug safety''. Clearly 
this balance seems tilted in the wrong direction. FDA managers 
needs to treat the scientists and review staff with 
professionalism and the basis for decision making needs to be 
good scientific principles
     FDA managers need to treat staff with professionalism--
Science is based on the scientific method, and as such, any one 
who uses this method, from the medical student to the senior 
attending, can make equally valid analyses and draw equally 
valid conclusions. As with school teachers, if most of their 
class fails the examination, they must take part of the blame. 
If FDA managers believe their staff is not using appropriate 
scientific analyses, then it is incumbent on these managers to 
train staff in these same principles and provide mentoring for 
them and career development paths. It is inappropriate and 
unprofessional to characterize scientists who raise scientific 
issues as ``disgruntled'' or to characterize a scientist work 
as ``junk science''. FDA managers need to realize that there 
are substantial issues with the relationships between managers 
are staff at FDA that need to be addressed. A Union of 
Concerned Scientists poll of FDA staff showed that 44 percent 
of FDA scientists did not respect their managers' integrity. A 
substantial shift in culture at FDA is needed, and this can be 
accomplished by making FDA place where people who follow the 
scientific method and who treat their peers with respect want 
to work and those who choose not to behave professionally don't 
want to work
     Joint authority of Office of New Drug and Office of 
Surveillance and Epidemiology regarding post-approval decision 
making. It is part of the scientific method that data, analysis 
and conclusions undergo peer review and re-analysis by others 
to confirm the conclusions of a given set of scientists. Also, 
it is only human nature that when one makes an important 
decision that may affect the lives of thousands or million of 
persons it is very disheartening to learn that decision may 
have resulted in people being harmed. However, it is also part 
of science that we learn more as more evidence accumulates. 
Lastly, systems function best when there are checks and 
balances and no one person or group of persons exerts absolute 
authority. The framers of the Constitution set up a bicameral 
legislature and three branches of government for exactly this 
purpose. For all these reasons there needs to be joint decision 
making authority between the Office that approves new drugs 
(the Office of New Drugs) and the Office responsible for 
evaluating drugs after approval (the Office of Surveillance and 
Epidemiology). The Enhancing Drug Safety and Innovation act 
could be strengthened by including provisions for this joint 
authority.
     Accountability for decision making and behavior at FDA and 
increase ``whistleblower'' protections -There needs to be 
accountability for FDA managers who treat staff 
unprofessionally, both from within FDA by senior managers and 
from oversight from Congress to ensure that accountability 
takes place. Increased transparency of the operations at FDA 
would discourage some from inappropriate behavior, and all of 
FDA would benefit from changing the perception held by many 
clinicians, academics and those in industry that FDA is a 
``black box'' in which operations, decision making and the 
scientific reasoning behind decision making seem unclear. There 
is no blind acceptance of data in science, and statements that 
``FDA cannot be second-guessed'' do not take into account that 
``second-guessing'' (also called peer review and confirmation 
of evidence) is part of science. One of the basic premises of 
the scientific method is we can never be sure we are correct, 
but we can always be proven wrong, so one needs to keep an open 
mind at all times. No one questions that FDA managers have the 
authority to render decisions, but with the authority comes 
responsibility. There is no such thing as the FDA, as FDA is 
made of up individuals. It would be best if no staff person at 
FDA ever has to ``blow a whistle'' on inappropriate use of 
science or failure to protect the public's health, but should 
this be necessary, FDA staff need to know they will not be 
risking their livelihood to protect patients. Therefore there 
needs to be increased whistle-blower protections such as those 
in the legislation proposed in the Swift Approval Full 
Evaluation act.
     Best Use of Science and Consistency of Decision Making 
within FDA and publication of guidance on risk-benefit 
analysis--One of the major complaints of drugs sponsors is that 
they receive inconsistent advice from FDA. While in some cases 
advice can and should change as science advances during the 
course of drug development program, some sponsors feel that 
they do not receive consistent scientifically-based advice from 
Division to Division within FDA across similar drug development 
plans in different therapeutic areas. This would seem at odds 
with using appropriate scientific methods to make decisions. 
FDA needs to train staff on the scientific and legal bases for 
drug evaluation, especially in that there are legally mandated 
standards for drug effectiveness that must be followed in order 
to justify the potential adverse events of drugs. FDA needs to 
formulate guidance which explains the scientific decision 
making process of balancing risks and benefits. While there 
needs to be some flexibility to accommodate individual cases, 
there are some basic principles which would apply to all 
situations, such as evaluating the frequency, severity and 
seriousness of adverse events weighed against the nature and 
magnitude of the benefits of a medical intervention. FDA 
reviews need to explain the scientific as well as legal basis 
for decision making and conclusions so that sponsors, 
clinicians and the public can understand the scientifically 
reasoning behind a decision. FDA reviews include a tremendous 
amount of data and analysis but is it not always clear how this 
data is synthesized into an overall decision.

