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72–917 PDF 2012

PDUFA V: MEDICAL INNOVATION, JOBS, AND 

PATIENTS 

HEARING 

BEFORE THE

SUBCOMMITTEE ON HEALTH 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED TWELFTH CONGRESS 

FIRST SESSION 

JULY 7, 2011 

Serial No. 112–70 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

COMMITTEE ON ENERGY AND COMMERCE 

FRED UPTON, Michigan 

Chairman 

JOE BARTON, Texas 

Chairman Emeritus 

CLIFF STEARNS, Florida 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOSEPH R. PITTS, Pennsylvania 

MARY BONO MACK, California 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE ROGERS, Michigan 

SUE WILKINS MYRICK, North Carolina 

Vice Chair 

JOHN SULLIVAN, Oklahoma 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

BRIAN P. BILBRAY, California 

CHARLES F. BASS, New Hampshire 

PHIL GINGREY, Georgia 

STEVE SCALISE, Louisiana 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

GREGG HARPER, Mississippi 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

PETE OLSON, Texas 

DAVID B. MCKINLEY, West Virginia 

CORY GARDNER, Colorado 

MIKE POMPEO, Kansas 

ADAM KINZINGER, Illinois 

H. MORGAN GRIFFITH, Virginia 

HENRY A. WAXMAN, California 

Ranking Member 

JOHN D. DINGELL, Michigan 

Chairman Emeritus 

EDWARD J. MARKEY, Massachusetts 

EDOLPHUS TOWNS, New York 

FRANK PALLONE, JR., New Jersey 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

LOIS CAPPS, California 

MICHAEL F. DOYLE, Pennsylvania 

JANICE D. SCHAKOWSKY, Illinois 

CHARLES A. GONZALEZ, Texas 

JAY INSLEE, Washington 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

ANTHONY D. WEINER, New York 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DORIS O. MATSUI, California 

DONNA M. CHRISTENSEN, Virgin Islands 

SUBCOMMITTEE ON HEALTH

JOSEPH R. PITTS, Pennsylvania 

Chairman 

MICHAEL C. BURGESS, Texas 

Vice Chairman 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

MIKE ROGERS, Michigan 

SUE WILKINS MYRICK, North Carolina 

TIM MURPHY, Pennsylvania 

MARSHA BLACKBURN, Tennessee 

PHIL GINGREY, Georgia 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

JOE BARTON, Texas 

FRED UPTON, Michigan (ex officio) 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

JOHN D. DINGELL, Michigan 

EDOLPHUS TOWNS, New York 

ELIOT L. ENGEL, New York 

LOIS CAPPS, California 

JANICE D. SCHAKOWSKY, Illinois 

CHARLES A. GONZALEZ, Texas 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

JIM MATHESON, Utah 

HENRY A. WAXMAN, California (ex officio) 

(II) 

(III) 

C O N T E N T S 

Page 

Hon. Joseph R. Pitts, a Representative in Congress from the Commonwealth 

of Pennsylvania, opening statement ................................................................... 1 

Prepared statement .......................................................................................... 3 

Hon. Michael C. Burgess, a Representative in Congress from the State of 

Texas, opening statement .................................................................................... 4 

Hon. Frank Pallone, Jr., a Representative in Congress from the State of 

New Jersey, opening statement .......................................................................... 4 

Hon. John D. Dingell, a Representative in Congress from the State of Illinois, 

opening statement ................................................................................................ 5 

Hon. Fred Upton, a Representative in Congress from the State of Michigan, 

opening statement ................................................................................................ 6 

Prepared statement .......................................................................................... 8 

Hon. Phil Gingrey, a Representative in Congress from the State of Georgia, 

opening statement ................................................................................................ 10 

Hon. Henry A. Waxman, a Representative in Congress from the State of 

California, opening statement ............................................................................. 10 

Prepared statement .......................................................................................... 13 

WITNESSES

Janet Woodcock, Director, Center for Drug Evaluation and Research, Food 

and Drug Administration .................................................................................... 16 

Prepared statement .......................................................................................... 18 

Answers to submitted questions ...................................................................... 154 

Paul J. Hastings, President and Chief Executive Officer, OncoMed Pharmaceuticals, Inc. ........................................................................................................ 77 

Prepared statement .......................................................................................... 80 

Jonathan S. Leff, Managing Director, Warburg, Pincus LLC .............................. 93 

Prepared statement .......................................................................................... 95 

Marc Boutin, Executive Vice President and Chief Operating Officer, National 

Health Council ...................................................................................................... 110 

Prepared statement .......................................................................................... 112 

Ellen V. Sigal, Chair and Founder, Friends of Cancer Research ........................ 122 

Prepared statement .......................................................................................... 124 

Allan Coukell, Director of Medical Programs, Pew Health Group, The Pew 

Charitable Trusts ................................................................................................. 129 

Prepared statement .......................................................................................... 131 

SUBMITTED MATERIAL

Statement, dated July 7, 2011, of the American Hospital Association, submitted by Mr. Engel ............................................................................................. 58 

Letter, dated February 8, 2012, from Jeanne Ireland, Assistant Commissioner 

for Legislation, Food and Drug Administration, Department of Health and 

Human Services, to Mr. Dingell ......................................................................... 150 

(1) 

PDUFA V: MEDICAL INNOVATION, JOBS, AND 

PATIENTS 

THURSDAY, JULY 7, 2011 

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, Rayburn House Office Building, Hon. Joseph R. Pitts (chairman of the subcommittee) presiding. 

Present: Representatives Pitts, Burgess, Shimkus, Rogers, 

Myrick, Murphy, Blackburn, Gingrey, Latta, Lance, Cassidy, Guthrie, Upton (ex officio), Pallone, Dingell, Engel, Capps, Gonzalez, 

and Waxman (ex officio). 

Also present: Representatives Bilbray and Christensen. 

Staff present: Gary Andres, Staff Director; Clay Alspach, Counsel, Health; Howard Cohen, Chief Health Counsel; Ryan Long, 

Chief Counsel, Health; Alan Slobodin, Deputy Chief Counsel, Oversight; Jeff Mortier, Professional Staff Member; Andy Duberstein, 

Special Assistant to Chairman Upton; Debbee Keller, Press Secretary; Chris Sarley, Policy Coordinator, Environment and Economy; Heidi Stirrup, Health Policy Coordinator; Lyn Walker, Coordinator, Admin/Human Resources; Carly McWilliams, Legislative 

Clerk; Kirby Howard, Legislative Clerk; Rachel Sher, Minority Senior Counsel; Stephen Cha, Minority Senior Professional Staff Member; Alli Corr, Minority Policy Analyst; Karen Lightfoot, Minority 

Communications Director and Senior Policy Advisor; Eric Flamm, 

FDA Detailee; and Karen Nelson, Minority Deputy Committee 

Staff Director for Health. 

Mr. PITTS. The subcommittee will come to order. The Chair recognizes himself for 5 minutes for an opening statement. 

OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN CONGRESS FROM THE COMMONWEALTH 

OF PENNSYLVANIA 

The Prescription Drug User Fee Act, PDUFA, was first authorized by Congress in 1992 with the goal of expediting human drug 

applications through the Food and Drug Administration’s approval 

process. Under the Act and in subsequent reauthorization, the drug 

industry pays user fees to FDA, and FDA commits to meet performance goals such as reviewing applications within a certain period of time. This construct was designed to give industry certainty 

and predictability, but also to speed new drugs and treatments to 

the public. Details of the agreement between FDA and industry 

2 

will be published on September 1st of this year, and by January 

15, 2012, FDA will send its final recommendations to Congress. 

The current PDUFA authorization expires September 30, 2012, 

and it is my intention to have the reauthorization legislation 

signed into law by June 30 of next year. PDUFA is too important 

to leave to the last minute. The drug industry employs thousands 

of people here in the United States, providing good jobs that we 

cannot afford to lose. 

The forthcoming study from Patel Memorial Institute has found 

that every job in the biopharmaceutical sector supports nearly six 

additional jobs in the greater economy. If PDUFA is not reauthorized, this study estimates that 130,000 to 260,000 jobs would be 

lost. Americans are the most innovative people on Earth. 

Given certainty, predictability and transparency in the approval 

process, venture capitalists will continue to fund new research and 

companies will continue to develop new and innovative drugs. 

What we have heard, however, is that certainty, predictability and 

transparency oftentimes do not characterize the FDA’s approval 

process. Frustrating both the drug sponsors and the public who are 

waiting for treatments and cures to everyday maladies, chronic illnesses and terminal diseases. 

The American people expect and have a right to expect that the 

Federal Government is doing everything possible to ensure that 

drugs on the market are safe and effective. They also have a right 

to expect that applications for life-enhancing and lifesaving drugs 

are not languishing on a reviewer’s desk at the FDA. It is my hope 

that the new agreement balances both of these considerations, and 

I look forward to hearing from FDA, the drug industry, patient advocates and researchers today on our panels. 

I yield the remainder of my time to Dr. Burgess. 

[The prepared statement of Mr. Pitts follows:] 

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OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A 

REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS 

Mr. BURGESS. I thank the chairman for yielding. 

I am mindful of the fact that the last reauthorization was June 

of 2007, so it is a little over 4 years ago. At that time, I was concerned about some of the restrictions that this committee placed on 

the advisory panels that advise the FDA about the approval or nonapproval of drugs and devices. One of my concerns was we didn’t 

follow the Institute of Medicine guidelines that no more than 40 

percent of the people who are on the advisory committees have an 

interest in the product under consideration, and it was the will of 

the committee over my objections that no one on these advisory 

panels should have any interest or perhaps even any knowledge of 

the drug or device being considered. 

I thought that was a serious and glaring oversight on the part 

of this committee, and I discussed it with then-Chairman Dingell 

extensively and offered amendments that were repeatedly voted 

down on party lines. But that is an oversight that I hope that this 

committee can now correct in this reauthorization period. 

It appears we saw it unfortunately on display with the Avastin 

advisory panel last week in that there, to the best of my reading 

of the makeup of that group, there was not a specialist who dealt 

with breast cancer patients on that advisory panel so that there 

was no one on that advisory panel who actually followed a patient 

who was on Avastin for their breast cancer. Now we are left to defend the decision from the advisory panel to the FDA about the removal of that drug. And we are in a difficult position with Avastin 

because some people are apparently dramatically helped. Other 

people, the help is not so great. But it is, I think, incumbent upon 

us to get that right. 

Other things that I think we need to do, we need to discuss the 

possibility of surrogate endpoints for studies within the FDA. Certainly that was useful in the early days of the AIDS research back 

in the 1980s. And the fact that we base everything upon survival 

statistics now and we are not looking at things like tumor burden 

or some other surrogate endpoint I think is a mistake on the part 

of our advisory panels. 

I thank the chairman for yielding the time and I yield back the 

balance of my time. 

Mr. PITTS. I thank the gentleman and recognize the ranking 

member of the subcommittee, Mr. Pallone, for 5 minutes for an 

opening statement. 

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

Mr. PALLONE. Thank you, Chairman Pitts, and I welcome today’s 

hearing on this very important subject. 

Five years ago, this committee led the way in making grade 

strides in FDA policy and safety measures. In fact, some have said 

it was the most extensive overhaul of FDA policy and procedure in 

decades. What is important to note, however, is that this committee 

worked through the issues in a bipartisan manner, and I am proud 

of the consensus that we reached. 

5 

That legislation was supported by members, consumer groups 

and industry stakeholders. Together we recognized the need for a 

strong and well-resourced FDA to complete its mission. In addition, 

we accepted the reality that FDA must have the ability to be wellversed on the best science in order to get the safest and most effective drugs to the marketplace. 

Now, in doing so I recognize that FDA must minimize the inappropriate burden it placing on the drug companies so that they do 

not stifle innovation. America’s competitiveness depends on our 

ability to innovate and keep America number one, and as such I 

continue to believe that the government must be responsible for facilitating an environment where Americans can continue to innovate. This is the key to creating new thriving industries that will 

produce millions of good jobs here at home and a better future for 

the next generation. That said, we must not sacrifice safety and efficacy in exchange for innovation. PDUFA has been a true success 

and we must build on that success. We can’t move backwards 

under the auspices of economic benefits. 

So, Mr. Chairman, I hope we can move in the same bipartisan 

spirit as we did in 2007. Even more so, I hope that we can produce 

consensus legislation free of conflict and contentious issues. I look 

forward to working with you and my colleagues on this committee 

as this process moves forward and I welcome today’s hearing as a 

first step towards that goal. 

I wanted to yield 2 minutes to my good friend from Michigan, 

Chairman Dingell, but I still have another minute left, so let me 

say that I would like to close by commenting on the importance of 

the Drug Safety Enhancement Act. That is a bill that I coauthored 

with Mr. Dingell and Representatives Waxman and DeGette. 

High-profile risks associated with the globalized drug supply like 

the Heparin crisis of 2007 have put Americans’ lives at risk and 

our bill would equip FDA with the authorities and resources this 

it needs to keep peace with an increasing international marketplace of products so that Americans can have confidence that drugs 

they rely on will help them get better and not make them more 

sick. 

So as we move forward, I will continue, Mr. Chairman, to make 

reference to the Drug Safety Enforcement Act and that bill because 

I do think it is important and also has a place during this PDUFA 

debate. 

I see the gentleman is here. I yield to Chairman Dingell. 

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

Mr. DINGELL. Mr. Chairman, I thank the gentleman and I thank 

you for holding today’s hearings. I ask unanimous consent to revise 

and extend my remarks because of the shortness of time here. 

I commend you for the hearing today with regard to the FDA 

amendments that we are discussing with regard to PDUFA. This 

is important. If everyone will recall, it has been accepted, it has 

been a tremendous success because of the cooperation between government and industry. 

6 

However, we need to address more problems. Commonsense authorities, like mandatory recalls, subpoena power, ability to seize 

and destroy imported drugs and raw materials at the border, making delay or refusal for inspection a prohibited act, are now needed 

to ensure that Food and Drug has the capabilities to properly oversee safety of our drug supply. 

These are authorities that would be given FDA under H.R. 1483, 

the drug safety bill I introduced with my colleagues Mr. Waxman, 

Mr. Pallone and Mrs. DeGette. These are authorities that are desperately needed in order to address the safety of our American public. I would note that without them, imports of dangerous components and raw materials of pharmaceuticals, as in the case of Heparin, continue to threaten the well-being of our people. 

My colleagues will remember that in the last Congress, we 

passed a food safety bill, which gave many of these authorities to 

Food and Drug, and which was, in fact, supported by the industry. 

It passed out of this committee by a heavy majority. It also passed 

the House and the Senate by a very large majority, and it is now 

standing to help and protect the American people. 

I would hope that we would follow the example that we set last 

Congress when we worked together in a remarkably bipartisan 

fashion to see to it that we went well beyond just scratching the 

surface with regard to food safety and do a similar thing with regard to prescription pharmaceuticals and so move to protect the 

health, safety, life expectancy and to ensure that pharmaceuticals 

will not cause harm or death, particularly where it is from imported raw materials for the manufacture of finished products. 

I thank you, Mr. Chairman. I thank the gentleman from New 

Jersey. I yield back the balance of my time. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

full committee chairman, Mr. Upton, for 5 minutes. 

OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF MICHIGAN 

Mr. UPTON. Thank you, Mr. Chairman. 

This is the first hearing of the 112th Congress on the reauthorization of Prescription Drug User Fee Act in the current state of 

medical innovation in America. I look forward to discussing FDA 

regs and how they effect innovation, job creation and the American 

patient’s accession to life-improving drugs. 

Congress last reauthorized PDUFA in 2007 with the Food and 

Drug Administration Amendments Act. That law as we know expires in September of 12, 2012, which is why our work to reauthorize this law begins today. 

One area that the committee will examine is the lack of predictability and certainty at the FDA. These problems at FDA appear 

to be stifling American innovation, costing Americans jobs and obviously hurting American patients. Another area we will examine 

is the risk-benefit analysis used by FDA when approving drugs and 

whether the agency is striking the right balance on delicate issues. 

These are concerns that the FDA is failing to consider the views 

of patients who need access to lifesaving drugs, including those 

drugs that carry some risk. 

7 

The committee will evaluate provisions of the Food and Drug Administration Act amendments, including those affecting advisory 

committees in the risk evaluation and mitigation strategies. The 

rigid unrealistic conflict of interest provision has prevented in my 

view the FDA and its advisory committees from utilizing some of 

science’s best minds and left advisory committee slots unfilled. We 

have to look at the implementation of this provision as to whether 

it really has caused delays in the approval process. 

Our goal has to ensure America remains the leader in medical 

innovation. When the law works properly, the field creates new 

jobs and ensures American patients do have access to the best 

therapies available. 

I thank the chairman, and I yield the balance of my time to Dr. 

Gingrey. 

[The prepared statement of Mr. Upton follows:] 

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OPENING STATEMENT OF HON. PHIL GINGREY, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF GEORGIA 

Mr. GINGREY. I thank the overall chairman for yielding to me. 

I believe the Prescription Drug User Fee Act reauthorization 

gives an opportunity to review the ways in which we can help improve the FDA approval process. In an age where our economy is 

fighting an international battle to remain the leader in medical innovation and the jobs that goes with those industries and patients 

in other countries have access to medical treatments that American 

patients do not, we need all hands on deck. No longer can we afford 

to sideline experts simply because of their ties to industry. 

One idea I believe that deserves consideration, Mr. Chairman, is 

drawing from the joint NIH–FDA Leadership Council. This council 

was created in 2010 to spearhead collaborative efforts to improve 

the FDA regulatory review process. This initiative is a good, 

proactive first step toward improving and modernizing the FDA. 

However, I believe if we are going to be truly successful in improving both the efficiency of the FDA as well as our understanding of how emerging technology can be used to improve regulatory review, other parties need to be at the table. Agencies like 

the CDC and Homeland Security, experts from the drug industry 

and academia, as well as patient advocates all need to be involved. 

A stakeholder group made up of various agencies, scientific leaders 

and business and academia and patient advocates can help support 

the FDA in its mission to advance regulatory science as well as 

other meaningful reforms and emerging public health issues. I look 

forward to working with Dr. Hamburg, the chairman and this committee on the issue. 

In addition, this committee has spent years studying the oncoming public health threat posed by antibiotic resistance. It is a 

threat to our patients, it is a threat to our troops, and in the hands 

of terrorists, our national security. My colleagues and I on this 

committee, four Republicans, three Democrats, have introduced 

H.R. 2182, the GAIN Act. If we are to have the drugs needed to 

fight the looming threat of drug resistant bacteria, our legislation 

is an important first step in that fight. I hope to see it considered 

by this committee, this Congress, the 112th. 

With that, Mr. Chairman, I thank the overall chairman for yielding to me and I yield back the remaining time. 

Mr. PITTS. The chair thanks the gentleman and at this time recognizes the ranking member of the full committee, Mr. Waxman, 

for 5 minutes for an opening statement. 

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

Mr. WAXMAN. Thank you, Chairman Pitts, for holding this hearing today. 

I think we can all agree that it is critically important that there 

be a vibrant and flourishing innovation in the pharmaceutical industry. The medicines this industry has brought us have saved 

countless lives and improved the quality of life for people the world 

over. Unfortunately, by most accounts we are in the midst of a dramatic slowdown in drug development in the U.S. The reasons for 

11 

the slowdown are complex and multifaceted. At a time when you 

would expect there to be a surge of innovation, for example, because there is an unprecedented number of drugs coming off patent, the opposite appears to be true. I hope our witnesses will help 

us understand what is causing this innovation deficit and what we 

can do to help our drug companies succeed. 

A rising chorus of voices have begun to assert the view that it 

is the FDA that is responsible for this downward trend. These critics claim that the FDA takes far longer to approve drugs than its 

counterparts in Europe. Some claim it takes the U.S. twice as long 

as Europe. Others claim it takes three times as long. These claims 

may sound convincing, but we have yet to see the data to support 

them. 

