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87–645 PDF 2014

FDA CHECKUP: DRUG DEVELOPMENT AND 

MANUFACTURING CHALLENGES 

HEARING 

BEFORE THE

SUBCOMMITTEE ON ENERGY POLICY, 

HEALTH CARE AND ENTITLEMENTS 

OF THE

COMMITTEE ON OVERSIGHT 

AND GOVERNMENT REFORM 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED THIRTEENTH CONGRESS 

FIRST SESSION 

DECEMBER 12, 2013 

Serial No. 113–101 

Printed for the use of the Committee on Oversight and Government Reform 

( 

Available via the World Wide Web: http://www.fdsys.gov 

http://www.house.gov/reform 

(II) 

COMMITTEE ON OVERSIGHT AND GOVERNMENT REFORM 

DARRELL E. ISSA, California, Chairman 

JOHN L. MICA, Florida 

MICHAEL R. TURNER, Ohio 

JOHN J. DUNCAN, JR., Tennessee 

PATRICK T. MCHENRY, North Carolina 

JIM JORDAN, Ohio 

JASON CHAFFETZ, Utah 

TIM WALBERG, Michigan 

JAMES LANKFORD, Oklahoma 

JUSTIN AMASH, Michigan 

PAUL A. GOSAR, Arizona 

PATRICK MEEHAN, Pennsylvania 

SCOTT DESJARLAIS, Tennessee 

TREY GOWDY, South Carolina 

BLAKE FARENTHOLD, Texas 

DOC HASTINGS, Washington 

CYNTHIA M. LUMMIS, Wyoming 

ROB WOODALL, Georgia 

THOMAS MASSIE, Kentucky 

DOUG COLLINS, Georgia 

MARK MEADOWS, North Carolina 

KERRY L. BENTIVOLIO, Michigan 

RON DESANTIS, Florida 

ELIJAH E. CUMMINGS, Maryland, Ranking 

Minority Member 

CAROLYN B. MALONEY, New York 

ELEANOR HOLMES NORTON, District of 

Columbia 

JOHN F. TIERNEY, Massachusetts 

WM. LACY CLAY, Missouri 

STEPHEN F. LYNCH, Massachusetts 

JIM COOPER, Tennessee 

GERALD E. CONNOLLY, Virginia 

JACKIE SPEIER, California 

MATTHEW A. CARTWRIGHT, Pennsylvania 

TAMMY DUCKWORTH, Illinois 

ROBIN L. KELLY, Illinois 

DANNY K. DAVIS, Illinois 

PETER WELCH, Vermont 

TONY CARDENAS, California 

STEVEN A. HORSFORD, Nevada 

MICHELLE LUJAN GRISHAM, New Mexico 

Vacancy 

LAWRENCE J. BRADY, Staff Director 

JOHN D. CUADERES, Deputy Staff Director 

STEPHEN CASTOR, General Counsel 

LINDA A. GOOD, Chief Clerk 

DAVID RAPALLO, Minority Staff Director 

SUBCOMMITTEE ON ENERGY POLICY, HEALTH CARE AND ENTITLEMENTS

JAMES LANKFORD, Oklahoma, Chairman 

PATRICK T. MCHENRY, North Carolina 

PAUL GOSAR, Arizona 

JIM JORDAN, Ohio 

JASON CHAFFETZ, Utah 

TIM WALBERG, Michigan 

PATRICK MEEHAN, Pennsylvania 

SCOTT DESJARLAIS, Tennessee 

BLAKE FARENTHOLD, Texas 

DOC HASTINGS, Washington 

ROB WOODALL, Georgia 

THOMAS MASSIE, Kentucky 

JACKIE SPEIER, California, Ranking 

Minority Member 

ELEANOR HOLMES NORTON, District of 

Columbia 

JIM COOPER, Tennessee 

MATTHEW CARTWRIGHT, Pennsylvania 

TAMMY DUCKWORTH, Illinois 

DANNY K. DAVIS, Illinois 

TONY CARDENAS, California 

STEVEN A. HORSFORD, Nevada 

MICHELLE LUJAN GRISHAM, New Mexico 

(III) 

C O N T E N T S 

Page 

Hearing held on December 12, 2013 ...................................................................... 1 

WITNESSES 

Scott Gottlieb, M.D., Resident Fellow, American Enterprise Institute 

Oral Statement ................................................................................................. 2 

Written Statement ............................................................................................ 5 

Peter Huber, Ph.D., Senior Fellow, Manhattan Institute 

Oral Statement ................................................................................................. 13 

Written Statement ............................................................................................ 15 

Mr. Paul Hastings, President and Chief Executive Officer, Oncomed Pharmaceuticals, Inc. 

Oral Statement ................................................................................................. 20 

Written Statement ............................................................................................ 22 

Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, 

Food and Drug Administration 

Oral Statement ................................................................................................. 42 

Written Statement ............................................................................................ 45 

APPENDIX 

Opening Statement by Rep. Speier ........................................................................ 74 

Opening Statement by Rep. Cartwright ................................................................ 76 

Department of Health and Human Services Response to Questions for the 

Record. .................................................................................................................. 77 

(1) 

FDA CHECKUP: DRUG DEVELOPMENT AND 

MANUFACTURING CHALLENGES 

Thursday, December 12, 2013 

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON ENERGY POLICY, HEALTH CARE AND

ENTITLEMENTS, COMMITTEE ON OVERSIGHT AND GOVERNMENT REFORM, Washington, D.C. 

The subcommittee met, pursuant to call, at 1:35 p.m., in Room 

2154, Rayburn House Office Building, Hon. James Lankford [chairman of the subcommittee] presiding. 

Present: Representatives Lankford, Gosar, Meehan, Speier, 

Duckworth, and Lujan Grisham. 

Staff Present: Will L. Boyington, Press Assistant; Molly Boyl, 

Deputy General Counsel and Parliamentarian; Daniel Bucheli, Assistant Clerk; Katelyn E. Christ, Professional Staff Member; John 

Cuaderes, Deputy Staff Director; Linda Good, Chief Clerk; Emily 

Martin, Counsel; Sharon Meredith Utz, Professional Staff Member; 

Sarah Vance, Assistant Clerk; Jaron Bourke, Minority Director of 

Administration; Krista Boyd, Minority Deputy Director of Legislation/Counsel; Aryele Bradford, Minority Press Secretary; Courtney 

Cochran, Minority Press Secretary; Yvette Cravins, Minority Counsel; Adam Koshkin, Minority Research Assistant; Juan McCullum, 

Minority Clerk; and Daniel Roberts, Minority Staff Assistant/Legislative Correspondent. 

Mr. LANKFORD. Committee will come to order. I would like to 

begin this hearing by stating the Oversight Committee mission 

statement. We exist to secure two fundamental principles. First, 

Americans have the right to know that the money Washington 

takes from them is well spent. And second, Americans deserve an 

efficient, effective government that works for them. 

Our duty on the Oversight and Government Reform Committee 

is to protect these rights. Our solemn responsibility is to hold government accountable to taxpayers because taxpayers have the right 

to know what they get from their government, we will work tirelessly,in partnership with citizen watchdogs, to deliver the facts to 

the American people and bring genuine reform to the Federal bureaucracy. This is the mission of the Oversight and Government 

Reform Committee. 

I am going to waive our opening statements today from the ranking member and myself because we have votes that are coming 

very soon and I want to make sure that we get the opening statements from our guests that are here on the first panel. It looks like 

those votes will be called fairly shortly. When they are called, we’ll 

2 

slip away, vote, and then we’ll come back and we’ll do questions 

from then and then obviously move on to our second panel. 

But with that, I would like to recognize Ms. Speier. One of the 

panelists is from her district, actually. I want to give a chance for 

her to be able to recognize him. 

Ms. SPEIER. Mr. Chairman, thank you, and I, too, will submit my 

opening statement for the record. 

I do want to take great pleasure in introducing someone who I 

have known professionally for a number of years. He is the CEO 

of OncoMed Pharmaceuticals, and that’s Paul Hastings, who is 

with us this afternoon. OncoMed is located in my district and is 

doing groundbreaking work on stem cell therapies that could provide important alternatives for the treatment of cancer. And Mr. 

Hastings is what you would refer to as a serial startup CEO and 

has done great work over many decades. 

So, thank you, Mr. Chairman. 

Mr. LANKFORD. All members will actually have 7 days to be able 

to submit opening statements for the record as well. 

Let me introduce the other two panelists as well. We have two 

prolific writers that are here. Dr. Scott Gottlieb is the resident fellow at the American Enterprise Institute, and Mr. Peter Huber is 

a senior fellow at the Manhattan Institute, all done significant 

work and research in the area. If you are not familiar with our 

topic today, we are dealing with the FDA and the drug approval 

process. 

And so glad to have all three of you here as experts in this conversation. 

So, pursuant to committee rules, all witnesses are sworn in before they testify, so if you could please stand. Raise your right 

hand. 

Do you solemnly swear or affirm the testimony you are about to 

give will be the truth, the whole truth, and nothing but the truth, 

so help you God? 

Thank you. You may be seated. 

Let the record reflect all the witnesses answered in the affirmative. 

In order to allow time for discussion, I would ask you to keep 

your testimony, your oral testimony to about 5 minutes. You’ll see 

the clock in front of you. All of you are veterans at this table before, and so we would ask you to do that oral statement, as you 

know full well. All of you have submitted a tremendous amount of 

written information as well. That will go into the permanent record 

also. 

Mr. Gottlieb, be glad to be able to receive your opening statement. 

WITNESS STATEMENTS 

STATEMENT OF SCOTT GOTTLIEB 

Dr. GOTTLIEB. Thanks a lot, Mr. Chairman, Ms. Ranking Member. Thank you for the opportunity to testify today before the committee. My name is Scott Gottlieb. I am a physician and resident 

fellow at the American Enterprise Institute. I previously worked at 

3 

FDA as the agency’s deputy commissioner and at CMS as a senior 

adviser to the administrator. 

I want to address the issues related to FDA’s review and approval of novel treatments for serious diseases that aren’t adequately addressed by available medicine. The FDA has been effectively implementing provisions included in the last reauthorization 

of the Prescription Drug User Fee Act related to breakthrough 

therapies. I believe these provisions are having a noticeable impact 

on FDA’s willingness to embrace new approaches to expedite the 

development of these sorts of new treatments, but I still believe 

there is more that can be done. 

The drug development process itself has become long and costly 

owing to regulation that serves to add to premarket burdens, but 

often without meaningfully improving the safety of drugs or what 

we know about their effectiveness, and we are not taking full advantage of what science has made available, not only in terms of 

new and more targeted therapies, but better ways for evaluating 

them. 

The review staff at FDA is a dedicated and well-intentioned clinical group of people who are often leading experts in their respective fields, but they are also heavily influenced by outside voices, 

and it’s often the critics talking the loudest. Years of complaints 

about FDA’s oversight of drug safety, about the high cost of drugs 

relative to their perceived benefits at the time of initial market 

entry, and criticism about the science that FDA uses in its review 

processes from vocal academics who often have their own parochial 

views in these matters, all of these things have taken a toll on 

FDA’s culture. 

Over time, it is sanding down people’s willingness to take the 

risk of adopting new approaches to the agency’s work, even around 

areas of unmet medical needs that might not have anything to do 

with the concerns that incited the initial concerns. 

The result is that a fear of uncertainty now pervades the review 

process. When it comes to drugs targeted to unmet medical needs, 

I believe it’s a fear of uncertainty around efficacy that is having the 

most profound impact of how drugs are being developed. FDA staff 

is often unwilling to take risk when it comes to observations 

around drug efficacy. They require experiments that leave little 

doubt that the magnitude of the benefit observed in a trial is not 

a function of any statistical chance. In short, they want to conduct 

pristine experiments that leave little uncertainty about the results 

describing a drug’s efficacy that they are precise and beyond any 

statistical doubt. 

Here it’s important to distinguish between the magnitude of the 

benefit being observed and the believability of that result. I am not 

talking here about FDA’s concern that a drug must show a certain 

amount of benefit. Some threshold of measurable benefit is always 

necessary to provide a proper balance against known risks. 

Rather, it’s how FDA guarantees the believability of that observation of benefit that I believe is having the most significant delay 

on the development of new drugs. FDA requires longer, larger 

trials to get pristine statistical results. This makes their ultimate 

decision around the approval easier since evidence is clear, but it 

also adds to time and cost. 

4 

I believe there are ways to enable faster development of new 

drugs for unmet diseases and timelier access, while still ensuring 

that future patients will have appropriate information. We need to 

focus on reforms that will help the review culture at FDA evolve 

when it comes to these issues. I want to offer some suggestions 

that are aimed towards these ends. 

First, we should consider changing how clinical effectiveness is 

defined in the setting of rare diseases. FDA insists that there is a 

single standard for establishing safety and effectiveness. I think 

the FDA needs clearer direction around when we as a society want 

it to exercise its existing discretion to streamline development programs. This doesn’t mean that safety and effectiveness isn’t firmly 

established for the drugs aimed at rare disorders. It only means 

that we are making a much more explicit acknowledgment of 

FDA’s existing discretion to adjust trial requirements based on the 

circumstances. 

Second, the breakthrough therapies pathway has been a successful legislative effort and its implementation by FDA has had a palpable impact on the review process. But a full-throated embrace of 

the spirit of this legislation requires a cultural change at FDA that 

is invariably slow to unfold. For these reasons, we might also consider changing the organizational structure of FDA to hasten the 

adoption of these provisions. 

Specifically, rather than allow drugs aimed at very rare disorders 

to be reviewed alongside drugs targeted to more common maladies, 

we might consider carving out the novel breakthrough drugs into 

a separate group inside FDA, a sort of skunk works charged with 

implementing novel review requirements and regulatory science. 