                         III. Outputs from FDA

    FDA serves the public and therefore needs to communicate 
with the scientific community, clinicians and patients as well 
as drug sponsors.
     Transparency of decision making and reviews at FDA--The 
Belmont Report in 1979 on the protection of subjects in human 
research pointed out that research is the pursuit of 
generalizable knowledge. For research to be ethical the 
knowledge obtained must be generalizable in order to justify 
exposing subjects to the risk of the research. If research is 
not generalized, that is, shared with others in the scientific 
community then it is inherently unethical. Therefore it is 
incumbent upon FDA and drug sponsors to share the information 
from all clinical trials. A registry that includes a listing of 
all clinical trials including the results of these trials would 
allow knowledge to be generalized. The Enhancing Drug Safety 
and Innovation Act includes such a provision. It is important 
that data from earlier phase trials be included in such 
registries and databases as these earlier phase trials often 
form the basis for evaluation of further adverse events post-
approval. In addition the results of these trials, not merely 
that fact that they are ongoing or completed, need to be 
included in any database in order for the results to be 
generalizable. FDA reviews should be published on the FDA 
website within a reasonable period of time (no longer than a 
few weeks) in order for the scientific community to evaluate 
the basis for FDA decision making. This form of peer review is 
part of the scientific process.
     FDA staff should have a right to publish and participate 
in scientific meetings--As noted previously, FDA reviewers need 
to keep current with the science in their field. This means FDA 
staffers need to share their knowledge with those outside FDA 
as well as gaining knowledge themselves from scientists outside 
FDA. FDA reviewers need to be able to share their analyses with 
the scientific community and the need to FDA managers to ``make 
one decision'' should not bar a scientific discussion among the 
scientific community. The Supreme Court ``make one decision'' 
and yet members of the Court still publish a minority as well 
as a majority explanation of their findings. Therefore, FDA 
should publish a Summary Basis of Approval (SBA) for each 
medical intervention which would include a discussion of any 
and all scientific differences during the review process and an 
explanation and scientific reasoning for the final conclusions.
    The IOM report tells us that now is the time to address the 
important issues in evaluating drug safety that have needed to 
be addressed for some time. In order to address this urgent 
public health issue, we need to act now. Congress should 
include provisions for strengthening the evaluation of drug 
safety in any reauthorization of PDUFA. A recent Harris poll 
showed that the public is losing confidence in FDA, and the 
only way to restore that confidence is by action, not merely by 
words or reshuffling of the structure of FDA and without new 
resources and authority. We can address the important issues in 
evaluating drug safety in an efficient way without slowing 
bringing important medical advances to patients. Safety and 
efficiency and not mutually exclusive goals and more focus on 
post-approval activities need not slow pre-approval 
evaluations. However, we need to learn from recent events and 
take action today to avoid another Vioxx or Ketek tomorrow. 
Congress can help FDA start down the road to being the foremost 
authorities on pharmacoepidemiology, to work closely with the 
scientific community to gather data and to develop new methods 
and analyses, to come up with cogent scientifically based 
approaches to evaluating the balance of risks and benefits of 
drugs, and help FDA achieve its stated mission of protecting 
and advancing the public health. Most FDA staffers are 
courageous public health servants. Please give them the tools 
they need to do their jobs for all of us.
                              ----------                              

    Mr. Pallone. Thank you. And we will take questions of the 
panel now. Thank all of you again for being here. I am just 
going to recognize myself for 5 minutes for some questions, and 
I wanted to ask a couple questions of Ms. Thompson.
    First of all, let me thank you for all the good work you do 
with the Elizabeth Glaser Pediatric AIDS Foundation. I am 
familiar with it, and I really know that you do a great job. 
But I found your testimony interesting because you suggest that 
the goals of a strong and robust drug safety system and at the 
same time, innovative medicines are not necessarily mutually 
exclusive, that you could possibly do both. And I am wondering 
if you could elaborate more on why you think that doesn't have 
to be an either/or scenario? In other words, if we were to pass 
drug safety legislation that built upon what is already 
included in the PDUFA IV proposal, that included stronger 
monitoring and enforcement provisions--in other words, like if 
we did what Mr. Waxman and Mr. Markey have included--do you 
think that would kill innovation? Or would we still be able to 
be innovative, so to speak?
    Ms. Thompson. Well, I think we strongly believe that it 
won't, in fact, kill innovation. What the IOM has proposed and 
what, I think, has been picked up both in the Waxman-Markey 
bill and the Kennedy-Enzi bill is to address this new paradigm 
of looking at safety concerns throughout the life cycle of the 
drug. So it is really taking the FDA back, in some senses, to 
its roots under the original 1938 statute, which was all about 
safety. Of course, efficacy wasn't added until 1962.
