[Senate Hearing 112-905]
[From the U.S. Government Publishing Office]
S. Hrg. 112-905
FDA USER FEE AGREEMENTS: STRENGTHENING FDA AND THE MEDICAL PRODUCTS
INDUSTRY FOR THE BENEFIT OF PATIENTS
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HEARING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED TWELFTH CONGRESS
SECOND SESSION
ON
EXAMINING FOOD AND DRUG ADMINISTRATION (FDA) USER FEE AGREEMENTS,
FOCUSING ON STRENGTHENING FDA AND THE MEDICAL PRODUCTS INDUSTRY FOR THE
BENEFIT OF PATIENTS
__________
MARCH 29, 2012
__________
Printed for the use of the Committee on Health, Education, Labor, and
Pensions
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
TOM HARKIN, Iowa, Chairman
BARBARA A. MIKULSKI, Maryland
JEFF BINGAMAN, New Mexico
PATTY MURRAY, Washington
BERNARD SANDERS (I), Vermont
ROBERT P. CASEY, JR., Pennsylvania
KAY R. HAGAN, North Carolina
JEFF MERKLEY, Oregon
AL FRANKEN, Minnesota
MICHAEL F. BENNET, Colorado
SHELDON WHITEHOUSE, Rhode Island
RICHARD BLUMENTHAL, Connecticut
MICHAEL B. ENZI, Wyoming
LAMAR ALEXANDER, Tennessee
RICHARD BURR, North Carolina
JOHNNY ISAKSON, Georgia
RAND PAUL, Kentucky
ORRIN G. HATCH, Utah
JOHN McCAIN, Arizona
PAT ROBERTS, Kansas
LISA MURKOWSKI, Alaska
MARK KIRK, Illinois
Daniel E. Smith, Staff Director
Pamela Smith, Deputy Staff Director
Frank Macchiarola, Republican Staff Director and Chief Counsel
(ii)
C O N T E N T S
__________
STATEMENTS
THURSDAY, MARCH 29, 2012
Page
Committee Members
Harkin, Hon. Tom, Chairman, Committee on Health, Education,
Labor, and Pensions, opening statement......................... 1
Enzi, Hon. Michael B., a U.S. Senator from the State of Wyoming,
opening statement.............................................. 2
Murray, Hon. Patty, a U.S. Senator from the State of Washington.. 34
Roberts, Hon. Pat, a U.S. Senator from the State of Kansas....... 35
Mikulski, Hon. Barbara A., a U.S. Senator from the State of
Maryland....................................................... 37
Burr, Hon. Richard, a U.S. Senator from the State of North
Carolina....................................................... 38
Whitehouse, Hon. Sheldon, a U.S. Senator from the State of Rhode
Island......................................................... 40
Isakson, Hon. Johnny, a U.S. Senator from the State of Georgia... 41
Bennet, Hon. Michael F., a U.S. Senator from the State of
Colorado....................................................... 41
Merkley, Hon. Jeff, a U.S. Senator from the State of Oregon...... 43
Blumenthal, Hon. Richard, a U.S. Senator from the State of
Connecticut.................................................... 45
Franken, Hon. Al, a U.S. Senator from the State of Minnesota..... 46
Witnesses--Panel I
Woodcock, Janet, M.D., Director, Center for Drug Evaluation and
Research, Food and Drug Administration, Silver Spring, MD...... 4
Prepared statement........................................... 6
Shuren, Jeffrey, M.D., J.D., Director, Center for Devices and
Radiological Health, Food and Drug Administration, Silver
Spring, MD..................................................... 18
Prepared statement........................................... 19
Witnesses--Panel II
Wheadon, David E., M.D., Senior Vice President of Scientific and
Regulatory Affairs, Pharmaceutical Research and Manufacturers
of America, Washington, DC..................................... 48
Prepared statement........................................... 50
Radcliffe, Sara, Executive Vice President, Health, Biotechnology
Industry Organization, Washington, DC.......................... 54
Prepared statement........................................... 56
Gaugh, David R., R.Ph., Vice President for Regulatory Sciences,
Generic Pharmaceutical Association, Washington, DC............. 60
Prepared statement........................................... 62
Nexon, David, Ph.D., Senior Executive Vice President, Advanced
Medical Technology Association, Washington, DC................. 67
Prepared statement........................................... 68
Coukell, Allan, B.Sc.Pharm., Director of Medical Programs, the
Pew Charitable Trusts, Washington, DC.......................... 72
Prepared statement........................................... 74
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.:
Senator Casey................................................ 82
(iii)
FDA USER FEE AGREEMENTS: STRENGTHENING FDA AND THE MEDICAL PRODUCTS
INDUSTRY FOR THE BENEFIT OF PATIENTS
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THURSDAY, MARCH 29, 2012
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The committee met, pursuant to notice, at 10:06 a.m. in
Room SH-216, Hart Senate Office Building, Hon. Tom Harkin,
chairman of the committee, presiding.
Present: Senators Harkin, Mikulski, Murray, Hagan, Merkley,
Franken, Bennet, Whitehouse, Blumenthal, Enzi, Burr, Isakson,
and Roberts.
Opening Statement of Senator Harkin
The Chairman. The Senate Committee on Health, Education,
Labor, and Pensions will please come to order.
Last summer, FDA Commissioner Margaret Hamburg testified
before this committee describing the history and importance of
the user fee agreements between the FDA and the industries that
it regulates. She detailed the impact that user fees had on
FDA's ability to ensure that new medical products get to
American patients as quickly as possible.
Since then, we have had hearings on a number of policy
areas relating to the FDA, including supply chain security,
medical devices, and drug shortages. While we were engaged in
those hearings, and a lot of related behind the scenes work,
the FDA and industry were negotiating and finalizing this
year's user fee agreements.
Today, in our last hearing of this reauthorization process,
we turn the spotlight to those agreements. We will focus on how
the Prescription Drug User Fee Agreement, or as it is known,
PDUFA, how it will improve FDA's review of the most novel drug
products, and enhance the agency's commitment to regulatory
science.
We will discuss the exciting new Generic Drug User Fee
Agreement--wouldn't you know it--called GDUFA, which is
expected to slash review times to a third of current levels,
drastically improving the speed with which generic products are
made available to patients.
We will also hear about the new Biosimilars User Fee
Agreement--ready for this one--BsUFA, which will shepherd the
nascent generic biologics industry as it grows and matures.
On the device side, we will discuss the importance of the
hard-fought Medical Device User Fee Agreement--one more time--
MDUFA, to improving the device review process while stimulating
safety standards.
In our first panel, Dr. Janet Woodcock and Dr. Jeff Shuren,
the Directors of FDA's Drug and Device Centers, respectively,
will discuss the critical role user fees play in helping them
ensure that medical products are safe and effective, and that
they reach patients as quickly as possible.
In our second panel, Dr. David Wheadon from PhRMA, Miss
Sara Radcliffe from BIO, and Mr. David Gaugh from GPhA will
discuss the drug user fee agreements.
The device industry, including members of the Medical
Device Manufacturers Association, and the Medical Imaging
Technology Association will be represented by Dr. David Nexon
of AdvaMed.
Finally, Mr. Allan Coukell will join us, from The Pew
Foundation, to explain the benefits these agreements will have
for patients and consumers.
The testimony of today's witnesses will reflect strong
agreement on the following points: these agreements were
carefully negotiated and it is essential that we pass them.
They are critical to FDA's ability to do its job, to the
medical products industry's ability to survive these
challenging economic times, and most importantly to the
patients who are the primary beneficiaries of this longstanding
and valuable collaboration between the FDA and the industry.
After months of negotiation, the FDA and industry have
crafted a win-win agreement that they stand behind, and they
have done their job well. Now it is time for us to do ours. If
we fail to authorize these agreements on time, the FDA will
have to fire nearly 2,000 from its staff. Without adequate
staff, review applications of the drug and device approval
process will grind to an unacceptably low and slow pace.
Patients whose health and lives depend on new medical
treatments will suffer the devastating consequences. We cannot
let that happen.
We cannot let policy disagreements, or Presidential
election year politics, or other politics keep us from doing
our part to translate into legislation the arrangement and the
deal that the FDA and the industry have struck for the benefit
of American patients.
