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25–718 2018

EXAMINING FDA’S PRESCRIPTION DRUG USER FEE 

PROGRAM 

HEARING 

BEFORE THE

SUBCOMMITTEE ON HEALTH 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED FIFTEENTH CONGRESS 

FIRST SESSION 

MARCH 22, 2017 

Serial No. 115–18 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

(II) 

COMMITTEE ON ENERGY AND COMMERCE 

GREG WALDEN, Oregon 

Chairman 

JOE BARTON, Texas 

Vice Chairman 

FRED UPTON, Michigan 

JOHN SHIMKUS, Illinois 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

STEVE SCALISE, Louisiana 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

GREGG HARPER, Mississippi 

LEONARD LANCE, New Jersey 

BRETT GUTHRIE, Kentucky 

PETE OLSON, Texas 

DAVID B. MCKINLEY, West Virginia 

ADAM KINZINGER, Illinois 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILL JOHNSON, Ohio 

BILLY LONG, Missouri 

LARRY BUCSHON, Indiana 

BILL FLORES, Texas 

SUSAN W. BROOKS, Indiana 

MARKWAYNE MULLIN, Oklahoma 

RICHARD HUDSON, North Carolina 

CHRIS COLLINS, New York 

KEVIN CRAMER, North Dakota 

TIM WALBERG, Michigan 

MIMI WALTERS, California 

RYAN A. COSTELLO, Pennsylvania 

EARL L. ‘‘BUDDY’’ CARTER, Georgia 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

MICHAEL F. DOYLE, Pennsylvania 

JANICE D. SCHAKOWSKY, Illinois 

G.K. BUTTERFIELD, North Carolina 

DORIS O. MATSUI, California 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

JERRY MCNERNEY, California 

PETER WELCH, Vermont 

BEN RAY LUJA ́ N, New Mexico 

PAUL TONKO, New York 

YVETTE D. CLARKE, New York 

DAVID LOEBSACK, Iowa 

KURT SCHRADER, Oregon 

JOSEPH P. KENNEDY, III, Massachusetts 

TONY CA ́ RDENAS, California 

RAUL RUIZ, California 

SCOTT H. PETERS, California 

DEBBIE DINGELL, Michigan 

(III) 

SUBCOMMITTEE ON HEALTH

MICHAEL C. BURGESS, TEXAS

Chairman 

BRETT GUTHRIE, Kentucky 

Vice Chairman 

JOE BARTON, Texas 

FRED UPTON, Michigan 

JOHN SHIMKUS, Illinois 

TIM MURPHY, Pennsylvania 

MARSHA BLACKBURN, Tennessee 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILLY LONG, Missouri 

LARRY BUCSHON, Indiana 

SUSAN W. BROOKS, Indiana 

MARKWAYNE MULLIN, Oklahoma 

RICHARD HUDSON, North Carolina 

CHRIS COLLINS, New York 

EARL L. ‘‘BUDDY’’ CARTER, Georgia 

GREG WALDEN, Oregon (ex officio) 

GENE GREEN, Texas 

Ranking Member 

ELIOT L. ENGEL, New York 

JANICE D. SCHAKOWSKY, Illinois 

G.K. BUTTERFIELD, North Carolina 

DORIS O. MATSUI, California 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

BEN RAY LUJA ́ N, New Mexico 

KURT SCHRADER, Oregon 

JOSEPH P. KENNEDY, III, Massachusetts 

TONY CA ́ RDENAS, California 

ANNA G. ESHOO, California 

DIANA DEGETTE, Colorado 

FRANK PALLONE, JR., New Jersey (ex 

officio) 

(V) 

C O N T E N T S 

Page 

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

Texas, opening statement .................................................................................... 1 

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

Hon. Gene Green, a Representative in Congress from the State of Texas, 

opening statement ................................................................................................ 4 

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

New Jersey, prepared statement ........................................................................ 100 

WITNESSES

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

Drug Administration ............................................................................................ 5 

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

Jeff Allen, PH.D., President and CEO, Friends of Cancer Research .................. 54 

Prepared statement .......................................................................................... 56 

Kay Holcombe, Senior Vice President of Science Policy, Biotechnology Industry Organization ................................................................................................... 71 

Prepared statement .......................................................................................... 73 

Anne Pritchett, PH.D., Vice President of Policy and Research, Pharmaceutical 

Research and Manufacturers of America ........................................................... 84 

Prepared statement .......................................................................................... 86 

SUBMITTED MATERIAL

Statement of Rare Disease Legislative Advocates, submitted by Mr. Guthrie .. 101 

Statement of the Epilepsy Foundation, submitted by Mr. Guthrie ..................... 102 

Statement of NVCA, submitted by Mr. Guthrie ................................................... 104 

Joint statement of the National Organization for Rare Disorders and Friends 

of Cancer Research, submitted by Mr. Guthrie ................................................. 106 

(1) 

EXAMINING FDA’S PRESCRIPTION DRUG 

USER FEE PROGRAM 

WEDNESDAY, MARCH 22, 2017 

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON HEALTH, COMMITTEE ON ENERGY AND COMMERCE, Washington, DC. 

The subcommittee met, pursuant to call, at 10:15 a.m., in room 

2322 Rayburn House Office Building, Hon. Michael Burgess (chairman of the subcommittee) presiding. 

Present: Representatives Burgess, Guthrie, Upton, Blackburn, 

Griffith, Bilirakis, Long, Bucshon, Brooks, Hudson, Carter, Green, 

Engel, Butterfield, Matsui, Sarbanes, Schrader, Kennedy, 

Ca ́ rdenas, and Eshoo. 

Staff present: Adam Fromm, Director of Outreach and Coalitions; 

Jay Gulshen, Legislative Clerk, Health; Carly McWilliams, Professional Staff Member, Health; Alex Miller, Video Production Aide 

and Press Assistant; Jennifer Sherman, Press Secretary; Danielle 

Steele, Policy Coordinator, Health; and John Stone, Senior Counsel, 

Health; Jeff Carroll, Minority Staff Director; Samantha Satchell, 

Minority Policy Analyst; Kimberlee Trzeciak, Minority Health Policy Advisor; and C. J. Young, Minority Press Secretary. 

OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A 

REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS 

Mr. BURGESS. I ask everyone to take their seats. The subcommittee will come to order, and I will recognize myself for an 

opening statement for 5 minutes. 

Today’s hearing marks the Health Subcommittee’s second opportunity to consider the reauthorization of several key FDA user fee 

programs. The Prescription Drug User Fee Act authorized the Food 

and Drug Administration to collect user fees from industry to support the approval of new drugs and biologics, and is a top priority 

for this committee. 

This was first authorized in 1992, and while there is always 

room for improvement, the Prescription Drug User Fee Agreement 

has been a success bringing safe and effective new products to patients in a timelier manner. Every 5 years since, pursuant to a 

process set forth in statute, Congress has reauthorized the program 

after reviewing the recommendations from the Food and Drug Administration, industry, patient groups, and other stakeholders. 

The committee has been reviewing the Prescription Drug User 

Fee Agreement since December when it was transmitted to Congress and publicly posted. As I stated in our hearing on the generic 

2 

and biosimilar programs earlier this month, Chairman Walden and 

I are committed to shepherding the user fee legislation through 

committee following regular order and getting it to the House floor 

with ample time to spare. 

Reauthorization of the user fee agreements every 5 years provides an opportunity, an opportunity to examine, an opportunity to 

improve upon the state of discovery, development, and delivery of 

medical therapies in America. For instance, in 2012, the reauthorization of the user fees in the Food and Drug Administration’s 

Safety and Innovation Act established the Breakthrough Therapy 

Designation. This program expedites the review and approval of 

promising new drugs that show early evidence of efficacy in serious, life-threatening diseases with an unmet clinical need. 

Under this program, over 165 products have been granted breakthrough designation which means more treatments, which means 

more cures, are being prioritized for patients suffering from some 

of the most debilitating conditions. I am pleased that the user fee 

agreements considering now will continue to build upon the success 

of the Breakthrough Therapy program. 

A unique factor in the negotiations of these user fee agreements 

was its overlap with the development of the 21st Century Cures 

Act, a bill enacted in December of last year after a multi-Congress 

effort led by Representative Fred Upton and Representative Diane 

DeGette. Over the course of the 113th and 114th Congresses, members of this subcommittee worked to uncover opportunities to 

strengthen and opportunities to streamline the process by which 

cures are discovered and then made available to patients. The resulting law touches each step of the process through which new 

treatments come to the bedside. 

I am encouraged to see in our witness’s testimony that the Prescription Drug User Fee Agreement VI will dedicate resources to 

complement the implementation of the many priorities, the many 

priorities of the 21st Century Cures bill. In particular, I like the 

fact that the FDA will formalize a structure to incorporate patient 

input and patient experience into the benefit-risk assessment of 

products that are actually under development. This is a good thing. 

Patients have the most at stake and they deserve to be heard. 

I am also encouraged that the Food and Drug Administration 

will dedicate resources to modernize clinical trials and evidence development including the utilization of real-world evidence in investment in biomarkers. Real-world evidence has the potential to increase sufficiency and foster robust data collection and analysis. 

Advancing development of biomarkers has significant promise to 

accelerate regulatory decision making and expedite the pace of clinical trials without sacrificing standards for efficacy and safety. 

Other provisions incorporated into the proposal for PDUFA VI— 

OK, you made me say it—PDUFA VI. I was trying to just call it 

the user fee agreements—reflects the top priorities of this committee in the 21st Century Cures Act. Again I want to reiterate my 

commitment to ensuring that this reauthorization stays on track. 

We all know there are a lot of competing influences this year, but 

this year will mark the fifth renewal by Congress, and it is widely 

agreed that the prescription drug user fee agreements will provide 

3 

for the timely review of new drug and new biologic license applications. Again I want to underscore that is a good thing. 

I thank all of our witnesses for being here, particularly Dr. 

Woodcock. Thank you, and welcome again back to our humble little 

subcommittee for one more hearing. I look forward to hearing from 

each of you and more about the agreement that is before us today, 

and I will yield back the balance of my time. 

The chair now recognizes the gentleman from Texas, the ranking 

member of the subcommittee, Gene Green, 5 minutes for an opening statement, please. 

[The statement of Mr. Burgess follows:] 

PREPARED STATEMENT OF HON. MICHAEL C. BURGESS

The Subcommittee will come to order. 

The Chair will recognize himself for an opening statement. 

Today’s hearing marks the Health Subcommittee’s second opportunity to consider 

the reauthorization of several key FDA user fee programs. The Prescription Drug 

User Fee Act (PDUFA) authorized FDA to collect user fees from industry to support 

the approval of new drugs and biologics, and is a top priority for this Committee. 

It was first authorized in 1992 and, while there is always room for improvement, 

PDUFA has been a remarkable success, bringing safe and effective new drug products to patients in a more timely manner. Every 5 years since, pursuant to a process 

set forth in statute, Congress has reauthorized the program after reviewing recommendations from FDA, industry, patient groups, and other stakeholders. 

The Committee has been reviewing the PDUFA VI agreement since December, 

when it was transmitted to Congress and publicly posted. As I stated at our hearing 

on the generic and biosimilar user fee programs earlier this month, Chairman Walden and I are committed to shepherding the user fee legislation through Committee, 

following regular order, and getting it to the House floor with ample time to spare. 

Reauthorization of the user fee agreements every 5 years provides an opportunity 

to examine and improve upon the state of discovery, development, and delivery of 

medical therapies in America. For instance, the 2012 reauthorization of PDUFA in 

the Food and Drug Administration Safety and Innovation Act, commonly known as 

FDASIA, established the Breakthrough Therapy Designation. This program expedites the review and approval of promising new drugs that show early evidence of 

efficacy in serious, life-threatening diseases with unmet clinical need. Under this 

program over 165 products have been granted breakthrough designation, which 

means more treatments and cures are being prioritized for patients suffering from 

some of the most despairing conditions. I am pleased that PDUFA VI will continue 

to build upon the success of the breakthrough therapy program. 

A unique factor in the negotiation of PDUFA VI, was its overlap with development of the 21st Century Cures Act, a bill enacted last year after a multi-year initiative led by Representative Upton and Representative DeGette. Over the course 

of the 113th and 114th Congresses, members of this subcommittee worked to uncover opportunities to strengthen and streamline the process by which cures are discovered and made available to patients. The resulting law touches each step of the 

process through which new treatments and cures come to market. I am encouraged 

to see in our witnesses’ testimonies that PDUFA VI will dedicate resources to complement the implementation of many of the priorities in 21st Century Cures. 

In particular, I am pleased to see that FDA will formalize a structure to incorporate patient input and experience into the benefit-risk assessment of products in 

development. Patients have the most at stake, and they deserve to be heard. I am 

also encouraged to see that FDA will dedicate resources to modernize clinical trials 

and evidence development, including the utilization of real-world evidence and investment in biomarkers. Real-world evidence has the potential to increase efficiency 

and foster robust data collection and analysis. Advancing development of biomarkers has incredible promise to accelerate regulatory decision-making and to expedite 

the pace of clinical trials without sacrificing standards for efficacy and safety. 

Numerous other provisions incorporated in the proposal for PDUFA VI reflects 

the top priorities of this Committee in the 21st Century Cures Act, and I want to 

reiterate my commitment to ensuring this reauthorization stays on track. This year 

will mark the fifth renewal by Congress, and it is widely agreed that PDUFA VI 

will provide for the timely review of new drug and biologic license applications. I 

4 

thank our witnesses for being here today and I look forward to hearing more from 

each of you about the agreement before us today. 