    So by providing FDA the resources that it needs to maintain 
its scientific excellence, the resources that it needs to 
integrate more fully safety concerns both into the drug review 
process and into the post-market surveillance process, I think 
you have got the perfect recipe for enabling innovation to 
continue and, in fact, supporting it because one of the areas 
that has suffered under PDUFA is the FDA science base.
    And FDA, in order to support the innovation that is coming 
out from industry, needs to be the leader in terms of 
regulatory science and in terms of advancing the tools and 
techniques that are going to support regulatory discovery and 
how that discovery gets translated into new therapies.
    Mr. Pallone. Thank you. In your testimony, you call for 
giving FDA authority to require testing for off-label uses of 
drugs. But if Congress granted FDA such authority, how would 
that match up with the Pediatric Incentive Program? How exactly 
would those two programs work together? Would granting such 
authority obviate the need for the incentive program? If you 
would explain.
    Ms. Thompson. Well, the answer is no, it would not obviate 
the need, but we begin with the position that three-quarters of 
the prescriptions that are written for children are written off 
label. And the Pediatric Incentive Program, the program you 
referred to, BPCA, Best Pharmaceuticals for Children Act, 
provides a voluntary mechanism where FDA can go out and, if the 
drug is still on patent, it can recommend to a manufacturer 
that the manufacturer conduct certain studies to determine 
effectiveness and/or safety in children.
    But that only applies on a voluntary basis. Obviously under 
the stick part of that equation, the pharmaceutical research 
side, that legislation for the most part applies only to new 
drugs. And there is a very high standard that FDA has to meet 
to require studies now, very high safety finding or danger 
finding that the FDA has to make.
    So providing new authorities in combination with the 
existing carrot-and-stick approach under pediatrics is really 
essential if the FDA is going to be able to identify safety and 
effectiveness for children.
    Mr. Pallone. Thank you. I am just going to try to get in a 
couple questions here to Ms. Van Syckel. Thanks again for being 
here. But in your testimony, you don't specifically call for 
the repeal of the user fee system. In fact, you suggest that it 
should be expanded, but you call for it to be decoupled from 
obligations made to the industry. Would you just comment 
further on that? And then I am going to ask you also a second 
question. You have been very vocal about improving 
communications about medications to patients and providers, and 
you have focused on the availability of the distribution of med 
guides. Is there something that you think Congress could do to 
improve communications about medication risks through changes 
to the med guide system? So second, the med guides, and third 
this whole idea of decoupling the user fee system.
    Ms. Van Syckel. OK, let us start with the med guides first.
    Mr. Pallone. OK.
    Ms. Syckel. First we have a bill, S. 2364, in New Jersey 
that is sponsored by Senator Codey and Senator Lance. We have 
got two good guys there. And what we are trying to do is these 
medication guides, we don't want to find them, if we get them, 
in the bottom of a pharmacy bag. So what we would like is to 
have parental informed consent. Look at the med guide with the 
doctor, go over the med guide, don't just put it in the bottom. 
I took this off the Internet. It is that simple. Doctors can do 
that.
    And I asked Assemblyman Conaway, because we had discussed 
this issued. And I said Doctor, have you seen the med guide? 
And he said yes, and I guess he assumed he had. And I said 
well, could you please tell me what to look for? And he 
couldn't tell me, and this is a doctor within New Jersey on the 
assembly.
    And I think it is important because everybody is so 
concerned about the thoughts of suicide. There is a lot more of 
side effects than just the thoughts of suicide, and those are 
newer, worse irritability, acting aggressive, being angry or 
violent, and acting on dangerous impulses. And I will give you 
an example from New Jersey. There was a young teenager who was 
an honor roll student, participated in peer groups. He was 
over-medicated, and he brought a cache of weapons to school, 
loaded guns, to even the point that the father, the parents 
didn't even know where he got the guns.
    So violence issue with the anti-depressants has become 
very--is something that we should all be concerned about, and I 
was so concerned that I attended a White House conference on 
school violence and school safety. And I did have an 
opportunity to speak to Attorney General Alberto Gonzales 
concerning this issue, and I have even spoken to Mr. Ferguson 
because I saw how my daughter attacked three police officers, 
assaulted her brother. I see how violent the children become. 
And the Attorney General asked Secretary Leavitt, sent him a 
letter back in October to look at the violence issue concerning 
the antidepressants.
    So if parents don't have this med guide, and I think it is 
very insulting for the FDA to say that there are some outsiders 
who should determine what parents need to know. This is what we 
need to know so if we make a decision to give them an 
antidepressant, we can monitor them. The doctor can't do it. 
The school district can't do it. It is up to the parents, and 
we need this vital information.