As we have from the beginning of this process, Senator Enzi
and I, and other members of this committee from both sides of
the aisle, are continuing to work together to clear the path to
authorization of the agreements that we will hear about today.
With that, I will turn to our Ranking Member, Senator Enzi.
Opening Statement of Senator Enzi
Senator Enzi. Thank you, Mr. Chairman and thank you for
holding this hearing today.
I also want to reiterate the comment that you just made
about the cooperation between both sides and all of the people
that have been involved and invested in getting this done. We
know that it has to be done by September, and I think we are
actually ahead of schedule on that, and hopefully we can stay
that way. There has been good cooperation from everyone; still
a few things to consider.
The subject of today's hearing is the Food and Drug
Administration's human medical product user fees; all of the
``UFA's'' today.
The first such agreement was enacted in 1992. It allowed
FDA to collect certain agreed upon user fees from drug
manufacturers in exchange for more timely, predictable,
premarket review. It decreased review times and increased
patient access to medicines. User fees are important to
America's patients, jobs, and innovation. User fees currently
support about 60 percent of the drug center's workforce, or
about 20 percent of the device center's workforce.
The current user fee agreements expire on September 30th of
this year, 6 months from now. If they are not timely
reauthorized, the FDA must layoff approximately 2,000
employees. That would derail the agency's premarket review
programs. It would threaten the biomedical industry jobs. It
would limit patient access to therapies and America's global
leadership in biomedical innovation.
I am committed to enacting user fee legislation in a timely
manner. I expect that all our witnesses today representing the
administration, industry, and patient consumer groups alike
share that commitment. They will brief us on the content and
merits of the proposed agreements.
The agreements contain important policies that will
ultimately help patients. The proposed prescription drug user
fee agreement would factor a better understanding of the
patient perspective into benefit-risk decisions. It would also
improve Risk Evaluation and Mitigation Strategies, or REMS.
REMS enacted in 2007 were intended to let the FDA ensure
that the benefits of a drug or biological product outweigh its
risks, but implementation of the law produced a delay and
confusion. The proposed agreement should go a long way toward
fixing those problems. For instance, by standardizing the
process and clarifying that the medication guides are not part
of REMS.
The proposed Medical Device User Agreement will help FDA
hire and train more reviewers, managers, and technical writers.
It will also improve the predictability of the pre-submission
process, and ensure that no submission is left behind.
The proposed Generic Drug User Fee Agreement will help the
FDA inspect more foreign establishments, and attack a large
backlog of applications. These new user fees will also help FDA
tackle the problem of drug shortages, providing the resources
needed to expedite the review and the approval of more generic
drugs.
The proposed Biosimilar User Fee Agreement will help get a
biosimilar program up and running, with measures to prevent
medication errors, resolve disputes, and authorize special
protocol assessments.
Today, the HELP committee will assess the proposed user fee
agreements to make sure they will advance the public health. We
need to make sure the policy is right. At the same time, we
also need to enact user fee legislation in a timely manner.
Patients, jobs, and innovation depend on it.
Toward that end, the HELP committee plans to mark up one
bill containing all four user fee agreements, and a small
number of bipartisan consensus policy riders will face several
obstacles that will make it difficult to enact these policies.
Many outside forces, in some cases extraneous to FDA issues,
all have the potential to derail our process, but the bill will
need very broad bipartisan support to pass the Senate.
I would encourage stakeholders to keep the big picture in
mind as they contemplate trying to include proposals that could
add cost, complexity, and/or controversy to the bill. We can
only succeed if we work together for the greater good.
On that note, I want to point out that the device under
director Jeff Shuren and AdvaMed senior executive vice
president David Nexon are both here today advocating for the
proposed medical device user fee. The negotiations concerning
these agreements were contentious, but in the end, through hard
work and compromise, they reached agreement.
In short, the FDA, industry, and the stakeholders have done
their job. Now it is time for us to do our jobs and to get a
bill done.
I thank Chairman Harkin for his leadership, commitment, and
courtesy. I thank the witnesses for coming today, and I look
forward to their testimony.
The Chairman. Thank you very much, Senator Enzi.
Now we will turn to our first panel. Our first panel will
be Dr. Janet Woodcock, Director of the Center for Drug
Evaluation and Research at the Food and Drug Administration. In
this position, Dr. Woodcock ensures that safe and effective
drugs are available to address public health needs.
Dr. Woodcock is no stranger to this committee. I was just
reading that Dr. Woodcock joined the FDA in 1986, has held
various leadership positions within the Office of the
Commissioner FDA, including Deputy Commissioner and Chief
Medical Officer, Deputy Commissioner of Operations, and Chief
Operating Officer and Director of the Critical Path programs.
We also have Dr. Jeff Shuren. He has been with FDA, I think
since 1998, if I am not mistaken--is the Director of the Center
for Devices and Radiological Health at FDA, and previously
served as Acting Center Director. He has held various policy
and planning positions within FDA from 1998 to the present
time.
Dr. Shuren received both his B.S. and M.D. degrees from
Northwestern under its honors program in medical education; his
J.D. from the University of Michigan Law School. I noted that
Dr. Woodcock, you received your M.D. from Northwestern
University. Is this some kind of ganging up by Northwestern
Medical School or something?
But welcome, both of you. Thank you for your service to our
country. Your statements will be made a part of the record in
their entirety, and I ask if you could sum them up within
several minutes.
Dr. Woodcock, welcome. Please proceed.
STATEMENT OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION, SILVER
SPRING, MD
Dr. Woodcock. Thank you, Mr. Chairman.
I would like to thank you and the members of the committee
for the opportunity to testify about the three drug user fee
proposals now before you for consideration. Included is a
proposal for reauthorization of PDUFA, and recommendation for
two new user fee programs: a groundbreaking program to support
the generic drug review process, and a program to support the
new biosimilars review activities.
Each of these proposals was negotiated with stakeholders,
including a transparent process that provided multiple
opportunities for public input. We feel that, taken together,
they will support a robust drug regulatory program that will
both encourage innovation and ensure that the American public
has continued access to high quality, safe, and effective
medicines. I would like to briefly describe each of these user
fee programs.
To start with PDUFA, Congress instituted this program
because patients in the United States were not getting access
to new medicines as quickly as people in other parts of the
world. This problem was known as ``the drug lag,'' and it was
particularly severe in the 1980s. In that decade, only about 10
percent of new medicines reached U.S. patients first.
PDUFA was started by Congress in 1992 and quickly improved
the availability of new medicines. I am a rheumatologist, a
doctor who treats autoimmune diseases and arthritis, and I can
attest to the revolution in therapy that has occurred since the
start of PDUFA. Diseases that were crippling now have effective
treatments that allow our patients to lead full lives.
Recently, I was on an airplane and my seat mate showed me
pictures of her garden that she maintained herself. Ten years
ago, she had been in a nursing home, confined to a nursing home
with crippling autoimmune disease. She was started on one of
the new therapies and now is active and leads a full life.
Since the start of PDUFA, increasing numbers of new
medicines have been available first in the United States.
Currently, we lead all other countries in introduction of new
therapies. But every 5 years, the user fee program must be
reauthorized and each cycle has brought new enhancements to the
program.
Recently, there has been a focus on improving drug safety
and successful innovations such as our Sentinel Initiative have
resulted from this.
For this cycle of PDUFA renegotiation, Congress directed us
to conduct a very open and inclusive process with significant
public stakeholder participation. We have done that, and we
believe that was wise direction on the part of Congress, and
the outcomes of the negotiation have improved as a result of
this participation.
The drug development enterprise, though, that brings new
therapies to patients is in a very different place than
previous PDUFA negotiations. Drug developers face many of the
problems of other industries due to the economic downturn. But
more significantly, there is a severe productivity problem
worldwide in which an ever increasing R&D investment is
producing even fewer new drugs than before. It is no
exaggeration to say this industry is in crisis.
At the same time, the scientific opportunities have never
been greater, and I can tell you it is incredibly frustrating
as a physician to see the expansion of biomedical knowledge,
and at the same time to watch the struggles and repeated
failures in developing new medicines.