Such a group might more readily embrace concepts that can change 

how we develop drugs, introducing greater efficiency, ideas like the 

use of adaptive trial designs, Bayesian statistical techniques, and 

wider use of molecular profiling and targeting of medicines. 

These are not new concepts, but they are very slow to gain adoption. In an agency where reviewers are under constant political 

pressure and time constraints, they don’t feel a lot of liberty to incorporate unfamiliar and new approaches, or take new risks in embracing concepts that are untried. So they stick with familiar constructs, even if these traditional approaches are unnecessarily costly and burdensome. 

These are just a few ideas on how to advance FDA’s science and 

make the process for the consideration of drugs aimed at vexing 

and unmet medical diseases more efficient. FDA has made great 

strides towards these ends through its recent implementation of 

breakthrough therapies. I would argue that to make further reforms, it would require measures that start to change the culture 

of FDA as it relates to these challenges. Thank you. 

[Prepared statement of Dr. Gottlieb follows:] 

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Mr. LANKFORD. Mr. Huber. 

STATEMENT OF PETER HUBER 

Mr. HUBER. Mr. Chairman, Madam Ranking Member, among 

Federal regulators, the FDA plays a uniquely strong role in regulating not just the product, but the development of the core science 

that allows the industry to design the products that do what we 

want them to do. 

The science at stake here is not drug science. There is no such 

thing. It is drug patient science. It is how the drug’s chemistry 

interacts with the patients. And drug designers can learn quite a 

bit by just studying biology, but at the end of the day, to get the 

science right, you do have to start prescribing the drug to patients 

and study what happens. 

So before it licenses a drug, the FDA issues something called an 

investigational license that scripts how we set about systematically 

and scientifically developing drug patient science, and those scripts 

have simply not kept pace, in recent years particularly, with what 

the best scientific investigations can now do and should be doing. 

The blinded, randomized trial protocols that the FDA still relies 

on overwhelmingly to this day were first used in 1938. They were 

expanded and formalized in the 1960s. They begin with conventional clinical definitions of the disease. The criteria used to select 

the patients to participate in the trials must be specified before the 

trial begins, or to a limited extent resolved in the very early phases 

of the trial when very few patients are involved. The doctors involved aren’t allowed to systematically explore molecular factors 

that affect how one patient may respond well to a drug and another may respond badly to the same drug even if they are presenting the same clinical symptoms. 

The only issues that these protocols address systematically are 

something called selection bias, which is a deliberate or inadvertent stacking of the data by doctors, or the placebo effect, which 

is wishful thinking by patients. The trials teach us next to nothing 

about how variations in patient chemistry affect responses to the 

drug. 

The FDA’s concerns about selection bias are legitimate, but modern molecular medicine hinges on the deliberate scientific selection 

of the right drug-patient molecular combinations. Patients suffering from the same clinically defined disease often present different clusters of molecular targets deep down. There is no such 

disease as breast cancer. There are at least 10 biochemically distinct breast cancers down there. We treat some with estrogen 

blockers and we treat others with estrogen itself. One of the estrogen blockers, its performance depends on liver genes, which determine whether the patient metabolizes that drug properly or not. 

And I could go on and on. There are diseases that change rapidly 

on the fly. The chemistry of cancer cells changes at a wild pace as 

it progress. So do HIV infections. Many of these fast-changing diseases require multi drug regimens and cocktails. Side effects add 

still more relevant patient side variation in the chemistry. 

A good trial of a good drug should culminate in prescription protocols that will make it possible for future doctors to prescribe the 

drug to the patients who present the molecular profiles that will 

14 

interact well with that drug. When we don’t do that, there are two 

major consequences. The first one is little noted but deserves a lot 

more attention. During the trials themselves, we may quite often 

be doing real harm unnecessarily to significant numbers of the patients involved. A consensus report issued a few years ago by a coalition of cancer experts drawn from the industry, academia, and the 

FDA itself says the FDA still relies on, ‘‘traditional populationbased models of clinical trials...that may form the antithesis of personalized medicine, and accordingly these trials expose large numbers of patients to drugs from which they may not benefit.’’ 

If you are saying that you are exposing large numbers of patients 

to cancer drugs from which they won’t benefit, you are saying quite 

something, because these drugs are very often toxic and powerful 

drugs, and you really don’t want to be prescribing them to the 

wrong patients for long. 

The second consequence follows directly from the first. If we are 

testing drugs in many of the wrong patients, many drugs that we 

do in fact need, because they would benefit significant numbers of 

patients, will not make it through these trial protocols, because to 

perform well, a drug has to be prescribed well. We know how to 

design what are called adaptive trials. In brief, you gather a great 

deal of data tracking, genomes, and proteins and other biomarkers 

that may affect the trajectory of the disease and side effects and 

cause different patients to respond in different ways. Patients can 

be added or removed from trials or treatment regimens can be altered to improve our understanding of the drug-patient molecular 

science. 

There are sophisticated statistical profile processes and algorithms that can handle this very complex data. Because the adapters learn and because the investigators learn and adapt as they go, 

the patients involved receive on average much better treatments. 

It really is high time to dispense with these old trial protocols and 

use the statistical methods of the future and the modern molecular 

tools that let us track and learn about all these factors. 

Mr. LANKFORD. Thank you. 

[Prepared statement of Mr. Huber follows:] 

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Mr. LANKFORD. Mr. Hastings. 

STATEMENT OF PAUL HASTINGS 

Mr. HASTINGS. Thank you, Chairman Lankford. 

Mr. LANKFORD. Mr. Hastings, do you mind turning your microphone on there? Thank you. 

Mr. HASTINGS. Sorry about that. 

Chairman Lankford and Ranking Member Speier, members of 

the committee, My name is Paul Hastings, chairman and CEO of 

OncoMed Pharmaceuticals, headquartered in Redwood City, California. I also serve as chairman of the BIO Emerging Companies 

Section Governing Board, which represents the small entrepreneurial and emerging biotechnology companies that often do not 

yet have a product on the market, and we are the majority of BIOs 

over 1,000 members. 

I personally have 27 years of experience in biotechnology and the 

pharmaceutical industry. My current company, OncoMed Pharmaceuticals, is working at the cutting edge of oncology research, focused on antibodies that target a specific set of cells within tumors 

known as tumor initiating cells. These cells drive the growth and 

metathesis of the tumor of the spread, and they can differentiate 

into various cell types within the tumor. Currently we have five 

products in clinical development, all discovered at OncoMed, and 

over 13 completed or ongoing clinical trials, with more than 280 patients receiving our investigational agents. 

We continue to pursue the discovery of additional disruptive and 

novel antitumor initiating product candidates. The U.S. biotechnology industry is working on treatments and therapies that 

have the potential to deliver new solutions to our most pressing 

healthcare needs and is a key element of an innovation-driven 

economy. We’ve come a long way in turning incurable disease to 

treatable disease, increasing the ability of patients to maintain 

independent lives. With the number of people over 65 increasing, 

improving the quality of life and ability for patients to maintain 

independence is a national imperative. Hundreds of companies like 

mine are working on these solutions with over 400 clinical trials 

currently underway focused on developing the next generation of 

medicines for over 200 diseases. 

This is also an industry poised to be a major contributor to a 21st 

century innovation-driven economy in the United States. However, 

we continue to face intense competition from other countries, as 

well as increasing R&D costs, regulatory challenges, and a contracted funding environment. 

This year, working with the FDA, we have seen positive signs 

that the biotechnology industry is recovering not only from some of 

the regulatory hurdles, but also from the economic crisis. Thirtynine biotech companies have gone public this year, including my 

own, marking the most active IPO market in a decade. Additionally, in 2012 the FDA approved 39 new molecular entities, the most 

approvals we have seen in 16 years. 

Now, while this is good news, the financial and regulatory environment continues to pose significant challenges to innovation and 

drug and biologic developers like ourselves. For example, first-time 

private financings, not public financings, but private financings, 

21 

venture capital financings, the lifeblood of the innovation biotechnology industry, these first-time financings for new companies 

are actually at the lowest we’ve seen since 1995. And while we’ve 

seen an increase in the number of approvals, we have also seen a 

steep increase in research and develop cost, much of which is associated with increased requirements and costs to run clinical trials. 

FDASIA contains several provisions designed in cooperation with 

industry and the FDA specifically to provide FDA with the resources and processes that encourage the utilization of modern 

tools and approaches, such as adaptive clinical trial design, and 

allow for more interactive scientific dialogue between the FDA, the 

industry, and patients. Some of the most exciting provisions in 

FDASIA now include an expanded accelerated approval pathway 

designed to improve on the historical success this program has had 

with developing game-changing medicines to treat HIV and AIDS 

and other cancers, as well as other diseases, and expand its utilization in other disease areas, and a new breakthrough therapy designation designed to get the most promising medicines to patients 

much more efficiently. 

However, while FDASIA included an agreement by the industry 

to significantly increase user fee funding for the FDA to help support FDA’s drug review activities and enable them and these new 

programs, sequestration has diverted a portion of these industry 

fees to an escrow account that has no practical purpose for the 

FDA, industry, or patients. This has severely hindered FDA’s ability to fully implement critical provisions of FDASIA that would improve our ability to more effectively develop and deliver innovative 

medicines to patients. This is the equivalent of our paying our utility bills and then being told we can’t access power, lights, or heat. 

BIO would like to thank Congress for proposing a 2-year delay 

in sequestration of user fees in the proposed budget agreement but 

urges Congress to rectify this irrational and counterintuitive situation by passing the FDA Safety Over Sequestration Act of 2013, 

sponsored by Representatives Leonard Lance and Anna Eshoo, 

with broad bipartisan support. 

While many new measures have been embraced and encouraged 

by Dr. Hamburg, Dr. Woodcock, and their colleagues and management at the FDA, it’s yet to be seen if the regulatory flexibility afforded by FDASIA is being fully embraced at and across the FDA 

reviewer level to advance the development of new therapies for 

unmet medical needs. Releasing user fees from sequestration, successful implementation of FDASIA, and enabling our colleagues at 

the FDA could significantly improve the ability of our industry to 

more effectively develop new medicines and get them to patients 

who need them. 

These actions could also help stimulate investment in early stage 

companies that are working on the next generation of medical discoveries and breakthroughs. The Biotechnology Industry Organization is committed to working with FDA and Congress to ensure 

these goals are achieved. Thank you for this opportunity, and I look 

forward to your questions. 

Mr. LANKFORD. Thank you. 

[Prepared statement of Mr. Hastings follows:] 

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Mr. LANKFORD. I recognize myself for the first round of questions, and we will go through the questions as we can, and we’re 

still not called for votes yet. You’ll hear the bells and the lights and 

everything else go off when that happens, and we’ll have a little 

bit of time to be able to move from there. 

Let me ask a couple of quick questions on this. I think I am 

going to work in reverse. 

Mr. Hastings, you talk about the venture capital being the lowest 

it’s been since 1995 on that. Do you have a gut feeling on why that 

is, why is the venture capital suddenly drying up when we have 

a record number of IPOs happening? 

Mr. HASTINGS. It’s a cycle. So, while now the public markets are 

doing well, the venture capitalists who have fueled all these early 

stage companies, had fueled them for so many years before the IPO 

market was open, that they drained themselves of a lot of their resources. They weren’t able to provide the returns to their investors. 

So when the public markets opened up and the public investors 

embraced the public markets, everybody on the public side did really well, but there’s a lot of catchup that’s being done now by the 

venture capitalists. So they now look like they haven’t provided 

their returns over the course of the 10 or so years prior to the public market opening up that their investors required, so those same 

investors invest in the public markets as well. 

Mr. LANKFORD. Okay. So, what’s your gut on how quickly that 

turns around? You’ve tracked this for a while, it sounds like. 

Yes, I track this constantly. It’s going to take a few years. So 

once the public markets continue to reward the venture capitalists 

for delivering these companies. So now, by the way, all those private investors, all the investors that are in OncoMed Pharmaceuticals on the private side, they won’t be able to cash out until 

the lockup period is over, and even then they have to see the company do well on the public markets in order for them to get their 

exit. All that takes a little bit of time, probably a couple of years 

before people start reinvesting now in the early stage venture financing. 

Mr. LANKFORD. Mr. Huber and Dr. Gottlieb, they are both recommending different ways of doing some of the trials and processes 

and things, and I want to be able to get to both of those in a moment. 

Mr. Hastings, though, what is the most expensive part or the 

most difficult or cumbersome part of the clinical trial or the R&D 

or approval process—you can broaden that as broad as you need to 

make it—of getting the actual drug through the research to development. What is the pricey, cumbersome part of that? 

Mr. HASTINGS. I’ll give you one example. There are many places 

along the development cascade where it gets expensive. In the 

early stages, for young companies, it gets expensive even in the 

Phase I or Phase II portion of the trial, particularly in Phase I 

when there is a lot of communication back and forth with regard 

to safety of the drug. And one of the areas that we’ve been working 

on is this informal communication where rather than having a letter-writing campaign back and forth, there is more dialogue between the reviewer and the company. Saving a month on that communication process could save a small company, and there has 

31 

been a lot of effort from both the FDA and the industry to work 

on that together. That’s been an example of something that’s improved dramatically. 

Mr. LANKFORD. Okay. 

Mr. Huber, let me ask you a quick question on it as well. The 

statement is interesting to me, the molecular profiles. How would 

that work for them, and expand that somewhat is what I’m saying, 

as far as the FDA, because that’s obviously a completely different 

paradigm than what they are currently doing on it. So how would 

that function in real life for them. 