    I guess I was kind of being diplomatic with PDUFA. If it 
were up to me in the great world, I would like to have it 
repealed. But it is not the perfect world, and I believe we 
need to focus more on an independent office of drug safety. I 
am trying to be diplomatic but I sometimes can't. I truly 
believe we need an independent office of drug safety. I agree 
with Senator Grassley and Senator Dodd on this issue. They have 
been at this issue for 4 years. They are knowledgeable.
    Mr. Pallone. OK, thank you so much. Mr. Deal.
    Mr. Deal. Mr. Theriault, I share your concern for 
counterfeit drugs. In a previous hearing that we had where the 
issue came up about adverse events, a questions was asked as to 
whether or not there was any way, with our current information, 
to distinguish adverse events that might have been caused by 
counterfeit drugs as opposed to brand-name drugs. And the 
general answer was no, there was not. Is there anything that we 
should to do to try to deal with that particular issue? And are 
there things that we might do that would--might have adverse 
consequences, thinking we were doing the right thing?
    Mr. Theriault. The adverse event reporting issue is 
something that I think is difficult, and I am not sure how you 
can differentiate between adverse events that are caused by 
counterfeits as opposed to legitimate medicine. From our point 
of view, the safety issue is addressable on a number of fronts. 
I think that stopping these personal use amounts of 
prescription medicines that come into the country, via the mail 
services and that sort of thing, is almost a no-brainer.
    We conducted a study about 2 years ago, and at the New York 
City mail facility alone, there were over 40,000 packages a day 
coming into that one mail facility that were identified as 
unapproved pharmaceuticals. Tightening the supply chain, 
requiring pedigrees, enforcing the pedigree aspect of PPNA. I 
think you can't regulate the Internet, but I think you can 
regulate the flow of products that are ordered on the Internet.
    Mr. Deal. Could you give us some idea what proportion you 
think are coming in from outside of the country versus 
counterfeiters who are operating within our own country?
    Mr. Theriault. In the last 10 years that I have been at 
Pfizer, we have had probably the most aggressive anti-
counterfeiting program in the industry. And I can't recall one 
counterfeiting manufacturing operation that we found in the 
United States. I would say the very, very high percentage of 
counterfeits in the 1990s comes from outside the United States. 
And that is why, when we address importation and issues like 
that, I think that unless we deal with the drugs coming in from 
outside the United States we are going to have a problem.
    Mr. Deal. Your written testimony indicates one particular, 
I think it was an Internet pharmacies supposedly in Canada. How 
big a problem is Internet pharmacy in this overall problem of 
counterfeiting?
    Mr. Theriault. Well, I think it is a huge problem. And to 
your earlier point, the woman who died in Canada, I think, was 
a U.S. citizen residing in British Columbia. As I understand 
the facts, the medicine she received came in an unmarked vial. 
There was no label, no safety information. There was very 
little possibility to determine where she bought those, and the 
Internet pharmacy that sell those things are up and down in a 
matter of days.
    So I think if you buy prescription drugs on the Internet, 
you are taking about a 50 percent chance of getting either 
counterfeit or unapproved generic medicines.
    Mr. Deal. And I suppose you would support increasing the 
penalties for the counterfeiting of drugs, would you not?
    Mr. Theriault. Yes, sir, I would. I think Congressman 
Rogers' bill is an excellent step in that direction.
    Mr. Deal. OK, I would like to briefly explore the 
procedures that are embodied at FDA now. I believe we refer to 
them as the critical path. Dr. Powers, since you have worked 
there, would you briefly comment on that initiative and whether 
you think it is appropriate?
    Dr. Powers. Sure, the critical path was initiated in March 
2004, which is an attempt for FDA to partner with folks outside 
the FDA, both academics and people in practice, to try to 
develop tools that would more efficiently help drug 
development, both in terms of measuring safety and 
effectiveness. It is a great idea, but it is one in which FDA 
is left in the position of having to suggest things to people 
outside the agency and really doesn't have funding at this 
point to be able to accomplish those things.
    So they published several, including one last week on 
generic drugs, saying here are some great things we would like 
to know the answers to, but are left without the resources to 
be able to do that in a lot of cases.
    For instance, let us take the issue of biomarkers. The way 
for us to explore whether those biomarkers are helpful in 
selecting which patients may benefit or which patients are at 
risk would mean looking at studies to see whether those 
biomarkers make any sense or not. And right now, FDA is left in 
the position of suggesting saying wouldn't this be a good idea.
    Mr. Deal. Money would help.
    Dr. Powers. It sure would.
    Mr. Deal. Thank you.
    Mr. Pallone. Mr. Ferguson.
    Mr. Ferguson. Thank you, Mr. Chairman. Thanks to all of our 
witnesses on our second panel. As most or some of you know, I 
spent my time in the first panel talking about medication 
guides. It is something I have spent a great deal of time on, 
and Lisa and I have actually worked on the issue a lot 
together.