OPENING STATEMENT OF HON. GENE GREEN, A 

REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS 

Mr. GREEN. Thank you, Mr. Chairman. I thank all our witnesses, 

both Dr. Woodcock, welcome back again, and our second panel for 

being here this morning. Today we are examining the sixth Prescription Drug User Fee Agreement, PDUFA VI. I think it is fair 

to say that we all support a strong FDA that is responsive to the 

needs of the patient community and the innovations of scientific research and healthcare delivery. 

I am pleased that Congress is moving judicially through the process of reauthorizing the user fee programs and honoring their negotiations that have led to the agreements, and PDUFA is the most 

mature of the user fee programs having first been enacted in 1992. 

Sometimes our committee seems like we are a little mature. 

The law lays out a detailed process for reauthorization that requires FDA to negotiate with industry to develop recommendations 

and that the agency solicit public input and hold public hearings 

and consult with Congress and patients and consumer advocates 

and other relevant parties. The recommendations that are a result 

of this process must also be available publicly for a period for public comment, and ultimately are required by statute to be transmitted to Congress. 

I was disappointed to see the line in the administration’s testimony that they do not stand behind these agreements and hinted 

towards reopening the painstakingly negotiated products. As we 

know, we are here today as the result of months of work between 

FDA and stakeholders to examine the program, figure out what is 

working and what can work better, and come to an agreement on 

how the program should be for the next 5 years through a public, 

drawn-out process. 

This process is a long one and the statutory deadline for reauthorization is coming up quickly. Congress has never flirted with 

neglecting its obligation to reauthorize in a timely and responsible 

manner. I sincerely hope that this holds true for the sixth reauthorization of PDUFA. Along with the other user fee programs, it 

must be reauthorized so FDA can do its work and patients maintain access to new therapies without a major disruption in the 

medical product ecosystem. 

PDUFA was first enacted as a way to reduce the time it took 

FDA to review new drugs and biologics and improve access to medical treatments more quickly. Over the years, the user fees provided under PDUFA have allowed the FDA to hire additional staff 

and improve the efficiency and predictability of the review process. 

Prior to the first PDUFA, the median time for FDA for approval 

of standard applications was 28 months. Today, the median time 

for approval for standard applications has been reduced to 12 

months, and first-cycle approval rates are at 95 percent. The U.S. 

remains the gold standard for drug approval and evaluation of 

safety and efficiency. 

The commitment letter for PDUFA VI includes a number of performance goals meant to help the agency with recruiting and reVerDate Nov 24 2008 13:42 Jan 30, 2018 Jkt 037690 PO 00000 Frm 00010 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-18 CHRIS
5 

taining the scientific and professional staff needed to keep pace 

with the science. For the first time, PDUFA VI also includes specified agency hiring goals. This builds on the hiring provisions in the 

21st Century Cures that will help the agency to compete with the 

private sector in terms of competitive salary, and gives the agency 

the authority to hire scientific and technical staff needed to support 

medical project review. 

There have been some that have criticized FDA for being a barrier to the access to innovative new drugs. This is inaccurate. Contrary to the description by the President and others who want to 

roll back patient safety measures, the FDA’s approval process is 

not slow and burdensome. Today, more than two-thirds of novel 

drugs are approved first by the FDA rather than anywhere else in 

the world. 

It is clear that PDUFA has been successful in meeting the goal 

of improving efficiency of the drug review process at FDA and ensuring patients have access to novel therapies. The policies and 

goals included in the agreements reflect what these stakeholders 

value and will help ensure advancements and improvements within 

the FDA and ultimately health care more broadly. 

I want to thank the agency and the stakeholders for their leadership on this agreement that will continue the trajectory of patientcentered innovation at the FDA. 21st Century Cures did a great job 

to advance such reforms and help get new cures from the lab table 

to the bedside. I look forward to hearing from the FDA and other 

witnesses on how this agreement will build on these successes and 

continue to advance the modern, efficient FDA and a healthy pipeline of medical breakthroughs. And I yield back my time. 

Mr. GUTHRIE [presiding]. The gentleman yields back his time. 

Mr. GREEN. Do we have any other opening statements? No, OK. 

Mr. GUTHRIE. We have none on our side. OK, we will turn to the 

witnesses. We want to thank all of our witnesses for being here 

today and taking the time to testify before the subcommittee. And 

each witness will have an opportunity to give an opening statement 

followed by a round of questions from members. 

And we have two panels of witnesses today, and we will begin 

with our first witness, Dr. Janet Woodcock, Center for Drug Evaluation and Research, Food and Drug Administration. We appreciate you being here. And, Dr. Woodcock, you are now recognized 

for 5 minutes to give an opening statement. 

STATEMENT OF JANET WOODCOCK, M.D., CENTER FOR DRUG 

EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION 

Dr. WOODCOCK. Thank you, and thanks to the members of the 

subcommittee for inviting me to testify at this important hearing. 

We are talking here about a program that has been going on for 

25 years, the prescription drug user fee program. And as result, as 

we have already heard, over that time U.S. patients have gone 

from being one of the last in the world to obtain access to new 

drugs to in most cases being the first patients in the world who can 

get access to innovative new therapies, all at the same time maintaining the standards that FDA has for safety and effectiveness of 

these therapies. 

6 

At the same time, we have moved from multiple cycle scenario 

to predominantly first-cycle approval for these drugs, meaning that 

the industry and FDA have enough communication, the standards 

are clear enough, they are able to submit a complete application 

that can be reviewed and approved without further delay. And this 

is a great time efficiency and resource efficiency for industry for the 

FDA and for the medical community alike. 

Also, this program has allowed us to accommodate the advances 

in medical science that have occurred recently over the last several 

decades. Congress and the U.S. investment in NIH and in biomedical research has caused tremendous growth in scientific understanding. Now we are really contemplating, we have approved 

drugs for example that are antisense oligonucleotides that act directly on people’s DNA. We are looking at multiple applications for 

gene therapies although none have been approved yet. We are looking at multiple cellular therapies that are under development. 

And so this promise that you have been hearing about science is 

really coming about and we have approved cures for various conditions such as hepatitis C, which has long been a scourge of people. 

So the next programmatic proposals, the enhancements for the 

sixth iteration of this, try to build on the accomplishments that we 

already have. And as has already been said, the first one is really 

aligned with the Cures legislation that was passed and that is enhancing the ability to capture patient voice in drug development. 

Not just on benefit-risks, but patients want to tell us what we 

should study, what matters to them. What do they want ameliorated about their disease? What is most important? How should we 

study it? 

They want to know, they want to tell us how trials should be designed that work for patients. People always wonder why there is 

so many dropouts in the trials, missing data. Well, because we designed the trials in a way that patients couldn’t participate. So the 

patient voice is critical, and then at the end of the day how much 

risk are people willing to trade off in uncertainty for the benefits, 

the potential benefits of any given therapy. And this will require 

a rigorous process to generate and develop all these data and bring 

the patients in, in a rigorous way. It is envisioned in Cures and 

laid out in Cures, and the programmatic enhancements of PDUFA 

VI would bolster our ability to do that in a timely manner. 

Also, there is support for the Breakthrough Therapy Program. 

Now what I will say about that is that is probably the first program that has really shortened drug development. As we have all 

said, drug review isn’t the problem. It occurs now in a timely manner, predictable manner, based on PDUFA. But drug development 

is still a very gnarly problem. It takes too long and it costs too 

much, right, and there are many failures. 

Breakthrough has been the first program as actually drug development time has been shortened, and you have heard that before 

this committee from a number of witnesses, taking several years off 

of drug development in the overall time it takes to get those drugs. 

Part of it is the quality of the compounds, the molecules that are 

developed under and given breakthrough, but also part of it is the 

support that FDA is willing to give. And so the new program would 

give additional resources. 

7 

There is also, as was envisioned in Cures, support for biomarker 

qualification also for the better use of surrogate endpoints, an advancement of clinical trial design, something dear to my heart and 

I would be happy to talk to you about; advances in the use of real 

world evidence, which is also a Cures theme; better communication 

with industry to make sure that we are always on the same page 

and we move things along; and then administrative improvements 

including oversight of some of the administrative processes, reports, and financial oversight, to make sure the management and 

planning of the program is as good as it can be. 

So I believe this captures in the programmatic proposals many 

of the modern themes that need to now address improvements in 

drug development and drug approval, and I would be happy to answer any questions. 

[The prepared statement of Dr. Woodcock follows:] 

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Mr. GUTHRIE. Thank you. I want to thank you for your testimony. We will now move to the first Q&A portion of the hearing, 

and I will begin the questioning and recognize myself for 5 minutes. 

So Dr. Woodcock, as part of 21st Century Cures, this committee 

included provisions that set up FDA Intercenter Institutes of Excellence in major disease areas to improve coordination across the 

agency. FDA has since established the Oncology Center of Excellence. Can you provide us with an update on how things are going 

so far and if there is anything we can do to help ensure smooth 

and timely implementation? 

Dr. WOODCOCK. Yes. The Oncology Center of Excellence is considered a joint venture by the three medical products centers, Center for Biologics, Center for Devices and Radiological Health, and 

Center for Drugs. And so we put this together jointly, it resides up 

in the office right above us. Dr. Richard Pazdur is the director of 

that office. 

And the procedures that we are running, they will review the 

clinical oncology, the medical oncology portion of any product that 

comes in with a medical oncology indication to any of the three centers. So they will do the medical part of that review, and Rick will 

direct it, but it will include oncologists from Drugs and Biologics 

as appropriate to that particular cancer area. 

So we have worked out the procedures and so forth and we expect those applications then will go before the Oncologic Drugs Advisory Committee and be heard. And then the Center, whichever 

Center has the product, will complete the rest of the product review which is about the quality of the product and the control of 

that quality, and then we will actually approve the application 

using the clinical recommendations from the Oncology Center of 

Excellence. 

And the Center also will be the outfacing, outward facing group 

that will interact with the medical oncology and patient community. 

Mr. GUTHRIE. OK, thank you. I want to yield time to my good 

friend from Virginia, Mr. Griffith. 

Mr. GRIFFITH. Thank you very much. I appreciate that. Dr. 

Woodcock, prior to the FDA’s encouraging the development of 

abuse deterrent opioids, manufacturers should be incorporating 

these technologies into their products and testing whether they 

deter various routes of potential abuse, intranasal, intravenous, et 

cetera. If they do, manufacturers need to be able to include this 

data in their product labeling and communicate this useful information to healthcare providers. 

I understand a recent exclusivity determination by FDA calls 

into question whether multiple manufacturers in the same product 

class could make such claims even if their data justifies it and even 

if they are using different technologies. Is that accurate? 

Dr. WOODCOCK. It is likely accurate. I think like many of the 

laws governing exclusivity that Congress passed long ago, they certainly didn’t foresee some of the situations. And we struggle all the 

time with trying to figure out how to apply exclusivity fairly and 

justly to everyone and yet not disadvantage public health goals 

that we may have. 

36 

Mr. GRIFFITH. And so you would agree it probably would discourage a manufacturer if they can’t go forward and discuss that; a 

company or a manufacturer might not invest as much if they think 

that somebody has beaten them to the punch by a few months. And 

so what you are recommending, if I understood your previous answer is, is that we probably should take a look at it and change 

the law? 

Dr. WOODCOCK. Well, I can’t go that far because of course that 

is your purview. 

Mr. GRIFFITH. Yes, ma’am. Thank you. 

Dr. WOODCOCK. But I do believe that times have changed. 

Mr. GRIFFITH. Yes, ma’am. I appreciate that. Speaking of product 

manufacturers being able to share useful scientific data and information about their products with doctors, I understand that some 

previous leaders at the Department of Health and Human Services 

would not allow FDA to work with Congress to clarify in a responsible and constitutionally sound manner how manufacturers can 

communicate truthful and non-misleading off-label information. 

Now as you and I were just discussing, I prefer that Congress 

work with you all to make the rules as opposed to leaving it to the 

courts to decipher. Will you commit to working with us to set up 

some clear rules of the road so folks know what they can communicate and what they can’t? 

Dr. WOODCOCK. Certainly. We will work with the administration, 

through the administration with you on this issue. 

Mr. GRIFFITH. All right, I appreciate that very much. 

With that Mr. Chairman, I appreciate the time and I yield back. 

Mr. GUTHRIE. I yield back my time and I recognize Mr. Green for 

5 minutes to ask questions. 

Mr. GREEN. Thank you, Mr. Chairman. And thank you, Dr. 

Woodcock, again for being here this morning. As I mentioned in my 

opening statement, I was disappointed to see the line in the administration’s testimony that they do not stand behind these agreements and hinted toward a reopening of painstakingly negotiated 

products. Can you explain to the committee what would happen 

should Congress fail to reauthorize PDUFA and the other user fees 

before the statutory deadline in September? 

Dr. WOODCOCK. If there is not a reauthorization, we must initiate our reduction in force process where we would prepare to let 

go of for the Center for Drugs is maybe 70 percent of the staff 

working on the process of review in new human drugs. And we do 

have carryover balance within the user fee agreements that we are 

supposed to hold some money back. In case the program terminates 

we can, over several months, have an orderly process to let go of 

the staff. And that we would have to start thinking about that in 

July because there are complicated personnel rules that have to do 

with who has to be notified first and so forth. 