Mr. HUBER. I was having dinner last night with a prominent 

oncologist from MD Anderson in Houston, and he said the real clinical trials begin after the drug is licensed. Now, I will emphasize, 

first of all, that cancer a very distinctive disease. It’s wildly dynamic. The cells are constantly mutating. And by the time a tumor 

grows at all, you don’t have one disease in there. You have a whole 

bunch. That’s what makes it so hard to attack it and why so often 

drug cocktails are used and so on. 

But in any event, the fact is that oncology has been the beneficiary of the accelerated approval quite often as one of two diseases. The other are HIV infections have gotten this. And the main 

advantage of accelerated approval in my book is that it releases 

oncologists to practice and to work out what the patient needs step 

by step. The answer is you begin prescribing drugs. These are targeted drugs increasingly that target one molecular receptor. And 

you can track very early on with modern diagnostic tools what’s 

going, not up at the clinical level, which takes quite a lot longer 

to surface, but much deeper down inside the patient’s body. I mean, 

it can be things that are not that much deeper down, like tumor 

shrinkage or so on, but you can also be looking at densities of cancer cells being shed from the tumor and circulating in the patient’s 

blood. The FDA calls these surrogate end points or intermediate 

end points. 

And you get feedback much faster. If you begin getting that, you 

can early on begin saying, look, we begin seeing different patterns 

of response. And it gets eye glazing when you talk about the statistics, but the fact is the statisticians know how to handle multidimensional trials where you’re exploring multiple factors as you 

go. We have mechanistic understandings of why certain receptors 

should be accelerating the progress of the disease, or if you inhibit 

them, slowing it down. You study these things and you adapt. 

I could give you one vivid example, if you will allow me. Memorial Sloan-Kettering in New York some years ago launched a trial 

using a kidney cancer drug to treat bladder cancer. It was an abysmal failure. Almost everybody that was treated with this drug did 

not respond well. However, one 73-year old woman responded extraordinarily well. In fact, 2 years later she is completely cancer 

free. 

Now, in the past, and certainly if this were all within the confines of one trial, you’d ignore that. I mean, one patient does not 

license a drug. Memorial Sloan-Kettering doctors went in and they 

searched for the biomarkers associated with cancer, they explain 

this, they couldn’t find one. They then did a whole tumor sequence. 

They just looked for everything that was in this one patient’s 

32 

tumor and they found the receptor that was being targeted by the 

kidney cancer drug. One patient in that group. It turns out about 

8 percent of bladder cancers have this receptor. And so then they 

launched a new trial. 

That is a slow motion adaptive trial. You learn something and 

then you change. You can do that internal to a single trial if you 

are working hard at it, but you have to do things that the FDA 

doesn’t allow. You actually have to be saying these are the people 

who are being treated with the drug. Let’s look at what’s the details. I mean, if you have toxicity problems and metabolism problems, same thing, we’ve got biomarkers for livers that metabolize 

things well or badly. You can look for them, and you can then converge on treatment protocols that work better. 

Mr. LANKFORD. Okay. We will follow up with FDA in the days 

ahead. Let me yield to Ms. Speier for her questions. They have 

called votes now. We have around 11 minutes or so on the vote 

count. I think what we will do is take Ms. Speier’s questions, then 

we’ll take a quick recess. We’ll have three different votes that are 

happening, and then we’ll come back and we’ll go at you with some 

more questions. Okay with that? So we get a quick break. 

Ms. Speier. 

Ms. SPEIER. Mr. Chairman, thank you. 

And thank you all for your testimony. 

The sequestration has really cut the limbs off of NIH funding to 

the tune of about $1.2 billion a year. From your perspectives, each 

of you, I want to know how that affects your ability to do your 

science. 

Mr. HASTINGS. Well, that’s a wide open question. So to me it goes 

all the way back to what and how we want to be perceived as a 

Nation, right? If we’re not getting behind STEM education from 

kindergarten through grade 12, all the way up through our university system and the NIH and getting behind innovation, it’s not 

then going to leave the technology transfer offices of our universities or the halls of the NIH and come with a license to an entrepreneur who then can develop that drug. 

So it’s a little hard to pinpoint exactly what sequestration does 

with the NIH in terms of what it might bring to our industry other 

than to say it’s huge, very broadly. You can’t really look at any one 

drug that came out recently and say that wouldn’t have happened 

under sequestration. I can’t think of one off the top of my head. But 

that’s the kind of thing that comes out, the thought process, the 

focus on innovation. And without that and without those jobs for 

those people to do those things, they are going to go to other places. 

Dr. GOTTLIEB. I’m less focused on NIH, just to pick up on what 

Mr. Hastings said about FDA. I think the sequestration has been 

problematic for the FDA insofar as what I see, and I wrote an article about this. A lot of the sequestered funds were funds that would 

have been targeted towards the areas of new regulatory policymaking, the things that were embedded in PDUFA, in particular, 

where FDA was going to advance or try to advance some of the scientific principles that we’re talking about here today. 

There were unfilled positions at the time that the sequester was 

imposed that will continue to probably go unfilled, but a large 

33 

chunk of the money that was taken out was taken out of the programs of new regulatory policymaking. 

Ms. SPEIER. Dr. Gottlieb, you suggest that there is a certain 

amount of risk that we should just be willing to accept, and I’d like 

to know what you think that percentage of risk should be in terms 

of the FDA process. 

Dr. GOTTLIEB. Yeah, I’m not sure you can, you know, articulate 

it in terms of a percentage. There is obviously a certain level of palpable risk we are always willing to tolerate, and it adjusts based 

on what the clinical circumstances are. And if you are facing a 

grave disorder and you don’t have other options, you’re willing to 

embrace quite a bit of risk. 

I cited in my written testimony the case of mucopolyscaccharide 

diseases, diseases that are inborn, there’s a metabolism where children are born, these are largely fatal diseases, they are terribly debilitating. I think families who have children with those disorders 

would be willing to embrace a large degree of uncertainty around 

a new drug, but in many circumstances say they are not able to 

because the clinical trial requirements are getting more difficult. 

Remember, I’m talking here about, in particular, risk around the 

benefit, not the safety. I’m talking about situations where the magnitude of the benefit that’s observed in a clinical trial can’t be firmly established because the statistical rigor hasn’t reached a high 

enough degree of, you know, suredness, if you will. So you see a 

certain magnitude of benefit and you have to probability address 

that and say, well, since it wasn’t a large trial and there were 

these flaws in the trial, we can be 70 percent certain that it’s going 

to deliver that 40 percent benefit. That’s the situation. 

Ms. SPEIER. But my understanding is that—and I’ve actually 

accessed compassionate use for the FDA for a number of constituents from time to time—my understanding has been that they have 

been very willing to allow the drugs to be used for compassionate 

use, which typically you would say in a case of a young child would 

be embraced. So do you find that at all being restricted in its availability? 

Dr. GOTTLIEB. No. I think FDA has been very flexible when it 

comes to individual patient INDs, but keep in mind there is two 

challenges there. One is that only certain physicians are going to 

be able to navigate that process in collaboration with their patients. It takes a certain level of sophistication and resources to 

work through that process. And that’s not a criticism of FDA. It’s 

just a hard process. So it is putting at a disadvantage a whole lot 

of patients who will never have access to that. 

The other thing is that if that’s what we’re dependent upon to 

make therapeutics available in these kinds of, you know, sort of 

grave situations, situations where there’s a real unmet need, the 

framework, the sort of framework on the industry side won’t be in 

place to make the drug broadly available. In today’s environment, 

especially with a lot of biopharmaceuticals, the manufacturing isn’t 

available until the time of approval. 

Ms. SPEIER. All right. Thank you. 

Dr GOTTLIEB. And so we are dependent upon that approval. 

Ms. SPEIER. I am going to try to get one more question to Mr. 

Hastings. 

34 

Dr GOTTLIEB. All right. 

Ms. SPEIER. Mr. Hastings, if there is one thing that you would 

recommend that we do to assist the emerging BIO companies to be 

successful in their interactions with the FDA, what would that be? 

Mr. HASTINGS. Enable the FDA, through some of the policies that 

we’ve put forth, some of the breakthrough therapeutic areas, which 

would allow us to, with appropriate risk, also see the reward for 

these patients. So taking some of the risk that Dr. Gottlieb was 

just talking about. There are certain diseases, like cancer, there are 

other diseases, chronic diseases, chronic inflammatory diseases 

where patients recognize some of the risks associated with therapies. And so enabling some of these breakthrough areas where we 

can get drugs approved quickly, safely to patients faster is the way 

to go, and there’s a number of those initiatives that I outlined in 

my testimony. 

Ms. SPEIER. Thank you. My time is up. 

Mr. LANKFORD. Actually all of our time is up for this point. I 

would like to take a recess for about 20 minutes. We have three 

votes in the series. Each one of the votes is about 5 minutes apiece 

in between. We’ll go over and do the votes, we’ll come right back, 

and then we’ll jump right back into pummeling you with some 

more questions if that’s all right with you. So let’s take a short recess. 

[recess.] 

Mr. LANKFORD. The committee will come back to order. I apologize for the delay on that one. We should not have votes again until 

about 4:30 or so, so that will be in the middle of the time period 

that we will have our FDA witness, so we will still have her on the 

stand at least until 10 I would assume tonight. Thanks for the 

delay on that. I would like to recognize Dr. Gosar for the next line 

of questioning. 

Mr. GOSAR. Thank you very much. Mr. Hastings, how much 

would you say the typical biopharmaceutical company spends annually on drug research and development? 

Mr. HASTINGS. It depends on the size of the company. But an in- novative company, our company has 90 employees, roughly $55 

million to $60 million a year. You could spend, companies with 400 

or 500 employees with multiple drugs in the clinic, you could spend 

$1 billion a year in R&D. 

Mr. GOSAR. And has that gone up over the years? 

Mr. HASTINGS. Yes. 

Mr. GOSAR. And what are driving those factors of raising those 

costs, R&D costs? 

Mr. HASTINGS. So in certain instances, it is what trial designs 

have turned into, the numbers of patients one needs to go into clinical trials, the amount of time it takes to file an I&D and get your 

first patient treated on a therapy, to enrolling patients in Phase I, 

II, and III clinical trials, not only in the U.S., but also globally. So 

it is a very large undertaking to do, even randomized Phase II clinical trials today. I call the randomized Phase II clinical trials today 

the old randomized Phase III trials of the past. They are roughly 

the same size as Phase III’s used to be. 

Mr. GOSAR. Got you. Mr. Huber, in his written remarks Mr. 

Hastings cites a 2012 Manhattan Institute study that found as 

35 

much as 90 percent of the development cost for many drugs approved by the FDA are incurred during Phase III clinical trials. 

Are you aware of this study? 

Mr. HUBER. I do definitely remember seeing it, but those numbers are not of my origin and I cannot speak further about them. 

Mr. GOSAR. So what would be your thoughts on those findings? 

Mr. HUBER. Clinical trials and certainly the time value of money 

are a very large component of the cost of getting a drug to market. 

I could not be any more specific than that. 

Mr. GOSAR. Got you. I am going to stay with you, Mr. Huber. 

How would you define a good clinical trial? 

Mr. HUBER. A good clinical trial is one that if the drug is good, 

ends up with enough guidance on prescription protocols that future 

doctors with high confidence prescribe the drug in ways that are 

likely to do more good than harm. Likewise, I might add one that 

rejects drugs that aren’t going to be able to meet that criterion. 

Mr. GOSAR. So do you think that randomized control trials are 

out-of-date? 

Mr. HUBER. Well, yes, I think they are. Yes. Yes is the answer. 

Not—I mean, there are some exceptions to every general statement, but, yes, they are not making full use of the tools we should 

be using. 

Mr. GOSAR. So what steps would you use to update those? 

Mr. HUBER. Well, President Obama’s Council of Scientific Advisors on Science and Technology issued a report last year that I cite 

in my written testimony. It is a pretty good starting point. I think 

things should go further. Others will be testifying before you today 

saying they have already gone further, and if they are, terrific, and 

the faster they move, the better. 

I do know that we should have been heading down this road a 

decade ago and high officials with excellent qualifications who I 

greatly admire who were sketching out what needs to be done to 

develop multi-dimensional data on how drugs operate. If it is happening, it sure is happening slowly. 

Mr. GOSAR. Very slowly. Dr. Gottlieb, can you define the clinical 

end point that the FDA requires in its trials? 

Dr. GOTTLIEB. Well, clinical end point is an end point. You know, 

the simple way to define it is it is something that can be experienced by a patient, so some kind of measure of clinical improvement that is going to be of benefit that the patient can appreciate. 

So the ability to breath better, a reduction in pain, certainly living 

longer, changes in morbidity and mortality, as opposed to a surrogate end point, which is an interim measure that presumably could 

correlate with a clinical outcome but isn’t something that is perceivable by the patient. It is a marker. 

Mr. GOSAR. Would you enhance that or enlarge that from your 

personal experience? 

Dr. GOTTLIEB. Enhance the use of surrogate measures? Certainly. I mean, FDA, I think, over a period of time, made wider use 

of surrogate measures, particularly in oncology, things like tumor 

shrinkage. I think the agency’s experience with that was mixed insofar as some of the surrogates that they relied on didn’t necessarily correlate with clinical benefit when they did the larger 

36 

studies, and so it left somewhat of an unhappy experience, and the 

agency became more skeptical of using surrogates generally. 

So I think where I would try to advance this is in trying to create 

some kind of pathway to better validate these surrogates more 

quickly. There is a lot of surrogates that make a whole lot of clinical sense, there is good theoretical reasons why they should correlate with a clinical benefit, but FDA is unwilling to rely on them 

or reluctant to rely on them because nobody has demonstrated 

that, and it is very hard to demonstrate that until you actually do 

the very long trial in the context of a drug, and by then you have 

sort of, you know, put a drug through an enormous clinical development program. 