    Lisa, we have heard your testimony today. Of course, I am 
very familiar with your own family's story. It is important 
that you continue to share that with folks, including in this 
setting, so people can just understand one family's situation 
and ordeal. And you had said before you represent kind of 
families in New Jersey, but you are not an official 
organization or group.
    Ms. Van Syckel. No, I am a mom.
    Mr. Ferguson. You are a mom. You are a parent like I am and 
so many of us are, trying to make sure you are taking care of 
your child and having information to take care of Michelle----
    Ms. Van Syckel. And Chris who is down in Florida.
    Mr. Ferguson. Yes. Now, with regard to the medication 
guides, you know that in 2004, we had our Oversight and 
Investigation Subcommittee hearings and investigations into 
this particular issue. And subsequent to that, these 
medications, SSRIs, who are prescribed for kids now are 
accompanied by or supposed to be accompanied by medication 
guides. That was after your family situation.
    Ms. Van Syckel. That is right.
    Mr. Ferguson. If you can hypothesize, I guess, or----
    Ms. Van Syckel. Finding out that the med guides weren't 
being distributed?
    Mr. Ferguson. Well, actually how would that have affected 
your own family situation? If you had been presented with a med 
guide when you filled that prescription for your daughter--I 
mean it is tough in hindsight to be able to go back and figure 
out what you would have done but----
    Ms. Van Syckel. And I don't believe I, at that time, would 
have known what to do because Michelle really didn't have 
depression or anorexia. It turned out she had Lyme disease, so 
we were desperate to help her. So would I have done this? I 
don't know. I may have, but armed with this information at 
least, I could have prevented the self-mutilation, the scars 
that are on her body today.
    We have a young girl who came to your office, and no one is 
immune to the side effects of the antidepressants, and this 
young girl, both of her parents work for the pharmaceutical 
industry. And if you look at her arms, do those look like 
little scratches to you? Cutting the word ``die'' onto the 
inside of your arm? Is that an acceptable side effect? I don't 
think so.
    Mr. Ferguson. Now, you----
    Ms. Van Syckel. But it is not here.
    Mr. Ferguson. You obviously are in touch with and work with 
other families who have had similar situations that we have met 
with.
    Ms. Van Syckel. They call me desperately seeking answers 
because they said my doctor told me it was safe and not to 
listen to the stories in the media, that they are parents that 
are--they are actually labeling parents like me.
    Mr. Ferguson. What do they say? And I have heard some of 
them talk. But what is the general sense among some of the 
families and parents that you know about the specific 
information that they could have with medication guides if they 
were being gotten into their hands properly?
    And we have obviously had a breakdown in the system, and it 
is normal and natural for parents or anybody who is concerned, 
who has a conscience, to want to try and figure out who is to 
blame and where to lay blame about this whole problem. But as 
we have found, there is a big breakdown in communication and 
responsibility and jurisdiction.
    And that is what we are trying to get to the bottom of. But 
at the end of the day, what we are finding is that there aren't 
assurances in the system as we would like them to be today, 
that every parent who has an SSRI prescribed for their child is 
getting this information.
    Ms. Van Syckel. Right, actually the parents in New Jersey 
are angry with the doctors because they said the doctors should 
know when they say it has a black box warning, I heard about 
increased risk of suicide, and the doctor downplays the side 
effect. But both parents, one who is a pediatric emergency room 
nurse at a large hospital in New Jersey, who lost her niece 
Brittany to a Prozac-induced cardiac arrest and then, of 
course, with the other teenager, they said had they been 
provided this information, the horror and the tragedy they 
endured never would have happened.
    And it has weakened the parents who have to make the 
decisions with their children. It is not the FDA's job. It is 
not the pharmaceutical companies' job. Parents, we don't want 
to harm our children. We want the best medical care for them, 
but I find it insulting that they believe that we don't know 
how to handle this type of information. Give me the worst 
scenario, and I will always pray for the best scenario.
    Mr. Ferguson. Mr. Chairman, I know I am out of time, but I 
think one of the reasons we work so hard on this issue is 
because at the end of the day, parents are ultimately 
responsible for the health care of their children. And that is 
why they go to doctors. That is why they perhaps take 
medications. That is why you consult with the widest variety 
and try and gather as much information as you possibly can to 
make the right decision for your own child. But you are 
handicapped from making that decision if you don't have all the 
information. That is why I think this med guide issue is so 
important.
    Ms. Van Syckel. Or if they choose to try the medication at 
least they have the information to monitor their child.
    Mr. Ferguson. That is right.