Despite these serious problems, we think we may be seeing a
turning point. Last year, we approved a very high number of new
medicines and this year we have approved, this calendar year,
eight novel medicines so far and many of them will make a
significant difference for patients. It is critical that the
regulatory system be able to change, and adapt, and keep
bringing this innovation to the public.
Through this process, we have developed a set of
recommendations as laid out in my written testimony. These
include new steps to incorporate these scientific advances into
our regulatory process. To put the patient in the center of
drug development by many patient-centered activities that are
going to be supported by the new process, and to further
enhance drug safety.
The second proposal is for a groundbreaking Generic Drug
User Fee. This program has two elements, one establishing a
timely predictable process for review of generic drug
applications, and establishing a worldwide level playing field
for manufacturers of generic drugs and their active
ingredients, so American consumers can receive the same
assurance of quality no matter where the drug is sourced from.
Finally, the user fee proposed are for the new biosimilars
program, which is also a groundbreaking program established by
Congress. This is intended to support implementation of this
landmark legislation. Since there is no existing biosimilars
industry in the United States, FDA worked with a wide range of
stakeholders in crafting our proposal.
The program differs from others in that fees are going to
be paid during drug development to assist in providing advice
because it is not known how to develop biosimilars for the U.S.
market.
In sum, these proposals will provide robust support for
essential drug regulatory activities in the United States, and
I look forward to answering your questions about them.
[The prepared statement of Dr. Woodcock follows:]
Prepared Statement of Janet Woodcock, M.D.
introduction
Mr. Chairman and members of the subcommittee, I am Dr. Janet
Woodcock, director of the Center for Drug Evaluation and Research
(CDER) at the Food and Drug Administration (FDA or the Agency), which
is part of the Department of Health and Human Services (HHS). Thank you
for the opportunity to be here today to discuss the fifth
reauthorization of the Prescription Drug User Fee Act (PDUFA),\1\ also
referred to as DUFA-V, as well as the negotiated recommendations for a
generic drug user fee program and a biosimilar user fee program.
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\1\ PDUFA was enacted in 1992 and authorizes FDA to collect fees
from companies that produce certain human drug and biological products.
Industry agrees to pay fees to help fund a portion of FDA's drug review
activities, while FDA agrees to overall performance goals, such as
reviewing a certain percentage of applications within a particular
timeframe. The current legislative authority for PDUFA expires on
September 30, 2012. On January 13, 2012, HHS Secretary Kathleen
Sebelius transmitted recommendations to Congress for the next
reauthorization of PDUFA.
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Background on PDUFA
FDA considers the timely review of the safety and effectiveness of
New Drug Applications (NDA) and Biologics License Applications (BLA) to
be central to the Agency's mission to protect and promote the public
health. Prior to enactment of PDUFA in 1992, FDA's review process was
understaffed, unpredictable, and slow. FDA lacked sufficient staff to
perform timely reviews, or develop procedures and standards to make the
process more rigorous, consistent, and predictable. Access to new
medicines for U.S. patients lagged behind other countries. As a result
of concerns expressed by both industry and patients, Congress enacted
PDUFA, which provided the added funds through user fees that enabled
FDA to hire additional reviewers and support staff and upgrade its
information technology systems. At the same time, FDA committed to
complete reviews in a predictable timeframe. These changes
revolutionized the drug approval process in the United States and
enabled FDA to speed the application review process for new drugs,
without compromising the Agency's high standards for demonstration of
safety, efficacy, and quality of new drugs prior to approval.
Three fees are collected under PDUFA: application fees,
establishment fees, and product fees. An application fee must be
submitted when certain NDAs or BLAs are submitted. Product and
establishment fees are due annually. The total revenue amounts derived
from each of the categories--application fees, establishment fees, and
product fees--are set by the statute for each fiscal year. PDUFA
permits waivers under certain circumstances, including a waiver of the
application fee for small businesses and orphan drugs.
Of the total $931,845,581 obligated in support of the process for
the review of human drug applications in fiscal year 2010, PDUFA fees
funded 62 percent, with the remainder funded through appropriations.
PDUFA Achievements
PDUFA has produced significant benefits for public health,
providing patients faster access to over 1,500 new drugs and biologics,
since enactment in 1992, including treatments for cancer, infectious
diseases, neurological and psychiatric disorders, and cardiovascular
diseases. In fiscal year 2011, FDA approved 35 new, ground-
breaking medicines, including two treatments for hepatitis C, a drug
for late-stage prostate cancer, the first drug for Hodgkin's lymphoma
in 30 years, and the first drug for lupus in 50 years. This was the
second highest number of annual approvals in the past 10 years,
surpassed only by 2009. Of the 35 innovative drugs approved in fiscal
year 2011, 34 met their PDUFA target dates for review.
Substantially Reduced Review Times
PDUFA provides FDA with a source of stable, consistent funding that
has made possible our efforts to focus on promoting innovative
therapies and help bring to market critical products for patients.
According to researchers at the Tufts Center for the Study of Drug
Development, the time required for the FDA approval phase of new drug
development (i.e., time from submission until approval) has been cut
since the enactment of PDUFA in 1992, from an average of 2 years for
the approval phase at the start of PDUFA to an average of 1.1 years
more recently.\2\
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\2\ Milne, Christopher-Paul (2010). PDUFA and the Mission to Both
Protect and Promote Public Health [PowerPoint slides]. Presentation at
the FDA PDUFA Public Meeting, Rockville, MD.
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FDA aims to review priority drugs more quickly, in 6 months vs. 10
months for standard drugs. Priority drugs are generally targeted at
severe illnesses with few or no available therapeutic options. FDA
reviewers give these drugs priority attention throughout development,
working with sponsors to determine the most efficient way to collect
the data needed to provide evidence of safety and effectiveness.
Reversal of the ``Drug Lag''
Importantly, PDUFA has led to the reversal of the drug lag that
prompted its creation. Since the enactment of PDUFA, FDA has steadily
increased the speed of Americans' access to important new drugs
compared to the European Union (EU) and the world as a whole. Of the 35
innovative drugs approved in fiscal year 2011, 24 (almost 70 percent)
were approved by FDA before any other regulatory agency in the world,
including the European Medicines Agency. Of 57 novel drugs approved by
both FDA and the EU between 2006 and 2010, 43 (75 percent) were
approved first in the United States.
Figure 1 below shows that since the late 1990's, the United States
has regularly led the world in the first introduction of new active
drug substances.\3\ Preliminary data show that in 2011, over half of
all new active drug substances were first launched in the United
States.
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\3\ Scrip NCE Review/Scrip Yearbook/Scrip Magazine (1982-2005),
PharmaProjects R&D Annual Review (2006-2010). New active substances
include novel chemical or biological substances not previously approved
to treat any disease. There is a close, but not complete overlap,
between new active substances and new molecular entities: new active
substances exclude radiopharmaceuticals.
In recent years, FDA's drug review times also have been, on
average, significantly faster than those in the EU. It is difficult to
compare length of approvals for fiscal year 2011, because many of the
drugs approved in the United States have not yet been approved in the
EU. A comparison of drugs approved in the United States and the EU
between 2006 and 2010 is illustrative, however. For priority drugs
approved between 2006 and 2010, FDA's median time to approval was 6
months (183 days), more than twice as fast as the EU, which took a
median time of 13.2 months (403 days). For standard drug reviews, FDA's
median time to approval was 13 months (396 days), 53 days faster than
the EU time of 14.7 months (449 days).
A recent article in the journal Health Affairs also compared cancer
drugs approved in the United States and EU from 2003 through 2010.
Thirty-five cancer drugs were approved by the United States or the EU
from October 2003 through December 2010. Of those, FDA approved 32--in
an average time of 8.6 months (261 days). The EU approved only 26 of
these products, and its average time was 12.2 months (373 days). This
difference in approval times is not due to safety issues with these
products. All 23 cancer drugs approved by both agencies during this
period were approved first in the United States.\4\
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\4\ ``Despite Criticism of the FDA Review Process, New Cancer Drugs
Reach Patients Sooner in the United States Than in Europe,'' Samantha
A. Roberts, Jeff D. Allen, and Ellen V. Sigal, Health Affairs, June
2011.