I am aware of only one peer review study comparing drug approval times in the United States and Europe, and it found the 

exact opposite. This study, which examined the approval of 35 new 

cancer drugs, was conducted by one of our witnesses today, the 

Friends of Cancer Research. It found that the FDA is actually approving these lifesaving therapies much faster than its European 

counterparts. 

Some view every decision FDA makes through the prism of 

whether it is good for the pharmaceutical industry. But that is not 

the right perspective. The question we should be asking is, what 

is the right decision for patients? It is in no one’s interests to have 

a weak FDA. American consumers depend on FDA to verify the 

drugs we are taking are truly safe and effective. If Americans lose 

confidence in the FDA, they will lose confidence in the pharmaceutical industry as well. 

We should all be united in the goal of ensuring that we have a 

strong, well-resourced FDA that is armed with a full compliment 

of authorities to protect us from unsafe drugs and to assure that 

these drugs work. That is FDA’s fundamental mission, and that is 

why I strongly oppose any legislative proposal that would prevent 

FDA from insisting on adequate data from clinical trials and force 

it to approve drugs on an incomplete record. These proposals would 

prove disastrous for the safety and efficacy of our drugs supplied. 

The title of this hearing suggests that our colleagues across the 

aisle believe that FDA’s mission should encompass job creation. 

Democrats have been leading the charge for legislation to promote 

jobs and we have been bitterly disappointed by the failure of the 

House to pass pro-jobs legislation. But we should not be misled. I 

hope we would all agree that FDA should not take jobs into consideration when it is reviewing the safety and effectiveness of a new 

medicine. We want FDA to ensure that the drugs we take are safe 

and effective. Whether jobs will be created is simply not a part of 

that scientific public health equation. 

I do believe there are areas in which the agency’s regulation of 

drugs could improve. For example, improvements in FDA’s scientific capacities will enable FDA to identify early end-points that 

can predict whether a drug will be effective which can result in better design of clinical trials and faster approval of new drugs. Making these kinds of strides require we work from real data, not selfserving urban myths. 

12 

We should require a significant influx of resources. It is ironic 

that at the same time they are complaining that FDA should do a 

better job, the Republicans in the House passed a budget and an 

appropriations bill that would gut FDA funding by over $500 million. 

I want to turn briefly to the fact that we have an increasing 

globalization of our drug supply. The world has changed from the 

time of the original Food, Drug and Cosmetic Act. Today, more 

than 80 percent of active pharmaceutical ingredients are manufactured abroad, with China and India comprising the largest sources. 

Just yesterday, The Wall Street Journal talked about poor regulatory oversight of Chinese pharmaceuticals. That is why it is important to look at the Drug Safety Enhancement Act, which will go 

a long way toward providing FDA with these much-needed resources. 

Mr. Chairman, our staff has reached out to your staff and Mr. 

Upton’s as well requesting we engage in a bipartisan process to 

look at this bill and work toward incorporating whatever we can 

ultimately agree upon into the PDUFA package next year. I hope 

we can count on this opportunity to work together because it is in 

the public interest. 

Thank you very much, Mr. Chairman. 

[The prepared statement of Mr. Waxman follows:] 

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Mr. PITTS. The chair thanks the gentleman. The chair thanks the 

members for their opening statements. Any other opening statements will be entered into the record. 

The chair thanks the witnesses for agreeing to appear before the 

committee today. Your written testimony will be made a part of the 

official record. We ask you summarize your opening statements in 

5 minutes. 

We have two panels today. The first panel contains a single witness. Dr. Woodcock is the Director of the Center For Drug Evaluation and Research at the Food and Drug Administration. 

Welcome, Doctor. You may begin your testimony. 

STATEMENT OF JANET WOODCOCK, DIRECTOR, CENTER FOR 

DRUG EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION 

Ms. WOODCOCK. Thank you, Mr. Chairman and members of the 

subcommittee. I am Janet Woodcock, Director of the Center For 

Drug Evaluation and Research at FDA, and I would like to thank 

you for this opportunity to testify about the prescription drug user 

fee program, or PDUFA, as I am going to refer to it. 

Congress instituted this program because patients in the United 

States were not getting access to new medicines as quickly as people in other parts of the world. This problem is called the drug lag, 

and it became particularly severe in the 1980s. 

The chart we have brought, which you can see over there, shows 

that PDUFA really had an impact on this drug lag. In the 1980s, 

as you see, fewer than 10 percent of new medicines reached American patients first. They were available first in other parts of the 

world. PDUFA was started in 1992 and, as the data show, it quickly improved the availability of new medicines to the point now 

where we lead the world in introduction of new medicines. 

I am a rheumatologist. I am a doctor who treats autoimmune diseases and arthritis, and I can attest to the revolution of therapies 

that has occurred since the start of PDUFA. Diseases that were 

crippling now have effective treatments that allow patients to lead 

full lives. 

Recently, my seat mate on a plane showed me pictures of her 

wonderful gardens that she cared for herself. She told me that 10 

years ago she was confined to a nursing home and it was only 

when she was started on a treatment, a new treatment for her 

autoimmune disease, that she was able to improve and is now active and well. This is the kind of treatments that we have seen 

coming out during the PDUFA period. 

So since the start of PDUFA, increasing numbers of new medicines were available first in the United States. Currently we lead 

all other countries in the introduction of new therapies. Every 5 

years, PDUFA must be reauthorized, and each cycle of reauthorization has brought new enhancements to the program. Most recently, 

there has been a focus on improving drug safety monitoring and 

that was the focus of the last cycle. Successful innovations, such as 

our sentinel initiative, resulted from that safety focus. 

For this cycle of PDUFA renegotiation, Congress directed FDA to 

conduct a very open and inclusive process with significant stakeholder participation. We have done so, as detailed in my written 

17 

testimony, and I believe the outcomes of the negotiation have really 

been improved as a result of this new process. 

Now, the drug development enterprise is in a very different place 

than previous PDUFA negotiation cycles. Drug development faces 

many of the problems other industries do right now due to the economic turn-down. But more significantly, there is a severe productivity problem worldwide in drug development in which an ever-increasing R&D investment is producing ever-fewer new drugs. This 

isn’t just true in the U.S. It is true everywhere. It is no exaggeration to say that the industry is in crisis. 

At the same time, the scientific opportunities have never been 

greater. It is incredibly frustrating to see the explosion in biomedical knowledge and at the same time to watch the struggles 

and repeated failures of drug development programs that try to utilize this knowledge. Despite these serious problems, things may be 

looking up. This year to date, FDA has approved 20 new medicines, 

just one short of the total approved last year, and many of these 

medicines are game-changers for patients. We do see a rise in new 

development programs coming into the FDA as well. 

We have been moving through the process set down by Congress 

for this cycle of PDUFA negotiations and we have developed a set 

of recommendations that are laid out in my written testimony. 

These include new steps to incorporate scientific advances into regulation so we can do what we can for the problems that industry 

is facing; also providing for meaningful patient input into the 

standards of benefit and risk that FDA applies to these new products; to provide a more transparent and predictability review process for sponsors, and there is quite a bit in there for that; and to 

further enhance drug safety. 

In closing, I would say that in addition to these challenges, the 

pharmaceutical industry and FDA does face the challenges of 

globalization, which are ever-increasing and are well covered, and 

I am sure you are aware of, both in clinical trials being done all 

around the world and medicines being made all around the world. 

We still have to ensure the safety and effectiveness for our patients. 

We look forward to working with Congress on all these challenges. We feel that the success that is demonstrated of PDUFA 

can be extended and we can do the right things, both for the patients in this country and for the industry that brings them new 

medicines. 

[The prepared statement of Ms. Woodcock follows:] 

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Mr. PITTS. Thank you. I will now begin the questioning and recognize myself for 5 minutes. 

Mr. GINGREY. Mr. Chairman, we cannot hear you. Your mic may 

not be working. 

Mr. PITTS. All right. I will hold it closer. 

According to reports from the California Health Care Institute, 

and Ernst & Young and testimony here today, FDA’s regulatory 

uncertainty is stifling American job creation. To compound the 

problem, foreign countries like those of the EU, China and India, 

are proactively trying too take American jobs by making their regulatory systems more predictable and efficient and creating an ideal 

innovation climate for companies. Given the importance of these innovator companies to our country and our Nation’s patients, these 

developments are disconcerting, to say the least. 

While foreign regulatory bodies are becoming more efficient, FDA 

appears to be going in the opposite direction. Is FDA, first of all, 

aware that these foreign countries are proactively trying to take 

American jobs? 

Ms. WOODCOCK. We are aware that both Europe, which has the 

Innovative Medicines Initiative, Singapore, China, many countries 

are looking to build a very strong R&D biomedical development industry in their countries. Absolutely. 

Mr. PITTS. The second question: What is FDA’s role in creating 

a hospitable climate for American innovator companies so that they 

can create jobs and create new lifesaving therapies for patients 

here? 

Ms. WOODCOCK. Well, first of all, I would like to start with the 

facts, all right? That chart shows when the U.S. is the country that 

first launches a drug in our country, and you can see that is continuing to go up. So that is compared to all other countries worldwide. 

You will also hear testimony about a comparison to Europe. And 

we are not in competition with Europe, but you can see in the U.S., 

the drug approval process is faster and drugs reach patients more 

quickly than in Europe. That is simply one comparison. However, 

we, since 2004 when we put out what was called the Critical Path 

Report, have been working with industry to try to solve a lot of 

both the scientific and regulatory problems that impede innovation 

and keep drug development from proceeding smoothly. 

So we are very aware of this. It is a problem for us as well as 

for the industry. The people who work at the Center for Drugs and 

regulate new drugs are doctors, and they are rheumatologists and 

they are pulmonologists and they are cancer doctors and infectious 

disease doctors. They know their patients need additional therapies 

and they want to see them out there for the patients. So this drug 

development enterprise is important for everyone and it is important to get it right. 

Mr. PITTS. And what has the FDA done to forestall the attempts 

by the EU, China and India to take our jobs? 

Ms. WOODCOCK. FDA has a very predictable drug review process. 

In fact, our review process is the most predictable part of drug development. If you can get through all the clinical phases of drug 

development where you test it on people, the process that FDA 

43 

uses is extremely predictable. And that is a result of the user fee 

program. 

Right now we have the highest rate ever of what we call first 

cycle approvals, which is if companies send in their application, 

they get it approved on the first try. And we have timelines for 

that and we meet our timelines of review. So we have a very predictable and open process, and companies usually come first to the 

United States with applications for their new drugs. 

Mr. PITTS. OK, another question. I have heard from many patients that they believe their interests are not taken into account 

during the FDA approval process. Patients, including those with 

life-threatening diseases, are willing to tolerate additional risk in 

order to try these new drugs that will hopefully save their lives. 

How does FDA take patients into account when reviewing new 

drugs and how does it account for patients and their willingness to 

tolerate additional risk? 

Ms. WOODCOCK. The patients are the most important part of 

this. It is really for patients that medicines are developed and that 

the FDA does the review process, and we fully understand that 

people facing more serious diseases are willing to take higher risks. 

For example, we have a drug for multiple sclerosis that causes 

sometimes a rare, very serious and often fatal brain disease, and 

that drug was briefly withdrawn from the market because of doing 

this. When we talked to the patients, they said we are willing to 

take this risk, because this drug really helps prevent the progression of multiple sclerosis. That drug is available now to patients because we understand that when you face such terrible diseases, you 

are willing to take risks. 

Mr. PITTS. My time has expired. I recognize the ranking member 

for 5 minutes for questions. 

Mr. PALLONE. Thank you, Mr. Chairman. And Dr. Woodcock, 

some of my questions are along the same topic, if you will, as the 

chairman. I guess this really shows that we are being bipartisan 

today. 

Most of my colleagues have been told that FDA is responsible for 

what is claimed to be a significant slowdown in development and 

marketing of new and innovative pharmaceuticals. Whether that is 

true or not, that is what we are told. 

There is a statement in Mr. Leff’s testimony, he is on the next 

panel, which sums up what I hear. He states, ‘‘While many factors 

have contributed to the escalating cost, time, and risk of new drug 

development, a changing regulatory environment at the FDA is the 

most significant.’’ 

He attributes this, in large part, to increasing public pressure on 

FDA to focus more on safety and lesson benefit in the wake of the 

emergence of safety problems associated with Vioxx in 2004. He 

further points to numbers showing that FDA approved an average 

of 36 new drugs and biologics per year from 1996 to 2004, but an 

average of only 21 per year from 2005 to 2010. 

My question is, how do you respond to these claims? Is it really 

true that there was a sudden dropoff in approvals right after 2004 

and that approvals in the years immediately preceding 2004 were 

well over one and a half times as frequent as in the years immediately after 2004, and has FDA really become too risk averse and 

44 

not focused enough on benefits such that maybe innovation is being 

blocked. 

Ms. WOODCOCK. Well, I appreciate these questions. As a physician, I will tell you, I think it is important, though, to establish the 

diagnosis before we move to treatment. So it is really important to 

understand the facts. 

The facts are, first of all, as we have already discussed, the FDA 

approves drugs and gets them on the market more regularly first 

than any other country in the world, all right? We are meeting all 

of our PDUFA goals for review times, so our review time is very 

prompt. We are approving more than two-thirds of critical new 

drugs, those important new drugs that will make a difference for 

patients, on the first round. After they are approved, we review 

them and then they get on to the market. And we have the highest 

rate historically in 20 years right now of these first round approvals. 

So FDA is moving promptly and is approving a high percentage 

of the drugs that are submitted to us. However, we can’t approve 

drugs that don’t come in the door. And this slowdown is worldwide. 

This is not a FDA phenomenon. The pharmaceutical industry is 

suffering a crisis and we are not seeing as many submissions to us, 

nor is the EU, nor are the other regulatory authorities around the 

world, and this scientific challenge I think is the major problem 

that we face. 

Mr. PALLONE. You have already, in response to the chairman’s 

question, mentioned Europe. I read a study published in the July 

issue of Health Affairs by Friends of Cancer Research, which found 

that FDA actually approves cancer drugs significantly more quickly 

than its counterpart in Europe. Now, that was just for cancer 

drugs. But how does FDA compare with Europe in approval times 

of other classes of drugs besides cancer drugs? 

Ms. WOODCOCK. This is true for all of the high priority drugs 

that are going to make a difference for patients. We don’t have all 

the data in a tabular form that we can give you, but we have 

looked into this. 

For example, we just approved two drugs for hepatitis C—treatment of hepatitis C. Hepatitis C has been poorly treated. The treatment has difficult side effects and it often leads to liver failure and 

need for liver transplant and even death. We have just approved 

two new drugs that have a high rate of what is called virological 

response or cure, so we expect that many more people will be able 

to be cured for hepatitis C. Those two drugs are not approved anywhere else in the world right now. 

Mr. PALLONE. Let me just ask you, would you say FDA could 

make some improvements in terms of helping industry proceed 

through the regulator process, and more specifically, where do you 

think the major roadblocks are going from earliest research to drug 

approval? Where can more effective improvements be made to 

shorten the time between discovery and marketing? 

Ms. WOODCOCK. The scientific breakthroughs we are currently 

experiencing with targeted therapy or personalized medicine or 

whatever, and I don’t have time to go into it here, are giving us 

new opportunities to have new development pathways. We have 

been giving very significant thought to that, and I think we will be 

45 

coming forth with some new development pathways that can help 

speed these medicines along and get them to patients sooner. 

This doesn’t involve FDA review, because if we get a really good 

product into FDA, we can review it and get it on the market really 

quickly. What people are alluding to is the development time takes 

a long time. So we have some ideas about how to improve drug development for these highly effective therapies and we will be starting some efforts on that. 

Mr. PALLONE. Mr. Chairman, could I just ask, I don’t know if she 

does have something that she could follow up with on that, but if 

I could ask through you if there is more information, you could 

send us in writing about those new trends, I would appreciate it. 

Ms. WOODCOCK. I would be happy to do so. 

Mr. PITTS. If you would provide that to the committee. 

The chair recognizes the vice chairman, Dr. Burgess, for 5 minutes of questions. 

Mr. BURGESS. I thank the chairman for the recognition. Dr. 

Woodcock, thank you for being here again. 

Reference was made to the European Medicines Agency, that is, 

the FDA is actually more rapid. Now, would it be fair to say that 

the timeline is more predictable at the European medicines agency 

and the FDA? 

Ms. WOODCOCK. Our timelines are very predictable. 

Mr. BURGESS. Does that include a timeline start to finish, or a 

timeline where you reset the clock because you have asked for new 

information or a different study to be done? Because this is the 

question that people come in with. I see people in my office literally 

every week with a drug or device who say that the FDA changes 

the rules of the game when we are deep into the process. I can’t 

get any of them to come here and testify before this committee because they are frightened, quite frankly, of you and your agency. 

They are scared to speak up because they know that that could 

reset the clock once again. 

Is this a fair criticism that I am getting from people who have 

drugs and devices before your agency? 

Ms. WOODCOCK. As I said, we ought to start with the facts. The 

facts show that we are approving a very high percentage of priority 

drugs, an extremely high percentage on the first cycle. So that is 

a 6-month review, all right, generally speaking. And so that is a 

very predictable review. 

The second issue you are raising is do we change the standards? 

Sometimes as we learn about side effects of drugs as they are on 

the market and we gain more information, then we do need to ask 

companies that have additional drugs in that class or whatever to 

look for those side effects and study them before marketing. So 

that does happen sometimes. 

Mr. BURGESS. It is not just sometimes. It seems like it happens 

all the time. Now, I have to be careful not to confuse drugs and 

devices, but let me talk about devices for just a moment. 

I met a physician out in West Texas who developed a method for 

conscious sedation that was much more safe than anything that he 

had used in his practice as an anesthesiologist. It came to him 

while he was watching his newborn son being circumcised. And 

while it turns out that this device would not help in newborn cirVerDate Nov 24 2008 11:31 Mar 09, 2012 Jkt 037690 PO 00000 Frm 00049 Fmt 6633 Sfmt 6633 F:\112-070 PDUFA V\112-70 PDUFA V-PENDING WAYNE
46 

cumcision, there are many other clinical applications where it 

would be very efficacious. As he told me this story, he said, just to 

put it in context for you, I developed this as a consequence of my 

son being a newborn and undergoing this procedure. And he is 

going to college this weekend, we are packing the car up to take 

him to wherever, and the device is no closer to being approved than 

it was 17 years before. 

Now, this individual no longer had a financial interest. It was 

simply because it was his baby literally, his idea that he wanted 

to see come to fruition and help patients. He sold it to a large medical manufacturing entity. But this thing was still bogged down in 

the process, and it was months and years of FDA advisory panels 

and this sort of thing. Even when they got clean bills by the advisory panel, then for some reason, the FDA would overrule and send 

them back to the starting point. 

He is not alone. There are other device manufacturers in my office, again, literally every week, and probably because this hearing 

is being televised, I will hear from a lot more of them now. But can 

you address that? We talked about the devices that are being offshored because the environment is more friendly in other locations. 

You admit that other countries are actively recruiting our 

innovators. Are you working on that? 

Ms. WOODCOCK. Certainly. The reason that drug companies are 

going offshore has to do with the cost of either manufacturing or 

the cost of doing clinical trials. They are still submitting drugs to 

the U.S., because we are a large market. And as you see, we get 

drugs on the market before any other country in the world most 

frequently. 

As far as—— 

Mr. BURGESS. I am going to run out of time, so let me go back 

to what you were talking about initially where you said your time 

line, that you are good, you are meeting your performance goals. 

There is a study from the California Health Care Institute where 

they talk about the FDA not meeting its goals and that your times 

have slipped since the last PDUFA reauthorization in 2007. Can 

you address that for us? 

Ms. WOODCOCK. Certainly. In the year or so after the passage of 

the Amendments Act, we were given a very large assignment of 

work by Congress in the Amendments Act which had many, many 

activities that we had to do. We made that our priority and accomplished those activities that we were directed to do by Congress. 

During that time, our goals did slip slightly and we failed to 

meet some of our goals, although we still had a very high performance. That situation has been rectified and we are now meeting 

and exceeding our user fee goals again. 