    Ms. Van Syckel. Because that is really important because we 
are with our children, 24/7. It is that important, and I have 
to say this because I believe it is very important. But back 
during the 2004 oversight and investigation, it was determined 
by the FDA and by Congress that antidepressants was a causal 
role in suicide. They used the word causal, but FDA negotiated 
the label.
    And now it is increased risk, and then we have the JAMA 
study that just came out where they say there is no increase 
and that the benefits outweigh the risks. But what that JAMA 
study failed and what the FDA failed to do was when the child 
stops taking the medication abruptly, cold turkey, that is when 
we see our suicide attempts. That is when we see our violent 
behavior. And FDA, during the adult hearings in this past 
December, they stopped with their method analysis, their 
investigation, day 1 of withdrawal. Now if they went for the 
next 30 days or 4 to 6 weeks, you would have seen some violent 
behavior, and you would have seen suicide.
    And we also have 150 percent increase of prescribing 
antipsychotics and Strattera to our kids. They also carry 
suicide labels, and I mean it is pretty sad when I look at the 
Medechi record in New Jersey and our new doctors, a 
psychiatrist, is giving it to newborn babies. Risperdal and 
Effexor, two deadly drugs, how were they administering that to 
a baby? We need to look into Zyprexa and Risperdal and why they 
feel the need that they have to medicate our toddlers.
    Mr. Pallone. Thank you so much. Mr. Waxman.
    Mr. Waxman. Thank you, Mr. Chairman. Dr. Ellenberg, I want 
to ask you what are the provisions in the administration's 
PDUFA proposal that allow user fee dollars to be put toward 
increasing FDA's access to outside population-based 
epidemiological databases. Information from these databases 
would obviously be useful for FDA in its efforts to detect 
safety signals earlier. This is an extremely positive 
development, and I am encouraged to see that it was included in 
the negotiated package.
    But I think we need to go further in terms of providing FDA 
with additional tools and authorities. One of IOM's 
recommendations to Congress was to provide FDA with the 
authority to require post-market studies. Can you tell us about 
the benefits and limitations of data mining? Can you also 
explain why, even if it has the enhanced ability to conduct 
this so-called data mining, FDA still needs to have the ability 
to require post-market studies?
    Ms. Ellenberg. Yes. Well, there are a number of different 
facets to understanding of risks of drugs post-marketing. Data 
mining is a tool that people have been trying to implement with 
the passive surveillance system, the reports that people send 
in. And that can be a useful tool. With several hundred 
thousand reports coming in every year, you can appreciate there 
has got to be some kind of automated way to pull out patterns 
that might need further investigation. And that is what data 
mining is. So that is one piece of post-marketing surveillance. 
And that might be the fastest way to actually identify a very, 
very strange, unusual, very rare adverse event because it could 
be reported from anywhere.
    That is not a good way to identify an increase in a fairly 
common background rate. So, for example, increased rates of 
heart attacks with a widely-used drug, you will not find that 
from a passive reporting system with data mining.
    Access to health care databases where you have information 
on thousands or hundreds of thousands of people and their 
ability to follow them over time, taking drugs, you might be 
able to get some information there. So I don't think it is one 
or the other. And sometimes----
    Mr. Waxman. You think both are very----
    Ms. Ellenberg. You need both, and you need the ability to 
sometimes carry out perspective studies that might even need to 
go beyond existing databases.
    Mr. Waxman. IOM also concluded that Congress needs to 
provide FDA with other authorities the agency currently lacks. 
For example, one, the authority to place a moratorium on DTC 
advertising and to require the specific warnings be 
incorporated into DC ads. Two, the ability to require that 
labels of new drugs carry a special symbol to indicate their 
newly approved status. Three, the ability to require that 
companies make label changes instead of just asking them to do 
so.
    Additionally, the IOM has said Congress should enhance 
FDA's enforcement tools to include things like civil monetary 
penalties, so that the FDA had other choices besides using its 
bully-pulpit to threaten using its only real enforcement tool, 
the nuclear option of removing the drug from the market. 
Obviously the administration's PDUFA legislation proposal does 
not incorporate these recommendations.
    In your view, if Congress were to act this year only on the 
drug safety-related provisions included in the administration's 
PDUFA proposal, would the very serious drug safety oversight 
problems that the IOM describes in its report be resolved?
    Ms. Ellenberg. Well, as a member of the IOM committee that 
put the report together, we all felt strongly that the whole 
package really ought to be adopted, and it was not something to 
pick and choose, use this one, use that one. So I do believe 
that these authorities would be helpful.
    It is very hard for me or probably anybody to assess really 
what will happen with this aspect, without this aspect. It 
would be very hard to predict, but it seems to me that those 
additional tools could be used by the FDA. Most of the things 
that you mentioned relate to adequate communication of risk to 
the public and the issues of what is in the label, ability to 
regulate DTC advertising. Those are all how do we get 
information on risks out to the public.