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Speeding Access to New Therapies
PDUFA funds help support a number of existing FDA programs to
expedite the approval of certain promising investigational drugs, and
also to make them available to the very ill before they have been
approved for marketing, without unduly jeopardizing patient safety.
The most important of these programs are Accelerated Approval, Fast
Track, and Priority Review. In 1992, FDA instituted the Accelerated
Approval process, which allows earlier approval of drugs that treat
serious or life-threatening diseases and that fill an unmet medical
need based on a surrogate endpoint that is reasonably likely to predict
clinical benefit but is not fully validated to do so, or, in some
cases, an effect on a clinical endpoint other than survival or
irreversible morbidity. A surrogate endpoint is a marker--a laboratory
measurement, or physical sign--that is used in clinical trials as an
indirect or substitute measurement for a clinically meaningful outcome,
such as survival or symptom improvement. For example, viral load is a
surrogate endpoint for approval of drugs for the treatment of HIV/AIDS.
The use of a surrogate endpoint can considerably shorten the time to
approval, allowing more rapid patient access to promising new
treatments for serious or life-threatening diseases. Accelerated
Approval is given on the condition that sponsors conduct post-marketing
clinical trials to verify the anticipated clinical benefit.
Over 80 new products have been approved under Accelerated Approval
since the program was established, including 29 drugs to treat cancer,
32 to treat HIV, and 20 to treat other conditions such as pulmonary
arterial hypertension, Fabry disease, and transfusion-dependent anemia.
Three of the thirty new molecular entities (NMEs) and new BLAs approved
in 2011 in CDER were approved under Accelerated Approval. Corifact, the
first treatment approved for a rare blood-clotting disorder, also was
approved under Accelerated Approval in FDA's Center for Biologics
Evaluation and Research (CBER) on February 17, 2011.
Fast Track is a process designed to facilitate the development, and
expedite the review, of drugs to treat serious or life-threatening
diseases that will fill an unmet medical need. Once a drug receives
Fast-Track designation, early and frequent communications between FDA
and a drug company are encouraged throughout the entire drug
development and review process. The frequency of communications ensures
that questions and issues are resolved quickly, often leading to
earlier drug approval and access by patients. For example, Zelboraf
(vemurafenib) was given a Fast-Track designation because it had the
potential to improve overall survival in patients with melanoma, the
most dangerous type of skin cancer. Because of convincing early
findings with this drug, FDA scientists worked proactively with the
sponsor during drug testing to encourage early submission of the
application. FDA approved Zelboraf in 2011 to treat patients with late-
stage (metastatic) or unresectable (cannot be removed by surgery)
melanoma.
In 1992, under PDUFA, FDA agreed to specific goals for improving
drug review times and created a two-tiered system of review times--
Priority Review and Standard Review. FDA aims to review priority drugs
more quickly, in 6 months versus 10 months for standard drugs. Priority
review designation is given to drugs that offer major advances in
treatment, or provide a treatment where no adequate therapy exists,
while Standard Review is applied to drugs that offer at most only minor
improvement over existing marketed therapies. FDA reviewers give
Priority Review drugs priority attention throughout development,
working with sponsors to determine the most efficient way to collect
the data needed to provide evidence of safety and effectiveness. For
example, on January 31, 2012, FDA approved Kalydeco (ivacaftor) to
treat patients age 6 or older with Cystic Fibrosis (CF) and who have a
specific genetic defect (G551D mutation), after a Priority Review. CF
occurs in approximately 30,000 children and adults in the United
States. The G551D mutation occurs in approximately 4 percent of
patients with CF, totaling approximately 1,200 patients in the United
States. CF is a serious inherited disease that affects the lungs and
other organs in the body, leading to breathing and digestive problems,
trouble gaining weight, and other problems. There is no cure for CF,
and despite progress in the treatment of the disease, most patients
with CF have shortened life spans and do not live beyond their mid-30s.
After the results of studies of ivacaftor showed a significant benefit
to patients with CF with the G551D mutation, ivacaftor was reviewed and
approved by FDA in approximately 3 months--half of the Priority Review
period. Ivacaftor is the first medicine that targets the underlying
cause of CF; to date, therapy has aimed at treating symptoms or
complications of the disease.
FDA also recognizes circumstances in which there is public health
value in making products available prior to marketing approval. A
promising but not yet fully evaluated treatment may sometimes represent
the best choice for individuals with serious or life-threatening
diseases who lack a satisfactory therapy.
FDA allows for access to investigational products through multiple
mechanisms. Clinical trials are the best mechanism for a patient to
receive an investigational drug, because they provide a range of
patient protections and benefits and they maximize the gathering of
useful information about the product, which benefits the entire patient
population. However, there are times when an individual cannot enroll
in a clinical trial. In some cases, the patient may gain access to an
investigational therapy through one of the alternative mechanisms, and
FDA's Office of Special Health Issues assists patients and their
doctors in this endeavor.
We are committed to using these programs to speed therapies to
patients while upholding our high standards of safety and efficacy.
Balancing these two objectives requires that we continue to evaluate
our use of the tools available to us and consider whether additional
tools would be helpful. We are eager to work with Congress in this
area, and we note that several of the enhancements proposed for PDUFA-V
are aimed at expediting the availability of new therapies and providing
FDA the scientific understanding necessary to modernize and streamline
our regulatory process.
Providing Guidance to Industry
Increased resources provided by user fees have enabled FDA to
provide a large body of technical guidance to industry that clarified
the drug development pathway for many diseases, and to meet with
companies during drug development to provide critical advice on
specific development programs. In the past 5 years alone, FDA has held
over 7,000 formal meetings with drug sponsors within a short time after
a sponsor's request. Innovations in drug development are being advanced
by many new emerging companies as well as more established ones, and
new sponsors may need, and often seek, more regulatory guidance during
development. In fiscal year 2009 through fiscal year 2011, more than
half of the meetings FDA held during drug development were with
companies that had no approved product on the U.S. market.
Weighing Benefit and Risk
It should be noted that FDA assesses the benefit-risk of new drugs
on a case-by-case basis, considering the degree of unmet medical need
and the severity and morbidity of the condition the drug is intended to
treat. This approach has been critical to increasing patient access to
new drugs for cancer and rare and other serious diseases, where
existing therapies have been few and limited in their effectiveness.
Some of these products have serious side effects but they were approved
because the benefit outweighed the risk. For example, in March of last
year, FDA approved Yervoy (ipilimumab) for the treatment of
unresectable or metastatic melanoma. Yervoy also poses a risk of
serious side effects in 12.9 percent of patients treated, including
severe to fatal autoimmune reactions. However, FDA decided that the
benefits of Yervoy outweighed its risks, especially considering that no
other melanoma treatment has been shown to prolong a patient's life.
As discussed in more detail below, PDUFA-V will enable FDA to
develop an enhanced, structured approach to benefit-risk assessments
that accurately and concisely describes the benefit and risk
considerations in the Agency's drug regulatory decisionmaking.
Challenges for the Current Drug Program
Although we can report many important successes with the current
program, new challenges have also emerged that offer an opportunity for
further enhancement. While new authorities from the Food and Drug
Administration Amendments Act of 2007 (FDAAA) have strengthened drug
safety, they have put strains on FDA's ability to meet premarket review
performance goals and address post-market review activities. In
addition, there has been a significant increase in the number of
foreign sites included in clinical trials to test drug safety and
effectiveness, and an increase in the number of foreign facilities used
in manufacturing new drugs for the U.S. market. While foreign sites can
play an important role in enabling access to new drugs, the need to
travel much farther to conduct pre-approval inspections for clinical
trials and manufacturing sites overseas has created additional
challenges for completion of FDA's review within the existing PDUFA
review performance goals, while at the same time trying to communicate
with sponsors to see if identified issues can be resolved before the
review performance goal date.
Despite these challenges, FDA has maintained strong performance in
meeting the PDUFA application review goals, with the exception of a dip
in fiscal year
2008-9, when staff resources were shifted within the discretion
afforded FDA to ensure timely implementation of all the new FDAAA
provisions that affected activities in the new drug review process.