Mr. BURGESS. According to this study, you have slipped 28 percent. It is fair to say the Democrats’ last reauthorization slowed 

you down. Let’s hope this reauthorization doesn’t perform similarly. 

Thank you, Mr. Chairman. I will yield back. 

Mr. PITTS. The chair thanks the question and recognizes the gentleman Mr. Gonzales for 5 minutes for questions. 

Mr. GONZALEZ. Thank you very much, Mr. Chairman, and welcome, Doctor. Quickly following up on Dr. Burgess’ question, it is 

very interesting, because I think there has been some comments 

47 

that we are losing jobs and such and investment in the United 

States because pharmaceutical companies want to do things outside of the United States, and the reason for that is the slow, cumbersome regulatory system that the FDA presents. 

Your response was that is not necessarily true. If cost is cheaper 

in another country, whether it is manufacturing or research and 

development, that is where the investment may be made, and it is 

strictly more on finances than anything else, eventually that particular company, whatever it manufactures, whatever it presents 

for consideration, is still going to come through FDA, that is right, 

and the reason, and you cited it, is that this is an incredibly lucrative market for pharmaceuticals, the United States of America. 

Would you say that in the United States of America, maybe there 

is a greater profit margin for pharmaceuticals than in other countries? 

Ms. WOODCOCK. I am not really qualified to comment on that. I 

am a doctor, not an economist. Sorry. 

Mr. GONZALEZ. Do you know of any literature that might support 

the proposition that because of the system that we have in the 

United States, we may well be paying more for a certain drug, the 

same drug that is available here in the United States as well as 

in other countries? 

Ms. WOODCOCK. Yes, I am certainly aware of that. 

Mr. GONZALEZ. How is FDA approval viewed? And I guess you 

can congratulate yourself because I assume it is very favorable, 

how is FDA approval viewed worldwide in other markets in other 

countries? 

Ms. WOODCOCK. Well, FDA has generally been viewed as say one 

of the gold standards. We provide a scientific and technical and 

highly unbiased review, and we base it on the evidence. We are 

really the only place in the world that goes down to the patient 

level data, and we get that data in and review it. So we are confident when we make a decision that is based on the actual evidence that has been generated. Many countries in the world look 

to FDA, all of our standards, our standards for manufacturing, our 

standards for clinical trials and so forth. But we have made a lot 

of efforts to harmonize those internationally through various arrangements that have been made. 

Mr. GONZALEZ. Let’s just say that there was just total reciprocity 

and you could sell a drug that was manufactured and approved by 

another country, this is a make-believe world. In your position, of 

all the countries, which regulatory agency regarding drug approval 

would you depend on before you would prescribe that drug for a patient? I know you are from the FDA and this may be quite an obvious answer. But seriously, if you were a physician in another country, wouldn’t it be FDA, the United States of America? 

Ms. WOODCOCK. Well, I certainly have spoken to many physicians and many regulators around the world, and our process is 

viewed as a very robust and excellent process that people look up 

to as a gold standard. 

Mr. GONZALEZ. We want you to do things timely, we want you 

to do it efficiently for all the right reasons, but not at the cost of 

quality and safety. That is the only point I think all of us would 

agree on. 

48 

How do other countries finance their regulatory—let’s say their 

FDA, their equivalent of FDA? 

Ms. WOODCOCK. In Europe, there are user fees. It is not the 

same arrangement because the countries give scientific experts to 

the process and there are multiple countries involved in the EU. 

There are different arrangements around the world. Many of them 

involve user fees of one type or another. Many countries do not 

have the personnel, scientific personnel and resources, to mount a 

kind of review that we do, so they rely upon conclusions from the 

World Health Organization, from the FDA, and from others. 

Mr. GONZALEZ. I guess my final question, I have 30 seconds, and 

that is, we have been referencing what FDA means in the United 

States and such. We do not defer to other governmental regulatory 

agencies in other countries for the safety of our pharmaceuticals, 

is that correct? 

Ms. WOODCOCK. That is correct. 

Mr. GONZALEZ. Thank you. I yield back. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman Mr. Shimkus for 5 minutes for questions. 

Mr. SHIMKUS. Thank you, Mr. Chairman. 

Dr. Woodcock, thank you. You are not an economist, and although we have a lot of physicians on the committee, most of us 

are not, so you are in good company here. 

From your opening testimony, the words I caught on to was the 

drug lag, R&D, investment, fewer drugs because of that. We are 

going to have a venture capitalist, I think, on the second panel, an 

investor, talking about, and that is where we are trying to marry 

how do we keep capital going into this. 

I don’t mind talking about the great job creating aspects of a 

thriving pharmaceutical industry that is putting safe and efficacious drugs out on the market. At a time when we are looking for 

job growth, that sector can do that, the telecommunications sector 

can do that, the energy sector can do that. But as my friend Charlie Gonzales was talking about, we still want it safe, and that is 

a big criteria. Globalization does play a big role, another word in 

your opening testimony. 

So it is in these concerns that we—the issue of our European 

competitors, who have some quality standards, may be starting to 

close that gap, plus Asian producers who may be closing that gap. 

But we have had concerns about what we receive there. This committee has had numerous testimony on stuff, not just on pharmaceuticals, but also, just food products and stuff that has been of 

great concern. 

Some of us have been focused on the antibiotics issue, which I 

would like to turn to a little bit, bacterial resistance to antibiotics, 

which I know is a concern to you all. Part of your guidance there 

was some concern that your agency was not giving adequate guidance for clinical trial design for new antibiotics, especially in the 

case where no treatment existed for a given infection. 

Can you discuss what progress the FDA has made in this area 

since you last testified? 

Ms. WOODCOCK. Certainly. We have been working with the foundation for NIH that convened a group that is working on endpoints 

for clinical trials for different classes of antibiotics. I think this is 

49 

very promising. We also have been having discussions about basically untreatable infectious diseases, multiple drug-resistant infections and how one would do trials, and we do hope to get out some 

guidance on that. 

We don’t know either, all right? This is unchartered territory. So 

we can put our best ideas forth, but we don’t have all the answers 

about how to study these. I think we will show considerable flexibility in the standards that we apply when we are talking about 

diseases, infectious diseases that really lack any alternative treatment. 

Mr. SHIMKUS. Can you give me any thoughts on the need for new 

antibiotics to treat resistant infections? 

Ms. WOODCOCK. The bugs are always ahead of us, all right, and 

that is something we just have to live with, that the infectious organisms can mutate very rapidly. We give antibiotics out to a lot 

of people. We put the bugs under selective pressure, and bingo, we 

have resistant organisms that we can’t treat very well. 

So this is an ongoing problem where we need a robust pipeline 

of new antibiotics, and to some extent, we need some effective antibiotics that we don’t use very much, all right, that we hold in reserve for those types of situations, because if we use them broadly, 

then the bacteria become resistant. 

Mr. SHIMKUS. On a separate issue now, talking about the FDA 

advisory committee and situations in which an individual may be 

disqualified because they have worked on a clinical trial for an unrelated product, not a related product, and that is, I think, an 

issue—is that true? Do you know of cases where someone has been 

disqualified because they worked in a clinical trial for an unrelated 

product, and does that hurt in this clinical time lag that we are 

kind of debating today? 

Ms. WOODCOCK. Yes, it is true. It is also true we have difficulty 

recruiting qualified people and having highly qualified panels. In 

some cases, we have had to delay advisory committees because of 

the difficulty, because once we go through in great detail, all the 

financials of the individuals we have nominated, we find that they 

have to be excused from participating. 

Mr. SHIMKUS. Thank you, Mr. Chairman. Thank you, Dr. 

Woodcock. 

Mr. PITTS. I thank the gentleman and recognize the gentlelady 

from California, Ms. Capps, for 5 minutes for questions. 

Mrs. CAPPS. Thank you, Mr. Chairman. 

And thank you for your testimony, Dr. Woodcock. 

I would like to reiterate for a minute what others on the panel 

have been saying. 

The PDUFA program has largely been a successful and creative 

partnership, in my opinion. And I look forward to working with my 

colleagues on both sides of the aisle to strengthen the program during this reauthorization process. Moreover, I think a lot of what we 

have heard today reinforces the importance of giving the FDA the 

resources it needs to ensure that the agency can do its work independently and in a timely manner while ensuring patient safety. 

While the FDA’s drug review process has a great number of 

strengths, I am concerned about reports that clinical trials data 

submitted to the FDA do not routinely include reporting based on 

50 

sex or other important demographics. For example, one study found 

that, despite FDA regulatory requirements that require the reporting of a broad range of demographic data, more than one-third of 

the time this information is not being provided. In addition, a 2007 

study specifically looking at heart disease clinical trials—and, of 

course, heart disease being the number-one killer of women—found 

that only 25 percent of trials report sex-specific results in scientific 

journals. 

These issues were highlighted in a 2010 Institute of Medicine report entitled, ‘‘Women’s Health Research: Progress, Pitfalls, and 

Promise,’’ which found that—and this is a quote from the report— 

‘‘inadequate enforcement of recruitment of women and of reporting 

data by sex has fostered suboptimal analysis and reporting of data 

on women from clinical trials and other research.’’ 

Its recommendations included specific strategies for the agency. 

And another quote from them, which I am sure you know about: 

‘‘For medical products, drugs, devices, and biologics that are coming 

to the market, the FDA should enforce compliance with the requirement for sex-stratified analysis of the efficacy and safety and 

should take those analyses into account in regulatory decisions.’’ 

Unfortunately, as you know, there is a limited transparency with 

these applications, making it difficult for the public or prescribing 

physicians to know if any improvements on this data collection are 

being made. So my question is, can you discuss this work with us, 

please? What has FDA done to address the gaps in these data? 

Ms. WOODCOCK. Well, interestingly, when I started at the Center 

for Drugs in 1994 for the first time, I was instrumental in getting 

this regulation done that required reporting by sex, of how many 

women were in trials, you know, what the results were by sex and 

so forth. 

I don’t know the answer to your question. I am going to have to 

get back to you. My impression was that we have standard tables 

on reporting by sex, both for outcomes as well as how many people 

were recruited in the trial and all the other variables. So I am very 

surprised to hear what you have to say, and we can get back to 

you on this. 

Mrs. CAPPS. Well, I do—I think this is really important. I want 

to make sure that—there are a number of diseases, not just heart 

disease, that have different symptoms for the different genders. 

And I am under the impression and this article would give—the Institute of Medicine report in 2010 would indicate that there is limited transparency within that application process. So that it would 

be very difficult for the public, it would be difficult for FDA, and 

it would certainly be difficult and challenging for the medical provider to know if any improvements on the data collection are being 

made. 

And I look at the legislation I have introduced in this—that 

passed out of the House in the past, the HEART for Women bill, 

which specifically addresses this issue to ensure that these important data are being used to keep all Americans healthy. 

So if you have any final thoughts—this is a topic I want to see 

thoroughly explored by the Food and Drug Administration and a 

report submitted back to us on whatever findings that you have. 

51 

Ms. WOODCOCK. I think part of the problem that we have in getting timely data on this and providing it is that we don’t get all 

the information in a standardized electronic format. If we did that, 

we could easily run reports on these standard tables and we could 

tell everything there is to know about reporting by sex. 

In the new PDUFA recommendations that we are putting forth, 

there is a requirement that we get standardized all-electronic data. 

And this would extremely help transparency of this issue and many 

others. 

Mrs. CAPPS. Mr. Chairman, I think this is a really important 

topic. 

And I would like to request that we have follow-up data that you 

provide, FDA provides, to us on the progress that has been made 

and/or any other changes that should occur so that we can get this 

information. 

Ms. WOODCOCK. I would be happy to do so. 

Mrs. CAPPS. Thank you very much. 

And I yield back. 

Mr. PITTS. The chair thanks the gentlelady and recognizes the 

gentlelady, Ms. Myrick, for 5 minutes for questions. 

Mrs. MYRICK. Thank you, Mr. Chairman. 

And thanks for being here and for your thoughtful comments 

today. 

My concern is about the FDA’s ability to approve potential drugs 

to treat deadly diseases. For example, we know a drug like Avastin 

has toxicities that aren’t well-tolerated by some patients, but for 

some patients, especially metastatic breast cancer patients, it does 

not extend their survival, but for others it does extend their survival. And metastatic breast cancer patients are facing a deadly 

disease, as we all know, and many are willing to take that toxicity 

risk if the drug helps keep them alive. I believe you said that in 

your testimony today. 

And so I applaud your efforts, you know, to promote the need for 

biomarkers and screening tests so that scientists and physicians 

have more certainty about which patients respond to certain particular treatments. But if we don’t have the screening tests now, 

I don’t think we should restrict access or pull approval for a drug 

simply because we are not sure how to define the category of patients who will respond. 

So why can’t the FDA approve the drug with appropriate warnings for doctors and patients by informing the doctors that many 

of their patients might not respond and that there are risks involved, I mean, as an example? 

Ms. WOODCOCK. Well, I cannot comment on the Avastin situation 

very specifically. The Center for Drugs has made a recommendation, and now it is before the FDA commissioner. And we have had 

a hearing and so forth. 

Generally speaking, if we have found that a drug saves lives, 

then we will approve it, regardless of many serious side effects, as 

long as the survival advantage is not outweighed by mortality 

caused by drug side effects, OK? 

Mrs. MYRICK. Yes. 

Ms. WOODCOCK. So we have many, many drugs—we have recently approved several cancer drugs—— 

52 

Mrs. MYRICK. Right. 

Ms. WOODCOCK [continuing]. That are very toxic—— 

Mrs. MYRICK. Right. 

Ms. WOODCOCK [continuing]. All right? And people know, if they 

are going to take those drugs, they may be facing—they may die 

from the side effects. That is true of cancer treatment. But they are 

trying to extend their lives. 

Mrs. MYRICK. Well, I know there are women who have taken this 

particular drug, Avastin, you know, for 3 or more years, and they 

are still doing well, so. I understand, it is just a little frustrating, 

because I know if you are in a position where you really have this 

disease and you want to do everything you can to extend your life. 

One more question on this same line. The FDA and the European Union’s drug-approval body reviewed the same data on 

Avastin as a metastatic breast cancer treatment. And I understand 

it is approved there for HER2-negative metastatic breast cancer, 

and it is widely used in Europe for those patients. 

So what is the difference? How do you explain the difference between what they are doing and what we do? Because I know it is 

all global, and we look at all of it together. 

Ms. WOODCOCK. We do look at all the same data. We have certainly talked to the EU about their decisions. Sometimes we reach 

different decisions. We approved Avastin for a deadly brain cancer—— 

Mrs. MYRICK. Right. 

Ms. WOODCOCK [continuing]. Called ‘‘glioblastoma’’ that they did 

not approve Avastin for. So sometimes various experts come to different opinions. 

But I can assure you that we have—our breast cancer oncologists 

at FDA are dedicated to the treatment and, hopefully, eventual 

cure of breast cancer and getting the best possible agents out there 

for women. 

Mrs. MYRICK. Oh, no, I don’t have any question about that. I 

guess my question is more about the fact of how we restrict some 

of these when they do work for a large share of women, even 

though there is a mortality rate in allowing the usage for those 

women for those drugs. 

Ms. WOODCOCK. The trials that we looked at—and this is from 

the Center for Drugs, again, because it is up on appeal right now— 

but in the trials that were done of Avastin in breast cancer, there 

was no survival advantage at all. And there was also no—— 

Mrs. MYRICK. But—and I understand. But the point is, if it is 

helping some people and they are willing to take the risk, I guess 

I go back to the same thing, should we not allow them to have that 

opportunity? And that is really where I am coming from. 

Ms. WOODCOCK. I understand. 

Mrs. MYRICK. I yield back, Mr. Chairman. 

Mr. BURGESS. Would the gentlelady yield to me for a moment? 

Mrs. MYRICK. Yes. 

Mr. BURGESS. Just on that question on Avastin, just looking at 

the list of people who were on the advisory panel last week who 

rendered this opinion, I don’t see anyone—maybe you can educate 

me differently—I don’t see anyone that would have had the ongoing 

daily treatment of breast cancer patients under his or her control. 

53 

You had a lot of experts and a lot of oncologists, but I didn’t see 

a specific specialist in the specialty of metastatic breast cancer. 

Wouldn’t you want someone like that on a panel rendering that 

type of opinion? 

Ms. WOODCOCK. Well, this was not run by the Center for Drugs, 

and so I can’t comment. I agree, there was no breast cancer expert, 

to my knowledge, on that panel. 

Mr. BURGESS. Thanks, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

ranking member of the full committee, Mr. Waxman, for 5 minutes 

for questions. 

Mr. WAXMAN. Thank you very much, Mr. Chairman. 

Ms. Woodcock, good to see you again. 

I mentioned in my opening statement that we want to ensure 

that innovation in the pharmaceutical industry is vibrant. This is 

an important national priority. I also think it is important to assure that the drugs that reach patients are both safe and effective. 

That is the mandate to FDA. 

When critics assert that FDA is somehow stifling innovation, we 

need to look very carefully behind those claims and insist that we 

have reliable and accurate data to substantiate them. Without this 

kind of data, we can very quickly get to a place where the so-called 

solutions are being proposed to a problem that may or may not 

exist in the first place. 

The same critics allege FDA’s slowness is because of regulatory 

changes that I fear could prove—they are suggesting some of these 

regulatory changes—for instance, some have suggested that Congress pass legislation preventing FDA from having the ability to insist on critical trial data that FDA feels is necessary and force it 

to approve drugs on the basis of less information. 

Specifically, some have also suggested that the FDA be required 

to approve drugs for certain conditions on the basis of a single 

study instead of two randomized, placebo-controlled trials. In 1997, 

we did adopt a law that gave the FDA discretion to do less than 

two randomized trials, and then we hear critics claiming that FDA 

has not used this discretion, always insisting on two trials. 

Now, we are not scientists; we rely on you to make scientific decisions at the FDA. But we hear all the time about how FDA is taking too long and asking for information that is not necessary. 

Can you comment on this? Is it true that FDA has failed to use 

the discretion we gave you in PDMA and that the agency always 

insists on two trials? Would FDA be concerned about legislation 

that spelled out the number or type of clinical trials that the agency could look at in assessing a drug application? 

Ms. WOODCOCK. Well, first, let me say, I would be concerned 

about trying to legislate at a more detailed level what type of evidence is required. We try to match the evidence to the situation, 

the requirement of evidence to the situation. So for rare diseases 

or mortal diseases, less evidence usually is required. 

For example, we did a study of orphan data, and half of orphan 

approvals were based on a single trial, one trial. Recently, this 

year, we have approved seven orphan or rare disease indication, all 

right? Some new products, some efficacy supplements. For one of 

those, there was no human trial—it was done on animal data—to 

54 

show efficacy, right? In one of them, there were 17 patients. And 

this was a rare disease. But there wasn’t a randomized trial. We 

compared how the patients were doing before they took the drug 

compared to how they did after they took the drug. 

Mr. WAXMAN. So you use that discretion like you have under the 

law to set up priorities, how serious the disease is, how small the 

population may be that is being affected by a particular disease or 

would be helped by a particular drug. And you feel that if we 

micromanaged your activities by specifying that this trial is all that 

is needed or that trial is sufficient, that we would end up with, 

what, stultifying FDA or not letting you do your job? 

Ms. WOODCOCK. We might slow things down. 

Mr. WAXMAN. Slow them down even further? 

Ms. WOODCOCK. That is what I think, because we would be involving a lot of lawyers and whether we were obeying the law in 

medical decisions that we were making. Nothing against you lawyers, but sometimes that slows things down a little bit. 

I would say that we have considerable flexibility. And, say, a 

drug for headache pain that is going to be used by millions of people, all right, you want to know more about that—you want to 

know it is not going to cause a stroke, for example—than a drug 

here for the orphan indication or for a disease where people are 

dying and they don’t have any other alternatives. We have great 

flexibility in the standards that we apply. 

Mr. WAXMAN. Has there been a change in FDA’s protocols for reviewing drugs? In other words, has there been something where, 

according to Mr. Leff, who is going to testify in a while, that FDA 

has shifted to a more cautious decision-making posture, begun to 

require more and more data to provide a higher degree of statistical proof of both efficacy and safety? And it sounds like FDA has 

somehow formally changed the drug review process. Is that an accurate statement? How do you respond to that? 