    Mr. Waxman. Well, along those lines, IOM recommended 
Congress pass legislation that would require companies to 
register and report the results from their clinical trials and 
public available database. Can you tell us what lead to this 
recommendation and why the IOM felt it was necessary to create 
a mandatory system?
    Ms. Ellenberg. Well, the concern is that studies may be 
done that suggest that there may be an increased risk or 
suggest something that is not favorable about a drug and that 
if nobody knows that study was done, if that is hidden under 
regulations, and then other studies are done that maybe don't 
show that, well it would be hard to know if you have a whole 
picture, whether this is something we should worry about or 
not. If we don't see the studies that suggest that there might 
be a problem, they don't know that there might be a problem.
    So there certainly has been a move toward making these 
public. I think there was a provision----
    Mr. Waxman. But do you think it ought to be mandatory? 
Because it could be voluntarily be made public.
    Ms. Ellenberg. I think that many companies are voluntarily 
making these public. I don't know the extent to which they are 
doing that now so----
    Mr. Waxman. Mr. Chairman, if you permit, I have one last 
question, and I would like to pursue it. We heard from Dr. 
Galson on the first panel about FDA's system for handling the 
steadily increasing number of AERs the agency receives, and you 
describe this trend in your testimony also. He told us they got 
a half million AERs, and I understand that approximately 
200,000 were for serious and unexpected conditions. He said 
that the staff available to review those reports has been 
limited by resources. In fact I understand that there are only 
20 epidemiologists who review all of those reports.
    Dr. Galson also described the upgrades to the agency's IT 
system that would help to review these reports that FDA would 
make with an increase of PDUFA dollars for that purpose. But he 
said it would be only $4 million. I am concerned that that may 
not be enough. Can you describe in more detail the situation 
with respect to the agency's review of AERs and comment on 
whether you think $4 million would be enough to complete what 
would be a massive overhaul of FDA's IT infrastructure?
    Ms. Ellenberg. No, I don't think $4 million would be enough 
at all. I think you need probably more than that just to do a 
reasonable overhaul, a reasonable redo of the adverse event 
reporting system to incorporate the data mining, making that 
routine, training reviewers, having enough reviewers to look at 
it. But as I said before, that is just a single piece, a single 
component of the needed system. The Centers for Disease Control 
has a series of databases that they use from the Kaiser 
Permanente system, and I think they spend something like $10 or 
$15 million a year to maintain that system so that if there are 
vaccine adverse events that people are concerned about, vaccine 
safety issues, they can really go right to that system and try 
and get answers very, very quickly.
    And it is that kind of a linkage of databases that FDA 
needs to have access to investigate drug safety problems as 
well.
    Mr. Waxman. OK, thank you. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. Dr. Burgess.
    Mr. Burgess. Thank you, Mr. Chairman. Dr. Levine, let me 
just ask you since this question just came up and you were 
referenced, do you have a concept of what the dollar 
expenditure was to develop the data operation that you have at 
Permanente?
    Dr. Levine. To develop the data operation?
    Mr. Burgess. Right, the continual data observation that you 
have.
    Dr. Levine. I know that the development of our fully 
automated medical record system, including the inpatient and 
outpatient pharmacies, is in the billions of dollars. The piece 
in terms of vaccine safety, which was developed with our 
Vaccine Center and the CDC, I don't know the cost of the 
implementation. That was a stand-alone system.
    We are currently involved in trying to roll all of our 
legacy and stand-alone systems into a single fully-automated 
medical record, which will actually enable projects like the 
one we did with the FDA and the ones we are doing with the CDC 
to be done much less expensively because the maintenance of 
those legacy systems is extraordinarily expensive. And I share 
the concern about what you can do with $4 million, just based 
on what it costs us to do anything in IT.
    Mr. Burgess. Let me ask you a question just to put it in 
context. How many covered lives are there in Permanente?
    Dr. Levine. In the present Kaiser Permanente Medical Care 
Program, there are 8.7 million covered lives. In northern 
California, it is about 3.35 million.
    Mr. Burgess. But that system which you described that cost 
X million dollars, that covers----
    Dr. Levine. All 8.7.
    Mr. Burgess. How long did it take to develop that?
    Dr. Levine. We are midway through the implementation, and 
development is going hand and hand. We are using software from 
the Epic Systems, which is one of the largest medical record 
systems based in Madison, Wisconsin. It was developed for 
outpatient systems, and we are working with Epic to adapt their 
product to our very large population.
    Mr. Burgess. And that is probably a topic for another 
hearing, Mr. Chairman, but it does show the size and the scope 
of the problem. Dr. Loew, let me ask you, you referenced a 
figure of 3 percent of medications that were taken off the 
market. Is that the correct way to phrase that?
    Ms. Loew. That is correct. In the past 20 years, the 
withdrawal rate has been consistently around 3 percent.