Mr. GOSAR. Do you see any interim type of facility or group that 

could actually mitigate that? 

Dr. GOTTLIEB. Well, you know, people always talk about having 

independent entities like the NIH invest in trials just for the purposes of validating surrogates. You know, I think the FDA has 

flexibility, has a lot of authorities that it could use to, you know, 

take some risk around the uncertainty that pervades these surrogate measures to allow drug trials to go forward. 

You know, one of the examples that I cited recently was polycystic kidney disease where it is a genetic disease. You inherit it 

over the course of a lifetime. You develop cysts in your kidneys and 

eventually your kidneys fail and you go on to end stage renal disease. The question is could a reduction in the accumulation of these 

cysts be a valid surrogate for a clinical trial? 

FDA has been reluctant to accept cyst reduction or reduction in 

the propagation of cysts as a valid surrogate in the past, although 

it makes a whole lot of theoretical sense that if you can reduce the 

accumulation of these cysts, obviously it is going to, you know, prolong the length that your kidneys function. 

These are the kinds of things I think we need to look for these 

opportunities where there are these surrogates that make a whole 

lot of clinical sense and theoretical sense and either take the risk 

of allowing the trials to go forward on the basis of them or find a 

way to validate them more quickly. 

Mr. GOSAR. You kind of breached my next question. How important is it for the FDA to use its accumulating experience when conducting clinical trials as outlined in your written remarks? 

Dr. GOTTLIEB. Right. And I cite the example of 

mucopolysaccharide diseases where if you look at—this is a sort of 

cluster of related disorders, but they are each treated by distinct 

drugs. Very rare. Some of them only have hundreds of afflicted patients. If you look at the initial drug that was approved in this 

broader class, it was approved on the basis of, I think, about a 20- 

patient open label non-randomized study, probably as least rigorous as you can conceive of. And then there were subsequent approvals for a number of other drugs and with each approval, the 

theoretical basis for understanding why a replacement enzyme 

would work in one of these diseases was more firmly established, 

yet with each subsequent approval, the clinical trial requirements 

got harder and not less. And you can’t argue that it was a function 

of the fact that there was available therapy because there wasn’t. 

37 

Each disease was distinct, so the subsequent therapies were only 

going to treat one of these diseases. 

I think those are situations where when the agency has knowledge that it is accumulating in a clinical setting like that, it needs 

to find a way to make wider use of that so that it can lower barriers to entry as it gains more knowledge in an area and not raise 

them. 

Mr. GOSAR. Got you. Thank you, Chairman. 

Mr. LANKFORD. Ms. Duckworth. 

Ms. DUCKWORTH. Thank you, Mr. Chairman. 

Mr. Hastings, thank you for appearing here today and offering 

your testimony. I want to touch on a few points you highlighted 

where you speak to FDA’s regulatory environment has improved in 

recent years, but you noted that there are additional ways to improve efficiency, timeliness and consistency of drug evaluation. I 

am specifically interested in how the FDA communicates with you 

and your members. 

I understand that according to your internal survey, the majority 

of your member companies believe that communications with FDA, 

while it has improved, it has really been affected by sequestration, 

especially recently. Have your members, Mr. Hastings, expressed 

disappointment that the Industry Liaison Office that was anticipated by PDUFA V has yet to be fully staffed because of sequestration? 

Mr. HASTINGS. So, yes. The Office of Enhanced Communication, 

I am paraphrasing it, was an attempt to create an office whereby 

folks could call in if there were communications issues. But one of 

the things I was just sharing with Dr. Woodcock earlier is that the 

whole intention of the enhanced communication provision we had 

in PDUFA was for a cultural shift to occur inside the agency such 

that we actually wouldn’t need that office to communicate with our 

reviewers. 

What has interestingly happened and could be a side effect of sequestration, there is only one person in that office that I know of 

right now versus the five or six that were going to be there, but 

some of the communication between reviewers and companies has 

gotten better. And when you look at the survey, in areas like oncology, which is the area that we are studying, that communication 

has gotten markedly better. So rather than writing letters back 

and forth and taking 30 days each time a letter gets written to 

have the other person have the opportunity to respond, a simple 

phone call takes place. So a cultural shift has been very beneficial. 

The issue that we have right now is we would like to that very 

positive example and make it extend across all the division and all 

the reviewers so that each company, no matter what therapeutic 

area they are, is benefiting from that same enhanced communication. Now, would that office, the Office of Enhanced Communications, had it been staffed up without sequestration, would that 

have helped? It probably would have in some of those other areas. 

So I think the main beef we have about sequestration, again, is 

that these are fees that we are paying on top of what we pay in 

taxes and everything else, and we are paying those fees in order 

to enable. And like I mentioned, it is a little bit like paying your 

electric bill and then being told you can’t have power. 

38 

Ms. DUCKWORTH. No, the power is there. You are just not allowed to access it. 

Mr. HASTINGS. Right. But I think—and we have been working on 

this for many, many years now, enhanced communications, and we 

are seeing some good progress. So I don’t want to pin this all on, 

well, it is that one office that is going to solve this issue. It is more 

a reviewer cultural issue. And I will say for the Office of Oncology, 

there is an openness to communication. Now, again, what is going 

to help them communicate more openly with us is that they are effectively staffed, they are effectively funded, so they actually have 

time to pick up the phone and have a conversation with us. 

Ms. DUCKWORTH. So I am just a teeny bit confused. So you said 

that office should be staffed at—should have four or five people 

right now only has one because FDA can’t staff it up due to sequestration. But you are saying just that one person is more responsive. 

Or are you saying because they are not there you are just talking 

directly to the reviewer and not going through the office? 

Mr. HASTINGS. What I am saying is it is great to have that office 

and that office is going to be helpful, but the whole concept was 

to have open communication with reviewers which are not in that 

office. 

Ms. DUCKWORTH. Okay. But that is happening now and that has 

improved? 

Mr. HASTINGS. Right. So the mere fact that we are paying attention to the issue on both sides has made the issue better, right? 

Ms. DUCKWORTH. Right. 

Mr. HASTINGS. And so the fact that—it would be great for the office to be staffed because I think in general being staffed appropriately is going to help, but equally important as that office are 

individual reviewers in individual divisions having good communications with sponsor companies. 

Ms. DUCKWORTH. Are there any fears that if that office staffs up 

completely, there will be another layer of bureaucracy and that the 

communications directly with the reviewers will stop because people will feel like they have to go through that office? 

Mr. HASTINGS. No. 

Ms. DUCKWORTH. No fears of that? 

Mr. HASTINGS. Absolutely not. No. I mean, companies don’t work 

that way. You have a relationship with your reviewer and you have 

communication with that reviewer. If a hiccup should occur, there 

are a number of ways one can help to remedy that, including talking to that office about ways to enhance the communication. 

Ms. DUCKWORTH. Great. Thank you very much. I yield back, Mr. 

Chairman. 

Mr. LANKFORD. Thank you. Mr. Meehan. 

Mr. MEEHAN. Thank you, Mr. Chairman, and I want to thank 

this very distinguished panel for taking your time and giving us 

your expertise in this area. I represent an area in which there are 

a higher degree than normal of businesses associated with bio and 

technology and others and have actually tried to work with some 

of my constituents as we have negotiated the process of dealing 

with the agencies, and I also worked as a prosecutor acting on behalf of the agencies at certain times. 

39 

So I have seen it from both sides. But if I was to look from 500 

feet, there is just a tremendous frustration with the inability to 

have people make decisions, and I am not sure that I understand 

exactly why that is. What I see, frequently, is the process being 

used as a mechanism to avoid decisionmaking. And I can appreciate that if a wrong decision is made, there can be implications. 

But the very process we have is designed to somehow negotiate 

that fine area. 

My experience, in a number of cases, was the concern of clients, 

when I say clients, I mean constituents, who were afraid to be too 

aggressive in dealing with the FDA for the very fear that what 

would happen is now we will be further pushed back in their efforts. And every time a new order is made for a new trial, you are 

implicating potentially millions of dollars and longer periods of 

time. So why does it take so much time to make decisions? 

And I will conclude my questions with what I would find would 

be these 30-day periods, Mr. Hastings, you are talking about the 

communication, no communications would take place. There would 

be substantial amounts of information put together by very qualified people, the best in the business, in the form of making the 

case. And on the 29th day, they would get another letter asking for 

more information. So it was almost like every time the clock would 

reach the moment, something else would be put into place, the 

time would toll and there would be more requests, until ultimately 

you got to a point there was a decision-maker and somebody would 

say you know, what you are right, and a few times we broke 

through. But I am struggling with this problem. And I want to see 

both sides. But you are out there too. What do you see? What is 

the solution? 

Dr. Gottlieb, your written testimony speaks to, I think what you 

said was a failure for people to—you know the language—the fear 

of uncertainty pervading. So you understand my questions. Maybe 

you could each in order respond to my concerns and tell me what 

you think. 

Dr. GOTTLIEB. Well, I think generally there is a lack of appreciation for the time and cost of capital inside FDA, and it is probably 

not something you would expect them to be very cognizant of. But 

there is a significant time—cost to time when you are running a 

development program, even more so than getting advice back from 

the FDA that you have to run a bigger clinical trial. That can be 

funded and financed if you are a biotech company, but the time 

itself is a lot of lost capital. 

And the cycling has always been a problem. The multiple cycles 

has always been a problem. In FDA, there has been over time various efforts to try to address multiple cycle reviews but it is a significant problem. 

I would argue the process isn’t just used to avoid decisions. I 

think the process is used to try to tee up easy decisions. From my 

perspective, the reviewers in the early development stages of a 

drug program have a lot of autonomy or a fair measure of autonomy to prescribe what they think the clinical trial requirements 

should be to the companies. And when the companies get advice 

back from the medical reviewer they are very reluctant to challenge it in many cases. They follow it. 

40 

So if you are a medical reviewer and you know you are going to 

be ultimately responsible for making an approval decision or a decision to reject the drug, what you want is very clear evidence to 

make that decision. And so if you have discretion, you could prescribe a very rigorous clinical trial that is going to lead you to a 

place where you are ultimately are going to have very clear evidence. But there is a significant cost to that. 

So I think the process is used to try to make easier decisionmaking and that is what—and that is what ends up delaying the 

development programs. 

Mr. MEEHAN. Let me ask the other panelists to respond to sort 

of the sentiments that I expressed. Mr. Huber. 

Mr. HUBER. Well, I would like to try answering from a slightly 

different perspective. In 1981, or 1982 it was, that HIV surfaced as 

AIDS, people hadn’t yet identified the virus, it was a real sense of 

panic. I arrived in Washington right around that time and there 

was a palpable sense of, gee, something really terrible is happening 

once people realized what is going on. 

In the late ’80s as AZT emerged and through the 1990s, the FDA 

was remarkably agile and willing to bend its rules. It carved—the 

accelerated approval rule was spawned during that time. They 

began doing treatment INDs during that period, basically a parallel 

track of actually prescribing the drugs through hospitals and clinics and so on to make what was available, and there wasn’t that 

much available, broadly available. 

It is astonishing what was accomplished during that period of a 

substantial number of drugs to treat the secondary effects of HIV, 

the AIDS-related disorders, and then a whole series of HIV drugs. 

We needed a whole bunch because the virus is so nimble you have 

to attack it from multiple points to subdue it. And also a number 

of cancer drugs were also the beneficiaries during that decade. 

And I think anybody who looks retrospectively at this believes 

that—you know, medicine was really advancing very well. We accomplished fantastic stuff. There was—despite talk of the biases of 

one side or the other, there was really quite a bipartisan coalition 

to do this, and we beat what was thought to be and what was, in 

fact, an extraordinarily difficult virus. 

You know, it is possible to make decisions fast in this city when 

people are really sufficiently united and scared. And the President’s 

own, the PCAST report I mentioned earlier, by all accounts the accelerated approval process overall, which does what it says, it is a 

conditional approval, but it does approve drugs much faster, has 

had—I think very few people think it has done anything other than 

more good than harm, okay? You can move these things quickly if 

you want to and you can get, I won’t say invariably good results, 

but many more good results than bad ones. 

Mr. MEEHAN. Thank you. Mr. Hastings. 

Mr. HASTINGS. I would like to first speak to the fear of retribution comment you made earlier. If I was fearful of retribution, I 

wouldn’t be sitting here, I have to say. 

Mr. MEEHAN. Was it a fair comment? Do you think others may 

feel that way? 

Mr. HASTINGS. I think it is. I think it is. I just want to say I 

think it is a very individual thing, but I do believe with good diaVerDate Aug 31 2005 08:29 May 01, 2014 Jkt 000000 PO 00000 Frm 00044 Fmt 6633 Sfmt 6633 C:\DOCS\87645.TXT APRIL
41 

logue and adults in the room, decisions can get made. And I will 

tell you that in my experience, now having been doing this for a 

number of years, what we need to do in Washington now is become 

25 percent of our jobs as CEOs of biotechnology companies, and 

that engagement, when you have that engagement and there is 

good dialogue, good things can come out of that. 

Now, I will just give you an example from my company and I will 

juxtapose that to an example from a colleague of mine. One of the 

benefits of being the chairman of the Emerging Company Section 

of the Biotech Industry Organization is I am with a roomful of 

CEOs as big as this room every quarter. 

So we had a situation not too long ago where there was a 30-day 

period and on the 30th day we got an answer and it was yes, where 

you might get an answer and it could be no. So if the answer is 

no, invariably they are going to ask for more information if they 

want you to turn it around to a yes. 