Mr. GREEN. OK, thank you. There seems to be a misunderstanding about the drug development process. We hear often that 

new therapies take about 10 years to develop and some seem to 

think that means the application languishes at the agency for a 

decade. In fact, the FDA review is the final step in the development 

process and more efficient than ever. 

37 

Can you explain to this committee how PDUFA VI builds on the 

past successes of the program and helps the agency work with 

stakeholders to not be a bottleneck but a strong partner in getting 

these new treatments to patients in need? 

Dr. WOODCOCK. Certainly. Obviously we have prioritization programs for breakthrough drugs and for priority drugs where they 

are reviewed in shorter times. We have gotten some reviews out in 

3 months, and a drug approved and on the market after the application is submitted where it is a breakthrough. 

So, but that doesn’t mean that the development time is short. 

The development time still is quite long and the failure rate of 

drugs in development is still very high. Perhaps in some areas nine 

out of ten drugs that get into human testing fail during human 

testing at huge cost. So a lot of the efforts we are working on, I 

believe patient focused drug development, the innovative clinical 

trials, the surrogate endpoints, and biomarkers, all of which are 

encompassed in the proposed programmatic changes, will help with 

this drug development phase and making it as short as possible. 

As I said, the Breakthrough Therapy Program has actually 

worked and some of those development programs in the clinic have 

only been a couple years, so the time to patients has been shortened dramatically. 

Mr. GREEN. Can you explain to this committee how PDUFA VI 

builds on the successes of the program in the past and helps the 

agency work with stakeholders to not be a bottleneck but a strong 

partner in getting new treatments to the patients in need? Or that 

is my question. OK, let me get to the next one. 

Many provisions of the user fee agreements resemble ideas we 

advanced in Cures, things like biomarker qualification programs, 

incorporation of the patient perspective in decision making, and the 

advancement of innovative clinical trials are goals we have shared. 

I am concerned about the impact that the administration’s proposed hiring freeze would have on FDA, and could it be made hard 

to advance these shared goals? 

User fees under PDUFA also assist the FDA in hiring and retaining staff necessary to support the activities associated with review of drug applications. The commitment letter for PDUFA VI includes a number of performance goals meant to help the agency 

with recruiting and retaining the scientific professional staff needed to keep pace with science. In fact, for the first time, PDUFA VI 

also includes specific agency hiring goals. This builds off the hiring 

provisions in the 21st Century Cures. 

Can you discuss further how the PDUFA VI will help the FDA 

to hire and train the scientific technical workforce needed to fulfill 

the goals agreed to in the commitment letter? 

Dr. WOODCOCK. Well, for really the first time, this programmatic 

proposal in PDUFA VI really focuses on some of the administrative 

processes and tries to set in place some oversight over hiring and 

so forth, and some new scientific recruitment staff and so forth that 

would enable us to hire scientists. As I said, the science has really 

come along, and so we are talking about really high-tech kind of 

treatments in humans, such as gene therapy in humans and so 

forth, and we need the scientific staff that are qualified to evaluate 

those and make sure they are safe as well as that they work. 

38 

Mr. GREEN. Well, my time is almost up. And I know our goal is 

to make sure you have the resources to do it quicker and not lay 

in another level of bureaucracy to make it even longer. Thank you, 

Mr. Chairman. 

Mr. GUTHRIE. Thank you. The gentleman yields back. Mr. Upton 

is recognized for 5 minutes. 

Mr. UPTON. Well, thank you, Dr. Woodcock. It is great to see you 

again, and I know all of us on both sides of the aisle here really 

appreciated your work and your input from the very beginning on 

getting 21st Century Cures ultimately to the President. And we 

knew that by expediting the approval of drugs and devices we were 

going to need require you all at the FDA to help us and to help 

chart that course for us and provide the right resources so that you 

would be able to do your job. 

And obviously PDUFA VI is very important, very important. And 

alarming of course to us, a good message to us is if we don’t get 

it done by summer or show that we have made progress by July 

and August, certainly by September, that you would actually have 

to RIF 70 percent of the staff, is quite alarming and ought to serve 

as turning up the burner for us to get our job done, as we have 

in the past in a very strong bipartisan way, ultimately getting this 

bill to the President. 

A question for you, Diana DeGette and I sent a letter a couple 

weeks ago to OMB asking about the federal hiring freeze that the 

President announced as it relates to the implementation of 21st 

Century Cures. And of course as you know we came up with offsets, dollar for dollar matching to help with the half billion dollar 

increase that we gave for the FDA. 

Yesterday, it is my understanding that you told the Senate 

Health Committee—and I have to again compliment Lamar Alexander and the great work that they did over there. But yesterday 

you told the Health Committee that the White House did give the 

FDA permission to move forward with hiring on the select user fee 

positions needed to implement Cures. I don’t know if that is a 

quote or not, but that is my understanding. 

Can you provide some more detail? We have not heard back. It 

is my understanding we have not heard back from our letter that 

we sent to the White House, but can you tell us more details about 

the type of hiring that is going to be needed to implement 21st 

Century Cures and what guidance you have been able to get from 

both OMB and the White House and which select user fee positions 

is the FDA hiring? 

Dr. WOODCOCK. Well, I am not in a position to discuss that particularly, I can talk about what programmatic needs there will be. 

Clearly, the patient focused drug development is going to need different kind of scientists than we have traditionally had. We have 

had laboratory scientists who are looking in test tubes and doctors 

who are—we are going to need social scientists and other folks who 

can actually talk to people and get rigorous evidence about what 

their needs and preferences are and who can work on instruments, 

say, patient reported outcome measures and so forth. So that is one 

category that we don’t necessarily have enough of. 

In addition, on real-world evidence that is some different types 

of science that we will need to have people who can analyze that, 

39 

big data, and so forth. And interesting, we have already had multiple outside parties approach us who are using real-world evidence 

in different ways and they want to collaborate with us and we are 

working with them, some of them in the Oncology Center of Excellence. So we will need data scientists of that sort. 

And Breakthrough Therapy, which I know isn’t Cures, but will 

need basically people who in specific disease areas particularly rare 

diseases. We also commit to integrate rare disease expertise within 

the review teams where there are rare diseases. We are seeing 

more and more rare diseases being treated. 

So we have very focused needs in specific places for a specific 

kind of scientist, and I am sure that the Biologic Center with the 

rise in gene and cell therapy and that more or less explosion and 

also regenerative medicine, they are going to need specific types of 

scientific expertise. 

Mr. UPTON. Great. Well, thanks again for your work and we look 

forward to continuing the process as we get this thing done too. I 

yield back. Thank you, Mr. Chairman. 

Mr. GUTHRIE. Thank you. The gentleman yields back and Mr. 

Schrader is recognized for 5 minutes. 

Mr. SCHRADER. Thank you very much, Mr. Chairman, and 

thanks, Ms. Woodcock, for being here again. Very impressive results; I don’t know if it is appropriate, but the graphs that are in 

your written testimony, I think, are pretty dramatic and you 

should share those with us when you come in and give your testimony. It would be pretty interesting, I think, for everyone to see 

that with the work of the committee and follow-through by FDA 

that the first drug approvals have dramatically increased and it is 

really pretty impressive. So make sure you show yourself to advantage when you become before us here. 

I appreciated these comments on the Breakthrough Therapy Program with regard particularly to new and innovative drugs with 

unmet needs. We are finding that in the generic area that once 

again there are unmet needs despite the fact there may have been 

a product and there is either a sole source or no source alternative. 

Any thought of how the breakthrough process you are currently 

using on the brand name side might translate into the generic 

sphere of development? 

Dr. WOODCOCK. Our analysis of the issues with generics is more 

that, you know, about ten percent of what we call reference drugs, 

the brand drugs, never get a generic filed to them. And so this 

seems to be a market phenomenon, competition is only attracted 

where people think they can make money by competing, and the 

small source products and so forth. 

Now in the generic drug user fee program, the second one that 

we are proposing, the programmatic enhancements include a program to help with complex generics. And those are ones that actually people might not try to enter the market because it is hard, 

where, say, you are using an autoinjector or you are using a very 

complex molecule and so it might be hard. 

So there, and we have agreed that we would set up a pre-program similar to kind of like the prescription drug user fee where 

before they send in the application we have meetings with them 

and we give them advice and we help them develop their products, 

40 

so by the time they get the application in the door it actually could 

be approvable. 

So that would help with those types of products, but the 

small—— 

Mr. SCHRADER. I guess where I was going—and that is very good 

and I think that is outstanding and hopefully a benefit to a lot of 

the companies out there. But I was going, say we are able to encourage a manufacturer to come to market through a variety of different means. We have a bill, Gus Bilirakis and I are trying to find 

what is the appropriate way to get and incentivize folks to come 

to market; make it worth their while as you put it. 

But once they are there it would be nice if you used that breakthrough approach that has been so successful to also, you know, 

hasten things through. And I think to, and help us encourage them 

to come to market and be successful, if they knew that breakthrough approach was going to be applied that might incentivize 

things also. 

Dr. WOODCOCK. Well, we would be happy to work with you. In 

medicine we have a saying: First do no harm. And sometimes there 

are unintended consequences and I think it would be worth discussing, because there is such a commercial hit that the innovators 

take when they get a generic competition on the market that any 

provisions that they can sue us about or send us citizen petitions 

or obstruct a process cause delays, and I believe that needs to be 

taken into account as you think about incentivizing. 

Mr. SCHRADER. We are trying to do that. We have a REMS portion of our bill to try and make sure that it is being used appropriately for safety purposes and not block competition in the market. So we are trying to listen to you and your advice. 

Dr. WOODCOCK. We would be happy to work with you in this. 

Mr. SCHRADER. Second question on the biomarkers. I think that 

is a great idea because it takes as you said, many times it takes 

awhile to get these drugs to market and many of them do fail. And 

so a lot of the manufacturers want to have some idea if they are 

on the right track and you want to have some idea if they are on 

the right track, so early intervention and changing things would be 

appropriate. 

Taking a blood pressure measurement or whatever the appropriate biomarker is, how do you follow through on that as the 

medication goes through the market, or a product goes through the 

market, to make sure that number one that the biomarker does 

turn out to be an accurate reflection of what the drug’s ultimate 

outcome is, and then, once the drug is on the market, how do you 

go back and reassess the biomarkers to make sure they are actually meaningful indicators for you and for the companies? 

Dr. WOODCOCK. We have a program known as Accelerated Approval. For some biomarkers such as blood pressure, their benefit 

is unequivocal and we don’t need to keep proving over and over 

again that lowering blood pressure keeps you from getting strokes 

and so forth. We know that. But many other biomarkers are, quote, 

surrogate endpoints that we aren’t a hundred percent sure that 

they are going to translate into benefit, and therefore we would 

give an accelerated approval it is called. That is kind of a misnomer, kind of misleading, but what that means is we are approvVerDate Nov 24 2008 13:42 Jan 30, 2018 Jkt 037690 PO 00000 Frm 00046 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-18 CHRIS
41 

ing us based on the biomarker, but they have to do further studies. 

They are required to do further studies after approval to show that 

their drug actually causes clinical benefit. 

So you get on the market earlier, that is the accelerated part, but 

you still have to deliver that proof. 

Mr. GUTHRIE. Thanks. The gentleman’s time has expired. I will 

recognize Mr. Lance for 5 minutes for questions. 

Mr. LANCE. Thank you very much, Mr. Chairman. It is always 

good to see you, Doctor. I am encouraged to see that the Rare Diseases Program staff will be integrated into review teams for rare 

disease development programs to provide unique expertise. Could 

you please speak to the relationship between PDUFA and 21st 

Century Cures as it relates to drug development tools such as realworld evidence, complex trial designs, and biomarkers, and the importance of getting the agreement to the President’s desk by the 

end of July? 

Dr. WOODCOCK. Certainly. Well, what was negotiated in PDUFA 

VI bolsters certain aspects of Cures with additional resources, and 

also would have specific timelines put in place and agreements. 

Some of those are slightly different, but we can reconcile them all 

kind of defaulting to whatever the earliest thing we agreed to is, 

we would do it then, all right. 

Mr. LANCE. Yes, Dr. Woodcock. 

Dr. WOODCOCK. So, for example, real-world evidence, their guidance and so forth we would put out. 21st Century Cures has a 

broader qualification process, so it includes patient reported outcomes, clinical outcome assessment, as well as biomarkers, whereas 

the PDUFA agreement is about biomarkers. However, we are going 

to put up the same process for everything, the Cures process, which 

puts in place timelines and obligations on both the submitters and 

the agency. So we will put that across the board. 

We expect, as you all know from our discussions, the biomarkers 

to be the most difficult part of this, and so the PDUFA gives, envisions more support for the biomarker qualification process. 

Mr. LANCE. Thank you. Dr. Woodcock, 21st Century Cures included a provision on combination products and that provision directs the agency to improve coordination between the Device and 

Drug Centers. Considering both Centers are involved in this process, should there be some coordination between the agreements? 

Dr. WOODCOCK. Yes, and actually I believe there is. PDUFA VI 

provides some resources actually are envisioned for the Device Center, all right, to conduct these reviews. But I am pleased to say 

under the leadership of Dr. Rachel Sherman, who is deputy commissioner, we have made considerable progress already in combination products. We have put together a council, we have mapped the 

processes, we have improved the processes, we have developed 

standardized templates and so forth. So I think we have made a 

lot of progress already and that these efforts in Cures and in the 

user fee agreements will enhance that. 