Ms. WOODCOCK. No. I believe that we still have the standards of 

safety and effectiveness that we have always had, and we continue 

to apply them. 

We have learned, though—we have learned some things. For example, we have learned that drugs that raise blood pressure will 

cause a certain incidence of strokes. And so, for example, in obesity, if you are going to have a drug to treat obesity, maybe it 

causes weight loss, but if it raises the blood pressure—I mean, you 

are treating the obesity, in part, to decrease cardiovascular complications, OK? 

Mr. WAXMAN. Right. 

Ms. WOODCOCK. What if, in fact, you are actually going to increase them? 

So we have to know, because the standard is that it works, right? 

And patients take these drugs because they believe they are going 

to better their lives and better their health. And so, when we learn 

new medical facts, new scientific facts, we have to make sure that 

they are taken into account in the drug development program. But 

that is part of the standard of safety and effectiveness. 

Mr. WAXMAN. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentlelady, Ms. Blackburn, for 5 minutes for questions. 

55 

Mrs. BLACKBURN. Thank you so much, Mr. Chairman. 

And we appreciate that you are here, Dr. Woodcock. 

I want to stay with the line of questioning that Ms. Myrick had 

started with you, looking at this approval process. I had gone 

through the forensic cancer research report on FDA and the EMA, 

European Medicines Agency, looking at those approvals from 2003 

to 2010. And, you know, that said, well, FDA was faster than EMA. 

But when you look at the year by year on that—and I am sure you 

have done that—and you go back to 2007 or 2008, there is a significant narrowing of the lag in cancer medicine approval times between the FDA and the EMA. And that was repeated—the noting 

of that lag was repeated in the California Healthcare Institute— 

and I know you are familiar with that report—and also the Boston 

Consulting Group report. 

So I want to ask you four questions relative to that, because I 

think this should be of great concern with us. And it ties into what 

we hear from our constituents, who are concerned about the process that you are having individuals go through, as they try to file 

and go through the approval process. 

So here are the four questions for you on that: Number one, what 

accounts for these trends? Number two, is the FDA getting slower 

and more inefficient? Number three, is the EMA getting better and 

more efficient? And, number four, is it a combination of things? 

Because if we are getting slower, we need to nip this in the bud 

and we need to know what the precise problem is. Can you define 

that? 

Ms. WOODCOCK. Well, I can’t remember each one of your four 

questions—— 

Mrs. BLACKBURN. I will be happy to submit for writing. 

Ms. WOODCOCK. Right. 

The FDA most recently—our most recent data for 2011 show that 

we have the highest first-action approval rate we have ever had, 

which means the applications are coming in and they are getting 

out the door on the first cycle. And that, for priority applications, 

is 6 months usually. All right? So you can’t get too much faster 

than that, all right? 

The Europeans may be getting faster. Another hypothesis or 

thought is that the applications are getting better, all right? If the 

industry fully understands what the regulators want and they have 

a very important drug that is needed by the population, then it 

usually will move through the regulatory process in any country 

very rapidly. 

So we don’t feel we are in competition with the European Union 

or whatever. We were simply responding to criticism that it was 

taking us twice as long or three times as long as they. If the drug 

were approved simultaneously around the world and available to 

all patients with whatever disease, say, hepatitis C, that would 

probably be the best outcome. 

Mrs. BLACKBURN. Well, and I agree with you on that. And I 

think that the two things that we hear you could kind of distill 

down to companies that are spending billions of dollars, want to 

make certain that they are provided with both transparency and 

consistency in that FDA review process. And they want to make 

56 

certain that you all are conducting these with certainty and predictability. And as you well know, that has been a problem. 

One other question I wanted to ask you about, because I have 

written you about the PGAs and the issue that is there. And I was 

due a response—I am trying to find it—by the end of June, and I 

still have not had a response from you all about the products that 

are there, with the PGAs and what you are doing with those overthe-counter, unapproved, PGA-containing eyelash growth products. 

What are you doing to investigate the marketing of those products and to restrict those in the marketplace? And do you plan to 

take enforcement action against all companies marketing these 

companies without FDA approval? 

I think that all of us who look at the market for young women, 

we are very concerned about these products in the marketplace. 

Ms. WOODCOCK. Yes, we are looking into this issue. As you know, 

there are numerous products in the marketplace, dietary supplements, that have been contaminated with many dangerous drugs. 

And so we have been taking action on products that are contaminated with these drugs. And we are looking into this issue, and we 

will be happy to get back to you on our progress. 

Mrs. BLACKBURN. OK. I am speaking specifically of the eyelash—— 

Ms. WOODCOCK. I know. 

Mrs. BLACKBURN [continuing]. Growth. 

Ms. WOODCOCK. I know. 

Mrs. BLACKBURN. OK. Well, we were due a response by the end 

of June. 

Ms. WOODCOCK. Yes, I am sorry that you have not received that 

in a timely manner. 

Mrs. BLACKBURN. OK. And I think that we want to know that 

there is action taken against these unapproved—— 

Ms. WOODCOCK. Yes. 

Mrs. BLACKBURN [continuing]. Products. Thank you. 

I yield back. 

Mr. PITTS. The chair thanks the gentlelady, recognizes the gentleman, Mr. Engel, for 5 minutes for questions. 

Mr. ENGEL. Thank you, Mr. Chairman. I want to thank you for 

holding this important hearing today. As we all know, the reauthorization of PDUFA is vitally important to both patients and industry alike. 

As many of us remember, PDUFA was originally enacted in 1992 

to address the unusually long and unpredictable wait period that 

it used to take for new drugs to be approved for market consumption. At that time, it would take an average of more than 2 years 

for a new drug to be approved, which meant that patients would 

not have access to new medicines when they needed them, and innovation suffered. 

I am proud to say that, since then, we have come a long way in 

making more drugs available to patients while maintaining safety. 

I recognize that the system is not perfect, but we have come a long 

way. 

Mr. Chairman, as we move along in the reauthorization process, 

I look forward to working with the various stakeholders and my 

colleagues on the other side of the aisle to address ways in which 

57 

Congress can strengthen the FDA and achieve our common goals. 

I mention working with my colleagues on the other side of the aisle 

because I think it is very important that we remember that this 

is not a partisan issue. 

However, the appropriations bill that was passed last month cut 

the FDA’s funding drastically, and I think that was a mistake. How 

can we expect the FDA to do their job effectively and efficiently 

while at the same time take away the valuable resources they need 

to do it? This only hurts patient safety, and it also hurts one of our 

strongest and most innovative industries. 

So, Dr. Woodcock, let me ask you this. Today we are discussing 

legislation that authorizes prescription-drug user fees, which are 

critical to the FDA’s ability to approve drugs more quickly while at 

the same time the House is cutting the funding. Can you tell me 

how you plan to reconcile these cuts and see that new, innovative 

drugs continue to come into the market in a timely manner? 

Ms. WOODCOCK. Well, I mean, any cuts would make various programs at FDA more difficult. We also approve generic drugs, and 

the flow of those is important to keeping health-care costs under 

control in the United States. And we would become more challenged, I think, in our review of generic drugs if we had substantial 

cuts. We also manage post-market drug safety problems, and that 

requires a considerable amount of resources and effort. 

We also keep guard over quality of all the drugs in the United 

States. And, as has already been mentioned, the import of drugs 

from all around the world and manufacture around the world have 

challenged us to make sure that we are able to ensure high quality 

of the U.S. drug supply. So that would be a challenge. Also, clinical 

trials are conducted all around the world, and so we are having to 

inspect those clinical trials wherever they might be held. 

In addition, as you alluded to, this would have an impact on our 

ability to promote innovation in new drug regulation and in drug 

development, which is something that is very dear to my heart. 

Mr. ENGEL. Let me ask you—as you know, many doctors and 

hospitals are struggling to cope with unprecedented drug shortages 

in the United States. Drug shortages obviously lead to delays in 

treatment and force the use of alternative drugs, which can result 

in unintended consequences. This shortage is endangering cancer 

patients, heart-attack victims, accident survivors, and many other 

ill people. 

So let me ask you this. Before I ask you this, I want to ask the 

chairman for unanimous consent to put into the record a statement 

from the American Hospital Association on behalf of our hearing 

today. 

Mr. PITTS. Without objection, so ordered. 

Mr. ENGEL. OK, thank you. Thank you, Mr. Chairman. 

[The information follows:] 

58 


72917.031
59 


72917.032
60 


72917.033
61 

Mr. ENGEL. So let me ask you this, Doctor. From the FDA’s perspective, what is the problem with drug shortages, and how can we 

address it? 

Ms. WOODCOCK. Drug shortages have multifactorial problems, all 

right? They are related, often, to drugs that are off-patent, that 

only have one manufacturer that is approved in the United States, 

and that eventually have aging facilities. 

We work tirelessly to try and ameliorate drug shortages in the 

United States. And, from our point of view, although there are 

these structural problems, what would help us the most would be 

to have early notification if a company is planning to stop making 

an essential drug or temporarily go out of production, so that we 

could make arrangements to substitute something else, to get another drug available for doctors and patients. And we have been 

able to do that many times when we have actually had advanced 

notice. 

Mr. ENGEL. Let me ask you—the final question is, you mentioned 

in your testimony that the FDA allows access to investigational 

products through clinical trials. And this allows patients who may 

need a treatment that is not currently on the market to access innovative treatments. You mentioned also in your testimony that 

are times when patients cannot enroll in critical trials. 

Could you explain why and what some of the challenges are that 

these patients face when considering the clinical trial? 

Ms. WOODCOCK. Well, there is difficulty in the U.S. in accessing 

clinical trials. But there is a broader issue of treatment access, 

which is a person who lacks alternative therapy and there is no 

other approved drug that might work for them, so they would like 

to access an investigational product—drug. 

We recently passed regulations about a year ago that broadened 

and liberalized and rationalized access protocols for investigational 

drugs. The FDA believes that people with serious illnesses who 

lack alternative therapy should be able to get investigational drugs 

on a treatment basis. 

Mr. ENGEL. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Georgia, Dr. Gingrey, for 5 minutes. 

Mr. GINGREY. Mr. Chairman, thank you. 

And, Dr. Woodcock, thank you very much for your testimony. 

Let me ask you a couple of quickies. Did you tell the committee 

that your specialty is rheumatology? 

Ms. WOODCOCK. Yes. 

Mr. GINGREY. OK, thank you. 

In regard to my colleague from North Carolina, in regard to the 

question on Avastin, can you assure the committee the decision on 

Avastin—and I guess that final decision is in the hands of the commissioner at this point; it looks like it probably will not be approved for advanced breast cancer, although it will continue to be 

approved for colon, and you mentioned a type of brain cancer that 

it is still approved for—this decision, can you assure us, is not 

based on the cost of that drug? 

Ms. WOODCOCK. We never look at the cost of drugs when we are 

doing our decisions. It is not within our mandate, and it is not 

something that we look at. 

62 

Mr. GINGREY. You never look at the cost of the drug? 

Ms. WOODCOCK. No. 

Mr. GINGREY. OK. 

Mr. Shimkus brought up a question about the need for new antibiotics, and I think that your response to his questions was reassuring to me. And I think you probably know that Mr. Shimkus 

and myself and others on this committee, in a very bipartisan way, 

have introduced H.R. 2182, the GAIN Act, to try to get more antibiotics to the market and the problems that we have in regard to 

that, because if they are used properly, then the market for the 

sales of those drugs is very limited—— 

Ms. WOODCOCK. Right. 

Mr. GINGREY [continuing]. As it should be, if they are used properly. 

Can you also give me your thoughts on the need for new 

diagnostics to properly identify infectious diseases? For example, 

would new diagnostics have helped in the recent E. coli outbreak 

in Germany? 

Ms. WOODCOCK. Certainly. We feel that, particularly, point-ofcare diagnostics that could be used at the bedside by clinicians to 

rapidly identify the bacteria and also potentially resistance profiles 

would be just an outstanding advance in infectious disease. And we 

have certainly talked to the Infectious Disease Society about this 

and others. 

So if we could target our antibiotics better—as you well know as 

a clinician, we do a—whatever you call it—a shotgun approach to 

treatment until we have the cultures and we know what the patient has. And so, for many days or maybe total course of treatment, it may be empirical, and so we don’t know what we are treating. And this leads to a more widespread resistance, I believe. 

Mr. GINGREY. And that, of course, is part of our bill, as well. And 

I thank you for that response. 

Very quickly, my last point, I wanted to address the Sentinel Initiative, the post-market risk identification/analysis system. 

And the reason I wanted to be sure of your specialty of 

rheumatology, there is a drug—I think it is pronounced 

‘‘Remicade.’’ Am I correct? 

Ms. WOODCOCK. Yes, uh-huh. 

Mr. GINGREY. —Remicade, that was approved. And I wanted to 

ask you, if you know, was that approved under orphan drug status? 

I know it has been on the market maybe for as much as 20 years— 

well, maybe not quite that long. But the drug being used for 

Crohn’s disease and with pretty good results. But my understanding is that up to 5 percent of individuals will eventually, if 

they have taken that drug for Crohn’s disease, they will eventually 

come down with leukemia. And, you know, to me, that seems awfully high. And maybe I am being affected because it happened to 

a family member just recently, who ended up dying of her leukemia. She was helped tremendously several years ago by use of 

this drug. 

What is the threshold? A 5 percent, to me, risk from taking a 

drug and then ultimately developing leukemia, which is pretty lifethreatening—in her case, it was definitely life-threatening and lifeending—where is the threshold in regard to what we are looking 

63 

at in the Sentinel Initiative, the post-market analysis of these 

drugs? 

Ms. WOODCOCK. Well, generally what we are doing with all the 

immunosuppressant drugs is having registries and long-term follow-up. So we can also use Sentinel for evaluating these longerterm outcomes. But we are also watching patients observationally 

over time. 

And we can get back to you on what we know right now about 

the occurrence of malignancies as well as infections, opportunistic 

infections, as a result of all the classes of immunosuppressive drugs 

that are used. 

Mr. GINGREY. Dr. Woodcock, I would really appreciate that, both 

as a Member of Congress and personally. I would really appreciate 

you getting back to me with a report on that. And I thank you very 

much. 

Ms. WOODCOCK. I would be happy to do that. 

Mr. GINGREY. I yield back. 

Ms. WOODCOCK. And if I may say one thing about this, this really illustrates the balance of benefit and risk, because malignancies 

are not apparent immediately, all right? And so, you could say, 

well, this is a wonderful drug, we should just get it out there, and 

everyone should take it. But what we find out is, yes, there are 

breakthrough—tuberculosis, whatever, and there are also cancers 

that occur late. And this is where we have an obligation to patients 

to find out as much as we possibly can, so they can make their decision. 

Mr. GINGREY. Thank you. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman, Mr. Latta, for 5 minutes for questions. 

Mr. LATTA. Well, Doctor and Director, thanks very much for 

being with us today. I really appreciate your testimony today. 

And just to kind of maybe follow up a little bit of the questioning 

that has already been asked, but one of the areas that I would like 

to go into is about especially on the obesity and diabetes side, with 

the drugs out there and the therapies that are being brought forth, 

and especially with the FDA approval process. Because, as we all 

know, especially young and old alike, both these, diabetes and obesity, are affecting a huge portion of our population and increasing 

our costs. Especially, it is a huge driver on the Medicare side. 

And the question is, what are you doing to encourage the development of new therapies to treat these diseases, especially using 

your authority under REMS—— 

Ms. WOODCOCK. Pardon me. I am having trouble hearing you. 

Mr. LATTA. OK. You know, this is sometimes also the room that 

we use for our telecommunications subcommittee. And I am sorry— 

is that better? 

Ms. WOODCOCK. Yes. 

Mr. LATTA. OK. The way some of our mikes pick up. 

But the question I have then is, what are you doing encourage 

the development of new therapies to treat these diseases, especially 

using your authority under REMS to follow the drugs closely after 

their approval? 

Ms. WOODCOCK. We share the understanding of the need for new 

treatments for diabetes and for obesity. And I would point out that 

64 

for diabetes, in early 1990s, there were only two types of therapies 

available for the treatment of Type 2 diabetes, and now we have 

11 new classes of drugs that are out there. So there has been a tremendous blossoming of attempts to get new therapies for diabetes 

out there. 

And, in fact, we are seeing the pipeline continue. And we have 

put out guidance about cardiovascular risk in diabetes drugs that 

companies have been able to deal with and follow, and we have approved new diabetes drugs recently. So we see a robust pipeline 

there. 

In obesity, the problem is different. We have had to take three 

obesity drugs off the market because they cause stroke. We have 

had to take another class of obesity drugs off the market because 

of heart-valve disease. And you can see with young people, if we 

expose them to an agent widespread that causes heart-valve disease, we would have another epidemic on our hands. So we must 

make sure that these products have adequate safety. 

But we recognize the obesity epidemic. And what we are doing 

is we are going to have a scientific meeting about obesity and cardiovascular safety. And we are also planning to have a series of 

stakeholder meetings, where we bring in the very attritions and 

the patient groups and the FDA and other experts to talk about 

how diabetes drugs should be developed. And I think this will be 

very helpful to the industry. 

Mr. LATTA. Let me ask this. I think you said that you took several off the market last year. I believe also, if my information is 

correct, that the FDA also denied three consecutive applications for 

approval of new obesity drugs last year. 

Ms. WOODCOCK. That is correct. 

Mr. LATTA. Now, was that for the same reasons, or what was the 

cause of that? 

Ms. WOODCOCK. Different—well, one drug had a blood-pressure 

problem, which was the reason we had to remove other diabetes 

drugs off of the market. They were causing strokes. Last year, we 

removed a drug, Meridia, from the market because of stroke. A 

trial was done that showed that even though people lost weight, 

they still got an increased number of strokes when they took this 

weight-loss drug. So it was removed from the market. 

So one of the problems that we are identifying is many of the 

weight-loss drugs increase blood pressure, and we have to make 

sure they are not causing an excess of strokes, OK? But some of 

the other weight-loss drugs have other types of problems that we 

are looking at. 

Mr. LATTA. Thank you very much. 

And, Mr. Chairman, I yield back. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Kentucky, Mr. Guthrie, for 5 minutes for questions. 

Mr. GUTHRIE. Thank you, Mr. Chairman. 

Thank you, Dr. Woodcock. 

I know you all have a difficult job anytime you approve a drug 

as you go forward. And just think about the long term as you move 

forward, of course there is a—so it is a quandary. But there are a 

lot of people waiting on the approvals as you move forward. 

65 

And my friend, Ms. Myrick, Representative Myrick, covered some 

of it, but I just got a text this morning from my brother, and I am 

going to share this a little bit. Well, first, my brother called me yesterday. He has a best friend in the Navy, was in the Navy, whose 

wife had breast cancer. And they were one of the ones who flew 

from Seattle, Washington, to, I guess, Baltimore a couple of weeks 

ago. And the text says, ‘‘Thanks for talking to Nancy yesterday. 

She knew we were having this meeting. They are great people, and 

thanks for the quick response. The bottom line is, they have been 

through a lot, and she has lived much longer than she was supposed to.’’ And I really read that to give you that line. 

And it seemed like with Avastin that—I talked with her quite a 

while on the phone yesterday, and she said her mother has breast 

cancer but very localized. And she realizes Avastin wouldn’t be 

something that her mother should be taking. But she did say, when 

she discovered she had breast cancer, when they found the breast 

cancer, she had four tumors on her liver. I think that is what she 

said. And so, therefore, it looked like she had made the decision. 

She realizes the toxicity, but she really believes that Avastin is— 

and she is distraught—has really increased her life expectancy. 

So the question—and maybe this wasn’t your area, as you said— 

was Avastin not approved for breast cancer because of the side effects or because there is no clinical proof that it actually works? 

Ms. WOODCOCK. Avastin was approved under accelerated approval for breast cancer. It was already on the market for other 

cancers, all right? 

Mr. GUTHRIE. Right, right. 