But what we are seeing, what I was seeing recently was that 

particular case took 30 days. I have had situations where it has 

happened sooner, okay? But 30 days I got a yes. Great. Now I have 

a colleague who didn’t get an answer in 30 days in another division. So I think that inconsistency needs to be dealt with. But I 

also think that part of that inconsistency has to do with the volume 

of work people have and the proper staffing and the proper funding 

of the agency, and, again, going back to user fees, making sure that 

user fees are being spent to actually enable the FDA. 

So I do think there is variability. I think the retribution thing, 

there are mechanisms now within the FDA that if there is a person 

who is behaving in a way which is professionally inappropriate, 

that you can go and get that issue solved. And I don’t know how 

many folks may have mentioned to you the fear of retribution if 

you had asked them what did you do about that, but that is what 

I often do. And sometimes there are—you know, they are not aware 

of the mechanism or they don’t partake in the mechanism and then 

all of a sudden this becomes a big problem. 

Mr. MEEHAN. I think they often make cost benefit analysis of the 

things. 

Mr. HASTINGS. Could be. Could be. 

Mr. MEEHAN. I don’t want to overstep my time, so I appreciate 

the time you gave me, Mr. Chairman. 

Mr. LANKFORD. Thank you. To the panel, let me recognize Ms. 

Speier again. 

Ms. SPEIER. Thank you, Mr. Chairman. I just want to thank our 

panelists for participating today under what are difficult circumstances at the end of the year with everything else being equal. 

I do want to make a point though as they have presented. I think 

that we here in Congress have to take a certain amount of blame 

for the period of time, and I don’t believe it is right now, but the 

period of time when the FDA started to hold back, because the first 

thing that would happen when there was a bad outcome with a 

drug is that the FDA was hauled up here by us and scrutinized 

and beaten up and pummeled about their process and how could 

this have happened? And I think the result was that these FDA 

representatives would go back and say, all right, then, you know, 

42 

we will just put the brakes on many of these approvals. So we have 

got to take some responsibility I think for what has happened. 

I think more recently, and I think it has been testified to today, 

there has been a loosening of the process within the FDA and 

strategies employed that show that there are new pathways that 

are working, maybe not in every area, but certainly in some that 

show promise. And I guess the silver lining in the sequestration is 

that if it gets to the point where people actually get on the phone 

and talk to each other, that is really a good sign. So maybe we can 

enlist more of that in the future. 

Mr. LANKFORD. And the good news of that comment for me, Ms. 

Speier, is that Mr. Meehan and I, we were not here earlier during 

that time in Congress, so we can—I am grateful for your time here. 

Thank you for what you have contributed both in written form and 

oral form. We will continue to tap on your research in the days 

ahead, both in what is being written and the insight you can bring. 

So I appreciate you very much. We will take a short recess in order 

to reset the panel and to have our second panel. 

We now welcome our second panel of witnesses. Dr. Janet 

Woodcock is the Director of the Center For Drug Evaluation and 

Research of the Food and Drug Administration. I am very glad you 

are here and that you sat in obviously on the first panel as well, 

and I look forward to just some of the conversation about that. 

Pursuant to committee rules, we do swear in all of our witnesses 

before they testify, so if you would please rise and raise your right 

hand. (Sworn.) 

Mr. LANKFORD. Let the record reflect that the witness answered 

in the affirmative. Since you are the sole witness on this panel, we 

typically do a 5 minute time period on the clock. You are welcome 

to do that. We are going to receive your written testimony which 

will be part of the permanent record. We will be glad to be able 

to receive your oral testimony now. We won’t be as attentive to the 

clock, and we will follow up with questions from there. Thank you. 

STATEMENTS OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG EVALUATION AND RESEARCH, FOOD AND 

DRUG ADMINISTRATION 

Dr. WOODCOCK. Thank you. Mr. Chairman, Ranking Member 

Speier and distinguished members of the committee, I am Janet 

Woodcock. I am head of the Center For Drug Evaluation and Research at FDA. This hearing explores current challenges in drug 

development and manufacturing. And given the critical role that 

medicines play in the health of our population, these, I think, are 

very important and timely issues. 

One challenge that the other panelists already alluded to is the 

escalating costs and time required to develop new therapies. This 

problem was identified in FDA’s report on the critical path identified in 2004, but has only really gotten more serious since that 

time. 

The root cause, in my opinion, probably in contradistinction to 

some of the panelists can be boiled down to two major factors. The 

first is most investigational drugs that are taken into clinical trials 

are not successful. Perhaps 10 percent of the drugs get to the market. And about half of the drugs that are taken into Phase III trials 

43 

don’t work or are too toxic and are dropped at that point, which 

is a very expensive point. 

This extremely expensive failure rate has been difficult to address, although companies have been trying to address this in the 

last decade. And also over this decade, we have been working with 

academia and the industry to try and improve drug development 

tools, including biomarkers and other tools, that could help raise 

the success rate over this 10 percent mark. Until this happens, 

there are huge opportunity costs generated by this large scale of 

clinical failure. 

Now, the second factor is the hugely escalating cost of clinical 

trials, which have already been alluded to. Clinical development 

programs are plagued with multiple problems, including slow or no 

accrual at some sites, ever-increasing per patient cost, patient 

shortages and lack of data standards. The traditional clinical development program is inefficient and does not utilize most up-to-date 

technologies. Patient access is limited because only sites at major 

medical centers enroll patients typically. 

FDA has been working on these problems. We have been working 

in the clinical trial transformation initiative, which is a consortium 

we have with Duke University and multiple other stakeholders. We 

have been working on data standards. And we have been working 

very intensively with groups that are doing new trials, such as the 

I–Spy trial which is an adaptive trial that is being done in breast 

cancer, and a new master protocol for lung cancer. And both of 

these trials are innovative because they study multiple different 

drugs in the same trial, and thus enable a lot of savings of setting 

up one trial after another for each investigational drug, and I am 

happy to discuss any of this with you. 

Also we have been talking about the use of telemedicine to better 

reach patients who live outside of major medical centers. 

Now, a second issue and challenge relates to modernizing drug 

manufacturing. The United States is no longer the world leader in 

drug manufacturing, like many other manufacturing sectors that 

we have lost. We rely on foreign sources around the world for drugs 

critical to the health of U.S. citizens. The trend of moving drug 

manufacturing offshore is continuing. However, we now may have 

a chance to reverse this trend. 

Modern manufacturing methods that have only recently become 

technically feasible allow for continuous manufacturing from drug 

synthesis to the final drug form such as tablets or capsules. So you 

put in the raw chemicals at one end and you can get out pills at 

the other end. Such manufacturing requires much smaller but 

high-tech facilities staffed by a highly-educated workforce. There is 

also a trend toward using disposable manufacturing for the biologics, which again provides much savings. Environmental burdens 

for both of these are greatly diminished, and this was one of the 

barriers to continuing to building pharmaceutical plants in the 

United States. 

I believe the U.S. Should do whatever is needed to incentivize 

this type of manufacturing sector growth in the United States, both 

because we need better security of our drug supply, and because it 

would provide a manufacturing sector that would be very valuable. 

44 

The FDA has been encouraging and collaborating on this for about 

a decade, but I think there is now a unique opportunity. 

So there are multiple areas in which drug development continues 

to be a big challenge in also manufacturing and maintaining the 

drug supply, and I would be happy to discuss all of this with the 

committee. 

[Prepared statement of Dr. Woodcock follows:] 

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Mr. LANKFORD. Thank you. Let’s run through a few questions. 

We will take 5 minutes at a time and then come back and do a second round of conversation as well. 

The sequestration issue has come up multiple times in this, the 

sequestration of the user fees itself. These are paid by the companies to be able to expedite this. You and I have spoken on this before as well. What has been done at this point from FDA? Has 

there been communication with OMB to have a discussion about 

this? Because that is a user fee, and there is a lot of bipartisan 

frustration with OMB to say why has that been sequestered as 

well. That was different from the start. Tell me about the communications that is happening right now between the FDA and OMB? 

Dr. WOODCOCK. Well, I believe the administration certainly has 

communicated within itself. This was a ruling by OMB that according to how the budget was structured, that the user fees would be 

subject to sequestration, and that was done at the time the original 

sequestration was put into effect. 

Now, I realize Members of Congress have written to OMB about 

this and there has been multiple discussions, but it seems to be 

that it is felt that some type of overt action by Congress might be 

necessary to change this situation. 

Mr. LANKFORD. Has there been communication between FDA directly to OMB to talk about that, or is there just the assumption 

that that conversation was at OMB? 

Dr. WOODCOCK. No, I am sure that OMB—I personally haven’t 

had those conversations, but I believe those conversations have 

been—OMB is quite aware of this situation. 

Mr. LANKFORD. Oh, yes. Several comments have also come up on 

the President’s recommendations—the recommendations. There are 

several of them again that have been itemized as we have gone 

through the earlier panel as well. One of them, recommendation 

number three; expand the use and practice of FDA’s existing authorities for accelerated approval and confirmatory evidence. The 

FDA should make full use of accelerated approval for all drugs 

meeting the statutory standard of addressing an unmet need for a 

serious or life-threatening disease and demonstrating an impact on 

clinical end points other than survival or irreversible morbidity, or 

on a surrogate end point likely to predict clinical benefit. 

How is that coming in the conversation? I know you all already 

looked at this as well. Where is that? 

Dr. WOODCOCK. Yes. Well, some of that was substantiated in 

FDASIA that was passed last year. So we have issued a guidance 

on our expedited programs that further defines what unmet medical need is to make a standard definition of that. We certainly 

have talked about and are working on the issue of clinical 

endpoints short of clinical benefits, but likely predict clinical benefit. And we have full intent of applying accelerated approval to 

any area of unmet medical need. And I believe our breakthrough 

drug program that also was put in FDASIA demonstrates that we 

are very interested in this. Many of those have had potential clinical benefits based on surrogates and so forth. 

Mr. LANKFORD. So the guidance is being written currently on 

that. Tell me the timeframe on this as far as when this moves from 

conversation and we are drafting to done. 

56 

Dr. WOODCOCK. The draft guidance is out for comment and we 

should issue a final guidance soon. 

Mr. LANKFORD. Soon being tomorrow? Soon being six months? 

Dr. WOODCOCK. Within months I would expect. 

Mr. LANKFORD. Okay. Great. And then this ongoing conversation 

that has happened earlier that you are extremely aware of as well, 

this balance between safety and efficacy, access from patients coming in, whether it be the compassionate use that Ms. Speier had 

mentioned before or other methods to get patients that are terminal access to drugs faster, or even the information about the 

clinical trials out. 

So let me do two different sets of questions on that. One is the 

compassionate use and getting the information to doctors about 

how to go through that process and connecting and what the steps 

would be. So that is an information part of it. And the second part 

of it is the clinicaltrials.gov site, the information there, the access 

to that, helping more patients get involved in the trial process so 

they can be in the structure which not only helps them but helps 

others as well. Where are we on those two issues? 

Dr. WOODCOCK. Well, clinicaltrials.gov is intended to—is run by 

the National Library of Medicine and is intended to, among other 

things, alert patients or caregivers to where a trial might be opening up that they might be eligible for. 

Mr. LANKFORD. Do you consider that site up-to-date and the information accurate? 

Dr. WOODCOCK. I think the site is up-to-date on the existence of 

the trials. There has been a lot of controversy about the results section of that and whether that is up-to-date. But if you are talking 

about patients being able to enter into the trials, except for Phase 

I trials were not included, so there may be some Phase I trials. But 

those are dose escalation, early safety trials. 

Mr. LANKFORD. It has all the beauty of Craigslist when you go 

there as far as the site itself and its functionality, but the access 

to some of the results and the information is part of what my consideration is. How do we make sure that people not only get good 

accurate information there, but there is the possibility of they know 

about this early enough to get involved, and that physicians have 

access to that information. They know it is very, very timely. 

Dr. WOODCOCK. Well, I think that would be a matter of more 

publicity about the site through various patient groups, through 

other professional organizations that treat those given diseases, so 

that the information is disseminated out in that manner. 

Mr. LANKFORD. Does FDA have a good relationship with those 

patient advocacy groups? Is there an ongoing communication there? 

Dr. WOODCOCK. I have recently set up in the Center for Drugs 

a new group office for patient advocacy relations and professional 

relations, so we plan to be building that capacity within the Center 

For Drugs. 

Mr. LANKFORD. Okay. That would be very helpful, not only to patients, but also to physicians as well. 

Dr. WOODCOCK. Agreed. 

Mr. LANKFORD. And I want more information on that. I am going 

to try to honor time on this and recognize Ms. Speier. 

Ms. SPEIER. Mr. Chairman, thank you. 

57 

Dr. Woodcock, thank you for your decades and decades of service 

to our country and to the health of our country. 

Mr. Huber had mentioned in his testimony that the FDA clinical 

trials process is not suitable for new biologic and molecular medicines, and it essentially results in economically incurable diseases. 

How is the FDA responding to these new medical technologies? 

Dr. WOODCOCK. Well, I had a conversation with Mr. Huber. I 

don’t agree with his analysis. We have been in the forefront of 

pushing molecular medicine since 2000. FDA, I can offer this for 

the record, recently put out a booklet on all the things we are doing 

on personalized medicine. But for example, I think in 2003 I accepted the first award from the Personalized Medicine Coalition 

really on behalf of the center for our work, the first award they had 

ever given, for our work in driving personalized medicine along. 

And why would we do that? Because personalized medicine allows—because you try to eliminate people who don’t respond, you 

increase the size of the treatment effect so that you actually see 

how well a drug works in people and has a chance in working. 

Then on the safety side, you can eliminate people in advance who 

are at risk so the drugs can become safer by screening out people 

who are at high risk of side effects. 