Mr. LANCE. Do both Centers receive part of the user fee for combination products? 

Dr. WOODCOCK. Yes. 

Mr. LANCE. Is that the way it works? 

Dr. WOODCOCK. Yes. 

42 

Mr. LANCE. And as I understand it, the goal in fiscal year 2019 

is 50 percent, when the goal in fiscal year 2021 is 90 percent; is 

that accurate? 

Dr. WOODCOCK. I believe so. That is how we typically structure 

these goals. If we haven’t been keeping track the first year or so 

we try to find out what our baseline is. It may be 80 percent—we 

might hope so, OK—and then we ratchet it up after that. 

Mr. LANCE. Thank you, Dr. Woodcock. 

And Mr. Chairman, I yield back 1 minute, 25 seconds. 

Mr. GUTHRIE. The gentleman yields back and Mr. Ca ́ rdenas is 

recognized for 5 minutes for questions. 

Mr. CA ́ RDENAS. OK. I will try to yield back a minute and 25 seconds or more to keep up with the program here. Thank you very 

much, Mr. Chairman, for holding this hearing. 

Dr. Woodcock, what is the significance of September 2017 as far 

as your professional world goes? 

Dr. WOODCOCK. If these various user fee programs are not reauthorized at that time, we must initiate processes to let go of the 

staff and wind down the program. There is money in all these 

agreements to do that. There is some money held back. 

Mr. CA ́ RDENAS. Yes, money held back to wind it down—— 

Dr. WOODCOCK. That is all. 

Mr. CA ́ RDENAS [continuing]. Which only expends over a few more 

months. 

Dr. WOODCOCK. That is correct. 

Mr. CA ́ RDENAS. Are many of the people that would be let go, per 

se, if we legislatively failed to do our job here, would that—you are 

talking about jobs, people who are specialists, or what kind of jobs 

are they? 

Dr. WOODCOCK. Most of these are doctors and scientists. They 

are almost all at the Ph.D. or M.D. level. The physicians are generally some specialists, so we would have nephrologists or people 

who are specializing in medical imaging, and so hard to find people. 

Mr. CA ́ RDENAS. Is it fair to say that getting so close to September 

2017 creates kind of a little bit of nervousness amongst people who 

are trying to get their work done in such an environment? 

Dr. WOODCOCK. Well, what we would expect is the productivity 

would slow down as we approach the brink, tremendously. This has 

happened once before where we approached it and we lose staff. 

Our people are heavily recruited into other jobs and they aren’t 

paid as we have all discussed, they aren’t paid as much as private 

sector. And so I would expect we would start to lose people very 

early who would leave before they got their notice. 

Mr. CA ́ RDENAS. So to that point, if and when this, it seems to 

have happened before, the ramping up, once there is a restoration 

after the fact, isn’t the ramping up many times harder than it was 

in the ramping down? 

Dr. WOODCOCK. It is indeed. At least in the New Drugs Program 

where we need to hire physicians, the last time, and we didn’t come 

to a reduction in force, we just came sort of close to that, it took 

more than a year for the New Drugs Program to recover its losses, 

and its recruitment rate was slowed down which it already is slow, 

43 

because people have kind of lost faith in the viability of the program. 

Mr. CA ́ RDENAS. And something such as a year of that revamping 

to just restore back to where it was, doesn’t that cause a 

compounding effect potentially when it comes to the actual work 

being done going forward not only within the department but in 

the industry that happens to interact with you? 

Dr. WOODCOCK. Well, we would have to prioritize very carefully 

what work would be done. Public safety would come first, obviously, and we would probably not be able to give all the advice that 

we would like to give or that people would like to have from us. 

Mr. CA ́ RDENAS. So the stress is—I am interpreting this conversation as there would be stress involved in many ways actually expands beyond the department if in fact we weren’t able to timely, 

in a timely fashion get this restored. 

Dr. WOODCOCK. I believe that is very accurate. 

Mr. CA ́ RDENAS. Do our job legislatively by the September ’17 

deadline. 

Dr. WOODCOCK. Yes. 

Mr. CA ́ RDENAS. OK. So briefly, Dr. Woodcock, when it comes to 

what we have done on 21st Century Cures, and your department 

is complicit in making sure that we do well with that. But at the 

same time, when it comes to biomarkers can you please discuss further how PDUFA VI will help with these efforts and what further 

biomarker development activities PDUFA VI will provide resources 

for? 

Dr. WOODCOCK. Certainly. Both 21st Century Cures and the program envisioned in PDUFA VI both envision more effort going to 

biomarkers. 21st Century Cures sets up a structured program for 

what we call regulatory qualification, and what that means is new 

biomarkers, a different sort, we would tell people, the public, you 

can use this biomarker to make this decision about patients. 

Now that can be a very heavy decision say if it is a safety biomarker. We are saying we are trusting human lives to the results 

of this biomarker. So there is a lot of scientific work that has to 

go in to make sure that biomarker is providing reliable information 

to make that decision. 

And so what we are going to do, or are instructed to do under 

Cures and also under this PDUFA VI, is develop the evidence 

standards, OK. How much evidence, so everybody understands 

what kind of evidence you need in order to rely upon a new biomarker, and also then evaluate new nominated biomarkers through 

the Cures process that was set up against those evidence standards. So we have to do both of these, so we need the kind of scientists who are able to do that sort of work. 

Mr. GUTHRIE. OK, thank you. The gentleman’s time has expired. 

Mr. CA ́ RDENAS. Thank you, Chairman. 

Mr. GUTHRIE. Thank you. I now recognize Mr. Long for 5 minutes for questions. 

Mr. LONG. Thank you, Mr. Chairman, and thank you, Dr. 

Woodcock, for being here today. I would like to spend my time with 

you discussing a very vulnerable population, one that I personally 

focused on helping. Every year, nearly 200,000 newborns in the 

United States are admitted to neonatal intensive care units for 

44 

treatment. Due to the numerous challenges and despite current pediatric incentives, the last new drug for this population was approved in 1999. 

Last year my colleague on this committee Ben Ray Lujan and I 

introduced the Promoting Life-Saving New Therapies for Neonates 

Act and are working to introduce the bill this year. Our bill would 

create a new incentive model by providing a narrowly targeted, 

transferable exclusivity voucher to drug sponsors who successfully 

develop products for neonates. 

Do you believe the current pediatric incentives have been successful in stimulating therapy development for newborns? 

Dr. WOODCOCK. No, not particularly, I do not. 

Mr. LONG. Given the lack of development, can you identify the 

challenges that you see from a regulatory perspective at FDA as 

well as research and development challenges for the industry? 

Dr. WOODCOCK. Well, I believe that we have taken steps recently 

along with the American Academy of Pediatrics and others, and 

our new head of pediatrics at FDA is a neonatologist. And together 

with her and others we have put together a network of NICUs, because part of the issue is the NICUs did not standardize their 

treatment protocols and so everyone had a different treatment protocol. So if we were going to ask a developer, a drug developer, to 

develop a drug in NICUs, every NICU director would want a different protocol. 

So the first thing that had to be done was say what is the standard of care in the NICU, in the neonatal intensive care unit, and 

then you can say what are the biggest unmet medical needs for 

neonates, and then you can start talking about, OK, do we have a 

trial network or do we have some type of infrastructure that could 

actually evaluate a new therapy were it developed? And they are 

working on doing that internationally which is really good news. So 

I would be happy to update you on the progress on that. 

Mr. LONG. This is a tough population to test drugs on. 

Dr. WOODCOCK. That is right. 

Mr. LONG. Are there steps you believe we could take in the upcoming user fee process to help spur much needed development for 

this vulnerable patient population? 

Dr. WOODCOCK. I don’t know in user fee process. My belief is, 

and I have talked to the American Academy of Pediatrics about 

this, that the heads of neonatal intensive care units need to get 

their program together, decide what the standard of care is, decide 

what the unmet medical needs are, develop trial structures so they 

could test new drugs, and if they make—if you build it they will 

come, in my opinion. If you make a pathway clear that developers 

could use, then I believe they will develop products for neonates, 

sick neonates. And I believe it is needed. 

Mr. LONG. OK, thank you. And once again thank you for being 

here today taking your time to be with us. 

And Mr. Chairman, I yield back. 

Mr. GUTHRIE. The gentleman yields back. Ms. Matsui is recognized for 5 minutes for questions. 

Ms. MATSUI. Thank you, Mr. Chairman. 

Thank you, Dr. Woodcock, for being here. It is wonderful to have 

you here. First of all, I want to mention that I am concerned with 

45 

the President’s budget proposal and how it might impact the work 

that this committee is doing to reauthorize these vital agreements 

that they have. And I don’t think it would be wise to renegotiate 

the user fee agreements that FDA and the industry have worked 

so hard to reach, nor do I think it would be wise to impose drastic 

cuts to the agency’s budget authority that would endanger the 

FDA’s ability to collect these user fees. FDA performs many critical 

functions to keep our food and drugs safe and we cannot afford to 

compromise that. 

Now I am particularly concerned about both the development 

and the final price of drugs for patients with rare diseases. These 

populations are often neglected and left with little or no treatments 

or cures. I want to ensure that we take advantage of our robust research efforts in this country for these rare disease patients. 

I am pleased that there are many provisions in the negotiated 

PDUFA agreement that would make important advances for this 

rare disease community, particularly building on the effort to include the patient experience in drug development ensuring that 

staff at FDA who have expertise in rare disease are integrated 

across different centers. 

Dr. Woodcock, can you elaborate on the provisions in PDUFA 

that would help patients with rare diseases? 

Dr. WOODCOCK. Well, I believe the biggest help is actually going 

to be in the patient focused drug development. And why is that, because rare diseases often are so rare there are not any doctors who 

really know what happens to the people. And so what we are encouraging and we are seeing now is the patients are getting together and they are having their own patient focused drug development meetings. 

They are collecting, and we have given some grants out to help 

with this, they are collecting natural history on their disease so 

people actually know what happens to someone with the rare disease. Often it is very disparate. Not everyone with that rare disease has the exact same course, so then it is even harder to study 

them. 

So we are encouraging them to develop natural history so we can 

help with trial designs and then maybe even outcome measures, 

like what is the most burdensome part of the disease? What would 

they like ameliorated? So that then if a company comes along and 

wants to develop they have a pathway to develop. So that is all 

baked into these agreements in rigorous ways of collecting that information and helping patient groups so they can develop these 

things. 

But also of course there is an agreement to integrate rare disease 

staff into review teams so that there is more, it is not all about 

blood pressure meds and gigantic trials and heart disease, OK, it 

is about people who have the very rare diseases pose different 

problems in development. 

Ms. MATSUI. Right. OK, can you talk more about the Breakthrough Therapy Program and what successes had it had and what 

additional resources help FDA with approval of innovative orphan 

therapies? 

Dr. WOODCOCK. Well, we were completely surprised after the 

Breakthrough provisions were passed that we got so many applicaVerDate Nov 24 2008 13:42 Jan 30, 2018 Jkt 037690 PO 00000 Frm 00051 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-18 CHRIS
46 

tions, all right, and so it has been extremely successful in getting 

designations. We are only supposed to designate drugs that preliminary data, their early data they develop in the clinic shows it 

may be a game changer in the disease. It may change the disease; 

it isn’t proven yet. 

I can get back to you with the actual numbers, but we have designated hundreds of these to our surprise—we thought it would 

only be a handful—and we have approved many. And so this is 

great news for patients, because many times when we approve 

these they actually are a game changer for that disease. 

Ms. MATSUI. OK. That is wonderful. You testified that surrogate 

endpoints have been the basis for 60 percent of rare disease approvals. Can you explain surrogate endpoints in laymen’s terms 

and why they are important for rare disease approvals? 

Dr. WOODCOCK. Surrogate endpoints are something other than 

how a patient feels or functions or how long they live. So that is 

our gold standard for approval, it makes you feel better or makes 

you function better or it makes you live longer. But often diseases 

take a really long time, OK, to have their manifestations. And say 

for diseases where you are missing an enzyme—that is many rare 

diseases. So you are missing an enzyme and you start accumulating that substance inside your body instead of eliminating it. 

Ms. MATSUI. Right. 

Dr. WOODCOCK. And we can give back these enzymes now, so 

sometimes we have accepted the fact that in vital organs that material goes away, all right. Well, that has to be really good news. 

It is not a hundred percent sure that doing that will reverse the 

symptoms of the disease, but it is pretty plausible, right? So often 

we give an accelerated approval like we were talking about saying, 

OK, we will get it on the market. All the patients can start taking 

this because is it removing this stuff from the body, but we want 

you to show with a registry or other that actually they are feeling 

better eventually, to make sure that is the truth. 

Ms. MATSUI. OK. Thank you very much, and I have gone past my 

time and I yield back. 

Mr. GUTHRIE. Thank you. The time has expired, and we recognize Mr. Bilirakis for 5 minutes for questions. 

Mr. BILIRAKIS. Thank you so much. I appreciate it, Mr. Chairman. And thank you, Dr. Woodcock, for coming today again. 

Recently the FDA issued a request for comment on a proposed 

Office of Patient Affairs. Can you tell us what the goal of this office 

is, how it fits into the agency with its current patient related programs, and how this office would benefit patients? 