Ms. WOODCOCK. And then, subsequently, it was approved under 

accelerated approval. 

What that means is, then the drug developers have to prove that 

the promise, OK, that was approved under accelerated approval is 

real, all right? And so the company did additional trials, and they 

did not show any survival advantage. 

The original trial it got approved on showed something called 

progression-free survival. What that means is you live longer with 

your tumors not growing on scans. 

Mr. GUTHRIE. OK. 

Ms. WOODCOCK. All right? It doesn’t mean you live longer. It 

means that your tumors are stable longer. And so the original trial 

showed, in women getting Avastin, their tumors stayed stable 

longer, all right? 

Mr. GUTHRIE. OK. 

Ms. WOODCOCK. What we asked the company to say—well, show 

that means something, show that translates to either quality of 

life, better quality of life of the people or longer life of people, all 

right? And they were not able to show either of those in the subsequent trials that were done. 

That does not mean that Avastin is not an active drug, perhaps, 

for some women, but we do not know what women. And it does 

have very serious, potentially fatal side effects. 

Mr. GUTHRIE. Right. She recognized that. We had talked on the 

phone—and so the issue really wasn’t just the side effects and it 

could be fatal. But you are saying it really didn’t show that it extended the life as you move forward. 

66 

Ms. WOODCOCK. It did not. In that population. And that is not 

a population that is selected by some marker to respond well to 

Avastin. It may well be if they could come up with a biomarker and 

say, ‘‘These women are the women who should take this drug,’’ 

then it might be possible to figure out who the drug is good for. 

Mr. GUTHRIE. Uh-huh. So it could be a—and she could be 

one—— 

Ms. WOODCOCK. That is right. 

Mr. GUTHRIE [continuing]. A select group of circumstances that 

it affects—because drugs interact with all of us differently—that 

would actually—and I know from our conversations she is convinced that she is still here because she was on Avastin. 

And one other thing a lot of people have said—I only have about 

a minute, so I will just ask it really quick. You know, I do hear 

from a lot of our people in the drug field, pharmaceutical field, saying that they are having difficulty getting things approved. You 

have heard that from several of us here. You all must be hearing 

the same thing. And maybe what you are saying is 2011 has been 

better than 2010 and 2009 and 2007. 

So are you already acting to the fact that people said they are 

getting things difficult—like you said, 2011 has been pretty successful, but I am really not hearing people saying that, ‘‘We have 

had difficulty in the past, but it seems to be getting better.’’ So I 

don’t know if you are hearing the same thing. And just comment 

on that. I have about 40 seconds left. 

Ms. WOODCOCK. Well, I would propose to you that the people who 

come into your office are not the people who have had a successful 

experience. And so you have what we call a biased sample, all 

right? And even if, like, 90 percent of the people are getting 

through and we are having a tremendous—I am not saying all this 

will continue, but this year we are having an extremely high approval rate because the drugs that are coming in are—many of 

them are very significant advances, all right? 

But the people I think who come to talk to you continue to be 

the people who are having a difficult time. And so I don’t know 

that you would see any change in your experience. 

Mr. GUTHRIE. So they are not coming by to see us just to say, 

‘‘Thanks, it really went well’’? We hear that sometimes too. 

Thanks a lot. 

Ms. WOODCOCK. Thank you. 

Mr. PITTS. The chair thanks the gentleman, recognizes the ranking member emeritus of the committee, Mr. Dingell, for 5 minutes. 

Mr. DINGELL. Mr. Chairman, I thank you for the hearing. 

And I thank you for your courage. 

Ms. WOODCOCK. Thank you. 

Mr. DINGELL. I wanted to ask a ‘‘yes’’ or ‘‘no’’ question. I hope you 

will respond. 

Do you have the ability to fully control the safety of imported 

pharmaceuticals, yes or no? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have the authority to control the safety of 

raw materials or imported pharmaceuticals? 

Ms. WOODCOCK. No. 

67 

Mr. DINGELL. Do you have the authority and the resources you 

need to address the safety of components now being imported into 

this country, yes or no? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have the necessary authorities and resources to see to it that drugs are only imported from facilities 

overseas that are properly observing good manufacturing practices—that is a word of art—yes or no? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have the ability to see to it that raw-materials suppliers also engage in good manufacturing practices abroad? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have the resources needed to conduct foreign drug-facility inspections with the same frequency as domestic 

drug-facility inspections? 

Ms. WOODCOCK. No. 

Mr. DINGELL. How often can you get by to see a foreign drug 

manufacturer? 

Ms. WOODCOCK. Every 9 years or so. 

Mr. DINGELL. Every 9 years? 

Ms. WOODCOCK. Yes. 

Mr. DINGELL. You get by to see dog-food manufacturers every 

year or so. 

Ms. WOODCOCK. Yes, probably a little more—a little over a year. 

Mr. DINGELL. Do you need additional resources to increase inspections of foreign drug facilities? 

Ms. WOODCOCK. Yes. 

Mr. DINGELL. Do you need additional authorities to be effective 

in that? 

Ms. WOODCOCK. Absolutely. 

Mr. DINGELL. Do you have the ability to freely share information 

about a drug with your trusted domestic and foreign counterparts 

in the instance of something like another heparin crisis, yes or no? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you need this ability? 

Ms. WOODCOCK. Yes. 

Mr. DINGELL. Do you have a clear authority to require manufacturers to assure the safety of their food chain, yes or no? 

Ms. WOODCOCK. Their food chain? 

Mr. DINGELL. Yes—I am sorry, the supply chain. I apologize. 

Ms. WOODCOCK. Thank you. No, we do not. 

Mr. DINGELL. Do you need this authority? 

Ms. WOODCOCK. Yes. 

Mr. DINGELL. Do you have the authority to require manufacturers to notify you if they suspect their drug may have been counterfeited, misbranded, or adulterated? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have the ability to properly assure the safety of both raw materials for the manufacture of pharmaceuticals 

and pharmaceuticals as they are imported into this country? 

Ms. WOODCOCK. No. And I think we are one of the few countries 

that does not have that authority. 

Mr. DINGELL. Do you need this authority? 

Ms. WOODCOCK. Yes. 

68 

Mr. DINGELL. Do you have the authority to require companies to 

recall a drug, yes or no? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have that authority with regard to imports? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Do you have that authority with regard to raw materials and things like that? 

Ms. WOODCOCK. No. 

Mr. DINGELL. And components? 

Ms. WOODCOCK. No. 

Mr. DINGELL. Now, let’s go to the question of heparin. A lot of 

bad heparin got out because, currently, you couldn’t get over to 

China to see what the raw material was like and what was safe 

or unsafe with it. Is that right? 

Ms. WOODCOCK. That was part of the problem. 

Mr. DINGELL. What was the other part? 

Ms. WOODCOCK. I think the tests were out of date for heparin. 

Mr. DINGELL. The what? 

Ms. WOODCOCK. The testing standards, the U.S. standards, international standards. 

Mr. DINGELL. Were they adequate or inadequate? 

Ms. WOODCOCK. They were inadequate. 

Mr. DINGELL. OK. Do you have authority to address that problem? 

Ms. WOODCOCK. No, not fully. 

Mr. DINGELL. Not fully or just not at all? If you can’t do it fully, 

you can’t do it at all, can you? 

Ms. WOODCOCK. Can you repeat the question? 

Mr. DINGELL. Would you submit a brief monograph to this committee for the purposes of the record—— 

Ms. WOODCOCK. Certainly. 

Mr. DINGELL [continuing]. Explaining what happened in the heparin case and what abilities you need to address imports not just 

of finished products, pharmaceuticals, but also raw materials and 

components, please? 

Ms. WOODCOCK. We would be happy to do that. 

Mr. DINGELL. Thank you. 

I ask unanimous consent that the additional matters requested 

be inserted in the record at the appropriate point, Mr. Chairman. 

Mr. PITTS. Without objection, so ordered. 

[The information appears at the conclusion of the hearing.] 

Mr. DINGELL. Mr. Chairman, I thank you for your courtesy. 

And I thank our witnesses. 

Mr. PITTS. The chair thanks the gentleman, recognizes the gentleman from New Jersey, Mr. Lance, for 5 minutes for questions. 

Mr. LANCE. Thank you, Mr. Chairman. 

Good morning, Doctor. 

I have the honor of being the Republican co-chair of the Rare 

Disease Caucus. And I want to thank the progress that the FDA 

has made regarding the advancement of orphan product development. And given the fact that a large number of products approved 

by the agency are for orphan indications, it is clear to me that the 

FDA’s increased focus on development and approval of orphan 

69 

products is important to all stakeholders in the rare-disease community. 

I am particularly interested in learning more about the Office for 

Rare Diseases, created last year. As I understand it, the goal of 

that office is to facilitate and support research, product development, regulations and approval of biopharmaceuticals for the treatment of rare disorders and to serve as a focal point for stakeholders 

and developers of drug and biological products. 

If one of the primary objectives of the Office for Rare Diseases 

is to ensure collaboration among scientists and clinicians throughout CDER, what steps are being taken and what are the plans for 

the future to ensure adequate resources that are allocated to this 

office? 

Ms. WOODCOCK. Thank you. 

Yes, as part of enhancing regulatory science and expediting drug 

development within the proposals we have for the new user-fee program, we have a portion on rare diseases, which would improve resources, add additional resources to our attention to rare diseases, 

including to that office. 

Mr. LANCE. And will you be engaged in that activity? And what 

time frame, Doctor? 

Ms. WOODCOCK. The new user-fee program hopefully will be 

passed and be able to be implemented in 2013. And, at that point, 

we would have additional resources to put—— 

Mr. LANCE. So this would be an action probably we would take 

next year regarding PDUFA, next year? 

Ms. WOODCOCK. Yes. 

Mr. LANCE. Thank you. Well, I look forward to working with you 

and other interested stakeholders in this issue. It is important, I 

think, to the entire Nation and certainly important to the district 

and State I serve, which we believe is one of the medicine chests 

of the world. 

On a different topic, on biomarkers, innovative drug development 

is increasingly dependent on the use of new biomarkers of disease 

to target the right patients. Could you tell us what you are doing 

to encourage the use of biomarkers in drug development? 

Ms. WOODCOCK. Thank you. 

I think since 2004 FDA has really been in the forefront of this; 

we have been encouraging the use of biomarkers. And we have 

published numerous guidances. We have done a lot on something 

called pharmacogenomics, because a lot of these would be genetic 

markers. 

And we also now have a proposal in the new user-fee enhancements where we would like to enhance our activities on biomarkers 

and pharmacogenomics, because we feel this does have tremendous 

promise for patients and for drug development. 

Mr. LANCE. Well, thank you, Doctor. This is my first opportunity 

to meet you. I am new to the committee, and I look forward to 

working with you. 

And I yield back the balance of my time. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Louisiana, Dr. Cassidy, for 5 minutes for questions. 

Mr. CASSIDY. Thank you, Dr. Woodcock, for testifying. 

70 

Newly active substances, just so I am clear on the definition, if 

somebody has a drug and they make it a single-day therapy, a prolonged release if you will, as opposed to a QD, does that qualify the 

new—so it is just a truly new drug? 

Ms. WOODCOCK. Yes, it has to be first, you know, time and first 

exposure to humans of this molecule, basically. 

Mr. CASSIDY. Got you. 

Secondly, just to follow up on what Mr. Dingell asked about, 

man, if you are inspecting dog-food factories a little bit over a year 

but only going abroad every 9, couldn’t you redirect resources from 

the dog-food factory—I am saying that as a pet owner—to—and, of 

course, it sounds tongue-in-cheek, but, actually, it is a very serious 

question. 

Ms. WOODCOCK. Well, Congress directs resources to drug programs separately from foods or veterinary medicine. So they are all 

separated out, and we have to expend those based on the appropriation, OK? 

Mr. CASSIDY. So, would it be—not to put you in a box, but if Congress redirected some of the funds currently used for dog food, as 

an example, metaphorically if you will, to inspecting companies 

abroad to make sure they have good clinical or good manufacturing 

practices, would that be a reasonable thing? 

Ms. WOODCOCK. Well, I think, then, that is a tradeoff. The Congress has recently asked FDA to accomplish a great deal more 

tasks under food safety, with their new food-safety bill. And those 

inspectors are all busy trying to accomplish those activities. 

So we have tried—we are trying to redirect domestic inspection 

resources to do overseas inspections. And that has been the main 

effort that we are working on. 

Mr. CASSIDY. So, then, to follow up that, one thing you could do 

within this silo, almost, of funding is—because I have had domestic 

drug manufacturers complain, ‘‘Listen, I am checked every 6 

months, and yet my competition is checked every 9 years.’’ It isn’t 

a competitive issue for them; it is a drug-safety issue. 

So could you elaborate a little bit more on that occurring? Because it seems a very reasonable approach. 

Ms. WOODCOCK. Yes, I think that we are moving—we have been 

trying to move in that direction. That is a desirable thing to do, to 

have a uniform level of inspection around the world that is also 

risk-based, OK? So the riskiest plants should receive the most frequent inspections, whether they are in the U.S. or whether they 

are in China or elsewhere. It has just been logistically very difficult 

to accomplish this. 

Mr. CASSIDY. Now, again, just to, again, pursue—it just seems so 

logical. I mean, you are going to go buy a ticket to go to Bangalore 

and inspect the plant there. Why would that be logistically complicated instead of going to New Jersey? Granted, New Jersey is a 

train ride and Bangalore is a trip. But, nonetheless, it does seem 

as if maybe it is a prejudice, that probably the people in New Jersey have better practices or one that we trust more than maybe 

just a startup in Bangalore? 

Ms. WOODCOCK. Yes, the inspections are done by our field organization. It is not a part of the Center for Drugs. And they have a 

71 

union, and they have agreements about foreign travel and how 

much you can get people to go and do things overseas. 

Mr. CASSIDY. You mean there is a union agreement which is 

keeping us from being able to inspect foreign manufacturers? 

Ms. WOODCOCK. Partly. That is my understanding. 

Mr. CASSIDY. You mean the union agreement is keeping us from 

inspecting these more frequently than every 9 years? 

Ms. WOODCOCK. Well, the work conditions. It is just very difficult—my understanding; I don’t supervise that organization—to 

shift resources to have a larger number of foreign inspections done. 

Mr. CASSIDY. I have to admit, as a physician practicing, it gives 

me great concern for the safety of my patients that that is what 

is limiting our ability. 

Ms. WOODCOCK. We would be happy to get back to you with a 

more complete explanation. 

Mr. CASSIDY. Please. Because that is so incredibly troubling. 

Which union is that? 

Ms. WOODCOCK. Pardon me? 

Mr. CASSIDY. Which union is that? 

Ms. WOODCOCK. NTEU. 

Mr. CASSIDY. I only have 50 seconds left. Let me gather my 

thoughts after that. 

If we had not had that union agreement, would the heparin tragedy have been avoided? 

Ms. WOODCOCK. I think it would still be difficult to move people 

from their established inspection routine and get them to travel repeatedly overseas. 

Mr. CASSIDY. Why don’t we just—— 

Ms. WOODCOCK. But we are moving in that direction. 

Mr. CASSIDY. It may be difficult with the current employees, but 

it sounds like, if that is where the problem is, then we just need 

to find employees that will go, correct? 

Ms. WOODCOCK. Well, there is also a problem with resources. I 

don’t want to understate that, OK? That it is going to take more 

people to do all of these inspections overseas, and it would—it is 

not as efficient as inspecting a certain number of plants in a certain geographic area. 

Mr. CASSIDY. I accept that. But, on the other hand, if you are 

going to find out where the problems are, and if we can trace 

them—the bulk of them to these companies overseas, manufacturing plants overseas, it just seems that is where you should be 

looking. 

Ms. WOODCOCK. Well, we definitely should go where the money 

is. But I would say that we have certainly found manufacturing 

problems domestically recently. Some of them have been high-publicity problems. And we have to maintain good coverage of those 

firms, as well. 

Mr. CASSIDY. I accept that. On the balance, what would be the 

percent of the domestic versus foreign that have resulted in 

deaths? 

Ms. WOODCOCK. I don’t think we have that kind of data. 

Mr. CASSIDY. OK. 

I yield back. Thank you. 

72 

Mr. PITTS. The chair thanks the gentleman, recognizes the gentleman from Pennsylvania, Dr.—— 

Mr. DINGELL. I forgot to ask one question. Could I ask just one 

question? 

Mr. PITTS. Go ahead. Please. 

Mr. DINGELL. To the witness, if you please, H.R. 1438, the Drug 

Safety Enhancement Act of 2011, would this afford you the authorities you need to deal with the heparin problem? 

Ms. WOODCOCK. Yes. 

Mr. DINGELL. It would. 

Ms. WOODCOCK. Yes. 

Mr. DINGELL. Would you give us a little memo on why that is, 

for inclusion in the record? 

Ms. WOODCOCK. We would certainly be happy to. 

[The information appears at the conclusion of the hearing.] 

Mr. DINGELL. Mr. Chairman, you have been enormously courteous, and I thank you. 

And I apologize to my colleague for having interfered with his 

time. 

Mr. PITTS. That is all right. 

The chair thanks the gentleman and recognizes Dr. Murphy of 

Pennsylvania for 5 minutes. 

Mr. MURPHY. Welcome, Doctor. It is good to have you here. 

Ms. WOODCOCK. Thank you. 

Mr. MURPHY. There was an article in yesterday’s Wall Street 

Journal written by Roger Bate. I don’t know if you had a chance 

to see that. But in that, he pointed out a number of things about 

the risks that come to western firms from these small, hard-to-detect flaws, with the trace impurities from unhygienic practices, 

which seems to summarize what we are dealing with here. 

The FDA—excuse me—the Federal Food, Drug, and Cosmetic Act 

provides a drug is adulterated unless the methods used for the 

manufacturing of a drug product conform to current good manufacturing practices. Can you explain the role and importance of the 

good manufacturing practices that FDA looks at in their approved 

products? 

Ms. WOODCOCK. Good manufacturing practices are a quality system, and you are probably familiar with quality systems from other 

areas of manufacturing. These really apply to mass production. So 

it is one thing to make a drug in a laboratory and have a lot of 

scientists looking over it. It is another thing to make it in a factory 

and make millions of doses and make them repeatedly sterile, potent and uncontaminated, and that requires adherence to a quality 

management system. 

The good manufacturing practices is a set of codified regulations 

that FDA has that establishes kind of the minimum standards for 

doing that. 

Mr. MURPHY. Now, you have talked about the supply chain. I 

know Mr. Dingell brought that up, too. So what is preventing the 

FDA from updating its GMPs, requiring drug companies to verify 

their suppliers are complying with the law on providing quality ingredients? Can you tell me a couple of items there that are preventing you from doing that? 

73 

Ms. WOODCOCK. Well, it is possible with a very long process, we 

could modify some of the good manufacturing practices regulation, 

but others—I think of the things that Mr. Dingell—other authorities that he was referring to would require legislative authorization. 

Mr. MURPHY. In part of looking at that, you understand that this 

entire Nation is looking upon Congress to find ways to save money 

and also to look at health care costs, particularly Medicare and 

Medicaid which is spinning out of control. 

Is the FDA involved in or do you know of any other Federal 

agencies looking at a number of aspects? For example, when we 

look at some of these medications, and the estimates are, as an example, as much as 5 percent of ingredients may be impure, may 

have impure drug content, and we are looking at $1.74 billion and 

rising of imports here. 

Does anybody have any information on the impact on health 

care, such as drug shortages, and what that means to health care 

costs, tainted drugs that then effect extended stays in hospitals, return visits to physicians office and emergency rooms? Is that something that you or anybody else is studying the impact on health 

care costs? 

Ms. WOODCOCK. I wish we had that kind of data, but we do not. 

It is very difficult to link drug quality health problems with health 

outcomes, and Heparin was a dramatic example where we saw 

that. But we don’t have overall data like that, and I don’t know 

that anybody else does. 