So from our point of view, and I think from the patient’s point 

of view, personalized medicine can only be a positive. We have, in 

fact, been criticized by some in the community for pushing it too 

hard. So I believe we really—and I believe it is paying off now. It 

is paying off with the targeted therapies. A lot of the breakthrough 

drugs are targeted therapies, and I think that we are going to see 

increasingly targeted medicines over the next decade. 

Ms. SPEIER. I appreciate that clarification. Now, Mr. Gottlieb also 

stated that he saw one of the greatest challenges for the FDA in 

terms of innovation was the culture, and he believed that there is 

significant influence exerted by outside groups upon the FDA clinical group. I would like to give you the opportunity to respond to 

that. 

Dr. WOODCOCK. Well, I certainly read Dr. Gottlieb’s testimony. I 

have had conversations with him about this. And, of course, FDA 

has considerable flexibility in applying the safety and efficacy 

standards, and we basically use a sliding scale. So for a headache, 

a drug has to be pretty safe because no one wants to risk their life 

to cure their headache, right? On the other hand, for serious and 

life threatening diseases where there isn’t any alternative, there is 

a lot of tolerance of risk, and there is also greater tolerance of uncertainty about the effects, which is what Dr. Gottlieb was talking 

about. And as I understand his comment, it is very similar to what 

you said, which is that a lot of the criticisms over the years about 

drug safety issues have, in his mind, led to conservatism, even in 

the area where a lot of flexibility is indicated. 

Ms. SPEIER. So give us some good news, because I think there 

is some good news coming out of FDA, and particularly your area. 

So tell us from your perspective some of the good news. 

Dr. WOODCOCK. Well, I think from my point of view the good 

news is that the industry, we are really seeing, I think, a renaissance in the industry. We are approving a lot of drugs now that 

58 

are first in class or that are treating untreatable diseases, or that 

are advances in therapy and they are treating bad diseases better. 

The breakthrough program that was put in place by Congress 

last year, we have had over 100, I believe, requests and we have 

granted 34. And those designations that we give are where we 

think the drug is really a game changer in that disease, and if we 

grant that designation, we offer to really do a full court press on 

that drug and do everything we can to get it developed basically 

in the most, I call it parsimonious manner possible. In other words, 

what is the shortest path between where the drug is now, what we 

know about it, and what we need to know to get it on the market 

in the hands of doctors and patients. And I think there is a lot of 

enthusiasm, both internally and externally, about this breakthrough drug program and the promise of these drugs. 

Ms. SPEIER. Okay. Let’s talk about manufacturing for a moment. 

It is pretty stunning, and I think if the American people knew that 

40 percent of the drugs that we take are manufactured outside of 

the country, and 80 percent of the ingredients are manufactured 

outside of the country, they would be pretty appalled because there 

is just consternation about the supervision and oversight that goes 

on overseas. 

So tell us, and to your point, when there are shortages and there 

are tsunamis and there are other conditions that prevent us from 

accessing the drugs that our population needs, we are really left 

with a very difficult position to be in. So, how do we create more 

opportunities for manufacturing, or what is it going to take? 

I mean, I am thrilled that Apple computer has decided to bring 

jobs back to America. I might actually buy more Apple products 

now. But that was a ways in coming, and part of it is because we 

are now seeing transportation costs are more expensive. There are 

lots of reason why on the bottom line they are doing that. How can 

we create incentives for manufacturers to be manufacturing in the 

United States? 

Dr. WOODCOCK. Well, that is a very good question, and because 

I am not an economist, I am not like probably the best person to 

consult. What I am going to say is that FDA is trying to provide 

encouragement for advanced manufacturing, wherever it might be, 

because it is going to be safer, it is going to be reliable, it is going 

to enable personalized medicine because it is going to be much 

more agile than the kind of manufacturing that we have right now. 

But I do believe that it should be considered—incentives should 

be considered and States should consider this as perhaps an industry they would want to put in place incentives to bring back into 

the State, because I believe this will be a viable sector for a very 

long time, making drugs. 

But the technology, I am here to say that the technology has 

reached a point where this is reality; where we can see these 

plants can be built, they can decrease our vulnerability in the 

sense that we are relying on foreign sites of supply that may have 

many different things that might happen that mean a drug might 

become unavailable in the United States, and yet it is also a very 

good, I think, source of jobs. 

Ms. SPEIER. Thank you. My time has expired. 

Mr. LANKFORD. Mr. Meehan. 

59 

Mr. MEEHAN. Thank you, Mr. Chairman. 

Dr. Woodcock, I want to thank you too for your long distinguished career working in this area, and congratulations for your 

recognition. It is nice to receive an award. That is one of the few 

benefits of public service, that you don’t get the compensation 

sometimes in other ways. 

But I want to step off of the questioning that my good friend and 

colleague from California was asking you because you made a comment about the industry now expanding in Europe and other places 

and not here. But why do you think that is? 

Dr. WOODCOCK. My understanding is it is primarily they are setting up plants in India, China and many other parts of the developing world. And I don’t know, as I said, I am not an economic expert, but the analyses that have been published about this say that 

it is the environmental regulations, certain tax advantages, a lower 

cost labor force and the usual kind of factors that we see with manufacturing moving offshore from here. 

However, the new manufacturing methods require a high-tech 

labor force. They will have low environmental impact. It will be 

much diminished, all right? And it will require not a very large 

footprint of size of a factory to operate. So it is more like the kind 

of innovative high-tech industries that we really do see coming 

back to the United States or we would like to retain in the U.S. 

Mr. MEEHAN. What do we do? I mean, I accept the analysis. I 

don’t have a better analysis of it, and I suspect and do believe that 

it includes all among those, including tax policies and other things. 

But I do hear as well the time that it takes from somebody who 

has effectively a start-up concept to have it moved through Europe 

and approved and put into, you know—the chain of treatment, soto-speak, is much shorter than what we deal with in the United 

States. And you talked about time and cost being an expanded aspect of FDA, or at least the process here which FDA participates 

in here. And since we can hopefully deal with those other issues 

as well at some point in time, tax policy and those sorts of things, 

what can we do to do a better job of enabling the FDA to be timely 

in their response, or are you doing it correct? I am moved by your 

point that only 10 percent of the drugs actually get approved, that 

there are good reasons why it is appropriate to make sure we don’t 

put bad products out. But what is the difference between what Europe is doing and here? Why can they do it faster than we can? 

Dr. WOODCOCK. Which part do you say they are doing faster? 

Mr. MEEHAN. Well, it is my understanding, and maybe correct 

me if I am wrong, that there is an ability to take a start-up idea 

and move it through the clinical trials and get it to a point where 

it can be approved and put into commerce quicker than is done 

here, and that that is one of the driving forces, is the tremendous 

cost associated and the time delay. That if you can manufacture— 

get the drug approved and begin to manufacture and get it in, once 

it starts to work, it will find its way back here to the United States. 

But we have lost jobs and the other kinds of things that are associated with the development of the industry. 

Dr. WOODCOCK. Well, we keep figures on what we call the new 

molecular entities, the novel drugs, right, and where they are approved first in the world. And consistently over the past, at least 

60 

5 years, we have led the world in approvals of first on the market 

and we are above Europe. We are not in any competition with Europe, but we are about 50, 60 percent compared to all other markets, and then each sector, Japan, Europe, has a smaller percentage up to 100 percent. Last year I think we were at 60 percent of 

all new molecular entities. I can get you that figure. So I am not 

sure. That used to be, before the user fee program PDUFA, FDA 

approved drugs much later than in Europe. But that hasn’t been 

true for some time. 

Now, as far as manufacturing, we have more or less the same 

manufacturing regulations as the Europeans. So if a plant can be 

got up quicker in Europe, it would do with other permitting and, 

you know, other regulations related probably. But generally the 

manufacturing is going to India, China, other places, Brazil. 

Mr. MEEHAN. Okay. My time has expired, Mr. Chairman. I look 

forward to a round of follow-up questions. 

Mr. LANKFORD. And we will. And, Dr. Woodcock, if you don’t 

mind, we are just going to open the microphones and just have an 

ongoing conversation, so there may be multiple of us instead of a 

structured time period. That has been our habit I would say here 

once we get into the second round. So we will start throwing questions at you back and forth. 

You had mentioned first about the approval process faster here 

for some of the types—faster than Europe or Japan, and that has 

changed over the last several years. Is that still true for all types 

or are there certain types where Europe and Japan are still approving drugs faster than we are? 

Dr. WOODCOCK. Well, since I am under oath, my impression is 

that we—because of the user fee program we have deadlines. We 

approve most of the drugs on the first cycle, all right? So it is submitted in. The companies have really figured out what they need 

to give to us to get an approval and we have timelines for when. 

And I think my impression is for all the types of new drug applications, we are ahead of other countries. 

Mr. LANKFORD. Okay. Your ideas to bring down the cost, as I 

walked through the several issues of this particular hearing and 

got a chance to explore where FDA is moving on this and what is 

happening, the cost of drugs is significant, and every one of those 

companies say it is because of the cost of actually the trials process 

and everything else. So your idea is that you have seen to bring 

down the cost of that. I also want to ask you several other questions. But can we spend a little time on that? 

Dr. WOODCOCK. Certainly. To bring down the costs, we have been 

working on this for at least a decade, and recently, my idea of having these standing trials where many drugs could be tested in the 

same trial and you just keep running them through instead of setting up a new trial for every drug, which is extremely expensive 

and time-consuming. And the goal then would be to reach out to 

the community and enroll patients all through the United States, 

not limit it to major medical centers, so more patients have the opportunity. It decreases the time taken to recruit patients. 

Mr. LANKFORD. Who has done that at this point? How many have 

done that? Is that a pilot issue that you are working with or how 

would companies know they can try that? 

61 

Dr. WOODCOCK. It has to be done by consortia, and the I–Spy 

trial, the I–Spy 2 trial was the pioneer in this, okay. 

Ms. SPEIER. Where was that done? 

Dr. WOODCOCK. It was led out of UCSF through the foundation 

for NIH as a consortium, all right. So many companies, the FDA, 

NIH, everybody would be a part of that, set up that trial. It is a 

screening trial, and they screen breast cancer drugs with a biomarker to the point about personalized medicine. So they take high 

risk breast cancer patients and they are trying to improve the 

treatment so they can screen many drugs, and I won’t go into how 

that is designed. 

And then another one is now being set up by the National Cancer Institute, the FNIH, and FDA is participating in this, for lung 

cancer, where many patients can be recruited and they already 

have five drugs, and all investigational drugs, that they will be 

testing using biomarkers in that trial. So those are prototypes. But 

it is not widely adopted yet. 

Mr. LANKFORD. But that is obviously in an area where you are 

having a lot of patients and a lot of opportunity. You mentioned 

breast cancer. Lung cancer. Unfortunately, we have a lot of people 

in that. What can be done in some of the other drug processes 

where we don’t have as many people? 

Dr. WOODCOCK. Well, in rare diseases, I think certain groups like 

the Cystic Fibrosis Foundation have led the way. We recently approved a drug for cystic fibrosis, and that is a rare disease to start 

with, but it only treats 7 percent of those patients. But that Cystic 

Fibrosis Foundation already had the patients genotyped so we were 

able to identify—the company who was developing the drug was 

able to identify which patients that drug might work in and rapidly 

test them. So that drug is approved and on the market for cystic 

fibrosis. 

Mr. LANKFORD. So what kind of time period and cost did that 

change for that? That went from 12 years, 10 years I would assume 

is a typical process? 

Dr. WOODCOCK. Yes. I think it was remarkably shortened, but I 

can’t tell you how short that was. They did randomized trial, because this is a very novel approach, and they were able to show in 

a 48-week trial that they really improved markers for cystic fibrosis, lung function, and the children gained weight. 

So another idea that we have also is we have been discussing, 

and I know you all have been discussing with the community is a 

way to speed the introduction of antibiotics for drug resistant organisms. And that is a different idea that has been discussed, which 

is putting some kind of mark or logo or having Congress speak to 

a special mechanism that we would have a very limited drug development program, get those drugs into the hands of doctors, who are 

serious drug resistant organism infections, and have some kind of 

notation or mark on those drugs so that the doctors knew they had 

been developed by a very limited program and that good antibiotic 

stewardship should be used with them. 

Mr. LANKFORD. Okay. Only antibiotics in that program, though. 

Dr. WOODCOCK. It’s been discussed wider, and I think that’s a 

matter for ongoing discussion. But that would be one way to do it. 

Because the need is very great. The CDC said, I think, last year, 

62 

I believe, they said 23,000 people died from infections with drug resistant organisms, and we are behind that epidemic. As you have 

said, it takes a while to develop a drug, even if we shorten the 

time, and so we don’t have time, you know, anymore. We’re running out of time to get a handle on this epidemic. 

Mr. LANKFORD. Okay. So clarify that for me because you said 

‘‘we’re working on’’ several times there. Is this a process that is set, 

that you’ve done guidelines for, that’s done, or again, what is the 

timeframe on this? Is this done tomorrow? Is this done 6 months, 

6 years from now? 

Dr. WOODCOCK. What we’ve been discussing is that Congress 

would speak on this and tell us to establish a program. 

Mr. LANKFORD. You do not have the statutory authority to do 

that right now you feel? 

Dr. WOODCOCK. It would require regulations. 

Mr. LANKFORD. But if we did statute, you would have to promulgate regulations off that statute as well. 

Dr. WOODCOCK. I’m not a lawyer. Being under oath, I want to 

give you an exact answer. But I think we could probably do it with 

the statute. We might have to do guidance to help companies figure 

out how to do the programs, but I believe that we could probably 

implement something if we’re directed to in a statute directly. 

Mr. LANKFORD. Okay. I’ll just make sure. 

Congresswoman Speier. 