Dr. WOODCOCK. The thought is that many patients don’t understand the structure of FDA. FDA has long been divided into Centers, and if you are kind of inside Washington, you know you call 

the Biologic Center and you call the Drug Center. But what do you 

do if you don’t know even who to call, right. So the thought is for 

medical products, not for foods or whatever, but for medical products, if people have questions about medical products there ought 

to be a little bit of a front-facing, patient-facing unit that can help 

people figure out who to ask the question. And so that is, I think, 

a lot of the rationale behind it. 

47 

Mr. BILIRAKIS. All right, thank you. Dr. Woodcock, in the 21st 

Century Cures Act we were able to pass reform language to modernize the Office of Combination Products. As you know, combination products are products on the market that have elements of a 

medical device and a drug, like inhalers and insulin injectors. 

Many patients need and rely on combination products, as you 

know. 

While we worked on the 21st Century Cures, I asked FDA about 

innovation in the drug and device space as more and more innovative products may be combination products. At the time there were 

complaints from innovators about the slow and burdensome FDA 

process for approving combination products. One of your colleagues 

at FDA stated in an hearing, ‘‘That is a place that does require 

probably further discussion and whether or not there are changes 

to be thought about to make that intersection work better than it 

currently does.’’ 

Can you update us on what the FDA is doing on the drug side 

to implement the Cures language for combination products and 

what was agreed to in the user fee agreement? 

Dr. WOODCOCK. Certainly. Well, what we are doing, the Cures 

product calls for work on this and the user fee program, the drug 

user fee program, actually provides resources for review of the device portion, OK, so that has been agreed to. But in advance of that 

we have set up a combination product council at the agency. We 

have mapped the different processes. We have revised them to 

make them more efficient. We are tracking them. We have standard forms and so forth, and I think everyone agrees that that is 

all going much better now. 

So even in advance of implementing these we have gotten sort 

of the basics down about how to do these reviews more effectively 

given that we agree with you, this is the future of products. But 

the PDUFA program proposes that more resources be given to the 

Device Center to conduct these reviews of drug related, drug-led 

combination products of which many of these are. 

Mr. BILIRAKIS. OK, very good. I yield back, Mr. Chairman. Thank 

you. 

Mr. GUTHRIE. The gentleman yields back, and Ms. Eshoo is recognized for 5 minutes for questions. 

Ms. ESHOO. Thank you, Mr. Chairman. Welcome, Dr. Woodcock. 

Dr. WOODCOCK. Thank you. 

Ms. ESHOO. It is always good to see you. Mr. Long is not here, 

but I wanted to say for the record that in FDASIA when we built 

that and passed it, I had language in that that required 

neonatologists being hired, and that was back in 2012. So I will 

talk to him later. I will be happy to work with him, but I think 

that that is important to set down for the record. 

The PDUFA was enacted in 1992. I was running for Congress 

when that was put into place. And at that time drug review times 

were lagging and the FDA simply really couldn’t keep up with the 

flood of new drug applications. So through these user fees paid by 

applicants it has given the FDA the resources it needed to hire and 

support more staff very specifically to move the applications forward. 

48 

I think the program overall has been successful at reducing review time backlogs, and even though the President criticized the 

FDA during his joint address to the Congress for, ‘‘having a slow 

and burdensome approval process,’’ I think the facts really dispute 

that claim. And we are always looking to improve it, but it has 

been instrumental in promoting the improvements we have seen 

over the past 25 years. 

Now I want to talk about two bills that I authored. I am very 

proud of them. One the BPCA, the Best Pharmaceuticals for Children Act; and the other, PREA, the Pediatric Research Equity Act. 

Both of these programs were permanently reauthorized in 2012, 

but I think today we need some improvements. We know that children are not just small adults; that drugs work differently in them 

than in adults and they have to be studied specifically for their 

use. That is why I authored both of these pieces of legislation. I 

think they have a track record of success, because more than 664 

drug labels have been revised with important pediatric information 

as a result of the two bills. 

So my question to you, Dr. Woodcock, is what is the implication 

of the orphan drug exemption in PREA on children’s health? Are 

there examples of orphan drugs that would have benefited from a 

pediatric study but were not studied as a result of the orphan drug 

exemption in PREA? 

Dr. WOODCOCK. I have to get back to you on specifics, are there 

any. In general, the orphan diseases, the rare diseases are sort of 

throughout life. Many of them start in childhood and so children 

are usually studied. 

So much of the pediatric drug development problems were the 

fact that drugs were studied for adult diseases and there would be 

a few children who had them, relatively speaking, and they weren’t 

ever studied, right, and it was used off-label in them, but in many 

of the rare diseases that rare disease starts in childhood and continues through. 

But there may be some instances, and we can get back to you 

about where the rare disease predominates in adults. There are 

only a few children, and perhaps then the exemption means that 

those children may not be studied, but in talking to the rare disease and the orphan staff and the pediatric staff they don’t believe 

this is a large problem. 

Ms. ESHOO. Well, orphan drugs are, as you know they are currently exempt from PREA’s—— 

Dr. WOODCOCK. Yes. 

Ms. ESHOO [continuing]. Pediatric study requirements and that 

is why I am asking about it. Before the BPCA and PREA, the vast 

majority of drugs, more than 80 percent used in children were used 

off-label and without data on their safety or efficacy, and today 

that number has been reduced to approximately 50 percent, but 

that is still a lot. That is still a lot. 

Why, if FDA has the authority to issue civil monetary penalties 

for other violations of the Food, Drug, and Cosmetic Act, including 

violations of post-marketing requirements, do you think that the 

FDA should be prohibited from using that authority to ensure compliance with PREA post-marketing requirements? 

49 

Dr. WOODCOCK. That is a legal question and we would be happy 

to work with you and get back to you on that. 

Ms. ESHOO. But do you have any thoughts on it? You deal with 

legal all the time. 

Dr. WOODCOCK. I do. 

Ms. ESHOO. You live within a legal framework. 

Dr. WOODCOCK. That is correct. The civil money penalties provisions and those provisions are apparently rather difficult to operate 

and implement, but so I would prefer getting back to you with the 

agencies. 

Ms. ESHOO. Sure. That is fine. Thank you very much. 

Thank you, Mr. Chairman. 

Mr. GUTHRIE. Thank you. The lady yields back, and I now recognize Mrs. Blackburn for 5 minutes for asking questions. 

Mrs. BLACKBURN. Thank you, Mr. Chairman. 

Dr. Woodcock, you were so patient to come to us regularly, and 

we do appreciate it because we are so interested in making certain 

that things that are supposed to be done are tended to. 

As Chairman Upton mentioned, 21st Century Cures, the implementation there, of course the Children Count Act which I had had 

that component, that is something that we are going to watch very 

closely and so we do appreciate the updates. We know it takes a 

lot of time to come up here, but we are very appreciative. I just 

want to quickly look at the abuse deterrent opioids and the components that are there. March 2016, you did the draft guidance. 

When is there going to be the final guidance on that? What is the 

expectation? 

And then I want to know, I know we have touched around the 

edges on this, but talk a little bit about the actions that can and 

should be taken from you all to advance the abuse deterrent 

opioids and to get these into the marketplace, just a little bit there. 

And that is really my only two questions. 

Dr. WOODCOCK. Certainly. Well, as far as the guidance, it is very 

difficult ever to give a firm date certain when a final is going to 

come out. 

Mrs. BLACKBURN. Just an expectation or timeline. 

Dr. WOODCOCK. Well, let me just assure you that we are putting 

great effort into this, because really what we need to do, we think, 

is incentivize innovator development of various abuse deterrent formulations. The current ones, as we have already discussed, are 

kind of version 1.0 and surely we can do better, right. And so there 

has to be probably some incentives there. 

And then generics, we need a pathway so that the generics understand what they would have to do to show that they source exactly the same as the innovator, because uptake of these abuse deterrent formulations is lower because there are a lot of old opioids 

on the market that are very inexpensive that are not abuse deterrent. 

And that is often for health systems the preferred opioid to use 

to save money, so we need a progression of incentives and also a 

clear pathway. But the innovation needs to go from the innovators, 

the people who are out there trying to figure out better ways to 

deter abuse. 

50 

Mrs. BLACKBURN. Right, but are we talking 6 months, a year? I 

mean, when do you think there will be a final decision—— 

Dr. WOODCOCK. A final guidance for the generic? 

Mrs. BLACKBURN. Yes. 

Dr. WOODCOCK. I would hope within 6 months, I certainly would. 

Mrs. BLACKBURN. That is great. And then if you will speak just 

a little bit toward what further the FDA can do to spur the abuse 

deterrent opioids. 

Dr. WOODCOCK. Sure. There are many things we are trying to do, 

one of them though is trying to incentivize development of drugs, 

new drugs that don’t have these abuse liabilities to treat pain, and 

we have approved a number of them. They are often for specific 

conditions. 

For example, we approved one for neuropathic pain and that is 

now being used by the neurologist, those drugs, instead of opioids 

because opioids aren’t very good for neuropathic pain. So that cuts 

out one category of people who are getting these opioids. 

So we want to stimulate and we have been working on this for 

years with the outside world, scientific world, trying to stimulate 

the development of drugs that aren’t opioids that don’t have these 

abuse liabilities, because people are going to continue prescribing 

opioids for people in pain unless they have something else to offer. 

So also we have workshops and we work on abuse deterrent formulations to try and stimulate and work with innovators on new ways 

to deter abuse. 

Mr. GRIFFITH. The gentlelady yields back. Mr. Butterfield is recognized for 5 minutes for questions. 

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

Let me just begin by thanking you and Dr. Woodcock, for coming 

back. You have been at that table many times and thank you so 

very much. Chairman Burgess, who is not here today, but I want 

to thank him for holding this hearing on the Prescription Drug 

User Fee Agreement reauthorization. 

Since I came to Congress some 12 years ago back in ’04, Congress has come together under the leadership of both Democrats 

and Republicans to pass this important bipartisan legislation. Just 

last year we passed the 21st Century Cures Act that this committee drafted and passed unanimously to help boost the resources 

of the Food and Drug Administration and encourage the development of new treatments. 

For my constituents in North Carolina, developing new treatments can literally make the difference between life and death. 

Health outcomes for many in the communities that I represent are 

deeply concerning. Many of my constituents are African American 

citizens. By most measurable health statistics, outcomes for African 

Americans lag far behind. Supporting the reauthorization of 

PDUFA is important to finding new treatments to help reduce 

health disparities for my constituents and indeed Americans all 

across the country. 

Through additional resources made possible by PDUFA V, the 

FDA has been able to work with industry to make available new 

treatments for rare diseases through the Breakthrough Therapy 

Program. Through November of last year, FDA has granted, I am 

told, 165 breakthrough therapy requests. This includes treatment 

51 

in many areas that disproportionately impact my constituents and 

African Americans throughout the country. 

Breakthrough designations have been granted for diseases like 

HIV and hepatitis C, and colorectal cancer, all of which impact minorities at high rates. PDUFA VI has the potential to make advancements in areas from breakthrough therapies and real-world 

evidence to clinical trials and biomarkers. The additional resources 

made possible through the proposed new fee structure can help 

FDA build the workforce needed to complete these new tasks. 

However, this administration’s executive actions and proposed 

budget do not seem to understand the importance of FDA’s mission 

to help patients and improve public health. The impact of a hiring 

freeze on the FDA implemented by the Trump administration is 

still unclear. Also the administration’s budget proposal fails to understand the good-faith effort that has been put forth by the FDA 

and by industry and patient advocacy groups all working together. 

Now is the time to come together to support the FDA. Our constituents are counting on us, my colleagues, to work together in this 

space. 

Dr. Woodcock, I am excited by the innovations occurring in cancer drug development as cancer drugs are now being developed by 

molecular target. By identifying the drivers of the cancers, these 

new molecularly targeted drugs are achieving great new strides in 

treatment and providing greater health to cancer patients. These 

targeted drugs are often effective for many types of cancers. 

Question, are innovative new cancer treatments for adults also 

tested for children with the same targets as adult cancers? 

Dr. WOODCOCK. Not generally. The paradigm is changing and 

typically over time treatments for cancer as well as other disorders 

have been according to disease. So in cancer it is what we call histology, which basically means the organ that the cancer originated 

in. That is why we call it colon cancer or we call it whatever cancer, lung cancer, right. 

But these molecular alterations may go across diseases and it 

may be only a small subset of each of these cancers are driven by 

the same molecular alteration. That isn’t something that has really 

been looked at very closely in children. It may be that there are 

rare mutations in children that are the similar as the mutation in 

adult for these molecular targeted therapies. 

Mr. BUTTERFIELD. OK. Also my colleague Representative McCaul 

of Texas and I introduced the RACE for Children Act, H.R. 1231, 

to promote the discovery of new cures for children with cancer. 

First, the RACE for Children Act would provide that a drug company will provide a pediatric study plan of a drug pursuant to the 

Pediatric Research Equity Act if the drug is, ‘‘intended for the 

treatment of an adult cancer and is directed at a molecular target 

considered to be germane to the growth and progression of such pediatric cancer.’’ 

Do you believe this provision would create greater access to novel 

cancer drugs for pediatric cancer research? 

Dr. WOODCOCK. I am not able to comment on that at this time, 

but we would be happy to work with you on this. 

52 

Mr. BUTTERFIELD. All right. We are deep into this and we would 

like all the help we can get. Secondly, the RACE for Children Act 

would end the—I am over, yes. I yield back. 