Recent performance data show that FDA has returned to meeting or
exceeding goals for review of marketing applications under PDUFA. This
is shown in Figure 2.
However, FDA wants to meet not only the letter, but also the spirit
of the PDUFA program. That is, we want to speed patient access to drugs
shown to be safe and effective for the indicated uses while also
meeting our PDUFA goals.
The NDA/BLA approval phase of drug development is reported to have
the highest success rate of any phase of drug development. That is, the
percentage of drugs that fail after the sponsor submits an NDA/BLA to
FDA is less than the percentages that fail in preclinical development
and in each phase of clinical development. At the same time, it is
critical to our public health mission that we work with industry and
other stakeholders to take steps to reduce uncertainty and increase the
success of all phases of drug development. We must leverage advances in
science and technology to make sure that we have the knowledge and
tools we need to rapidly and meaningfully evaluate medical products.
The science of developing new tools, standards, and approaches to
assess the safety, efficacy, quality, and performance of FDA-regulated
products--known as regulatory science--is about more than just speeding
drug development prior to the point at which FDA receives an
application for review and approval. It also gives us the scientific
tools to modernize and streamline our regulatory process. With so much
at stake for public health, FDA has made advances in regulatory science
a top priority. The Agency is both supporting mission-critical science
at FDA and exploring a range of new partnerships with the National
Institutes of Health (NIH) and academic institutions to develop the
science needed to maximize advances in biomedical research and bring
the development and assessment of promising new therapies and devices
into the 21st century. With this effort, FDA is poised to support a
wave of innovation to transform medicine and save lives.
For example, FDA is working to improve the science behind certain
clinical trial designs. Recent advances in two clinical trial designs--
called non-inferiority and adaptive designs--have required FDA to
conduct more complex reviews of clinical trial protocols and new
marketing applications. Improving the scientific bases of these trial
designs should add efficiency to the drug review process, encourage the
development of novel products, and speed new therapies to patients.
FDA also has taken steps to help facilitate the development and
approval of safe and effective drugs for Americans with rare diseases.
Therapies for rare diseases--those affecting fewer than 200,000 people
in the United States--represent the most rapidly expanding area of drug
development. Although each disease affects a relatively small
population, collectively, rare diseases affect about 25 million
Americans. Approximately one-third of the NMEs and new biological
products approved in the last 5 years have been drugs for rare
diseases. Because of the small numbers of patients who suffer from each
disease, FDA often allows non-traditional approaches to establishing
safety and effectiveness. For example, FDA approved Voraxaze
(glucarpidase) in January 2012 to treat patients with toxic
methotrexate levels in their blood due to kidney failure, which affects
a small population of patients each year. Methotrexate is a commonly
used cancer chemotherapy drug normally eliminated from the body by the
kidneys. Patients receiving high doses of methotrexate may develop
kidney failure. Voraxaze was approved based on data in 22 patients from
a single clinical trial, which showed decreased levels of methotrexate
in the blood. Prior to the approval of Voraxaze, there were no
effective therapies for the treatment of toxic methotrexate levels in
patients with renal failure.
PDUFA Reauthorization
In PDUFA-IV, Congress directed FDA to take additional steps to
ensure that public stakeholders, including consumer, patient, and
health care professional organizations, would have adequate opportunity
to provide input to the reauthorization and any program enhancements
for PDUFA-V. Congress directed the Agency to hold an initial public
meeting and then to meet with public stakeholders periodically, while
conducting negotiations with industry to hear their views on the
reauthorization and their suggestions for changes to the PDUFA
performance goals. PDUFA-IV also required that minutes from negotiation
sessions held with industry be made public.
Based on a public meeting held in April 2010, input from a public
docket, and the Agency's own internal analyses of program challenge
areas, FDA developed a set of potential proposed enhancements for
PDUFA-V and in July 2010, began negotiations with industry and parallel
discussions with public stakeholders. These discussions concluded in
May 2011 and we held a public meeting on October 24, 2011, where we
solicited comments on the proposed recommendations. We also opened a
public docket for comments. We considered these comments, and on
January 13, 2012, we transmitted the final recommendations to Congress.
We are very pleased to report that the enhancements for PDUFA-V
address many of the top priorities identified by public stakeholders,
the top concerns identified by industry, and the most important
challenges identified within FDA. I will briefly summarize these
enhancements.
A. Review Program for New Drug Applications, New Molecular
Entities,
and Original Biologics License Applications
FDA's existing review performance goals for priority and standard
applications--6 and 10 months respectively--were established in 1997.
Since that time, additional requirements in the drug review process
have made those goals increasingly challenging to meet, particularly
for more complex applications like new molecular entity (NME) NDAs and
original BLAs. FDA also recognizes that increasing communication
between the Agency and sponsors during the application review has the
potential to increase efficiency in the review process.
To address the desire for increased communication and greater
efficiency in the review process, we agreed to an enhancement to FDA's
review program for NME NDAs and original BLAs in PDUFA-V. This program
includes pre-submission meetings, mid-cycle communications, and late-
cycle meetings between FDA and sponsors for these applications. To
accommodate this increased interaction during regulatory review, as
agreed to with industry, FDA's review clock would begin after the 60-
day administrative filing review period for this subset of
applications. The impact of these modifications on the efficiency of
drug review for this subset of applications will be assessed during
PDUFA-V.
B. Enhancing Regulatory Science and Expediting Drug
Development
The following five enhancements focus on regulatory science and
expediting drug development.
1. Promoting Innovation Through Enhanced Communication Between FDA
and Sponsors During Drug Development
FDA recognizes that timely interactive communications with sponsors
can help foster efficient and effective drug development. In some
cases, a sponsor's questions may be complex enough to require a formal
meeting with FDA, but in other instances, a question may be relatively
straightforward such that a response can be provided more quickly.
However, our review staff 's workload and other competing public health
priorities can make it challenging to develop an Agency response to
matters outside of the formal meeting process.
This enhancement involves a dedicated drug development
communication and training staff, focused on improving communications
between FDA and sponsors during development. This staff will be
responsible for identifying best practices for communications between
the Agency and sponsors, training review staff, and disseminating best
practices through published guidance.
2. Methods for Meta-analysis
A meta-analysis typically attempts to combine the data or findings
from multiple completed studies to explore drug benefits and risks and,
in some cases, uncover what might be a potential safety signal in a
pre-market or post-market context. However, there is no consensus on
best practices in conducting a meta-analysis. With the growing
availability of clinical trial data, an increasing number of meta-
analyses are being conducted based on varying sets of data and
assumptions. If such studies conducted outside FDA find a potential
safety signal, FDA will work to try to confirm--or correct--the
information about a potential harm. To do this, FDA must work quickly
to conduct its own meta-analyses to include publicly available data and
the raw clinical trial data submitted by drug sponsors that would
typically not be available to outside researchers. This is resource-
intensive work and often exceeds the Agency's on-board scientific and
computational capacity, causing delays in FDA findings that prolong
public uncertainty.
PDUFA-V enhancements include the development of a dedicated staff
to evaluate best practices and limitations in meta-analysis methods.
Through a rigorous public comment process, FDA would develop guidance
on best practices and the Agency's approach to meta-analysis in
regulatory review and decisionmaking.
3. Biomarkers and Pharmacogenomics
Pharmacogenomics and the application of qualified biomarkers have
the potential to decrease drug development time by helping to
demonstrate benefits, establish unmet medical needs, and identify
patients who are predisposed to adverse events. FDA provides regulatory
advice on the use of biomarkers to facilitate the assessment of human
safety in early phase clinical studies, to support claims of efficacy,
and to establish the optimal dose selection for pivotal efficacy
studies. This is an area of new science where the Agency has seen a
marked increase in sponsor submissions to FDA. In the 2008-10 period,
the Agency experienced a nearly fourfold increase in this type of
review work.
PDUFA-V enhancements include augmenting the Agency's clinical,
clinical pharmacology, and statistical capacity to adequately address
submissions that propose to utilize biomarkers or pharmacogenomic
markers. The Agency would also hold a public meeting to discuss
potential strategies to facilitate scientific exchanges on biomarker
issues between FDA and drug manufacturers.