Ms. SPEIER. Dr. Woodcock, the experience that Gilead just had 

where it had their hepatitis C drug approved with the recommendation by FDA to do additional trials, I believe, with a different cohort, maybe you could just explain. Because it was unusual but it showed flexibility within FDA, and Gilead was thrilled 

with the opportunity to kind of move that process quickly. 

Dr. WOODCOCK. Uh-huh. 

Ms. SPEIER. And I think it would be good for all of us to understand it. 

Dr. WOODCOCK. I would have to get back to you on that because 

I don’t know the details of it, but I will say that you asked for good 

news, I think the new generation of drugs for hepatitis that we are 

going to see is really good news because we have a lot of patients 

in this country who develop liver failure from hepatitis or develop 

liver cancer, and we believe the new generation of drugs may well 

be curative of hepatitis C, and that’s really big news. 

Ms. SPEIER. And it’s big news on a lot of levels because they become disability insurance recipients and Medicaid recipients and 

Medicare recipients, and that is a very costly procedure that they 

then go through in terms of dialysis and the like. So that’s good. 

Let me ask you this. You said that only 10 percent of the drugs 

that are considered actually get approved because there’s a failure 

in Phase III. Can you explain that to us? Is there some way we can 

find that out sooner so there’s not as much money invested by the 

drug companies? 

Dr. WOODCOCK. That’s the $64,000 question. All right. What happens is there’s attrition all the way through the drug development 

process. The attrition, before you get into people, so you do animal 

studies or something and you find toxicity, that’s not that expensive. But once you start doing trials, losing a drug somewhere durVerDate Aug 31 2005 08:29 May 01, 2014 Jkt 000000 PO 00000 Frm 00066 Fmt 6633 Sfmt 6633 C:\DOCS\87645.TXT APRIL
63 

ing the clinical development program is very expensive, and the 

longer you go and study the drug, the more sunk costs you have 

in that drug. 

And so in Phase I there is attrition often for toxicity. In Phase 

II there may be attrition because a drug doesn’t work. But remarkably, in Phase III, at least several years ago, the last time this was 

studied, there’s about 50 percent of attrition is in Phase III when 

you’ve spent a huge amount, maybe, you know, upwards of a billion 

dollars on developing the drug, and you find out it doesn’t work. 

Some of the drugs in Phase III don’t have any effect compared to 

placebo. 

Ms. SPEIER. But is that because for the first time they are being 

used or human beings? They are being used on human beings in 

Phase II, are they not? 

Dr. WOODCOCK. Uh-huh. 

Ms. SPEIER. So what is happening? 

Dr. WOODCOCK. It’s hard. For some diseases you can’t tell in 

Phase II. All you’re doing in Phase II is trying to get the dose right, 

maybe using a biomarker to try and figure out, you know, are you 

affecting the disease? But the disease may be a longer-term disease 

or it may take a while, and so you have to do a Phase III trial to 

see whether or not it actually works or not, and then you’re very 

sadly disappointed. 

For example, we just had a couple trials in Alzheimer’s disease, 

you know, that did not affect Alzheimer’s disease, and that is a bitter disappointment because we need treatments for Alzheimer’s 

disease, but it’s hard to tell in earlier trials whether or not you’re 

affecting dementia. 

Mr. LANKFORD. I’m jumping on this as well. 

Ms. SPEIER. Sure. 

Mr. LANKFORD. Going back to a statement, Doctor, that Mr. 

Huber made earlier where he talked about the drug that was set 

up for kidneys and they were using it for bladders and it was not 

successful on anyone but one, and it was flawless on that one. 

Dr. WOODCOCK. Uh-huh. 

Mr. LANKFORD. Is that the type of thing that we’re finding or 

we’re finding it’s effective on some so we’re looking for the molecular markers for that group and why you had, you know, 500 people in the study and it worked great on 12 and not on the rest, and 

so now you’re studying it, or you’re blanket saying this doesn’t 

work for everyone? 

Dr. WOODCOCK. It really varies by the disease. In Alzheimer’s we 

have don’t really have any good molecular markers yet. That’s 

what those biomarkers are working on. So those studies are what 

you call empirical. In other words, they are trial and error. And 

that’s a lot of the problem with drug development, it’s still trial and 

error. 

But in cancer, because we did the war on cancer that you all 

funded, and we have a tremendous amount of information about 

what makes that cancer a cancer. And as Mr. Huber was saying, 

it’s molecular changes, genetic changes in the tumor that do that, 

and some of them are driving the cancerous behavior. And if we 

can target that and turn it off, then the cancer subsides to some 

extent. And so that’s a new way of developing a drug where you 

64 

actually understand the mechanism and you can target that mechanism. 

And so, in cancer, we used to talk about breast cancer and colon 

cancer, but now we really talk about what is the driver, what mutation is driving that tumorous behavior and how can we turn that 

off. So that’s been a revolution, and I think that’s going to get better and better, but we need to focus on curing cancer. 

Mr. LANKFORD. Right. No, the point I’m trying to drive at, 

though, is in a large-scale study, it’s a Phase III, you have a lot 

of people that are involved in it. What do you do if you have a 

small group in there that it is successful for, that it is effective, but 

statistically, across the size of the group, it’s not? Is that something 

the drug company goes back and goes back to the drawing board 

and tries to determine that, or is it something FDA is involved in? 

What happens? 

Dr. WOODCOCK. Usually companies will submit subgroup analyses and they would give them a hypothesis, well, maybe it works 

in this group, okay, we don’t know why, but maybe it works in this 

group. And they would have to do more trials. Why? Okay, well, 

in a famous example, Richard Peto, who’s a statistician in the UK, 

did a subset analysis of a trial, and he showed that people with the 

astrological sign Virgo, okay, did much better than all the other 

people. And, you know, people say we should approve the drug 

based on these subset analyses, but the actual fact is you can do 

many of them and there’s always going to be one that the drug appears to work, and we see this all the time. That doesn’t necessarily mean it actually does work, just like the astrological sign 

Virgo is not a predictor of better cardiovascular outcomes. 

So, yes, if there is a convincing molecular marker, though, okay, 

that’s a hard scientific thing, not some kind of fishing expedition, 

then we might have a different approach. 

Ms. SPEIER. Could we talk about your staffing. Is all of your 

staffing—I should know this and don’t—subject to user fees or is 

there a percentage that is not subject to user fees? 

Dr. WOODCOCK. We have S&E funding that is subject to sequestration. We have PDUFA funding, and we have GDUFA, the generic drug user fee program has just set up funding, and funding 

for biosimilars drug user fee. The S&E is maybe about 30 percent 

of our funding. 

Ms. SPEIER. S&E is? 

Dr. WOODCOCK. The appropriated taxpayer’s dollars. 

Ms. SPEIER. It’s about 30 percent. 

Dr. WOODCOCK. Uh-huh. 

Ms. SPEIER. So what has that meant in terms of sequestration. 

I mean, how many jobs are no longer being—— 

Dr. WOODCOCK. I wish I could remember these figures, but it’s 

been a pretty significant hit that we’ve taken. Now, we’re able to 

hire under GDUFA anyway, but what you’ve been talking about 

here about the interaction of companies, innovator companies with 

the review divisions, has been hampered because those review divisions did not get the hires they expected under the new PDUFA 

program because of the sequester. 

Mr. LANKFORD. The generic group, you’re still able to hire. That 

money was not sequestered? 

65 

Dr. WOODCOCK. I’m very confused about this. I know that we had 

so many hires that we had to make, that we certainly are able to 

hire under GDUFA. I don’t understand. We could get back to you 

on the impact of the sequester. 

Mr. LANKFORD. Yeah, the question is whether user fees sequestered for the generic are not sequestered for the generic, do you 

know? You’ve made some hires there. I just didn’t know if that’s 

a function of the user fees. 

Dr. WOODCOCK. I think the answer is yes and no. I think the 

first year weren’t maybe because it was a new program. That’s why 

I’m confused. 

Mr. LANKFORD. Okay. 

Dr. WOODCOCK. And then it will be, but we can—— 

Mr. LANKFORD. Can we follow up on that? Because obviously it 

has been this ongoing conversation should the user fees have been 

sequestered at all. Okay. 

Dr. WOODCOCK. Yeah, okay. Uh-huh. 

Mr. LANKFORD. Pat, did you have anything you wanted to add? 

Jump in any time. 

Mr. MEEHAN. Well, I don’t want to jump in while you’re on a roll. 

And I kind of laughed to myself when you were hesitant to answer 

the question because you said, I’m not a lawyer. I was just with 

a guy who said, he saw the high priced lawyer and he asked him, 

he said, I’ve got two quick questions. If I give you a thousand dollars, can I ask you? And the guy said, absolutely, what’s your second question? So a bit of levity to help us. As a recovering lawyer, 

I have to take chances. 

The sort of the dialogue I exchanged with Dr. Gottlieb, among 

others, was not just anecdotal, dealing with the concerns about the 

timeliness of responsiveness, and you didn’t really have a chance 

to talk to it. 

Dr. WOODCOCK. Uh-huh. 

Mr. MEEHAN. And I think it has sometimes to do with the ease 

with which it is just to ask one more question and send it back. 

What can be done to assure that those who are managing their 

portfolios, particularly in light of the fact that PDUFA, MDUFA, 

have been put in place to ameliorate just this issue, that we are 

getting timely and responsive communication? And maybe it is just 

as, you know, Mr. Hastings identified, better communication all 

along. But I’m talking from knowledge of specifics where there 

would be communication, and in effect, send me what you have, 28 

days, no response, 29th day, the whole new raft of questions. So 

how as an agency can you oversee to assure that those who are 

managing their portfolios are doing it effectively? 

Dr. WOODCOCK. Well, it is a complicated question. These interactions are governed by agreements that are made under PDUFA, 

many of them, all right, and we track something like 25,000 transactions, right, every year. Don’t quote me on this. Something like 

that, or I can’t give you the exact number, right, but it is a very 

large number of transactions that occur, because we track not only 

all the filings for the marketing applications, but we have type A, 

B, and C meetings, we track how timely the meeting minutes are 

to get back on these meetings, how timely scheduling of the meetVerDate Aug 31 2005 08:29 May 01, 2014 Jkt 000000 PO 00000 Frm 00069 Fmt 6633 Sfmt 6633 C:\DOCS\87645.TXT APRIL
66 

ings are, et cetera, et cetera. So it’s very micromanaged, but again, 

that’s the process. It’s not the content. 

And I will say, in my opinion, if you pay too much attention to 

process, you often give short shrift to content, and to me that 

seems to underlie your question, too. 

Mr. MEEHAN. It did. I mean, I think that was the example, that 

once they got somebody else to step in and took the time to evaluate it, they realized the information was there and it was sufficiently explained. 

But I just appreciate the process, but I do think it’s this balance 

of when people feel comfortable to make decisions. And I do adopt 

my colleagues’ concerns that obviously people have come and been 

lambasted for having made the wrong decision, and it creates an 

environment in which people say, well, no decision is easier on me, 

so they don’t do it. How do we have to work together to assure that 

that happens? 

I just have a couple of follow-up questions. The President’s Council on Science and Technology put together their innovation package, and they had eight recommendations. I’m looking forward to 

going into greater detail into that. But you’ve been through it. 

What do you think, what stood out with you, to you, in that report, 

and what do you think we can work with you on to help do a better 

job of getting, you know, more effective cures to the market? 

Dr. WOODCOCK. Well, I think some of the things that Congress 

has already sort of instantiated in FDASIA around accelerated approval already alluded to have been helpful in having us pay more 

attention to our expedited programs. The other thing that struck 

me about the proposals in the PCAST report called for more 

translational science, because it’s hard for us to make decisions, 

you know, if the science isn’t there. 

Mr. MEEHAN. What do you mean by translational science? 

Dr. WOODCOCK. Well, you know, there’s basic science you can 

say, well, this pathway inside of a cell does this and that and the 

other thing, and then there is translational science which said this 

biomarker really is predictive of a good outcome. The more data a 

company or we have on that, the more confident everyone feels that 

we can, you know, put our money down on that, right. But if we 

have no data or say the rare diseases you’re talk about, we don’t 

have any data on the natural history of the rare disease, what people do is get a bunch of experts together and say, in my opinion, 

the disease progresses in this manner. 

Now, that’s been a problem not just for us, for the companies, because it turns out the disease does not progress in that manner 

and therefore their study they designed, you know, didn’t work. It 

wasn’t long enough, or, you know, it didn’t measure the right 

things or whatever. And so that’s translational science, is the 

science that supports actually studying the drug in people and actually enables you to study the drug effectively and quickly. 

So PCAST called for formation of a consortium where everyone 

would work together to enable this translational science and move 

it along, and I think that would be very helpful. I also think this 

other mechanism I already talked about for antibiotics would also 

be helpful in dealing with some part of that epidemic. 

67 

Mr. LANKFORD. Can now jump in as well? Help me understand 

again why you think you need a statute for the antibiotics in the 

new process, why you don’t feel like you already have statutory authority to do that, based on so many other areas, with the breakthrough, with the accelerated process, with all those things that 

are already in place, why do you need another statute for that? 

Dr. WOODCOCK. I think we have statutory authority or we could 

claim we did and do a regulation. That would take many years, in 

my experience nowadays. 

Mr. LANKFORD. Have you noticed how long it takes to get a bill 

through Congress? 

Dr. WOODCOCK. Well, I just have great faith in you. 

Mr. LANKFORD. That makes one. 

My concern is, as deadlocked as we are in so many different 

areas, my preference, and I’m not going to speak for all of us, 

would be you get started on what you feel like you have statutory 

authority for now and so we can have something in process. 

Dr. WOODCOCK. Right. 