Mr. GUTHRIE. I yield back. Thank you for yielding back. I see no 

questions on the majority side. Mr. Sarbanes, you are recognized 

for 5 minutes for questions. 

Mr. SARBANES. Thank you, Mr. Chairman. 

Thank you, Dr. Woodcock, for joining us. I have been here 10 

years, I think on four or five different committees. You are my alltime favorite witness. I just want you to know that. Because you 

are so professional in your presentations, so knowledgeable, and 

you play things straight, so I appreciate your being here. 

I am fascinated by this idea of including, incorporating realworld evidence in regulatory decision making. I mean the implications of it are kind of humorous because it suggests that up until 

now there hasn’t been real-world evidence in the process, but I certainly understand what it is meant to convey. 

And I was wondering if you would just talk a little bit about that 

topic. And obviously the agency is going to have to come up with, 

and I know you are in the process of doing this, a kind of formal 

process for identifying what qualifies as real-world evidence and 

then how it gets gathered and then how it gets translated back to 

the agency, how much weight is given to it as part of the overall 

analysis that is done by the staff there at the FDA. So if you could 

maybe just talk about that a little bit more that would be helpful. 

Dr. WOODCOCK. Certainly. Well, FDA runs actually one of the 

largest real-world evidence gathering operations that is around in 

the health area, which is our Sentinel System, which is for drug 

safety and was mandated by Congress. And there we have 193 million different people’s claims data that we can access, all right, 

anonymously, and we use that for drug safety analysis. 

And the Congress told us that that should be used first rather 

than requiring companies perhaps to do specific observational studies. And recently, as we have institutionalized this system there 

are four programs where we are able to do something in Sentinel 

and not require additional outside studies, but that is safety. 

Now on the effectiveness side, obviously you would only collect 

real-world data if the drug were on the market, OK, because before 

a drug gets on the market data is collected into clinical trials, it 

is not just collected into doctor’s offices. So that would be after a 

drug is marketed can we collect patient experience data to perhaps 

broaden the indication or add new indications or whatever. 

Mr. SARBANES. Can you comment on how sort of off-label use relates to that? 

Dr. WOODCOCK. Well, it does relate to it, because often, for example, let’s take these oncology drugs and these targeted drugs. So 

they target a specific target. We may approve it for a number of 

tumors, but then there may be somebody who comes in and they 

have a rare tumor or a tumor that this is an unusual type and they 

have that mutation. So the physician may treat them with the targeted agent and that would be considered off-label use although it 

is completely rational, right. 

So what we are working with a large number of outside parties 

who are gathering this information up in different ways and then 

53 

they want to collect that experience of the patients, those rare patients, and then perhaps if they responded and we can document 

that then maybe we can add that to the label and say if you have 

a rare patient like this come in they should be treated with this 

targeted therapy too. So that is an example. 

There also are registries, and some people consider those realworld evidence and some don’t. But we are trying to put registries 

together, get that registry information, make sure it is—— 

Mr. SARBANES. Just on that point again intrigued me. What 

would make certain people consider a registry real-world evidence 

and other people not consider it real-world evidence? 

Dr. WOODCOCK. Yes. Well, some people are sort of purists and 

they consider real-world evidence only collected like in the course 

of ordinary medical care and of stock, OK. Other people consider 

it evidence that is collected during the course of treatment even if 

you add a few bells and whistles. So we really don’t care. This is 

evidence outside of standard clinical trials, so let’s figure out for all 

of it what can we do to gather more information about performance 

of drugs outside of your traditional clinical trial. 

Mr. SARBANES. Would you imagine that at the end of this process 

adding this to your portfolio, if you want to call it that, that there 

would be maybe some kind of advisory council or group that the 

FDA would bring into the process of identifying real-world evidence? I mean, what kind of structures do you think we might see, 

or is it premature to—— 

Dr. WOODCOCK. I think what you would see is a series of policy 

sort of guidances or pronouncements by the FDA as we are able to 

broaden our uses of and examples of how we have used it. And in 

some of those cases we may take it to a specific advisory committee, say we think we should add these, say, tumors to the label 

because here is the real-world experience and it looks like these 

people respond and they would never get in a clinical trial because 

they are rare or whatever. 

So that I think is the kind of accumulating information. We can’t 

just have people sort of think great thoughts absent examples of 

what can be done. 

Mr. SARBANES. Right, thanks very much. I yield back. 

Mr. GUTHRIE. Yes, thanks, time has expired. And seeing no other 

members here to ask questions—well, thank you, Dr. Woodcock, for 

being here. I concur it is always great to have you here and you 

always do a good job. I appreciate it. 

Dr. WOODCOCK. Thank you. 

Mr. GUTHRIE. We will now transition to our second panel. 

Thank you. We want to thank all of the witnesses for being here 

today and taking the time to testify before the subcommittee. As 

a reminder, each witness will have the opportunity to give an opening statement followed by a round of questions for members. 

Our second panel of witnesses includes Mr. Jeff Allen, President 

and CEO, Friends of Cancer Research; Ms. Kay Holcombe, Senior 

Vice President of Science Policy, Biotechnology Industry Organization; and Dr. Anne Pritchett, Vice President of Policy and Research, Pharmaceutical Research and Manufacturers of America. 

54 

We appreciate you all being here, and we will begin the panel 

with Mr. Allen, and you are now recognized for 5 minutes for an 

opening statement. 

STATEMENTS OF JEFF ALLEN, PHD, PRESIDENT AND CEO, 

FRIENDS OF CANCER RESEARCH; KAY HOLCOMBE, SENIOR 

VICE PRESIDENT OF SCIENCE POLICY, BIOTECHNOLOGY INDUSTRY ORGANIZATION; AND, ANNE PRITCHETT, PHD, VICE 

PRESIDENT OF POLICY AND RESEARCH, PHARMACEUTICAL 

RESEARCH AND MANUFACTURERS OF AMERICA 

STATEMENT OF JEFF ALLEN 

Mr. ALLEN. Good morning, Vice Chairman Guthrie, Ranking 

Member Green, and members of the subcommittee. It is an honor 

to be here today to provide the perspective of Friends of Cancer Research. The current pace of scientific discovery represents an unparalleled opportunity to improve human health. The critical component to this is an FDA that is highly responsive to public health 

needs and able to evolve with cutting edge science. 

Prior to the initial user fee authorization in 1992, patients in 

other parts of the world were gaining access to new medicines more 

readily than Americans with only about ten percent of new treatments reaching U.S. patients first. Today that paradigm has been 

reversed. Funds through the PDUFA mechanism have allowed the 

FDA to make the review process more predictable, efficient, and accessible. In fact, our data indicates that for new cancer drugs approved by both the FDA and the European counterpart, 97 percent 

were available in the United States first. Furthermore, the FDA 

approved them on average nearly 6 months faster. 

This sixth authorization of the user fee agreement comes at a 

critical time for the agency and for patients. It will support numerous initiatives, a couple of which I would like to mention today. 

PDUFA VI advances the role of patients and their experiences. 

PDUFA V, in the 21st Century Cures Act, provided important steps 

to incorporate the patient perspective in drug development. 

The PDUFA VI agreement will further assist organizations, researchers, in collecting patient experience data, create channels for 

providing such data to the FDA, and it will help develop methods 

for analyzing it. PDUFA VI supports the Breakthrough Therapy 

Designation. This designation to expedite the development of highly promising new drugs has been rapidly implemented. To date, 

170 designations have been granted leading to 79 approvals. 

Upon examining the pre-market development time of new cancer 

drugs, we found that it was over 2 years shorter for breakthrough 

designated drugs than for those without the designation. PDUFA 

VI will provide resources necessary for continued success. PDUFA 

VI promotes qualification and use of drug development tools that 

can help identify patients for which a drug is likely to work, offer 

early indicators of toxicity to help improve patient safety, and in 

some cases indicate that a drug will have long term benefit. The 

agreement will help create a process in which new tools can be accurately assessed and ensure their appropriate use. 

PDUFA VI enhances the use of real-world evidence. Once a drug 

reaches real-world populations there may be unanswered questions 

55 

about its effects, particularly in patients not represented in clinical 

trials. The collection of real-world evidence allows for a greater understanding of drugs currently in use. By allocating user fee funding toward these programs, the FDA and other stakeholders will be 

able to identify limitations and explore different opportunities for 

the use of data collected from post-market experience. 

To that end, FDA approved labels should be a vitally important 

source of information to guide the safe and effective use of prescription drugs. However, in some instances, such as drugs that have 

gone off patent, labels may have become outdated and no longer reflect optimal use. This is illustrated by extensive discrepancies between FDA approved labels and widely accepted practice guidelines. 

The FDA could play a greater role in evaluating the relevant 

data to update the product label as appropriate and adjudicate between the uses backed by strong evidence and those backed by less 

persuasive information. This would establish a high standard for 

post-market evidence and make the product labels more useful. For 

the programs of this proposed user fee agreement to succeed, the 

full budget of the FDA must be robust and the capacity of which 

the agency can maintain and hire the best scientific minds must 

be unencumbered. 

Despite opportunities afforded by PDUFA VI, the passage of the 

21st Century Cures Act, and the enormous contributions of this 

committee, I would be remiss to state that the FDA and the people 

who rely on it are optimally positioned at present. The proposed 

cuts to biomedical research will put the brakes on the engines of 

discovery and jeopardize the development of new medicines for patients. Holding the FDA budget authority at stagnant levels prevents progress on agency functions that are not covered by user 

fees. 

Among the challenges that have been exacerbated in the current 

environment is the implementation of the FDA Oncology Center for 

Excellence, an innovative approach and a new model for collaboration. The potential of a detrimental budget and the presence of the 

current hiring freeze put the OCE and so many other transformational opportunities at significant risk. For the people who 

currently depend on safe and effective medicines, for those who are 

holding strong for the breakthroughs to come, and for every future 

patient, there isn’t time to waste. We urge Congress to swiftly pass 

the sixth reauthorization of PDUFA. Thank you. 

[The prepared statement of Jeff Allen follows:] 

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Mr. GUTHRIE. Thank you. Thank you for your testimony, and I 

now recognize Ms. Holcombe for 5 minutes for your opening statement. 

STATEMENT OF KAY HOLCOMBE 

Ms. HOLCOMBE. Mr. Vice Chairman, Ranking Member Green, 

and members of the subcommittee, Bio appreciates the opportunity 

to speak with you today about the sixth reauthorization of the Prescription Drug User Fee act. Let me begin by stating unequivocally 

that BIO strongly supports this PDUFA VI user fee agreement and 

its timely authorization. 

Nearly 25 years ago, completing action begun by this committee, 

Congress passed the first PDUFA after agreeing with FDA and the 

biopharmaceutical industry that providing additional staff funded 

by user fees would help FDA review applications more quickly. You 

were shown to be spectacularly right. Today in this final year of 

PDUFA V, FDA is the most efficient drug regulatory agency in the 

world. American patients are the beneficiaries. 

The success of PDUFA in bringing down the time of new drug 

review has led over the years to substantial expansion of the program in terms of the numbers and kinds of commitments FDA has 

made annually from increasing its efficiency in communicating 

with drug developers to enhancing its post-market surveillance and 

monitoring of drugs throughout their life cycles to applying best review practices across all review divisions to enhancing processes to 

review and approve therapies for rare diseases to executing systematic approaches to measuring the benefit-risk ratio of potential 

drugs and to seeking and incorporating patient perspectives in that 

assessment. 

What has worked relative to review of applications has also made 

a difference in drug development. In PDUFA VI that is taken to 

a new level. FDA formal review time is the mere tip of the iceberg 

of time patients wait for new drugs. Review timelines are significant not only because they are short, but also because they are predictable and predictability is critical for companies making investment decisions. It would be highly desirable if the same sort of efficiency and predictability were achieved throughout drug development. 

PDUFA VI builds on the proven premise that greater and more 

productive interaction between drug developers and FDA works. It 

leads to better outcomes and to more efficient development programs. A greater focus on drug development improvements in 

PDUFA VI is not at the sacrifice of what has been achieved for review times, 8 months for priority applications and 12 months for 

standard. 

The PDUFA VI goals, including expanding expertise in diverse 

statistical methods, piloting innovative clinical trial designs and 

computer modeling and simulation, use of biomarkers as surrogate 

endpoints, and more frequent and appropriate use of real-world 

evidence or big data will transform drug development. All of these 

goals which attempt to bring 21st century science to the fore in this 

agreement will augment, not completely replace, tried and true 

methods of data collection. In the end, these new approaches will 

add to the old to make drug development more efficient while not 

72 

compromising the statutory gold standard of substantial evidence 

of safety and effectiveness. 

PDUFA VI also will take patient focused drug development to 

new levels. The message of these commitments is that the patient 

voice truly matters, in the beginning when early studies show a 

promising treatment and at the end when FDA is making its decision about a product’s benefit and risk. PDUFA VI will bring the 

patient voice to the forefront, changing it from a voice with a compelling story to a voice that provides evidence, verifiable, valid evidence that is appropriate for the drug label. 

Finally, Mr. Chairman, I want to emphasize how crucial it is 

that FDA has the ability to hire and retain the people it needs to 

carry out its PDUFA goals and to do that without jeopardizing the 

other significant parts of its public health mission. PDUFA is a 

carefully negotiated agreement that takes account of input from all 

stakeholders including FDA, industry, patient and consumer 

groups, and others. The key questions on the table are what needs 

to be changed or enhanced and what is the actual verifiable cost 

of achieving those goals? 