    Mr. Burgess. The withdrawal rate. That is the term you 
used. Now, of that, can you just give us an idea of what the 
number of products were that were withdrawn, say, in the last 5 
years?
    Ms. Loew. Actually, I don't have that figure, but we can 
get that data.
    Mr. Burgess. Can you get that for us?
    Ms. Loew. Absolutely.
    Mr. Burgess. And would you have an idea as to how many of 
those were voluntarily withdrawn by the manufacturer, what 
problems came to light, and how many of those were enforcement 
actions by the FDA?
    Ms. Loew. I believe that in many situations, it is a 
voluntary withdrawal on the part of the manufacturer. A safety 
issue comes to light. They discuss it with the FDA and decide 
to withdraw the product from the market, but we will get you 
the exact data on that.
    Mr. Burgess. OK, I was just thinking back, and I can't 
recall an instance where there was an actual FDA recall. But I 
am sure it must have happened, but most of----
    Ms. Loew. The majority of the situations, if I recall, were 
all situations where the manufacturer had voluntarily taken it 
from off the market. But I can't verify that.
    Mr. Burgess. Great. If you could get that for us, that 
would be wonderful. We heard testimony from another witness on 
the panel that the drug manufacturers, in fact, they don't even 
pay attention to safety issues after the product has been 
approved because they have no incentive to do so. Is that an 
accurate statement?
    Ms. Loew. I would argue that the opposite is completely 
true. Pharmaceutical manufacturers take the safety of our 
products extremely seriously. There are, in fact, some 
extensive requirements for manufacturers to monitor their 
products in the marketplace, and there are a number of 
different tools. There are, of course, the adverse effects 
reporting systems that we have heard about today. If there is a 
serious adverse event that is detected that is an event that 
hasn't been previously seen, manufacturers have an obligation 
to report that to the FDA within 15 days and then to follow up 
15 days later with a full report. An additional report 
quarterly in the first 3 years of production on the 
marketplace, to quarterly submit reports to FDA on the adverse 
events that have been detected around the product.
    In addition to that, there is an annual report requirement 
where companies submit all new information that has become 
available on the product. The manufacturing rate of 
information, new clinical data, observational data, and so on. 
They are required to report that, so they take the obligations 
of monitoring the product in the marketplace extremely 
seriously. And it is, of course, in their best interest to 
ensure that is the case and, of course, the best interest of 
the patients.
    Mr. Burgess. Thank you. Mr. Theriault, let me just ask you, 
you talked about a number of things that are being done. A 
company that I became familiar with several years used a 
labeled isotope in like the parts per billion range to ensure 
that products were what they said they were, and I think they 
were talking about rap CDs at the point that they could put 
this isotope in ink that was on the label and that way, detect 
whether or not the counterfeit product had found its way into 
the supply chain.
    And I asked the question at that time could this apply to 
pharmaceutical agents as well because we are talking about a 
molecule that again would be in the parts per billion range. 
And the question obviously came up, well, how would the FDA 
look upon that? Have you had any experience with investigating 
those types of technologies?
    Mr. Theriault. We haven't looked at that technology. I 
think the FDA's preference right now is for RFID tracking, and 
we have got a pilot project around that right now. But I think 
one of the issues there is where does the authentication occur? 
Is it the patient who authenticates the product, the 
pharmacist, or somebody else in the supply chain? But to answer 
your question directly, I think that technology probably could 
apply.
    Mr. Burgess. There was a news story probably 4 or 5 years 
ago now from New Orleans where they did an analysis of not so 
much the active ingredient of the medication, but just the 
inert part of the pill, the vehicle that the medicine was 
contained in and found significantly high--for medicines 
purchased over the Internet--and found significantly high 
quantities of heavy metals, cadmium, liquid chromium. To your 
knowledge, is that still an ongoing problem?
    Mr. Theriault. It is. We have seen a number of cases 
involving heavy metals recently, and I think that the woman who 
died in British Columbia, I think the coroner said her death 
could possibly be related to heavy metals that probably she was 
taking.
    Mr. Burgess. Thank you, Mr. Chairman.
    Mr. Pallone. Let me thank our entire panel for being here 
this afternoon. I felt this was a good opportunity to hear from 
you and ask some questions that were really pertinent, and we 
appreciate it. A number of people asked if they could submit 
things for the record, both members and panelists. And, of 
course, we will do that. We will include those things in the 
record. And you may get additional written questions from some 
of us in the next 10 days, which we would like you to answer as 
well in writing. And again thank you all, and I thought it was 
very good today. We appreciate your help. And with that, the 
subcommittee meeting is adjourned.
    [Whereupon, at 3:05 p.m., the subcommittee was adjourned.]
    [Material submitted for inclusion in the record follows:]

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