Mr. MURPHY. Well, that is certainly troubling. While we are looking at this, I know that studies have said just when patients— 

when patients, we have looked at something like 75 percent of people don’t take their medication properly and a study recently said 

that is a $250 billion drain on the system. But then when they do 

take medications according to doctors orders, and we find out there 

are flaws with some of the content of generic drugs, I don’t want 

to malign generics because we are also encouraging physicians to 

write prescriptions for generics, and yet at the same time if we are 

not inspecting these plants properly we end up with causing more 

problems. 

So, does FDA have any positions they recommend then in terms 

of what other branches of government, Medicare and Medicaid 

should be doing? Are they requiring doctors to write prescriptions 

for generics while at the same time we can’t assure that those are 

pure? 

Ms. WOODCOCK. Well, I would point out that Heparin was not a 

generic drug. There were various versions of Heparin on the market, but that was not a generic drug. This is not necessarily a generic drug problem. This is pervasive drug quality problem, and we 

don’t have evidence that generics particularly have additional quality problems over innovator drugs. 

So I think physicians should write for generic drugs with confidence. But we do need to make sure we manage the supply 

chains, that we and mainly the companies have the systems in 

place to make sure that they maintain the quality of their drugs 

that are sold in the United States. 

74 

Mr. MURPHY. I appreciate you pointing that out about generics. 

That is a very important fact. We don’t want people to be worried 

about that. It has to do with the content that comes over. 

You had mentioned that plants can be inspected about once 

every 9 years. The GAO says it is more like every 13 years or so. 

Plus isn’t it true that when you are inspecting a plant in the 

United States, you can just show up on a surprise visit if you wish? 

Ms. WOODCOCK. Correct. 

Mr. MURPHY. And the chances of surprising someone in China is 

slim and none? 

Ms. WOODCOCK. Right. 

Mr. MURPHY. So they have a chance to change that. And so on 

this globalization of drug manufacturing and supplies, are there caveats that the FDA is saying then to manufacturers in the U.S. 

that even though you cannot inspect this, other standards you are 

asking them to handle on their own with this as well? 

Ms. WOODCOCK. Yes. Basically we feel that the ultimate responsibility lies with the manufacturer. We are not their quality assurance group. We are auditors to make sure that they are obeying 

the rules and that they are maintaining quality, and we audit all 

around to make sure they do that. 

There is also testing, which isn’t everything, but having good analytical tests for potency, sterility and making sure the manufacturers conduct those tests, and for impurities, can go a long way 

to help ensure the safety of the drug supply. 

Mr. MURPHY. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Michigan, Mr. Rogers, for 5 minutes. 

Mr. ROGERS. Thank you, Mr. Chairman. Thank you, Doctor, for 

being here. 

Is venture capital important in the development of the next generation of pharmaceuticals, do you believe? 

Ms. WOODCOCK. Yes, venture capital is very important to a segment of the drug development industry, the smaller and arguably 

more innovative side of the industry. 

Mr. ROGERS. They are targeting special treatments for cancer or 

for sepsis or all of those things, right? That is where the venture 

capital kind of flows to those innovative—so you are arguing it an 

important part hopefully of the next cure, we would hope? 

Ms. WOODCOCK. Certainly for innovation. The biotech sector depends on venture capital. 

Mr. ROGERS. I happened to be reviewing the testimony of someone on the panel, Jonathan Leff. I am just going to read some 

things from here just to get your perspective on this. 

‘‘During 2010 and 2011 to date, first time fundings of life 

sciences ventures, a key leading indicator of the health of the innovation ecosystem, has decreased by more than 50 percent due to 

prior years.’’ 

That is a problem, isn’t it? 

Ms. WOODCOCK. Yes. 

Mr. ROGERS. What would you attribute that problem to? 

Ms. WOODCOCK. The problem is due to the failure rate and the 

fact that—again, I am not an economist, but what I have been told 

is that these firms are not successful enough to merit the return 

75 

on investment, and also there is a longer term development cycle, 

that venture capital prefers a shorter return, and so biotech has become less attractive. 

Mr. ROGERS. So it is all the investors that are pulling out of the 

market. It wouldn’t have anything to do—here is his assessment. 

‘‘The FDA’s shift in recent years to an increasingly cautious riskaverse posture towards new drug approvals has the unintended 

consequence of reducing investment in life sciences innovation due 

to the significant additional time,’’ which you mentioned, ‘‘cost and 

uncertainty it has added to the drug development process.’’ True? 

Ms. WOODCOCK. Well, there is uncertainty in the drug development process, and that is the main problem. To lay it all at the feet 

of the FDA I don’t think is correct. McKenzie has recently done a 

study where they looked at failures in Phase III development, 

which is clinical—the last stage of clinical trials, and of products 

that failed there, fifty percent failed because they had no benefit 

compared to placebo. It is really hard to attribute that to the FDA. 

Mr. ROGERS. I certainly understand. But if the FDA doesn’t recognize it has a problem, we will never get any segment of that 

fixed? 

Ms. WOODCOCK. I recognize it. As I said in my oral testimony, 

I think there is a crisis in the industry, and it is pervasive and it 

is very concerning. 

Mr. ROGERS. What would be your recommendation for Congress 

to try to help us through that particular process? Can you clearly 

say that the added time and bureaucracy and investment is gaining—it is worth the sacrifice of losing innovation and attracting 

capital? Is it worth it? 

Ms. WOODCOCK. We feel that the scientific challenges are the 

problem, not the regulatory challenges. So I would disagree with 

Mr. Leff on this. And our data shows that we have a very high rate 

of first cycle approval. So it is hard to lay this at FDA’s feet. 

I was hesitating in responding to you because I have a whole list 

of prescriptions for this problem that I have been promulgating for 

some time, and I would be happy to share those with you outside 

of this venue, because they are fairly extensive. 

Mr. ROGERS. I would be delighted. With your permission, I would 

receive that at your earliest convenience. I think that would be 

helpful. 

The lines in the sand are hard things, and when you look at the 

real decrease in investment, to say that the FDA isn’t a part of 

that problem is a little concerning. Let me give you some other statistics here I find shocking. 

The venture capital funds raised have decreased 25 percent in 

2010 just over 2009, and that is the third consecutive year of decline. The share of venture capital invested in biotechnology declined from 18 percent in 2009 to 12 percent in 2010. From 2008 

to 2010, investment in U.S. Life sciences companies declined by $2 

billion. 

That is significant. And I agree with you, it is a crisis that we 

are going to have to deal with. As a cancer survivor myself, I hope 

somebody is willing to put up the capital to go through the process, 

and I want the FDA to understand that there are risks involved 

76 

and they should be part of the process to help quickly determine 

the efficacy of that particular drug. 

I am concerned that the risk aversion has crept into the FDA to 

a point that it is costing us innovation in the United States, and 

to me that is an unacceptable outcome. 

Do you think there would be any value in having a category of 

drug, and I heard the discussion earlier, you know, if I am sitting 

with my oncologist and my oncologist tells me that this is the particular drug that I have seen work, it has saved someone’s life, it 

has added years to their life, but the FDA says I can’t give it to 

you even if I explain all the risks involved, is there a better way 

to do that? 

Ms. WOODCOCK. Well, I don’t think the FDA—that is the FDA’s 

posture, that people can’t give drugs to patients. As I said earlier—— 

Mr. ROGERS. Well, if you take it off the market, it clearly is. 

Ms. WOODCOCK. Are you talking about Avastin? 

Mr. ROGERS. Yes. As an example. I just used that as an example. 

Ms. WOODCOCK. Avastin is on the market for other indications 

and will remain on the market. 

Mr. ROGERS. I don’t want to debate if you feel that is the right 

decision. But shouldn’t there be the opportunity—I tell you that, 

because many a Member will run into a constituent who will fly 

out of the country to get access to a drug because they have made 

the conclusion that their life is at a point where they are willing 

to take that risk. 

Ms. WOODCOCK. Right. 

Mr. ROGERS. Is there some value in that in the United States? 

Do we have to force people to go to Mexico to do this? 

Ms. WOODCOCK. We don’t stand between people getting investigational drugs if they have no other options, and we passed regulations about 18 months ago that provide a broad range of ways to 

access totally investigational drugs, especially for people who have 

exhausted other types of therapies. So we agree that people have 

a right to take substantial risk. 

Mr. ROGERS. At their own risk. 

Ms. WOODCOCK. Yes. 

Mr. ROGERS. I would love to work with you on the expansion of 

that. I think there have been some problems in the past and currently that I think we can, working together, solve this problem for 

literally thousands and thousands of people who are at a pretty 

emotional place in their life and are willing to take some risks. 

With that, I yield back. 

Mr. PITTS. The chair thanks the gentleman. 

That concludes our first panel. Dr. Woodcock, thank you very 

much for your testimony, for your answers to our questions. 

At this point, we will call the second panel. I think we will take 

5 minutes here just to check the mikes and then we will reconvene. 

[Recess.] 

Mr. PITTS. I think we are ready to reconvene. Our second panel 

has a number of witnesses, and I will introduce them and ask them 

to testify in this order. 

Paul Hastings is the President and Chief Executive Officer of 

OncoMed Pharmaceuticals. Jonathan Leff is the Managing Director 

77 

of Warburg Pincus. Mark Boutin is the Executive Vice President 

and Chief Operating Officer of the National Health Council. Dr. 

Ellen Sigal is the Chair and Founder of Friends of Cancer Research. Lastly, Allan Coukell is the Director of Medical Programs 

of the Pew Health Group of the Pew Charitable Trust. 

Your written testimony will be made a part of the official record. 

We ask that you summarize your opening statements in 5 minutes. 

Mr. Hastings, you may begin. 

STATEMENTS OF PAUL J. HASTINGS, PRESIDENT AND CHIEF 

EXECUTIVE OFFICER, ONCOMED PHARMACEUTICALS, INC., 

ON BEHALF OF BIOTECHNOLOGY INDUSTRY ORGANIZATION; JONATHAN S. LEFF, MANAGING DIRECTOR, WARBURG 

PINCUS, LLC; MARC BOUTIN, EXECUTIVE VICE PRESIDENT 

AND CHIEF OPERATING OFFICER, NATIONAL HEALTH COUNCIL; ELLEN V. SIGAL, CHAIRPERSON AND FOUNDER, 

FRIENDS OF CANCER RESEARCH; AND ALLAN COUKELL, DIRECTOR OF MEDICAL PROGRAMS, PEW HEALTH GROUP, 

THE PEW CHARITABLE TRUSTS 

STATEMENT OF PAUL J. HASTINGS 

Mr. HASTINGS. Thank you. Chairman Pitts, Ranking Member 

Pallone, members of the committee, my name is Paul Hastings. I 

am the President and Chief Executive Officer of OncoMed Pharmaceuticals. I am here testifying on behalf of the Biotech Industry Organization’s 1,100 members, where I serve as Vice Chairman of the 

Emerging Company Section; that would be small companies. I also 

chair the Bay Area Life Sciences Association, and I am a member 

of the board of the California Health Care Institute. All of these 

organizations represent innovative life science companies. 

I have over 25 years of experience in the biotechnology and pharmaceutical industry. My current company, OncoMed Pharmaceuticals, is developing molecules based on new understandings of 

how tumors grow and spread. Specifically, we are trying to block 

biological pathways critical for the survival of tumor initiating 

cells. These cells are more resistant to current therapies and promote the growth of cancerous tumors. Thus, our products offer real 

advancement in the treatment of cancer. We presently have three 

products in Phase I and Phase I–A clinical trials after being in existence for 6 years. 

Companies like mine are generating many new therapies to treat 

patients suffering from a myriad of unmet medical needs. Of the 

172 scientifically novel and orphan drugs approved from 1998 to 

2007, 52 percent of them were discovered or developed by biotechnology companies. We offer tremendous hope to patients, with 

over 3,700 new biotherapeutics in development. 

Biotechnology is an American success story. Our life science sector accounts for over 7 million in direct and related jobs. We create 

high-paying jobs in our companies and support employment and 

provide vital revenue for our universities and medical centers 

through the clinical trials we conduct, thus employing people in 

those important State and local universities and medical centers. 

We have a national imperative to foster the development of innovative treatments and therapies. 

78 

By 2030, almost one out of every five Americans will be 65 years 

or older, which means dramatically increased costs associated with 

treating chronic disease. Innovative medicines can help offset these 

costs by preventing or delaying the need for other costly services 

such as emergency room visits and hospitalizations. If you just simply reduce cancer deaths by 10 percent, that is equal to $4 trillion 

in economic value. 

Our position as global leadership is a position we can no longer 

presume to keep. We face international threats, such as India and 

China and the European Union increasing funding and incentives 

for biotech companies, while at the same time investment in the 

U.S. has decreased markedly. 

To encourage innovation and maintain U.S. leadership, we must 

have an FDA that is empowered and able to effectively and consistently review breakthrough treatments and therapies. There are 

several troubling trends that threaten to severely hamper our ability to innovate. For example, only half of the products submitted 

to the FDA are approved on the first submission. From the average 

of the previous PDUFA rounds of 2003 to 2007 to today, drug and 

biologic approval times have increased 28 percent, and between 

1999 and 2005 the average length of clinical trials grew by 70 percent. 

Regulatory uncertainty deters future venture investment in biotechnology companies. This results in longer time for development, 

not time for approval once drugs are submitted, longer time for development when you start the development process in Phase I; 

lower investment, fewer cures for patients, and not as many life 

science jobs. 

It is important to maintain a balanced and consistent regulatory 

system. To that end, among BIO’s top priorities throughout the 

PDUFA technical discussions was to promote innovation by fostering scientist-to-scientist dialogue between FDA and sponsors 

concerning high priority rate limiting scientific issues that arise 

during drug development. We are pleased that FDA agreed to 

adopt a new policy that timely interactive communication with 

sponsors during the drug development is a core activity to help 

achieve the agency’s mission. 

BIO believes that PDUFA should be reauthorized in a timely and 

expeditious manner. However, additionally, last week during the 

BIO international convention, we unveiled a package of policy proposals entitled Unleashing the Promise of Biotechnology: Advancing American Innovation to Cure Disease and Save Lives. This is 

a BIO initiative, with the thought in mind to come with you with 

not complaints but solutions. The FDA policy recommendations described in my written testimony are designed to ensure a clear and 

effective pathway for turning ideas into realities that will benefit 

patients and improve public health. The proposals are focused on 

creating a modern, forward looking FDA and creating more effective clinical research and development processes. 

Some of the highlights of our proposals include updating the 

FDA mission statement to reflect its role in advancing medical innovation; providing FDA with the management, budgetary and advisory authorities reflective of its role in regulating a quarter of our 

country’s GDP; providing FDA with authorities, expertise, impleVerDate Nov 24 2008 11:31 Mar 09, 2012 Jkt 037690 PO 00000 Frm 00082 Fmt 6633 Sfmt 6633 F:\112-070 PDUFA V\112-70 PDUFA V-PENDING WAYNE
79 

mentation mechanisms to ensure the development of forwardthinking strategies and implementation of modern regulatory 

science into their review practice; expanding and improving the accelerated approval pathway into a progressive approval mechanism 

for innovative products for unmet medical needs that would also 

serve to ensure a risk-benefit analysis that incorporates the safety 

and needs of patients in the real world. 

Lastly, proposals to further empower the FDA to utilize a weight 

of the evidence approach and ensure that the FDA communicates 

to sponsors in clear terms why risk was determined to outweigh 

benefits and why other agency authorities, such as REMS, are insufficient. 

Thank you for the opportunity to share with you our thoughts 

today. 

[The prepared statement of Mr. Hastings follows:] 

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Mr. PITTS. The chair thanks the gentleman. 

Mr. Leff, you are recognized for 5 minutes. 

STATEMENT OF JONATHAN S. LEFF 

Mr. LEFF. Thank you. Chairman Pitts, Ranking Member Pallone, 

and members of the committee, my name is Jonathan Leff. I am 

a managing director at Warburg Pincus, where I lead the firm’s investment efforts in biotechnology and pharmaceuticals. I have more 

than 15 years of experience as a life sciences venture investor and 

have served on the boards of and helped build more than 15 small 

entrepreneurial companies involved in developing novel therapies 

for a range of diseases, companies not unlike the one that Mr. 

Hastings described. It is my privilege to be here today. 

Venture capital provides the essential fuel for medical innovation 

by funding the development of novel therapies, an endeavor that 

requires hundreds of millions of dollars over many years or even 

decades. Venture capital has been a primary source of this vital 

risk capital, has funded the development of an entire generation of 

important new medicines, and has financed and helped build almost every successful biotechnology company in the U.S., creating 

well over 1 million high quality jobs. 

Today, however, the U.S. medical innovation ecosystem is in 

jeopardy. Life sciences venture capital is experiencing an alarming 

decline. The primary reason is that the cost, time and risk involved 

in developing new drugs and biologics have increased to 

unsustainable levels. As a result, vital risk capital is being diverted 

to other industries and to other countries. At a time when medical 

research is exploding with potential, many scientific discoveries are 

not being developed into new medicines due to lack of investment 

capital. 

While many factors have contributed to the escalating cost, time 

and risk of drug development, a changing regulatory environment 

at the FDA is the most significant. In the early 1990s, Congress 

and the FDA worked together to shape a new drug approval system 

designed to balance the goal of ensuring drug safety with the desire 

to speed new therapies to seriously ill patients. As a result of this 

balanced regulatory environment, for example, HIV is no longer a 

death sentence, cancer patients have access to many dozens of important new medicines, and the U.S. has established itself as the 

world’s leader in life sciences innovation. 

By the middle of the last decade, however, the political backdrop 

and public consensus that made all of this possible had changed. 

Following the safety issues with Vioxx, the public discourse began 

to heavily emphasize drug safety. Far from being congratulated for 

speeding new treatments to sick patients or for advancing medical 

innovation, FDA has instead come under heavy criticism for failing 

to do enough to ensure patient safety. 

Naturally, FDA officials have responded to this changing environment, including congressional hearings and media attention, 

and have shifted to a more cautious, risk averse posture in the new 

drug approval process, emphasizing the potential risks of new 

treatments more than their benefits to patients. My written testimony provides examples of how this shift has become evident. 

94 

Without question, protecting patients from harm is an essential 

element of what the public expects from the FDA. But so too is enabling the timely development and availability of new therapies. 

Finding the right balance is the central challenge of the new drug 

approval process. However, I want to emphasize that the way this 

balance is struck by regulators and by policymakers has tremendously important implications for U.S. leadership in medical innovation. 

FDA’s shift in recent years to an increasingly cautious posture 

toward drug approvals has had the unintended consequence of reducing investments to life sciences innovation due to the significant 

additional time, cost and uncertainty it has added to the drug development process. 

In the face of new hurdles to FDA approval, investors are moving 

away from critical areas, including cancer, diabetes, rare diseases 

and many others. I believe these problems are fixable if we act 

now. Twenty years ago, U.S. policymakers and the FDA rose to the 

challenge. We have the opportunity to do the same today. 

My recommendations are as follows: Strengthen FDA’s mission 

statement to reflect the importance of innovation; expand the accelerated approval pathway into a progressive approval system for 

new drugs that offer a significant advance; empower FDA to weigh 

all evidence in the context of the disease being treated in assessing 

benefit versus risk in new drug approvals; fully detail the FDA’s 

benefit-risk calculus when denying or delaying approval in favor of 

collecting more data; and, finally, ensure that FDA is provided with 

the resources that it needs to accomplish its mission. 

I look forward to working with the committee to reinvigorate and 

strengthen U.S. leadership in medical innovation. Thank you. 

[The prepared statement of Mr. Leff follows:] 

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Mr. PITTS. The chair thanks the gentleman, and recognizes Mr. 

Boutin for 5 minutes for an opening statement. 

STATEMENT OF MARC BOUTIN 

Mr. BOUTIN. Thank you, Mr. Chairman, Ranking Member 

Pallone, and distinguished members of the committee. My name is 

Mark Boutin, and I am the Executive Vice President and Chief Operating Officer at the National Health Council, which represents 

approximately 133 million people with chronic diseases and disabilities. 

Our membership includes large patient advocacy organizations 

like the American Cancer Society, the American Heart Association, 

as well as smaller organizations like the Alpha One Foundation 

and the Children’s Foundation. We provide a united voice for people with chronic diseases and disabilities. 