The majority of costs paid by user fees are for personnel. This 

agreement is carefully crafted to ensure that FDA can bring those 

people on board who are needed to meet the goals, employees who 

costs are paid by user fees. In PDUFA VI, the annual hiring goals 

are included in the agreement. This allows the public a line of sight 

into whether goals may fall by the wayside as a result of an inability to hire. 

Mr. GUTHRIE. Thank you. You need to summarize or is that your 

conclusion? 

Ms. HOLCOMBE. In conclusion, I want to reiterate BIO’s strong 

support for this agreement. It satisfies our basic goals of financial 

transparency, long-term program viability, hiring and retention improvements to ensure stability and achieve the agreed-upon goals. 

The vision of PDUFA VI is the vision of 21st Century Cures. Put 

patient needs—— 

Mr. GUTHRIE. Thank you. 

Ms. HOLCOMBE [continuing]. For access to new medicines first. 

[The prepared statement of Kay Holcombe follows:] 

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Mr. GUTHRIE. Thank you very much. Now Dr. Pritchett, you are 

recognized for 5 minutes for opening statement. 

STATEMENT OF ANNE PRITCHETT 

Ms. PRITCHETT. Good morning, Vice Chairman Guthrie, Ranking 

Member Green, and members of the subcommittee. I am please to 

appear before you to provide PhRMA’s perspective on the timely reauthorization of PDUFA. PhRMA, as you know, represents the 

country’s leading innovative biopharmaceutical research companies 

which are devoted to developing new medicines that enable patients to live longer, healthier, and more productive lives. We appreciate the opportunity to testify and share our views on PDUFA 

VI. 

For over 2 decades, PDUFA has helped to bring innovative medicines to patients by providing greater clarity and predictability in 

the science-based drug review process. Today, I just want to briefly 

share PhRMA’s perspective on the PDUFA program and key elements of the PDUFA VI agreement. 

First, I just want to note that we view user fees as an important 

mechanism to support the critical work of the FDA and human 

drug review process, and note as a result of this program over 

1,500 new drugs and biologics have been approved since 1992. The 

number of new medicines being approved on their first review cycle 

is at a historic high, and as we heard earlier, the review times 

have dramatically dropped by more than half since the 1990s as a 

result of this agreement. 

As a result of PDUFA, the U.S. leads the world in the introduction of new medicines and is a global leader in biopharmaceutical 

R&D. I would note at a time when other countries are seeking to 

attract and grow their own biopharmaceutical presence due to its 

far-reaching economic impacts, it is more critical than ever that we 

ensure that the U.S. retains its competitive advantages which includes a science-based gold standard regulatory system in the FDA, 

one that facilitates the ability of our industry to harness the latest 

scientific and technological advances and to translate those into 

new treatments and cures for patients. 

I would note that PDUFA VI is a result of extensive negotiations 

between the FDA and the innovative biopharmaceutical industry 

and it really includes unprecedented input across all stakeholders. 

Patients and patient advocates in particular played an important 

role by providing input on potential PDUFA VI goals through formal stakeholder meetings with the agency as well as frequent 

interactions with industry, and that feedback is reflected in several 

of the provisions. I would note failure to reauthorize PDUFA in a 

timely manner would obviously negatively impact the FDA’s ability 

to carry out its important role in fostering the introduction of new 

medicines to patients. 

And I want to briefly touch on some key elements of the agreement. First, obviously PDUFA VI facilitates science-based integration of the patient perspective into the development and regulatory 

review of innovative medicines. Over the course of PDUFA VI, FDA 

will be holding a number of workshops to gather stakeholder input 

to inform a range of guidances that are focused on how do we betVerDate Nov 24 2008 13:42 Jan 30, 2018 Jkt 037690 PO 00000 Frm 00090 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-18 CHRIS
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ter incorporate the patient element into all stages of drug development and review. 

Second, PDUFA VI enhances the FDA’s access to the tools, processes, and expertise necessary to ensure that the FDA is ready for 

the 21st century, the latest scientific advances in drug development 

and regulation. Specifically, as mentioned by other witnesses, there 

will be an increase in the FDA’s capacity to qualify biomarkers. 

The agreement advances the use of real-world evidence building on 

21st Century Cures facilitates the appropriate use of innovative 

clinical trial approaches. 

Third, PDUFA VI will accelerate the development and availability of new medicines to patients while providing the scientific 

and regulatory predictability that will foster a continued biopharmaceutical innovation. PDUFA VI not only builds upon the 

highly successful new molecular entity review program, which has 

led to shorter review times and an increase in first cycle reviews, 

but it builds upon it by incorporating additional metrics. 

Fourth, PDUFA ensures that the FDA will be able to hire and 

maintain a strong scientific medical and regulatory workforce to 

advance its public health mission. For the first time, PDUFA VI includes detailed hiring goals and includes dedicated resources for 

the recruitment and retention of a world-class scientific workforce. 

And I would note it also includes independent outside consultants 

to help facilitate the agency in developing a comprehensive hiring 

strategy. 

And finally, the agreement builds on key provisions of the 21st 

Century Cures Act by further advancing real-world evidence, incorporating that into a structured benefit-risk framework, patient-focused drug development, biomarker qualification, as well as includes a number of improvements to combination product review. 

I want to conclude by saying PhRMA and its member companies 

we are committed to working closely with the FDA, your committee, Congress, and all stakeholders to ensure the continued success of PDUFA in bringing safe and effective innovative medicines 

forward to address unmet medical needs for all patients. We believe that moving all of the UFA’s forward in a timely manner is 

important to supporting the FDA’s mission of protecting public 

health and promoting innovation, as well as critical to supporting 

our shared goals of fostering continued competition and innovation. 

Thank you for the opportunity to testify today. 

[The prepared statement of Anne Pritchett follows:] 

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Mr. GUTHRIE. Thank you all for your testimony, and we will now 

move into the question and answer portion for our second panel. 

And I will begin the questioning and recognize myself for 5 minutes. 

First, I would like to request unanimous consent for entering the 

following statements in the record: the Rare Disease Legislative 

Advocates, the RDLA blog, PDUFA RDLA, Congress Begins Process of Reauthorizing Prescription Drug User Fee Act; a letter from 

the Epilepsy Foundation, letter; number three, National Venture 

Capital Association blog post on PDUFA; and four pieces I am asking to enter into the record, National Organization for Rare Diseases and Friends of Cancer Research joint statement on PDUFA. 

Mr. GREEN. No objection. 

Mr. GUTHRIE. No objection, so ordered. 

[The information appears at the conclusion of the hearing.] 

Mr. GUTHRIE. So Mr. Allen, actually Mr. Sarbanes was talking 

about this earlier with Dr. Woodcock, and where I kind of wanted 

to look at about labeling. And after a drug is approved, more and 

more information is often learned about it. This can include new 

uses, more tolerable doses, et cetera. And for cancer drugs, can you 

talk about the disparity between the information in products labeling and how the drug is actually being prescribed and administered 

by oncologists? 

Mr. ALLEN. Sure. So typically a manufacturer would, if they are 

pursuing an additional indication for a drug, would take it and submit it through the supplemental new drug application at the FDA 

for that information to be evaluated. But in some instances like I 

mentioned, when a drug is off patent or perhaps even for a particularly rare population where a clinical trial is difficult or infeasible, 

or in some cases because the drug has been on the market for so 

long may be unethical, the label oftentimes doesn’t reflect the practice and the use of that drug over time. 

And what we found by comparing the FDA labels to practice 

guidelines that are constructed by medical oncologists is that the 

uses that are recommended by expert oncologists are usually far 

beyond that of what is contained in the FDA label. So the question 

is, should the product label have a role in the agency which we 

trust to evaluate medicines for them to get on the market, should 

they have a more active role in looking at potential label modifications further down the life cycle of the drug to ensure it is supported by the highest quality evidence. 

Mr. GUTHRIE. Do you think FDA needs to clarify when and how 

companies can provide such information? 

Mr. ALLEN. In terms of when it can be supplied to them? 

Mr. GUTHRIE. Yes. 

Mr. ALLEN. I think it could—— 

Mr. GUTHRIE. When it needs to be. 

Mr. ALLEN. The agency certainly does in terms of safety, but the 

same mechanisms aren’t in place with regards to alternative uses. 

So one could imagine that perhaps it is worth having a longer discussion about the ability for over a certain period of time perhaps 

after the patent expires that there be some process for review of 

post-market evidence in order to make sure that the way the drug 

is being used is supported by the highest quality of evidence, so the 

94 

people who are prescribing and using it are able to tell the difference between what is high quality and what is just an anecdotal 

use. 

Mr. GUTHRIE. OK. And I had another question, but I think you 

did answer it that do you believe FDA should play a more active 

role in updating product labeling, and you answered that actually 

when you answered the first question. 

Mr. ALLEN. Yes. I think it is worth a longer conversation because 

obviously there are resource implications. But given the oncology 

anyway there are highly qualified professional guidelines that 

might help the FDA conduct post-market analyses when it is appropriate to review a growing body of evidence. 

Mr. GUTHRIE. Right. Yes, that is something that we just need to 

work to make sure we can clarify that because I think Dr. 

Woodcock was sharing similar to that when she was talking to Mr. 

Sarbanes about, some oncologists has a different tumor that this 

actually has effect for and works for and would be logical to use, 

but we need to make sure that it can be done through the process. 

So thanks for your testimony, and actually I will yield back my 

extra minute and I will yield to Mr. Green, 5 minutes for questions. 

Mr. GREEN. Thank you, Mr. Chairman. 

Ms. Holcombe, current statute outlines a detailed process for reauthorization of the PDUFA. The FDA is charged not only with negotiating with the industry to develop recommendations, but also 

to solicit public input and hold public hearings and consult periodically with Congress and patients and consumer groups, among others. The recommendations that are a result of this process must 

also be available publicly for the public comment and ultimately required by statute to be transmitted to Congress by January 15th 

of this year. The process that led to the ultimate transmission of 

FDA PDUFA VI recommendations kicked off nearly 2 years ago in 

July of ’15. 

Ms. Holcombe, can you further discuss industry’s role in the reauthorization of PDUFA and particularly the timeline for these activities? 

Ms. HOLCOMBE. So as you point out, Mr. Green, this process 

began in July of 2015 with a public meeting at which all stakeholders were provided an opportunity to testify, and industry took 

advantage of that opportunity and presented our views about the 

importance of PDUFA in general and about some specific enhancements to the program that we would be seeking in our negotiations 

with FDA. Those negotiations kicked off approximately 2 months 

later and lasted then for over 12 additional months and were intensively focused on the calculation of what could be done and how 

much it would cost to do each one of those things. 

And both FDA and industry put ideas on the table, and those 

ideas were frequently, if not every single time, informed by the 

input of other meetings that were going on simultaneously with patients in the other groups that you mentioned, so it was a very long 

process and I would say mathematically and statistically a very 

precise process. 

Mr. GREEN. Well, since this is our sixth time on it, hopefully we 

learn something every time. 

Ms. HOLCOMBE. Well, we are getting faster. 

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Mr. GREEN. OK. The statute requires that a recommendation be 

transmitted to Congress no later than July 15th of ’17, a deadline 

they met. Does the statute allow the FDA to transmit recommendations for reauthorization at an alternative date? 

Ms. HOLCOMBE. Not that I am aware of. 

Mr. GREEN. OK. PDUFA expires on September 30th of ’17. What 

would be the impact for your member companies if Congress did 

not pass the reauthorization of PDUFA before the September 30th 

deadline? 

Ms. HOLCOMBE. I think we would describe the implications as titanic in nature. FDA would be required, if this were not reauthorized, to reduce its force by probably in the Drug Center alone about 

5,000-plus individuals, and those are the people who review our applications. But even more importantly than the review of applications, which as we have all said today is merely the tip of the iceberg of our process of drug development, it would absolutely disable 

any process that FDA has for talking to us during drug development about how to be more successful in our program. 

Mr. GREEN. Do you support and your industry support PDUFA 

VI recommendations as transmitted to Congress? 

Ms. HOLCOMBE. Yes, we do. 

Mr. GREEN. OK. You note in your testimony that the drug development process, the most time-intensive part of bringing a drug to 

market, it is my understanding that on average it takes between 

10 to 12 years to develop a drug. Recognizing this, we included in 

the 21st Century Cures a revision that would have FDA host a 

public workshop and issue guidance on innovative trials and designs and approaches. 

Would you please explain further how innovative trial designs 

may help your member companies in bringing treatments to market quicker and, in addition, would you discuss how PDUFA VI 

builds off of the Cures’ effort to support the use of innovative drug 

trial designs? 

Ms. HOLCOMBE. Yes. So as my testimony pointed out great minds 

think alike, and we in the industry as well as FDA itself agreed 

a hundred percent with you in your identification in 21st Century 

Cures of the importance of thinking of different ways to do clinical 

trials than the traditional way of randomized controlled trials. 

Often clinical trials have to enroll many, many people and they 

take a long time. And as Dr. Woodcock pointed out, they often have 

high dropout rates. Patients can’t stay in them, and these cause 

drugs to fail and at great expense to companies that are developing 

them. So innovative ways of thinking, creative ways of thinking 

could we do trials differently and therefore make them shorter and 

smaller but still come out with the substantial evidence of safety 

and effectiveness that we all need to have and the answer to that 

is yes, we can. 