Mr. LANKFORD. We have a responsibility to get our stuff done as 

well, but that has not gone as smoothly as it should and that we 

are capable of, obviously. And I would hate for FDA to sit back for 

2 or 3 years and wait on us to get something done, and then once 

it’s done, you have to promulgate rules based on that, and then 

we’re even farther behind. 

Dr. WOODCOCK. We had a public meeting on this, which is often 

a prelude to rulemaking. We have certainly been in discussions 

with companies that are interested in utilizing this pathway. 

Mr. LANKFORD. Okay. I do not want you to try to feel like I’m 

saying to you, though, leave statutory authority. If you do not have 

statutory authority, obviously don’t go outside of statutory authority. But if you have it and you feel like you already have it, validate it, and I would encourage you to get moving on it. 

Dr. WOODCOCK. Uh-huh. 

Mr. LANKFORD. So, again, I’m not going to try and speak for all 

of us, but while we do have a responsibility, things have bogged 

down significantly here. Fairly obvious, I think. 

Ms. SPEIER. I have a question. There was a period of time in the 

not-so-distant past when a number of companies had come to me 

with questions about their approval when they had two drugs that 

had been previously approved by the FDA. They were combining 

them for obesity and were having either a difficult time getting it 

approved or actually getting it denied, even though both of those 

drugs independently had already been approved by FDA. 

Can you talk about that on the one hand, and also about where 

we are in terms of obesity drugs? Because we all know this is a 

huge issue in terms of American health. 

Dr. WOODCOCK. Certainly. Well, when you—— 

Ms. SPEIER. And I need a quick fix. 

Dr. WOODCOCK. We’ve had a lot of obesity drugs have to be 

pulled off the market for safety problems, and primarily they were 

cardiovascular safety problems. And so, I think the FDA is trying 

to exercise caution on new obesity drugs but recognize this is another epidemic that we’re facing that needs some kind of new 

thinking as far as how to deal with it. 

68 

The sliding scale I talked to you about before. So if you have a 

drug that’s indicated for seizures, say, that drug’s benefit risk will 

be looked at in the light of what is epilepsy, what are the available 

treatments, who might use it, how much risk would they be willing 

to take, okay, to control their seizures. If you move a seizure drug 

or a drug for heart failure or something over to obesity, you say 

to yourself 30 percent of all adult Americans have obesity. How 

much risk of uncertainty of, say, heart attacks or strokes are we 

willing to take in that population—all right, that’s just an example—versus where you’re treating epilepsy where the people are 

facing risks if they continue to have seizures, right. And that’s the 

conundrum that we’re in. These drugs that we would approve for 

obesity, millions of Americans might be exposed to them, and they 

need to be relatively safe, unless, again, we were able to restrict 

them to the very people suffering from the most severe types of 

obesity. But that would be unlikely given the prevalence of the condition in the United States. 

In fact, we initially talked about this limited use scenario that 

we’re talking about for antibiotics also for obesity because the benefit risk for somebody who is severely obese is different than someone with mild obesity, or somebody who is severely obese and has 

a lot of morbidities from it. Heart disease. They have severe arthritis, mobility problems, and so forth. 

So the problem with, I think, obesity drugs is that eating is such 

a basic human instinct and function, any drug that’s going to significantly interfere with that is going to have powerful effects and 

may have effects in multiple domains, and we need a lot of creativity in that area to move forward. 

Mr. LANKFORD. We get into the issue of FDA making decisions 

for doctors and the labeling issues and the warnings and that kind 

of such, and I know that’s a constant struggle for you because 

you’re testing for a certain thing and you haven’t tested for other 

things. You put that into the market and physicians may use it off 

label. 

Dr. WOODCOCK. Uh-huh. 

Mr. LANKFORD. How is that moving within FDA? And quite 

frankly, with your opinion, in the culture of FDA? Do you feel like 

you’re clamping down on labeling and adding more because there’s 

this barrier between do you restrict more or do you give more information to doctors and just overload them with information and say, 

read it, make the decision, because you’re going to go off label anyway, or is it stronger off label, don’t use it, restrict it, from FDA’s 

perspective? 

Dr. WOODCOCK. Well, generally speaking, and I think this isn’t 

well understood, but FDA accepts the fact that off label use can be 

appropriate, and that’s a part of the practice of medicine for most 

drugs, okay. 

There are drugs that we have special restrictions that are called 

REMS, and these were put in as part of the FDAAA legislation 6 

years ago, I believe, and we had them before through regulation 

where you’d restrict distribution of a drug, and sometimes you have 

to say we’re only using it for this. 

And a premier example is, like, the drug Accutane is for severe 

acne. It’s a very effective drug, and severe acne can be a really bad 

69 

condition, but it was widely used for all kind of acne because it 

works, right. But it’s a major human teratogen, and so it causes 

major birth defects if used in a pregnant woman. And we were getting reports every year of use in pregnant women every year, every 

year, even women who were started on the drug and never had a 

pregnancy test. 

So we, you know, put gradually more and more restrictions, and 

now that drug is highly restricted in that you have to get pregnancy tests before or not be of childbearing potential to get 

Accutane if you’re a woman. And we hate to do that because that 

really burdens the healthcare system. On the other hand, we have 

some of these very dire side effects that the healthcare system has 

not shown itself to be capable of managing without further intervention. 

So you’re right, we walk a narrow line there. We don’t want to 

overly restrict, but sometimes the side effects are so dire, and it 

might be that the drug might not be available unless he had that 

restricted program in place. 

Ms. SPEIER. Can we speak about pediatric cancer for a moment? 

Within the NIH budget less than 4 percent of the funding goes to 

the research around pediatric cancer, and there’s a lot of off label 

use of drugs for pediatric cancer. So can you just give us a sense 

of where FDA is in terms of evaluating drugs for paeds, as they 

refer to them. 

Dr. WOODCOCK. Well, we’ve had a strong pediatric program because the Best Pharmaceuticals for Children Act, BPCA, and so 

there has been quite a response by the pharmaceutical industry to 

those programs. And, you know, they get extra exclusivity if they 

fulfill certain requirements. We just celebrated 500 drug labels that 

have been updated with pediatric information. 

Now, that said, though, pediatric cancer is different, and why? 

Because the cancer arising in a child is usually not the same as 

the adult condition. And these pediatric programs were set up to 

study conditions that occur in adults and then study them lower 

and lower ages and then get that information. But it stands to reason that the kind of mutation that would occur in a child, you 

know, when they are just born or when they’re young, is different 

than the kind of mutations that occur over a lifetime in a cell type 

and cause cancer. So that progression that we see in other diseases 

hasn’t happened as much in the pediatric diseases, and I believe 

the pediatric cancer community is concerned about this. 

We’ve tried to encourage companies to study right away drugs in 

childhood cancers if they seem appropriate. Often you’d study a disease in adults first and then study children, but in fact, when you 

have a life-threatening disease like cancer it’s appropriate to study 

the children right away also. But the question is, what is the right 

drug for that cancer in children? 

I personally believe that the genomic revolution that we were 

talking about earlier where we begin to understand the sequences, 

the driving mutations in the cancers is really going to help us, but 

we also are finding some of the pediatric cancers are actually multiple diseases put together, just like an adult cancer is. 

70 

So we have a pediatric oncologist, a very senior pediatric 

oncologist on staff at the Center for Drugs, and we are really trying 

to encourage development in this area. 

Mr. LANKFORD. Mr. Meehan, you had a question? 

Mr. MEEHAN. Just a final question, and maybe it’s not fair to 

even ask it, and if you don’t want to respond don’t. But thinking 

outside the box, I mean, you labor in the vineyard, and there must 

be times where you sit and think, you know, if we built the mousetrap a little different way, maybe we could have success. And I’m 

asking the question sort of guided by the fact that you’re hearing 

some of these wealthy industrialists or others who are saying that 

with their life’s savings now they want to be the person, for instance, that cures Alzheimer’s, and they’re going to put everything 

into this effort. And I don’t know whether that is the kind of thing 

that we ought to be encouraging, where we say, let’s just cure Alzheimer’s, let’s create this Center for Excellence that does it, let’s 

keep it here in the United States so they don’t send it overseas to 

do it, which they’re referring to. Does that make sense or are we 

better off doing what we’re doing trying to not choose winners and 

losers? 

Dr. WOODCOCK. That’s a really profound question, I think. I 

mean, I really can’t give advice to Congress. I believe that patient 

advocacy groups in many diseases have made tremendous strides 

in advancing the treatments and cures for their diseases. So that 

disease focus can be very beneficial in getting treatments advanced 

and so forth, and they’ve done a great job, partly because they understand what’s needed. And often what’s needed is these clinical 

trial networks getting the outcome measures, doing the natural 

history, really understanding the disease very well, so when treatments come along they don’t fail, you know, they can be tested rapidly and figure out how desirable they are. 

Mr. MEEHAN. You have mentioned communication a number of 

times. Are we missing opportunities in this age of the ability of the 

NSA to drill down into the most intimate details anywhere? But 

no, we’re collecting more information than we’ve ever done before. 

We’ve got the ability to assimilate information better than we have 

before, and we are creating more medical records, albeit they’re 

still too much on paper and other kinds of things. But with this 

bulk of records out there, are we losing an opportunity to mine 

what we already know to significantly enhance or advance the ability to understand the things that we’re trying to take on? 

Dr. WOODCOCK. I don’t know. Often the medical records, for example, aren’t detailed and standardized well enough to provide 

these natural history outcomes that we’d really like to have. We 

have the Sentinel System that we’ve set up, which is really pretty, 

I think, novel and innovative. We have 120 million lives of data all 

behind the firewalls of the data partners, the insurance companies, 

or healthcare system. But we have it all standardized, we can 

query it, and we use that for drug safety analysis, okay. So we use 

that existing data. And they’re starting to randomize, cluster randomize within these kind of systems and answer important questions by doing experiments out there. 

I believe that telemedicine and recruiting people through social 

media and so forth is probably something we really should do, and 

71 

that would be a way to really reach patients who are out there and 

whose doctors aren’t telling them or they don’t know about availability of trials and so forth. I think we’ve just started to scratch 

the surface on how well that can serve us. 

Mr. MEEHAN. Well, I thank you. I guess we could go on all day. 

But I am very, very grateful for the work that you do and for your 

presentations here today. Thank you. 

Thank you, Mr. Chairman and Ranking Member, for holding this 

hearing. 

Ms. SPEIER. Actually, the gentleman from Pennsylvania just triggered, and your response triggered a question for me. The 

ClinicalTrials.gov. At Google you can actually elevate your status, 

so to speak, by paying for it. And so if you were to Google cancer, 

you can have ClinicalTrials.gov come up first. Who would be responsible for making that decision as to whether or not that should 

be an expenditure we make? 

Dr. WOODCOCK. That site is maintained by the National Library 

of Medicine, it’s part of NIH. 

Ms. SPEIER. Okay. So that’s a question to ask them. 

Let me just conclude, Mr. Chairman, by saying that I think we’ve 

got just a gold mine in you, Dr. Woodcock, and I thank you for the 

competency and professionalism that you’ve showed for so very 

long. And I hope that this will be a beginning of an opportunity for 

us to find more ways to work together, and I really think that pursuing the manufacturing of drugs here in the United States is worthy of our time and attention, and your assistance would be greatly 

appreciated. 

Dr. WOODCOCK. Absolutely. 

Mr. LANKFORD. I’d agree with that as well. And I also want to 

thank you for the time to be able to spend here and the time, both 

in preparation of your written statements. You made a comment 

earlier that you don’t give advice to Congress. Again, that would 

be one of the few Americans that doesn’t do that. That’s the wonderful thing about a republic, everyone can give advice to Congress. 

But through this there were a lot of to-do’s that come out of this. 

Let me give one statement just from me on it. You’re doing a lot 

of pilots, you’re doing some outside-the-box thinking of what can we 

do on that. We want to encourage that and to say continue to do 

that. The companies, we have a lot of companies that are now IPOs 

that are jumping in with different ideas. 

Dr. WOODCOCK. Uh-huh. 

Mr. LANKFORD. We want to continue to encourage the innovation 

that helps everyone. I’d also like to continue to encourage you, as 

you’ve already started in your office, in communicating with the advocacy groups for each of these different diseases. They want the 

communication with you. 

Dr. WOODCOCK. Yes. 

Mr. LANKFORD. As much as you can spur that and then also connect the dots between groups, for instance, what’s happened, as you 

mentioned before, with the cystic fibrosis organization. There may 

be others that are interested in that that may not even know that 

is occurring, but if it fast tracks that and if there are ways that 

these different outside groups can do, they are looking for things 

that will help. If there are things you can clearly articulate that 

72 

would help, they would like to know that, and they need to be able 

to hear that from you. They are very connected to NIH in the funding. They need to be connected to you in the same way to know not 

only what’s the research out there that’s being done, once the research is done, how can we fast track solutions. 

Dr. WOODCOCK. That’s right. 

Mr. LANKFORD. So, I would encourage that, as well as increased 

information to physicians on clinical trials so that for these rare 

diseases, especially, physicians know about the clinical trial process 

and can get their patients into it. Be much better than the compassionate use and other ways, and we can have the research ongoing 

on it. 

So those are quick admonitions in that, but you need to let us 

know as well what we need to do statutorily, and we’ll continue the 

conversation about the antibiotics. But if there are things that you 

need from us, we want to help in that. 

Dr. WOODCOCK. Thank you. 

Mr. LANKFORD. And we’ll work in a bipartisan way to be able to 

get that done. 

So with that, with no other questions on the dais on that, this 

hearing is adjourned. 

[Whereupon, at 4:25 p.m., the subcommittee was adjourned.] 

(73) 

APPENDIX 

MATERIAL SUBMITTED FOR THE HEARING RECORD

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