Our membership also includes organizations such as the American Academy of Cardiology, nonprofits with interests in health, including family care giving organizations, and business and industry. Our governance is controlled by the patient advocacy organizations, and we represent patients, not consumers. 

I make that point because often patients and consumers are confused. While we have a lot in common, we are at opposite ends of 

the same spectrum. We define patients as people with chronic diseases and disabilities. They are people who will use the health care 

system to manage their daily lives. They will use the health care 

system until they die. 

Consumers use the health care system on an ad hoc basis, often 

for acute instances. An easy way to put your arms around it is 

imagine that you have mild hay fever. It acts up in spring. There 

are many options to address hay fever, over-the-counter prescriptions. But I can tell you if a new product comes to market and it 

has serious side effects, perhaps it causes severe headaches, rashes, 

diarrhea, vomiting, you are not going to be willing to take a risk 

on that new medicine. 

But if you discover that you are having intestinal problems, you 

go to your doctor after putting it off for some time and you are diagnosed with pancreatic cancer and you are told you have 11 

months to live, your willingness to take a product that might extend your life by 6 months will dramatically increase. You might 

be quite happy to take that same product that causes the rash, severe headaches, diarrhea, vomiting. It doesn’t change your tolerance for risk for the hay fever medicine. Benefit-risk is an incredibly complex issue and one of the things I would like to address 

today. 

As has already been referred to earlier, the patient advocacy 

community actually chained themselves to the fence at FDA and 

NIH nearly 20 years ago asking for significant change, and as a result of that, they went to the FDA and said, let’s be allowed to 

have early access to treatments. And the FDA appropriately said, 

no, we are not going to allow you to have access to those treatments. We don’t know what the risks of them are. 

The patient community said, you know what? I am going to be 

dead in 2 years, I am willing to accept that risk. And the FDA responded and Congress responded with the first iteration of PDUFA. 

111 

As a result, we have seen dramatic improvements in terms of early 

access to new treatments and the development of new treatments, 

and we in the patient community have been very pleased with the 

success of these products. 

Unfortunately, the patient communities, somewhat naively, 

thought we were done. We are relatively new to advocacy. We really only started about 25 years ago. We actually stepped back to a 

large extent from the FDA and the environment shifted, and what 

we have seen is significant change. We are back at the table now 

saying that we need to look at these issues in different ways. 

What I would like to do is address two interrelated issues, the 

first being benefit-risk, the second being conflict of interest. 

As I said, benefit-risk is a complex issue. The FDA is charged 

with looking at benefit-risk from a population-based model. But as 

we know, benefit-risk is very much an individual decision. It is 

very personalized to the individual person and their family caregivers. 

Take for example Mark Stecker, who is somebody that about 7 

years ago was walking in Manhattan and realized he had a limp. 

Shortly thereafter he was diagnosed with MS. He is now confined 

to a wheelchair, and he runs a blog, and he is very articulate about 

saying that he is very interested in assuming far greater risk than 

he is currently allowed. 

I would say to you, many people in the disability and disease 

community feel the same way. While we had great success for HIV 

and AIDS, to some extent cancer and to a lesser extent heart disease, there are many conditions, from rare diseases to larger conditions like Alzheimer’s, MS and other neurologic conditions without 

effective treatments, with many people willing to accept risk that 

they are often not allowed to. 

As I said, this is complex, and risk determinations can vary from 

condition to condition. Somebody with Alzheimer’s is probably more 

likely to take a risk than somebody with heart disease. It can 

change even within an individual. If you think about somebody 

with breast cancer that is in their late twenties and they have two 

children, their willingness to take a risk that might extend their 

life long enough to see their children grow up and get married, because it is very pronounced. But you could have another woman in 

her eighties with the same diagnosis who might choose a different 

product that is going to allow her to have better quality and perhaps less longevity. 

At this point in time, it is important to recognize that there is 

no Federal regulatory body anywhere in the world that has identified benefit-risk or crafted a clear framework for benefit-risk. As 

part of the PDUFA negotiation, the stakeholder community was involved, and this was a huge priority for the patient community, 

and we were able to work with the FDA and industry to insert a 

benefit-risk analysis into the agreement. This will allow for a great 

deal of consistency, transparency and effective communication. It 

will allow for the benefits to be more clearly defined and it will 

allow for contacts and credibility. 

I apologize for running over my time. Thank you. 

[The prepared statement of Mr. Boutin follows:] 

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Mr. PITTS. The chair thanks the gentleman, and recognizes Dr. 

Sigal for 5 minutes. 

STATEMENT OF ELLEN V. SIGAL 

Ms. SIGAL. Good afternoon, Chairman Pitts, Ranking Member 

Pallone, and all members. It is a great honor for me to testify 

today. 

My name is Ellen Sigal. I am chair of Friends of Cancer Research. Friends of Cancer Research is a Washington-based think 

tank. We publish. We are involved with the American Cancer Society, professional societies, patient groups, advocates. Our sole mission is really the integration of science for better treatment for patients. 

This is very personal for me, as it is for all of you. Friends started 15 years ago when I lost my 40-year-old sister, leaving a 4-yearold child. Since then, my mother died of pancreatic cancer, my father died of prostate cancer, my husband has cancer, and there is 

no one that we all don’t know that isn’t impacted. So this mission 

is quite personal for me and for all of you. 

My testimony today is intended to give a perspective on what can 

be done. First of all, the urgency of getting new life-saving treatments to patients in the safest and quickest possible way; the importance of maintaining our global competitiveness; and finally to 

realize the full potential of biomedical research and the role that 

all sectors play. None of these things can be accomplished without 

a fully resourced and scientifically vigorous FDA. 

For many years we have been hearing about the slowness of FDA 

and particularly in oncology, so the agency has been portrayed by 

many critics as slow and inefficient compared to other countries. 

The criticism is particularly concerning in the field of cancer, where 

severely ill patients have few effective options. A new Friends of 

Cancer Research study published in Health Affairs revealed that 

FDA is approving anti-cancer drugs much faster than its overseas 

counterpart, the European Medicines Agency. What is important is 

the standard is high. It is the gold standard on both. 

Of its findings, our study revealed that FDA not only approved 

more cancer drugs than Europe, but they did so at a significantly 

faster rate. FDA approved average drugs in 182 days, while EMA 

averaged 350 days. Access to new medications 5 1⁄2 months sooner 

has undoubtedly improved the lives of 1.5 million Americans diagnosed with cancer every year. 

While we praise this and we think this is very important, this 

cannot be accomplished nor sustained without appropriations needed to continue this effort. I have very specific recommendations 

that are in my testimony, and I would like to talk about a few of 

them. 

First and foremost, FDA has to have the scientific tools, the regulatory science programs better to enable them to make these very 

complicated decisions. Whether it is adaptive trial design, validation of biomarkers, it is urgent that they have the resources to 

really have this. We believe very strongly and support the continuance of accelerated approval process. Ten of the 32 new oncology 

products in our study utilized this mechanism. 

123 

We also are recommending expedited development programs to 

address challenges to the current multi-phase sequential development process. This could be particularly important to ensure scientific rigor for targeted therapies. We want to ensure that FDA 

has the highest quality access to the best expertise possible in 

making informed decisions, and we believe patients have a very important role at that table and that role has to be accelerated. 

A weakened, underfunded FDA will cause companies to take research overseas, creating a loss of jobs and billions of dollars in investment, it will threaten our standing as global leader, and, most 

importantly, it will delay getting potentially lifesaving treatment to 

patients battling disease and illness. 

The role of the Food and Drug Administration as a component 

of medical innovation is critical, but successful innovation does not 

solely include the FDA. Our data indicates that the end stage review is on average half the duration of the FDA U.S. and EMA. 

While this indeed translates to American cancer patients gaining 

access to new drugs, it does not address the fundamental challenges to advancing health innovation that are currently facing our 

society. 

In order to resolve the larger problem, all of the sectors represented at this hearing today and several of those that are not 

must at all times set aside the individual interests and work towards the common goal of improving the health of the country, 

both economic and personal, through innovation. As patients, we 

all have been and we all should demand it. The people will all work 

on behalf of the deserved. We are asking that everyone work together towards these goals. 

Thank you. 

[The prepared statement of Ms. Sigal follows:] 

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Mr. PITTS. The chair thanks the gentlelady, and now recognizes 

Mr. Coukell for 5 minutes for an opening statement. 

STATEMENT OF ALLAN COUKELL 

Mr. COUKELL. Mr. Chairman, Ranking Member Pallone, members of the subcommittee, thank you for the opportunity to present 

testimony. 

My name is Allan Coukell. I am a pharmacist by training and 

Director of Medical Programs in the Pew Health Group, whose mission is to improve the health of all Americans through research and 

critical analysis. 

Pew’s work addresses a range of FDA-related issues, but my 

focus today is the safety and security of the pharmaceutical supply 

chain. Next week we will release a report entitled ‘‘After Heparin: 

Protecting Consumers from the Risks of Substandard and Counterfeit Drugs.’’ Our research for that report included dozens of interviews with industry and regulatory experts and was informed by 

a recent public meeting that brought together pharmaceutical manufacturers, distributors, pharmacies, the FDA, State regulators and 

other analysts and stakeholders. 

The meeting heard that while the vast majority of drugs in our 

pharmacies and medicine cabinets are not counterfeit or adulterated, drug manufacturing has changed dramatically in recent 

years. It has become globalized and increasingly outsourced, and 

this creates new risks, risks dramatically illustrated not long ago 

with the intentional adulteration of the blood thinning drug Heparin. 

In 2007, health officials began to receive the first of what would 

ultimately be more than 500 reports of patients who experienced 

unusual adverse events, some of them fatal, after receiving this 

drug. The problem was traced to a contaminant, a substance introduced in place of the pure drug, and this occurred not in the premises of the U.S. manufacturer, but in China where the drug’s raw 

ingredient was sourced from a complex network of suppliers. 

The evidence suggests that the adulterant was introduced deliberately on a large scale and for economic gain. Whoever made it 

must have known that the substance wouldn’t be detected by the 

standard tests. By one estimate, the crime netted more than $1 

million in profit. 

Later investigations pointed to other failures that underlined the 

need for systemic improvement. In particular, the manufacture did 

not audit its supplier over several years. The FDA approved the 

Chinese plant without an inspection, partly because agency databases confused two different facilities. Inspectors later found manufacturing quality issues, including poor control of incoming materials. And neither the FDA nor the manufacturer was ever able to 

gain complete access to that upstream supply chain. 

The incident represents a clear breach of the U.S. drug supply, 

and to this date no one in any country has been held accountable 

nor has Congress acted to update the statutes that govern drug 

manufacturing. 

What we heard at our meeting from a variety of experts was that 

without changes to the system, another such event is inevitable, 

not if, but when. 

130 

The number of drugs and ingredients made at non-U.S. sites 

doubled over the past decade. About 40 percent of our finished 

drugs and 80 percent of their active ingredients now come from 

overseas, often from developing countries. Current law requires 

FDA to inspect every 2 years here in the U.S., but is silent on the 

frequency of foreign inspections and the FDA lacks the resources 

to do regular foreign inspections. 

When manufacturing shifts to low cost environments with reduced oversight, consumers are at risk, from the deliberate acts 

and also from failures to meet quality standards. 

Our report reviews some other recent examples, including the 

problem of so-called show shadow factories, where drugs are coming from a hidden source instead of the official factory. We discussed cases in which manufacturers falsified or concealed records, 

and we note the risk of U.S. patients receiving counterfeit or stolen 

drugs that penetrate our domestic distribution system. 

Let me give you one more example, a substance called DEG that 

has been linked to numerous mass poisonings around the world. 

Five years ago, this sweet-tasting liquid was mistakenly used to 

make cough syrup, killing dozens. The syrup had been labeled as 

something else. It had passed through a series of brokers in China 

and in Europe, each relabling it presumably without testing. Many 

of those who died were children. This occurred outside the U.S., but 

70 years ago this same substance killed more than 100 Americans 

and led Congress to pass the Food, Drug and Cosmetic Act. 

So recently there have been important steps by the FDA and by 

individual companies to tighten the supply chain. Nevertheless, we 

must update the act for the 21st century. Pew advocates a number 

of key reforms, including measures to ensure that manufacturers 

themselves better assess risk and ensure safety and steps to ensure 

they are held accountable; increased inspections overseas and new 

enforcement tools for the FDA, including the ability to order drug 

recalls; and improved oversight of drug distribution, including national standards for wholesalers and assistance to track and verify 

the authenticity of drugs. 

I will conclude just briefly with a recent poll, a poll we commissioned last year among likely voters, that showed Americans are 

concerned about this issue, and across the political spectrum they 

overwhelmingly, upwards of 80 and 90 percent, favor many of the 

provisions I have outlined. 

This committee has long taken a bipartisan interest in the safety 

of the drug supply. The American public supports those efforts, and 

we should not await another tragedy. 

Thank you, and I welcome your questions. 

[The prepared statement of Mr. Coukell follows:] 

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Mr. PITTS. The chair thanks the gentleman and thanks the panel 

for the testimony. We will now begin questioning, and I will recognize myself for 5 minutes for that purpose. 

First of all, Mr. Hastings, I have had the opportunity to talk to 

many small and mid-sized American biotech companies, and they 

are struggling right now partly because of increasing review times 

at FDA and the lack of predictability at FDA. 

Have you experienced these problems or do you know a company 

who has, and what issues are biotech companies facing today related to FDA? 

Mr. HASTINGS. We work very—is this on? No. There we go. Sorry 

about that. 

Whenever there are regulatory uncertainties, there are delays. A 

big piece of data that is missing today is not the speed of approval 

once an NDA is filed, but the speed to which we can enter a drug 

into the clinic, file an IND, get it through Phase I, get it into Phase 

II. Many of us who are lucky enough to get it into Phase III would 

be happy with approval times that are faster and more expedient 

than other countries. That would be great. But there is a whole 

process that occurs before the drug even is filed for an NDA, and 

I think it is important for us to work with the FDA, as we have. 

As I mentioned, the biotech industry’s focus here is on streamlining the whole process, not just the approval process once the 

NDA is filed. 

Mr. PITTS. Mr. Leff, would you like to comment on that? 

Mr. LEFF. Sure. Thank you, Mr. Chairman, I would be happy to. 

I think the central issue, the central impact that FDA is having 

on investors in medical innovation is, as I said in my statement, 

the increase in the time, the cost, and the risk of development. So 

it is not review times per se, although obviously we all want fast 

and efficient review times. It is the requirements that FDA is increasingly imposing for developers of drugs to move their drugs 

through clinical trials and get them in front of FDA. 

So when Dr. Woodcock made the observation that FDA is having 

a problem approving more drugs because they are not seeing more 

drugs, they are seeing fewer drugs submitted than in the past, I 

think that is absolutely right. The reason FDA is seeing fewer 

drugs submitted than in the past is because people like me and 

hundreds of other people like me making investment decisions on 

drugs that are in development or discoveries that are being turned 

into drugs are increasingly deciding that the cost, time and risk 

have become too high, and that is a function of the risk averse decisionmaking that has increased at FDA over the past decade. 

Mr. PITTS. Mr. Hastings, how many jobs does the bioscience sector account for, both direct and indirect? 

Mr. HASTINGS. I think I mentioned 7 million jobs indirectly and 

directly. 

Mr. PITTS. Seven million total. What else can we do in the FDA 

space to help create jobs? How would fixing the issues at FDA help 

these companies create jobs? 

Mr. HASTINGS. Mr. Chairman, I believe that the way to create 

jobs is to foster innovation, not at the expense of safety or efficacy. 

One of the proposals which is to make innovation a part of the mission statement, which, by the way, the European Union has in 

140 

their mission statement, and then hold people accountable for innovation. 

You know, innovation could be when somebody is going through 

the process of—I will give a very practical example. I am running 

a startup company and I file an IND and I get my drug into Phase 

I. In the middle of my Phase I trial, there is an issue. Any kind 

of issue could come up in Phase I. The way the system is set up 

is I can pick up my phone or my regulatory person can pick up the 

phone and call the FDA. And the FDA are bound by these guidelines, by the way. The phone call takes place. It needs to be followed up by a letter, which comes usually 30 days later. Then you 

have 30 days to respond to that letter. Then they have 30 days to 

respond to that letter. 

Now, in that whole process, which in my mind could be handled in a phone call, I spent as a startup biotech CEO $4 million a 

month on the burn of the company while the letter writing campaign was going back and forth. 

This is not the FDA’s fault. These guidelines are guidelines that 

have been put in place, and I think they should be looked at as, 

you know, how can we streamline communication. Again, not once 

the NDA is filed, but how do we help companies innovate by making the process smoother in areas which are not going to create 

more risk? I think this would be a major. 

So if that occurs, I don’t have to go to my venture capitalist and say I am writing a letter now and $4 million of burn is looking at 

us right down the face. He hears that $4 million and says if I could 

invest that $4 million in Facebook, I could get a return in a month. 

You are going to burn that. I am going to need to give you—now, 

for me I need $1 billion to develop a drug, right? So that $4 million, 

which is huge in the early stages of a drug company’s evolution, 

is just a tiny portion of what it is going to take. 

So each dollar is very, very important. So for innovation and 

streamlining, making processes and helping the FDA, by the way, 

make processes that are less bureaucratic, providing them with the 

staff they need to actually answer the phone calls, which is something we have been working on together, would be very helpful. 

Mr. PITTS. The chair thanks the gentleman. 

My time has expired, and the chair recognizes the ranking member, Mr. Pallone, for 5 minutes. 

Mr. PALLONE. Thank you, Mr. Chairman. I am going to start 

with Mr. Hastings also. 

BIO recently released policy recommendations contained in the 

document ‘‘Unleashing the Promise of Biotechnology: Advancing 

American Innovation to Cure Disease and Save Lives.’’ I appreciate 

the need for the kinds of proposals listed under the heading of Advancing Regulatory Science and Innovation. But I wanted to focus 

on one as an example, the need to enhance FDA’s access to external scientific and medical expertise. 

The FDA has repeatedly cited the need to make improvements 

in the area of regulatory science, and as the BIO policy document 

mentions, FDA has struggled to keep up with the rapid pace of scientific and medical knowledge techniques and technology. And you 

know FDA launched a major regulatory science initiative designed 

to build on the achievements of programs like the critical path iniVerDate Nov 24 2008 11:31 Mar 09, 2012 Jkt 037690 PO 00000 Frm 00144 Fmt 6633 Sfmt 6633 F:\112-070 PDUFA V\112-70 PDUFA V-PENDING WAYNE
141 

tiative. The other proposals in that section also seem to make a lot 

of sense to me. 

But my problem is that each of these concepts that you mentioned or that, I should say, the document mentions would demand 

a significant infusion of resources if there is any hope for the FDA 

to implement them. That is my opinion. 

I just wanted to ask you if you agree with that, that we need 

more resources to do these kind of things? 

Mr. HASTINGS. I think respectfully—— 

Mr. PALLONE. I think you lost the mike. The reason I am asking 

you this is—go ahead. I am sorry. 

Mr. HASTINGS. Somebody up there where you folks are a few 

minutes ago had an overreaction to an issue with a union, right? 

So I think if we can all work together to look at ways to prioritize. 

First of all, there is no question that our industry supports the 

FDA being adequately staffed. We actually had an initiative a few 

years ago to help them get staffed. So we would be all for helping 

them get staffed. But we also understand there are budget crises 

under way right now. 

So I would submit, running a business, and having run many 

businesses, private and public businesses, that there are always 

ways to reallocate resources to do things. 

External advisory boards are external people. You pay them 

when they walk through the door. When they leave, you stop paying them. That is a much more efficient use of capital than head 

count. So if there are opportunities to use external advisers to help 

keep regulatory science moving. In the case of FDA, by the way, 

they have very few regulatory science employees. They would like 

to have more. Again, we are working on this initiative. So there are 

many ways to do this. 