Mr. GREEN. OK. Mr. Chairman, I know my time has expired. 

And Mr. Allen, I would like to submit some more questions to you, 

but obviously FDA is working with you on the off-label usage that 

practitioners learn, and we need to be able to learn what they are 

learning so we can actually make those pharmaceuticals available 

and go back through the FDA process as brief as we could do to 

make sure those cures are there. So thank you, Mr. Chairman. 

96 

Mr. GUTHRIE. Thank you. Thank you. The gentleman’s time has 

expired. Dr. Bucshon, you are recognized for 5 minutes for questions. 

Mr. BUCSHON. Thank you, Mr. Chairman. First of all, I mean, I 

also want to go on the record saying I have concerns about the 

budget proposal as it relates to research, the NIH and above. I 

don’t think that is a partisan issue. 

The question I have is as we transition to new models to approve 

medicines we have been talking about that whether that is changes 

in clinical trials or other things, how do you see the legal environment evolving to allow this to happen? I will start with Dr. 

Pritchett. Because, I mean all of us are realists. I was a medical 

doctor before, as you transition to a new way to approve a product 

there is going to be people out there that are looking to throw a 

wrench into the gears by saying it didn’t prove what it was supposed to prove and that is why my particular client has been hurt. 

And so I mean there are legal ramifications of trying to do this 

also, any thoughts? 

Ms. PRITCHETT. So I think as I understand your question, as we 

think about looking at innovative, new approaches to clinical trials, 

collection of real-world evidence and how do we apply this to drug 

development and then how do we ensure that we are using them 

in a robust way so that we are reducing any potential concerns related to liability, ensuring that we aren’t approving medications 

without appropriate evidence—— 

Mr. BUCSHON. Essentially that is the question, because that is 

one of the things that drives up costs of drug approvals. Everybody 

has to look at those issues, but a percentage of the drug costs are 

because of these type of issues. My question would be basically is, 

I mean, yes, what are our thoughts about that? Do we need, I mean 

obviously we are working on tort reform in other areas. Any 

thoughts on that process as it relates to the drug product development? 

Ms. PRITCHETT. So I am not prepared to discuss that today. We 

would be happy to come back and have further discussions with 

you. I would note that as we look at the PDUFA process, part of 

the engagement by FDA in providing very clear guidances to industry is to help avert any potential concerns from a liability perspective, et cetera, but I think this is an important topic that we would 

welcome to have further discussion. 

Mr. BUCSHON. OK, because I could see that the FDA and others 

very quickly retract their thoughts on these things as soon as we 

have some big class action lawsuit against the FDA and everybody 

else. 

Ms. PRITCHETT. I think that is a very important issue that you 

are raising and we would greatly appreciate coming back and having further discussion on that topic. I appreciate you raising it. 

Mr. BUCSHON. OK, great, any other comments from the other 

panelists? 

Ms. HOLCOMBE. I think one of the important things to recognize 

about PDUFA VI is that in some respects takes account of this type 

of concern by initiating under PDUFA VI pilot programs, where the 

agency and the industry are going to work together to pilot these 

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proaches and determine whether in fact with input from outside 

stakeholders, whether these kinds of designs, this kind of way of 

developing drugs is going to produce the sort of good evidence, solid 

evidence that we need to make sure this product is safe and effective when it goes on the market. 

Mr. BUCSHON. OK, anything else? Well, anyone, for all of you, 

can anyone give us a sense of how they envision the FDA utilizing 

the authorities in 21st Century Cures Act in PDUFA VI, that the 

provisions involving the use of real-world, so-called real-world evidence to support their decision making how we would envision that 

being incorporated? 

Ms. HOLCOMBE. Well, I think as Dr. Woodcock said, FDA already 

uses real-world evidence in the determination, making determinations about potential safety signals of marketed drugs. So the question is in PDUFA VI, is it possible to use real-world evidence, i.e., 

patient experience with drugs in the marketplace from medical 

records or from your Apple watch? Is it possible to harness those 

data, to validate those data, and to use those data to understand 

more about how the drug is working, and would those data be helpful then in making a decision about perhaps broadening an indication for a drug that is very narrowly indicated or adding an indication, which goes to the point that Dr. Allen was making about how 

the drug label can become out of date when medical practice is 

ahead of what was known at the time the drug was produced. 

Mr. BUCSHON. OK. I will just make a quick comment. That is 

why other issues we are working on like interoperability of electronic medical records is going to be really key to this type of thing. 

I think everyone would agree to that and I yield back. 

Mr. GUTHRIE. The gentleman yields back. Seeing no questions 

from this side, Ms. Brooks from Indiana is recognized for 5 minutes 

for purpose of asking questions. 

Mrs. BROOKS. Thank you, Mr. Chairman. 

Dr. Pritchett, PDUFA VI creates a significantly revised fee structure which replaces current levies on manufacturing facilities and 

on products. Can you explain this revised fee structure and how is 

it beneficial for all parties? 

Ms. PRITCHETT. I would actually yield to Kay who was directly 

involved in the negotiations and I wasn’t, who I think would be 

better. 

Mrs. BROOKS. I wondered about that after one of her previous 

answers, but I was suggested to you. So Ms. Holcombe, would you 

like to share with us? 

Ms. HOLCOMBE. The reason for looking at a different way of collecting fees was to try to make sure that we had a system that was 

administratively as simple as it could be so that it was not so costly or so burdensome on either the FDA and companies. So the way 

fees used to be collected was they were divided one third among 

manufacturing facility fees, product fees, and application fees. 

There were two things wrong with that, at least two. 

One thing was that it placed equal emphasis in terms of percentage of dollars collected on all three components, including the application fee which is the least predictable source of revenue. There 

is very little perfect ability to predict the number of applications 

that are going to come into FDA on an annual basis. They have a 

98 

lot of experience so they can give you a range, but if you collect 50 

instead of 60 that makes a huge difference in the total revenue 

that you are collecting. So could we reduce the dependence on the 

application fee and increase the dependence on other fees? 

The second thing that was wrong was the manufacturing facility 

fee, which is a nightmare to calculate mostly because drugs aren’t 

just manufactured like I make mine in my facility and you make 

yours in your facility. Lots of people make drugs in the same facility, so figuring out whose was where when and how often and so 

forth. So could we offload that fee, could we calculate the rest of 

the fee based on number of products? 

And so we calculated what would that mean if we did certain 

percentages of collection from that new fee and certain percentage 

from the application fee? And we developed, or FDA actually developed, not I personally, a tool that companies could use and they 

could plug into this tool how much money they had paid in fees in 

previous years and how much they would pay under some new sort 

of split of the fees. 

Mrs. BROOKS. What is the tool referred to by the FDA? 

Ms. HOLCOMBE. We called it a widget, OK. 

Mrs. BROOKS. OK. 

Ms. HOLCOMBE. Yes, my terminology, sorry. It was a tool that allowed you to manipulate the percentage based on, so the total fee 

collection, let’s say, is $800 million. If you collected ten percent 

from applications and 90 percent from products, what would that 

mean for each company? How much would they pay? 

So they would plug in their own numbers, like how many applications did they think they would be submitting next year and how 

many products do they have on the market? And they figured out, 

bingo, up came this number; this is how much you pay. Well, then 

they could change that from 10/90 to 20/80. How much would you 

pay based on your number of products on the market and the number of applications you anticipate submitting, how much would you 

pay? 

And using that tool, we figured out collectively with all of our 

companies that the ratio that had the least negative impact on the 

most companies was a 20 percent application fee, 80 percent program fee collection. And although a small number of companies on 

a percentage basis, out of all the long list of companies that pay 

fees, did see that their fees would go up slightly, the vast majority 

of companies saw that their fees actually would go down. 

How could that even be, right, but it was. I mean, math, it is just 

a wonderful science. 

Mrs. BROOKS. And if those fees go down what happens? 

Ms. HOLCOMBE. The total amount of money collected is still the 

same because it is spread out across all fee payers. 

Mrs. BROOKS. OK, thank you. I am sorry my time is up, but 

thank you for explaining it. 

Ms. HOLCOMBE. I am sorry I don’t know the math involved in it. 

Mrs. BROOKS. I yield back. OK, thank you. 

Mr. GUTHRIE. Thank you, and the gentlelady yields back. Mr. 

Bilirakis is recognized for 5 minutes for questions. 

Mr. BILIRAKIS. Thank you. Thank you, Mr. Chairman. I appreciate it very much. 

99 

Ms. Holcombe, back in the 2000s it was recognized that there 

was a lack of good information on the safety and efficacy of drugs 

for the pediatric population. Can you talk about some of the incentives that came about to encourage more pediatric clinical studies? 

Ms. HOLCOMBE. So the Best Pharmaceuticals for Children Act 

combined with the Pediatric Research Equity Act have been a very 

successful way to get more drugs studied in pediatric populations 

so that information can go on the drug label and pediatricians 

know how to dose the drugs for children. The incentive that has 

caused that to be so successful was the addition to whatever regulatory exclusivity the company might have on its product for adults 

of 6 months for doing these pediatric studies. 

And we believe at BIO that incentives such as this one can be 

very effective in increasing the number of products that are developed in areas for which there is high unmet medical need but very 

difficult populations or areas of interest, such as, for example, intractable antibacterial resistant conditions. These are tough and 

there is just no good way of doing it. So incentives can be very effective and they have been for pediatric studies. 

Mr. BILIRAKIS. What about the rare disease space? Again there 

are about 500 approved rare disease drugs, but 7,000 rare diseases 

affecting approximately 30 million Americans. They are taking 

medication off-label, and I know the stories because I hear from my 

constituents on a regular basis. They take the drugs off-label not 

knowing if their drugs are safe and effective for their conditions or 

if it is proper dosage—that is so important—and fighting with their 

insurance companies on coverage of these medications. 

Does it make sense to incentivize development for a targeted 

population when there are clearly defined needs? 

Ms. HOLCOMBE. Yes. 

Mr. BILIRAKIS. Thank you. Last month my colleague and I, G.K. 

Butterfield, introduced the OPEN Act for the second time. Much 

like the BPCA, it creates an incentive to run more clinical trials 

in the rare disease space where 95 percent of diseases have no FDA 

approval treatments. This would bring more approved drugs to 

these patients. 

The OPEN Act has the potential to result in hundreds of new 

drugs and treatments for individuals with rare diseases. Only 150 

rare disease patient groups, over 150 at last count, I think it is 

more than that support this bill. The OPEN Act was part of the 

House 21st Century Cures Act, and while it fell out at the 11th 

hour, unfortunately, I am going to continue to push for this legislation. It is a priority for me. Do you have any comments on that? 

And of course I welcome cosponsors for this legislation as well. 

Ms. HOLCOMBE. So it is clear that without the Orphan Drug Act 

we would not have 500 treatments for rare diseases. It is also a 

tragedy that we don’t have 7,500. And again we believe incentives 

can work. We don’t have an official position on your proposal, but 

definitely it merits more evaluation. 

Mr. BILIRAKIS. All right. Well, thank you very much. I yield back, 

Mr. Chairman. 

Mr. GUTHRIE. Thank you. The gentleman yields back, and seeing 

no other members wishing to ask questions I would like to thank 

all of our witnesses for being here today. 

100 

And pursuant to committee rules I remind members that they 

have 10 business days to submit additional questions for the 

record, and I ask the witnesses submit their response within 10 

business days upon receipt of those questions. 

Without objection, the subcommittee is adjourned. 

[Whereupon, at 12:18 p.m., the subcommittee was adjourned.] 

[Material submitted for inclusion in the record follows:] 

PREPARED STATEMENT OF HON. FRANK PALLONE, JR. 

Thank you, Mr. Chairman. I appreciate the opportunity today to discuss the reauthorization of the Prescription Drug User Fee Act. PDUFA has been incredibly successful at bringing reviews of new drug applications down by more than half, and 

providing patient access to treatments more quickly, and often before any other 

country. 

PDUFA has also encouraged innovation by bringing stability and predictability to 

the review of new drug applications. FDA has been able to hire the review staff and 

scientific and technical experts needed to keep pace with science and increase the 

efficiency of the review process. However, more work needs to be done and I am encouraged by how PDUFA VI builds off of the successes of this user fee program. 

I am therefore disappointed to see what can only be referred to as a disclaimer 

in the testimony today from FDA. While it is true that the reauthorization proposals 

were negotiated under a previous Administration, the goals of the PDUFA program 

and the drug approval process remain the same—a fully resourced and staffed FDA, 

and an efficient and timely drug review process that is keeping pace with the scientific and regulatory advancements in this field. It is my hope that the Administration would understand how carefully crafted the current agreement is, and recognize 

that the reauthorization process started nearly two years ago. 

The agreement before us today is the result of many negotiations with industry 

and stakeholders, consultations with patients and consumers, and solicitation of 

public input. The resulting recommendations were transmitted to Congress in meeting the January 15, 2017 statutory deadline. Transmitting new recommendations at 

this point would go against this requirement, and run the very real risk of PDUFA 

not being reauthorized before the program expires on September 30, endangering 

the review of innovative new drug treatments and threatening the jobs of thousands 

of FDA employees. 

I intend to continue to work with my colleagues on the Committee and across the 

Capitol, as well as industry, to ensure that we do not let this happen. This is a 

strong agreement, and one that deserves our support. 

Thank you. 

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