4. Use of Patient-reported Outcomes
Assessments of study endpoints known as patient-reported outcomes
(PROs) are increasingly an important part of successful drug
development. PROs measure treatment benefit or risk in medical product
clinical trials from the patients' point of view. They are critical in
understanding drug benefits and harm from the patients' perspective.
However, PROs require rigorous evaluation and statistical design and
analysis to ensure reliability to support claims of clinical benefit.
Early consultation between FDA and drug sponsors can ensure that
endpoints are well-defined and reliable. However, the Agency does not
have the capacity to meet the current demand from industry.
PDUFA-V enhancements include an initiative to improve FDA's
clinical and statistical capacity to address submissions involving PROs
and other endpoint assessment tools, including providing consultation
during the early stages of drug development. In addition, FDA will
convene a public meeting to discuss standards for PRO qualification,
new theories in endpoint measurement, and the implications for multi-
national trials.
5. Development of Drugs for Rare Diseases
FDA's oversight of rare disease drug development is complex and
resource intensive. Rare diseases are a highly diverse collection of
disorders, their natural histories are often not well-described, only
small population sizes are often available for study, and they do not
usually have well-defined outcome measures. This makes the design,
execution, and interpretation of clinical trials for rare diseases
difficult and time consuming, requiring frequent interaction between
FDA and drug sponsors. If recent trends in orphan designations are any
indication, FDA can expect an increase in investigational activity and
marketing applications for orphan products in the future.
Another PDUFA-V enhancement includes FDA facilitation of rare
disease drug development by issuing relevant guidance, increasing the
Agency's outreach efforts to the rare disease patient community, and
providing specialized training in rare disease drug development for
sponsors and FDA staff.
C. Enhancing Benefit-Risk Assessment
FDA has been developing an enhanced, structured approach to
benefit-risk assessments that accurately and concisely describes the
benefit and risk considerations in the Agency's drug regulatory
decisionmaking. Part of FDA's decisionmaking lies in thinking about the
context of the decision--an understanding of the condition treated and
the unmet medical need. Patients who live with a disease have a direct
stake in the outcome of drug review. The FDA drug review process could
benefit from a more systematic and expansive approach to obtaining the
patient perspective on disease severity and the potential gaps or
limitations in available treatments in a therapeutic area.
PDUFA-V enhancements include expanded implementation of FDA's
benefit-risk framework in the drug review process, including holding
public workshops to discuss the application of frameworks for
considering benefits and risks that are most appropriate for the
regulatory setting. FDA would also conduct a series of public meetings
between its review divisions and the relevant patient advocacy
communities to review the medical products available for specific
indications or disease states that will be chosen through a public
process.
D. Enhancement and Modernization of the FDA Drug Safety
System
The enhancements for PDUFA-V include two post-market, safety-
focused initiatives.
1. Standardizing Risk Evaluation and Mitigation Strategies
FDAAA gave FDA authority to require a Risk Evaluation and
Mitigation Strategy (REMS) when FDA finds that a REMS is necessary to
ensure that the benefits of a drug outweigh its risks. Some REMS are
more restrictive types of risk management programs that include
elements to ensure safe use (ETASU). These programs can require such
tools as prescriber training or certification, pharmacy training or
certification, dispensing in certain health care settings,
documentation of safe use conditions, required patient monitoring, or
patient registries. ETASU REMS can be challenging to implement and
evaluate, involving cooperation of all segments of the health care
system. Our experience with REMS to date suggests that the development
of multiple individual programs has the potential to create burdens on
the health care system and, in some cases, could limit appropriate
patient access to important therapies.
PDUFA-V enhancements initiate a public process to explore
strategies and initiate projects to standardize REMS with the goal of
reducing burden on practitioners, patients, and others in the health
care setting. Additionally, FDA will conduct public workshops and
develop guidance on methods for assessing the effectiveness of REMS and
the impact on patient access and burden on the health care system.
2. Using the Sentinel Initiative to Evaluate Drug Safety Issues
FDA's Sentinel Initiative is a long-term program designed to build
and implement a national electronic system for monitoring the safety of
FDA-approved medical products. FDAAA required FDA to collaborate with
Federal, academic, and private entities to develop methods to obtain
access to disparate data sources and validated means to link and
analyze safety data to monitor the safety of drugs after they reach the
market, an activity also known as ``active post-market drug safety
surveillance.'' FDA will use user fee funds to conduct a series of
activities to determine the feasibility of using Sentinel to evaluate
drug safety issues that may require regulatory action, e.g., labeling
changes, post-marketing requirements, or post-marketing commitments.
This may shorten the time it takes to better understand new or emerging
drug safety issues. PDUFA-V enhancements will enable FDA to initiate a
series of projects to establish the use of active post-market drug
safety surveillance in evaluating post-market safety signals in
population-based databases. By leveraging public and private health
care data sources to quickly evaluate drug safety issues, this work may
reduce the Agency's reliance on required post-marketing studies and
clinical trials.
E. Required Electronic Submissions and Standardization of
Electronic Application Data
The predictability of the FDA review process relies heavily on the
quality of sponsor submissions. The Agency currently receives
submissions of original applications and supplements in formats ranging
from paper-only to electronic-only, as well as hybrids of the two
media. The variability and unpredictability of submitted formats and
clinical data layout present major obstacles to conducting a timely,
efficient, and rigorous review within current PDUFA-goal timeframes. A
lack of standardized data also limits FDA's ability to transition to
more standardized approaches to benefit-risk assessment and impedes
conduct of safety analyses that inform FDA decisions related to REMS
and other post-marketing requirements. PDUFA-V enhancements include a
phased-in requirement for standardized, fully electronic submissions
during PDUFA-V for all marketing and investigational applications.
Through partnership with open standards-development organizations, the
Agency would also conduct a public process to develop standardized
terminology for clinical and non-clinical data submitted in marketing
and investigational applications.
F. User Fee Increase for PDUFA-V
The cost of the agreed upon PDUFA-V enhancements translates to an
overall increase in fees of approximately 6 percent.
G. PDUFA-V Enhancements for a Modified Inflation Adjuster
and Additional Evaluations of the Workload Adjuster
In calculating user fees for each new fiscal year, FDA adjusts the
base revenue amount by inflation and workload as specified in the
statute. PDUFA-V enhancements include a modification to the inflation
adjuster to accurately account for changes in its costs related to
payroll compensation and benefits as well as changes in non-payroll
costs. In addition, FDA will continue evaluating the workload adjuster
that was developed during the PDUFA-IV negotiations to ensure that it
continues to adequately capture changes in FDA's workload.
Generic Drug User Fees
As a result of the Drug Price Competition and Patent Term
Restoration Act of 1984, commonly known as Hatch-Waxman Amendments
passed by Congress more than a quarter of a century ago, America's
generic drug industry has been developing, manufacturing, and
marketing--and FDA has been reviewing and approving--lower-cost
versions of brand-name drugs. This legislation and the industry it
fostered has been a true public health success. Last year,
approximately 78 percent of the more than 3 billion new and refilled
prescriptions dispensed in the United States were filled with generics.
In the last decade alone, generic drugs have provided more than $931
billion in savings to the Nation's health care system.\5\
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\5\ ``An Economic Analysis of Generic Drug Usage in the U.S.''
Independent Analysis by IMS Health, Sept. 2011, http://gphaonline.org/
sites/default/files/GPhA%20IMS%20Study%20WEB
%20Sep20%2011.pdf.
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This success, however, also has come to represent a significant
regulatory challenge, and delays in approvals of generic drugs have
emerged as a major concern for the generics industry, FDA, consumers,
and payers alike. Unlike the brand manufacturers who pay fees under
PDUFA, the generic industry does not pay a user fee to support FDA
activities related to its applications. Over the last several years,
the time it takes for FDA to approve a generic drug has nearly doubled
as FDA's resources have not kept pace with an increasing number of
Abbreviated New Drug Applications (ANDA) and other submissions related
to generic drugs. The number of generic drug submissions sent annually
to FDA has grown rapidly, reaching another record high this year,
including nearly 1,000 ANDAs. Drug Master Files \6\ have grown at a
comparable pace and have reached similar heights. The current backlog
of applications pending review is estimated to be over 2,500. The
current median time to approval is approximately 31 months, though it
should be noted that this includes time the application is back with
the sponsor to answer any questions FDA may have about the application.