Mr. PALLONE. The only problem that I have though, now we have 

this FDA funding bill that the House Republicans just passed, and 

that guts the FDA’s funding by $570 million. It is a cut of 21 percent from the administration’s request. So obviously I think there 

should be more resources. But if this goes through, we will have 

21 percent less than what the administration is requesting. 

How are we going to implement these types of things that are 

in this BIO document if we make cuts? It is one thing to add. But 

what about now if they cut 21 percent? 

Mr. HASTINGS. Again, I would argue that one could look at reallocation, and one could also look at the risk-benefit of where one 

invests one’s money. 

Mr. PALLONE. All right. I know that you are part of this—or I 

should say your organization is part of this alliance for a stronger 

FDA whose mission is to get increased resources for FDA. So, 

again, I think you can always find more efficiencies, but I think it 

is going to be very difficult to do any of these new innovations if 

we see a 21 percent cut, and I think that is why the Alliance for 

a Stronger FDA is trying to increase resources. 

Mr. HASTINGS. May I respond to that? No offense, but, you know, 

in our organization, when I hear an answer like that, I say to the 

organization, figure it out. 

Mr. PALLONE. It is one thing to be able to do what they are doing 

now. But to go into totally new areas with cuts in funding, I don’t 

142 

see how. But whatever—let me go to Dr. Sigal, because I only have 

40 seconds left here. 

I found the results of your study very interesting, the one comparing cancer approvals in the U.S. versus Europe, and I was surprised, given the claims about FDA’s role in the innovation downturn, to see a document like that. 

What prompted you to do that study and what did you expect to 

find? Were you surprised by what you found? 

Ms. SIGAL. I was very surprised. What prompted me was that we 

were hearing consistently from academic institutions, from developers, from biotech, from patients that the FDA is slower and 

things were getting approved faster in Europe, and we know the 

standards were very high in Europe. So we were very concerned 

and we did the initial research in house, we did it solely in house. 

And we were very shocked. As a matter of fact, we were so surprised that we had to validate it. 

I did not expect it. And I want you to know if in fact what we 

were told as urban legend were true and in fact we were slower, 

we would have published. So this was not a matter of getting data 

that we suspected was going to—we thought we were going to get 

data that showed that Europe was more innovative and faster, so 

we were very surprised at it and clearly it was very important. But 

there is still a lot more that needs to be done, because the science 

is complex and the agency is significantly underfunded for the innovation that they need to go forward. 

Mr. PALLONE. Thank you, Doctor. 

Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and recognizes Dr. 

Burgess for 5 minutes for questions. 

Mr. BURGESS. I thank the chairman. 

Just as a follow-up to Ranking Member Pallone’s observations, 

last year twice Dr. Sharfstein came before this subcommittee, once 

with the DeCoster egg farm hearing and once with a hearing about 

are there problems with the pipeline and restrictions in the pipeline of getting drugs and products from NIH to the consuming public and is the FDA part of that obstruction. And both times Dr. 

Sharfstein testified in response to a direct question by me, do you 

need more money, and he assured me that the FDA had all the 

money that it needed. 

I knew that that must be right, because for those of you who sit 

up nights reading the Federal Register, you may know that we 

passed, Congress passed, I voted against it, but there was a big 

health care law about a year and a half ago, and it included no new 

money for the Food and Drug Administration in that big new 

health care law. 

Mr. Hastings and Mr. Leff, let me just ask you a question. If an 

innovator comes to the FDA and they have got something, a drug 

or device, characterize it as a black box, if you will, it does something good for patients, if that innovator comes to the FDA and 

asks for the pathway, what are my steps to go through getting this 

drug or device approved? Are they going to get clear direction and 

clear instruction from the FDA as to what procedures to follow? 

Mr. HASTINGS. We will get guidance, some guidance or recommendations on what to do in a situation like that. 

143 

Mr. BURGESS. If it is truly innovative, maybe something that 

hasn’t happened before, are they likely to get an answer, ‘‘we are 

not sure and you need to start and then we will provide you guidance as go along.’’ 

Mr. HASTINGS. Well, it is very difficult in the case of a brand new 

innovation when there are no benchmarks to sometimes give guidance, because everybody is looking at the same thing and wondering what to do. I think that would therefore argue for the ability 

to communicate scientist-to-scientist and work together. This is 

also where some of these external advisers could come in and be 

very helpful experts in the field in terms of creating not a validated 

instrument that may take years to do this, but to create a risk-reward model to move that drug forward since it is the first in its 

class. That would be the ideal thing to do. 

Mr. BURGESS. Forgive me for interrupting, but time is very limited. On this risk-reward model that you just articulated, does that 

exist within the FDA? If an innovator comes to the FDA and says 

I have got this, help me know the stems I must take to develop this 

and have it approved by the FDA, is that model in fact in place? 

Does it work? 

Mr. HASTINGS. I mean, I can’t speak for the FDA. I think that 

model would probably work differently division by division, depending on who the reviewer is, depending on who runs the division. 

Mr. BURGESS. That is the regulatory uncertainty. Again, I have 

people come to my office all the time with these complaints that I 

don’t get clear direction about what I am going to need to provide 

and then it all changes in the course of development, and that obviously extends the timeline significantly. 

Mr. HASTINGS. Well, you made a very good point about changing 

it. And, again, I don’t think this is anybody’s particular fault, but 

I know of CEOs who are running diabetes companies where 

endpoints were changed in the middle of their Phase III clinical 

trials as they were ongoing and had to redo their Phase III clinical 

trial. Some of those companies shut down. 

Mr. BURGESS. Sure. I wish we had more time to explore that, but 

Mr. Coukell, I need to ask you, you talked about the Heparin issue 

which we have studied in this committee, and I just wanted to reassure you that we do have an active and open investigation now. 

Last Congress it was a little bit difficult to get information from 

the FDA. Margaret Hamburg went to China and presumably talked 

to some of these individuals who were involved with the companies 

that produced the product that was contaminated with the 

adulterant. And you are correct, the adulterant was a very clever 

molecule that could hide behind the normal active pharmaceutical 

ingredient in Heparin on the normal testing with the mass spec. 

It almost had to be a criminal mind that decided to do this. I don’t 

think it was accidental. 

But we have had significant difficulty in getting the data from 

the FDA as to where they are in this investigation, why the labs 

were confused and issues that you mentioned. I wanted to reassure 

you that the legislative remedy really is hard to come up with if 

you don’t have the results of your investigation. Unfortunately, this 

investigation has taken a lot longer than I would have ever thought 

144 

possible, but at the same time you run the risk of legislating with 

incomplete information. 

Mr. COUKELL. Yes, sir. I commend your ongoing interest in drug 

safety. I think it is very important. I think it would be highly desirable to find the culprit in that case. 

Nevertheless, I think Heparin illustrates, as I outlined in my testimony, a lot of weaknesses that we know about now, and it was 

a wake-up call for a lot of folks in the industry and for the FDA. 

They have all said that. The next time it happens, it probably won’t 

be Heparin. It will be somewhere else. I think we do know based 

on that case and others some of the things that we need to do now. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

ranking member emeritus, Mr. Dingell, for 5 minutes for questioning. 

Mr. DINGELL. Mr. Chairman, I thank you for your courtesy and 

for the recognition. I will direct my questioning to Mr. Coukell. I 

would observe that I have great concern for the tremendous 

amount of pharmaceutical medicines and ingredients that are coming in from abroad. So I would like to address this with yes or no 

answers here. 

An increasing number of drug manufacturers are turning to 

outsourcing for pharmaceutical ingredients and manufacturers. As 

you mentioned in your testimony, up to 80 percent of pharmaceutical ingredients and up to half of the finished pharmaceuticals 

are purchased from clients in India and China. FDA is currently 

required to inspect U.S. drug facilities every 2 years, but there is 

no required frequency for inspection of foreign facilities. Food and 

Drug says that they investigate foreign facilities about once every 

9 years. 

Is that sufficient or not? 

Mr. COUKELL. It is not sufficient. 

Mr. DINGELL. Now, until 2009 FDA did not have a dedicated 

staff for foreign inspections. Rather, employees qualified to do inspections would travel abroad. FDA now has a cadre of 15 inspectors dedicated to foreign facility inspections. 

Has this current cadre been sufficient to increase inspection of 

foreign facilities to a sufficient level that we can be comfortable 

that our supply of these pharmaceuticals is safe? 

Mr. COUKELL. They improved the local FDA’s local knowledge 

and have done some additional inspections, but they are not 

enough. 

Mr. DINGELL. Thank you. Now, beyond inspections, quality manufacturing is also critical to a safe drug supply. In 2009, FDA 

issued 34 warning letters regarding adherence to good manufacturing practices, nearly double what was issued in 2008, ensuring 

manufacturing quality gets more difficult as supply chains move 

overseas and are more outsourced. 

Are today’s GMPs sufficient to ensure manufacturing quality, yes 

or no? 

Mr. COUKELL. No, sir. 

Mr. DINGELL. As you have spoken to a number of stakeholders 

and experts about FDA’s oversight of foreign drug manufacturing, 

what if any consensus exists for increasing foreign oversight and 

resources to support? 

145 

Mr. COUKELL. I can’t answer that with one word, sir, but what 

I can tell you is we have been interested as we talked to stakeholders across the system, I have expected to have people say inspections aren’t the answer. We didn’t hear that. Inspections are 

part of an overall quality system. Some major sectors of the industry, including the generic manufacturers and the active ingredient 

makers, are on record as supporting fees to help fund additional inspections overseas, both for safety and to provide a level playing 

field for American manufacturers. 

Mr. DINGELL. Thank you. One approach to ensuring manufacturing quality would be to require manufacturers to implement 

quality systems that detail management responsibilities, risk management practices, supply chain management, record keeping 

amongst other components. 

Do you believe requiring manufacturers to have in place a quality system would improve the safety of our drug supply chain? Yes 

or no. 

Mr. COUKELL. Yes, sir. Those are recommendations now, but we 

need everyone to do it. 

Mr. DINGELL. Should such a requirement relate not only to finished manufactured pharmaceuticals, but also to components and 

raw materials? 

Mr. COUKELL. Yes. 

Mr. DINGELL. Transparency throughout the supply chain is of 

particular concern and a valid one given the Heparin incident, but 

Heparin is only one of the examples of our problems. Currently, 

FDA recommends but does not require that companies conduct an 

on-site audit of a supplier. 

Do you believe requiring companies to perform on-site audits of 

suppliers before a purchase agreement is made would improve supply chain safety? Yes or no. 

Mr. COUKELL. Our meeting heard that every supplier and subsupplier should be audited by somebody. 

Mr. DINGELL. Now, how frequent should these audits be to assure their effectiveness? 

Mr. COUKELL. I think that depends on the material and the level 

of risk. 

Mr. DINGELL. Could you give us some kind of a horseback guess? 

Mr. COUKELL. I think it is going to depend, sir. If is a long-established relationship and a simple synthesis, it would be quite different from a new relationship with somebody who is making a 

very complex molecule. 

Mr. DINGELL. Now, FDA recommends but does not require quality agreements with suppliers. Do you believe requiring quality 

agreements with suppliers would improve supply chain safety? Yes 

or no. 

Mr. COUKELL. Yes, sir, and I believe leading companies are already doing that. 

Mr. DINGELL. Mr. Chairman, I apologize. I have a couple more. 

May I pursue my business to its end? 

Mr. PITTS. You may proceed. 

Mr. DINGELL. Thank you. You are most courteous. 

More must also than done to ensure transparency and access to 

information for products being imported into the United States. 

146 

Do you believe requiring importers and customs brokers to register with the FDA would help to improve FDA’s general oversight 

of global drug production as well as drug safety assessments at the 

border? Yes or no. 

Mr. COUKELL. Yes. 

Mr. DINGELL. It is clear then that increasing foreign inspections 

and improving transparency and quality throughout the supply 

chain are necessary components to increasing the safety of our 

drug supply, and that would also include raw materials and components as well as finished products. I would also add, Mr. Chairman, 

that H.R. 1483 would address the vulnerabilities that we have just 

outlined. 

I thank you for your courtesy, and I thank our panel for their 

assistance to the committee. 

Mr. PITTS. The chair thanks the gentleman. 

Without objection, the chair recognizes Mr. Bilbray from California for 5 minutes for questions. 

Mr. BILBRAY. Thank you very much, Mr. Chairman. Thank you 

for a chance to ask questions. I want to thank the ranking member 

for being here, because I think that this is an issue that we can 

have a bipartisan effort on. From personal experience in working 

with the ranking member for probably a decade, about a decadeand-a-half I think it has been, we have had a bipartisan effort 

going on water quality issues. I think this is one of those things 

that the ranking member can join with the majority in actually addressing an issue that knows no party affiliation. 

Mr. Hastings, one of the crises that I am seeing in my district 

with my bio-med research people is the fact that we have lost 50 

percent of the venture capital for what we used to say in environmental issues would be the economic soup, the startup companies, 

the little guy who is the krill of the bio-system; in other words, 

where the ideas and the innovation comes from that the big guys 

eat up, adopt and then develop into it. We have lost 50 percent of 

that capital. It looks like we could lose 50 percent of that overseas 

if we don’t do something. 

One of the items that has been brought up to me is how do we 

infuse and get venture capital back into the field, and one of the 

items is the issue that we have over $2 trillion of American capital 

overseas. Do you think that it would help in trying to backfill that 

loss of 50 percent if the Federal Government looks at changing the 

repatriation laws here to hold harmless if they bring the money 

back for research and development? 

Mr. HASTINGS. Resoundingly absolutely. 

Mr. BILBRAY. Anybody else got a comment on that or concern 

with that? 

Mr. LEFF. Yes, I agree it would absolutely help and it would 

bring capital back into this country and release additional investment and innovation. The observation I would make, though, is 

that would be a one-time benefit to the system. It wouldn’t change 

the trajectory necessarily that we are on and the fundamental underlying reasons that capital is leaving investment and innovative 

life sciences companies. 

Mr. BILBRAY. I appreciate that. I was a public safety guy. I am 

just a lifeguard that triaged people and got more votes than the 

147 

next guy. But we do have a patient that is hemorrhaging, needs 

an infusion, an infusion to survive, and I think this is one thing 

we may be able to ask both sides to work on. 

Let me ask, Doctor, speaking of looking at systems, back in the 

nineties there was a bipartisan effort made that did things on the 

AIDS epidemic that we had not done for anybody else, extraordinary efforts. We broke the rules, changed the rules, forced the 

bureaucracy to respond, and I think history has proven that was 

a great success. 

Sadly, it looks like we did this great success and walked away 

from it. In those days we had Act Up, we had Men’s Gay Health 

Crisis Project, we had the Treatment Action Group putting pressure on us to change the system, and we actually allowed patients 

to be at the table. We allowed, and the doctor can go over it, whole 

different protocols for what was allowed to be counted as a positive 

action, and we basically broke the mold and tried innovative issues. 

Is there any reason in the world why we should not go back and 

look at what was successful in addressing the AIDS crisis and 

apply it to the crisis we are finding right now? A good example is 

why would we allow an AIDS patient on a review body for AIDS, 

but would not allow a cancer patient to have the same right to be 

able to participate? 

Doctor, I solicit your comment about how we can address that. 

Ms. SIGAL. Thank you for the opportunity. I think the HIV model 

is a wonderful model. It started activism, and, most importantly, 

it has had an impact. It helped patients, it helped science, and it 

made a huge difference. 

It is a complex scenario though, because there we had a fire 

marker. We had the CD 4. We had viral load. We knew what we 

were looking for. But it did start advocacy, and I would agree with 

you fully that patients have not only a role but a right to sit at 

the table. Ultimately these decisions impact them. They need 

knowledge, they need the ability to have the information, and they 

have the ability and should have the ability to be at the table when 

these decisions are made. 

We, along with the National Health Council and others, are 

working on that and believe that we have opportunities in the reauthorization of the User Fee Act to have a more active patient 

voice. It is essential that they be at the table, because we do impact 

them. 

Mr. BILBRAY. The one thing I saw work in the AIDS community 

was the degree of urgency was brought on to the bureaucracy, the 

sensitivity that they know had an impact, an adverse impact just 

by denying, that at least there was opportunity there. 

What I am concerned about is the study that you did showed 

that if you take the long-range, there was an item. But my question is, recently though it looks like the European Community’s review and our review are starting to close that gap since 2008. Do 

you have any way of explaining why though the trajectory looked 

real good on cancer drugs over the long term, recently it looks like 

we are converging or going to be crossing? In that study, did you 

identify why since 2008 it looks like the numbers are changing? 

Ms. SIGAL. Actually we did go past, we did look at that. And in 

fact, since we have concluded our study, we have had three more 

148 

approvals which they still do not have in EMA. So in fact the trend 

of earlier approval, faster approval, is continuing. 

The problem is the complexity of the science. The science is very, 

very, very hard. But this is not an issue of speed, this is an issue 

of quality, and I can tell you as an advocate myself we in the cancer community and other advocates of deadly diseases, childhood 

cancers, other cancers, are just as anxious as anyone to have these 

new drugs approved, because it will—— 

Mr. BILBRAY. Let me tell you as a father, I am in that category. 

Mr. Chairman, I appreciate the time. I think one of the things 

both sides need to talk about is the conflict of interest regulations 

that historically have been with FDA and these review bodies, because now you are getting, especially in cancer, you are getting 

items coming forward that the discipline is so limited of anybody 

who can make an informed decision that you have to bring somebody in from outside and somebody who has a connection to basically development and certain research to be able to get the expertise to make an informed decision. I don’t think any of these conflict of interest requirements that we put in in the past was meant 

to exclude people that were essential to making informed decisions. 

I hope both sides can look at modifying those rules. 

Mr. PITTS. The chair thanks the gentleman. That concludes the 

first round of questioning. We will go to one follow-up on each side, 

if we have any. Dr. Burgess. 

Mr. BURGESS. Thank you, Mr. Chairman. I appreciate the recognition. 

Mr. Boutin, if I could along that line of the advisory panels and 

the conflict of interest exclusions, are the restrictions on who can 

serve on advisory panels hindering activities to bring new drugs to 

market? 

Mr. BOUTIN. Yes. I think there is a real challenge. Right now, the 

FDA is charged with looking at multiple regulatory and legal requirements for conflict of interest, and the standards within each 

are not necessarily inconsistent, they are different. As a result, the 

FDA has had to look at how do we apply them all together. 

In the previous reauthorization of the prescription drug user fee, 

there was an additional requirement that compelled FDA to limit 

its use of waivers, and as a result they took a look at how they 

would apply the conflict of interest rules. In their new look, they 

acknowledge that they are being more strident in addressing the 

conflicts, and as a result what you are seeing is it harder to fill the 

advisory committees, and currently about 25 percent of the advisory committees are vacant, and as a result there is delays in having the advisory committees meet and the FDA has acknowledged 

that it has led to delays in the approval of new treatments. 

So from our perspective, we need to look at this carefully. Conflict of interest rules are important and we recognize they provide 

credibility and transparency to the process, and nobody is suggesting they should just be done away with. However, we have to 

balance the need for transparency and managing of conflict of interest with the need to ensure that we get treatments to people 

who need them. 

Mr. BURGESS. That was a subject of a lot of discussion when we 

marked up this bill in 2007 and recognizing that for some products. 

149 

Pediatric antineoplastic plasma medications, the universe of people 

that understands these is probably very small, and it is probably 

very difficult to find someone who has not worked in some way on 

the development of that product at some point along the line. This 

was really where we painted ourselves into a corner. 

Mr. Chairman, I hope we will be serious about fixing this. And 

your thoughts on things that we might do to relax or keep the appropriate focus where it needs to be but at the same time allow 

these advisory panels the ability to form and do their work, I think 

that is going to be critically important when we reauthorize. 

Thank you. 

Mr. PITTS. The chair thanks the gentleman. 

I don’t see any other questions. That concludes today’s hearing. 

I remind members they have 10 business days to submit questions 

for the record. I ask that the witnesses all agree to respond 

promptly to these questions. 

With thanks to the witnesses, this subcommittee is adjourned. 

[Whereupon, at 1:20 p.m., the subcommittee was adjourned.] 

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