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\6\ Drug Master Files are widely used to provide FDA with
information about the drug substance, also known as the active
pharmaceutical ingredient (API).
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The regulatory challenge of ensuring safe, high-quality generic
drugs includes inspecting manufacturing facilities, where the challenge
is not just one of numbers but also of geography. To keep pace with the
growth of the generic drug industry, FDA has had to conduct more
inspections as the number of facilities supporting those applications
has also increased, with the greatest increase coming from foreign
facilities. Currently, the number of foreign Finished Dosage Form (FDF)
\7\ manufacturers exceeds the number found in the United States. The
generic industry is also experiencing significant growth in India and
China, a trend expected to continue. Foreign inspections represent a
significant challenge and require significant resources.
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\7\ An FDF is the final drug product (e.g., tablet, capsule). An
FDF is made up of both API(s) and any inactive excipients.
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The generic drug user fee agreement is designed to address the
regulatory challenges mentioned above in an affordable manner. The
annual fee total proposed represents approximately one-half of 1
percent of generic drug sales. This modest cost should be offset by
benefits received by the industry, as faster review times will bring
products to market sooner.
Overview of the Proposed Generic Drug User Fee Program
To develop recommendations for a generic drug user fee effective
beginning fiscal year 2013, FDA conducted a process that involved the
generic drug industry and public stakeholders. In addition to the
negotiation sessions with industry trade associations, there were
numerous public stakeholder meetings open to all, including industry,
patient advocates, consumer advocates, health care professionals, and
scientific and academic experts. The final agreement and the goals FDA
and industry have agreed to were transmitted to Congress on January 13,
2012.
The Generic Drug User Fee Act (GDUFA) proposal, as negotiated, is
aimed at putting FDA's generic drugs program on a firm financial
footing and providing the additional resources necessary to ensure
timely access to safe, high-quality, affordable generic drugs. The
proposal focuses on quality, access, and transparency. Quality means
ensuring that companies, foreign or domestic, that participate in the
U.S. generic drug system are held to the same consistent high-quality
standards and that their facilities are inspected biennially, using a
risk-based approach, with foreign and domestic inspection frequency
parity. Access means expediting the availability of low-cost, high-
quality generic drugs by bringing greater predictability and timeliness
to the review of ANDAs, amendments, and supplements. Transparency means
requiring the identification of facilities involved in the manufacture
of generic drugs and associated APIs, and improving FDA's
communications and feedback with industry to expedite product access
and enhance FDA's ability to protect Americans in our complex global
supply environment.
The additional resources called for under the agreement will
provide FDA with the ability to perform critical program functions that
could not otherwise occur. With the adoption of user fees and the
associated savings in development time, the overall expense of bringing
a product to market is expected to decline. The program is expected to
provide significant value to small companies and first-time entrants to
the generic market. In particular, these companies will benefit
significantly from the certainty associated with performance review
metrics that offer the potential to dramatically reduce the time needed
to commercialize a generic drug, when compared to pre-GDUFA review
times.
In addition, the variety of funding sources for the program will
ensure that participants in the generic drug industry, whether FDF
manufacturers or API \8\ manufacturers, whether foreign or domestic,
appropriately share the financial expense and benefits of the program.
The broad range of funding sources, including and across facility and
application types, as well as the large number of each, ensures that
individual fees remain reasonable and significantly lower than
associated branded drug fees.
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\8\ An API is the drug substance responsible for the therapeutic
effect (e.g., the chemical aspirin that is combined with excipients to
produce the FDF aspirin tablet).
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As in all of FDA's other medical product user fee programs, under
the proposed generic drug user fee program, user fee funding would
supplement appropriated funding to ensure sufficient resources for the
Agency's generic drug review program, and guarantees are in place to
ensure that the user fees are supplemental to annual appropriations in
the budget.
Biosimilars User Fees
A successful biosimilars review program within FDA will spark the
development of a new segment of the biotechnology industry in the
United States. The Biologics Price Competition and Innovation Act (BPCI
Act) of 2009, which was enacted as part of the Affordable Care Act of
2010, established a new abbreviated approval pathway for biological
products shown to be ``biosimilar to'' or ``interchangeable with'' an
FDA-licensed biological product. With this new abbreviated approval
pathway, a biosimilar biologic can be approved by demonstrating, among
other things, that it is highly similar to a reference biological
product already licensed by FDA. Development of biosimilars is expected
to be less risky, less costly, and take less time; therefore, approved
biosimilars are expected to be less expensive than the reference
product. This program will provide significant benefits for patients,
making available more affordable treatments that clinicians will know
are biosimilar or interchangeable. The development of this new market
segment will expand the opportunities for technical innovation and job
growth.
Background
A biosimilar is a biological product that is highly similar to a
U.S.-licensed reference product, notwithstanding minor differences in
clinically inactive components, and for which there are no clinically
meaningful differences between the biosimilar product and the reference
product in terms of the safety, purity, and potency of the product.
Under the transition provisions in the BPCI Act, user fees for a
biosimilar biological product are assessed under PDUFA. Accordingly,
currently, user fees for biological products are the same, regardless
of whether the BLA is submitted under the new, abbreviated biosimilar
pathway or under the previously existing approval pathway for
biological products. However, PDUFA-IV expires on September 30, 2012,
and the BPCI Act directs FDA to develop recommendations for a
biosimilars user fee program for fiscal years 2013 through 2017. To
develop these recommendations, FDA consulted with industry and public
stakeholders, including patient advocates, consumer advocates, health
care professionals, and scientific and academic experts, as directed by
Congress. The final recommendations were transmitted to Congress on
January 13, 2012.
Program Funding and Metrics
The proposed biosimilars user fee program for fiscal year 2013 to
2017 addresses many of the top priorities identified by public and
industry stakeholders and the most important challenges identified by
FDA. The proposed biosimilars user fee program is similar to the PDUFA
program in that it includes fees for marketing applications,
manufacturing establishments, and products. However, there are some
differences because of the nascent State of the biosimilars industry in
the United States. For example, there are no currently marketed
biosimilar biological products; accordingly, the recommended
biosimilars user fee program includes fees for products in the
development phase to generate fee revenue in the near-term and to
enable sponsors to have meetings with FDA early in the development of
biosimilar biological product candidates.
As in all of FDA's medical product user fee programs, the proposed
biosimilars user fee program supplements appropriated funding to ensure
sufficient resources for the Agency's review programs. Under the
proposed biosimilars user fee program, FDA would be authorized to spend
biosimilars user fees on Agency activities related to the review of
submissions in connection with biosimilar biological product
development, biosimilar biological product applications, and
supplements. This would include activities related to biosimilar
biological product development meetings and investigational new drug
applications (INDs). It would also include development of the
scientific, regulatory, and policy infrastructure necessary for review
of biosimilar biological product applications, such as regulation and
policy development, related to the review of biosimilar biological
product applications, and development of standards for biological
products subject to review and evaluation.
The biosimilars user fee program would support FDA activities at
the application stage, such as review of advertising and labeling prior
to approval of a biosimilar biological product application or
supplement; review of required post-marketing studies and post-
marketing studies that have been agreed to by sponsors as a condition
of approval; the issuance of action letters that communicate decisions
on biosimilar biological product applications; and inspection of
biosimilar biological product establishments and other facilities
undertaken as part of FDA's review of pending biosimilar biological
product applications and supplements (but not inspections unrelated to
the review of biosimilar biological product applications and
supplements). Finally, it would support some activities at the post-
approval stage, such as post-marketing safety activities, with respect
to biologics approved under biosimilar biological product applications
or supplements.
conclusion
PDUFA-IV expires on September 30, 2012, and FDA is ready to work
with you to ensure timely reauthorization of this critical program. If
we are to sustain and build on our record of accomplishments, it is
critical that the reauthorization occur seamlessly without any gap
between the expiration of the old law and the enactment of PDUFA-V. The
passage of both a new generic drug user fee and a new biosimilars user
fee would allow FDA to build upon the success of PDUFA.
Thank you for your contributions to the continued success of PDUFA
and to the mission of FDA. I am happy to answer questions you may have.
The Chairman. Thank you very much, Dr. Woodcock.
Dr. Shuren.
STATEMENT OF JEFFREY SHUREN, M.D., J.D., DIRECTOR, CENTER FOR
DEVICES AND RADIOLOGICAL HEALTH, FOOD AND DRUG ADMINISTRATION,
SILVER SPRING, MD
Dr. Shuren. Mr. Chairman and members of the committee, I am
Dr. Jeff Shuren, Director of Center for Devices and
Radiological Health, or CDRH, at the FDA. Thank you for the
opportunity to testify today.
I am pleased to tell you that FDA and representatives from
the medical device industry reached an agreement on proposed
recommendations for the reauthorization of the Medical Device
User Fee Act, or MDUFA, the details of which we provided to you
on March 16.
These recommendations would authorize FDA to collect $595
million in user fees over 5 years to help fund a portion of the
agency's medical device review program with FDA agreeing to
certain overall performance goals. As required by law, we held
a public meeting yesterday and will receive public comments on
the proposal package until April 16 before sending a final
package to Congress in late April.
When I came to CDRH in 2009 in response to concerns
expressed by industry and others, we initiated a review of our
device premarket review programs. The following year, we
released two reports that concluded, as I have testified
before, that we have not done as good a job managing the review
programs as we should have.
The No. 1 problem we found was insufficient predictability,
which was leading to inefficiencies, higher costs for industry
and FDA, and sometimes delays in bringing safe and effective
products to market.
In January 2011, we announced a plan with 25 specific
actions that we would take that year to improve the
predictability, consistency, and transparency of our premarket
programs. We announced additional steps since then.
As of today, 27 actions have been completed or are well
underway. They are intended to create a culture change toward
greater transparency, interaction and appropriate balancing of
benefit and risk. They focus on assuring predictable and
consistent decisionmaking, and application of the least
burdensome principle, and implementing more efficient
regulatory processes.
We believe that these actions have had, and will have, a
visible, positive impact by providing greater predictability
about data requirements through guidance, reducing unnecessary
or inconsistent data requests through training, and policy and
process changes, implementing policies that lead to
appropriately balanced benefit-risk determinations, using
external experts more extensively and effectively, creating
incentives to conduct clinical studies first in the United
States, speeding up clinical trial approval decisions, and
implementing the innovation pathway.
Preliminary data indicates that the actions we have taken
have started to bear fruit. For example, the backlog of 510(k)
submissions that had been steadily increasing from 2005 to
2010, decreased for the first time last year and is continuing
to decline in 2012. However, we still have much work to do.
Reauthorization of MDUFA will provide the resources that
CDRH needs to continue improving the device review programs and
help reduce the high staff turnover that has adversely affected
review predictability and consistency.
The proposed MDUFA recommendations we have agreed upon with
industry will also include several important process
improvements.
For example, if a performance goal on a device application
is missed the MDUFA proposal would require FDA and applicants
to work out a plan to complete work on the submission, ensuring
that no submission is left behind. Requiring a new, substantive
interaction between FDA and an applicant halfway through the
targeted time for reviewing the application, would help assure
sufficient time for the applicant to properly respond to
appropriate questions. Clear criteria for when FDA will refuse
to accept an incomplete application means more efficient use of
resources to the benefit of both FDA and industry.
These and other proposed enhancements are intended to
achieve a shared outcome goal of reduced average total time to
the decision, which both we, and industry, believe is an
important indicator of a successful premarket review program.
The agreement we have reached with industry strikes a
careful balance between what industry agreed to pay and what
FDA can accomplish with the amount of funding proposed.
However, we are concerned that even if device user fee
resources are increased under MDUFA-III, additional new
legislative mandates imposed on CDRH could divert resources and
undermine FDA's ability to achieve the new performance goals.
When PDUFA was last reauthorized in 2007, as Mr. Enzi, you
pointed out, the addition of new policy-related requirements
ultimately resulted in FDA's drug review program having to
temporarily suspend meeting its PDUFA review goals in order to
meet the statutory mandates. We want to avoid such a situation,
so that CDRH can focus on meeting the ambitious new MDUFA
program goals and achieving timely access to safe and effective
devices, which is an objective that we share with industry,
healthcare professionals, patients, consumers, and you.
Mr. Chairman, we share your goal of timely reauthorization
of MDUFA, and I look forward to working with you toward
enactment of this critical legislation.
I commend the committee's efforts, and am pleased to answer
any questions the committee may have.
[The prepared statement of Dr. Shuren follows:]
Prepared Statement of Jeffrey Shuren, M.D., J.D.
introduction
Mr. Chairman and members of the committee, I am Dr. Jeffrey Shuren,
Director of the Center for Devices and Radiological Health (CDRH) at
the Food and Drug Administration (FDA or the Agency). I am pleased to
be here today to discuss reauthorization of the Medical Device User Fee
Act, or MDUFA.
Background on MDUFA
The enactment in 2002 of the Medical Device User Fee and
Modernization Act (MDUFMA I) was prompted by growing concerns about the
medical device review program's capacity and performance. MDUFMA I and
MDUFA II (enacted in 2007) authorized user fees for the review of
medical device premarket applications, reports, supplements, and
premarket notification submissions. These additional resources enabled
FDA to make its reviews more timely, predictable, and transparent to
applicants. MDUFA fees and mandated appropriations for the medical
device program helped FDA expand available expertise, modernize its
information management systems, provide new review options, and provide
more guidance to prospective applicants.
MDUFA authorizes FDA to collect user fees for certain medical
device applications, the registration of certain medical device
establishments, and certain other purposes. Small businesses may
qualify for a waiver or a reduced fee on certain submissions to FDA.
Of the total $292,707,540 obligated in support of the process for
the review of medical device submissions in fiscal year 2010, MDUFA
fees funded about 20 percent. The remainder of the funding was through
appropriations. Fees currently charged for device review under MDUFA
include $220,050 for a Premarket Approval (PMA) application for high-
risk medical devices (a business with gross receipts under $100 million
qualifies for the ``small business'' PMA fee of about $55,000, and for
firms with gross receipts under $30 million, the firm's first PMA fee
is also waived). For lower-risk devices cleared under the 510(k) review
program, manufacturers pay $4,049 per 510(k) application review ($2,024
for small businesses).\1\ As a point of comparison, PDUFA fees--nearly
$568 million in fiscal year 2010--currently account for about two-
thirds of the drug review program's budget, and the current fee for
fiscal year 2012 associated with review of a New Drug Application (NDA)
requiring clinical data is $1,841,500.\2\
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\1\ See U.S. FDA, ``Medical Device User Fee Rates for Fiscal Year
2012,'' 76 Federal Register 45,826-45,831 (Aug. 1, 2011), available at
http://www.gpo.gov/fdsys/pkg/FR-2011-08-01/html/2011-19335.htm.
\2\ See U.S. FDA, ``Prescription Drug User Fee Rates for Fiscal
Year 2012,'' 76 Federal Register 45,831-45,838 (Aug. 1, 2011),
available at http://www.gpo.gov/fdsys/pkg/FR-2011-08-01/pdf/2011-
19332.pdf.
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The medical device user fee program has produced benefits for
public health. A better-resourced premarket device review program has
enhanced FDA's abilities to help bring more safe and effective medical
devices to the market, while keeping pace with the increasing
complexity of technology and changes in clinical practice. Since MDUFA
II was reauthorized in 2007, FDA has approved 106 original PMAs and
cleared more than 13,000 devices under the 510(k) program.
For example, approvals have included devices intended to address
unmet needs in the pediatric population, such as the first heart pump
designed to support the hearts of infants to adolescents until they
receive a heart transplant, and the first percutaneous heart valve
(approved for both children and adults).
The device program also has approved important new laboratory
tests, including an emergency-use diagnostic test in response to H1N1
outbreak in humans, and the first quick test for malaria. Device
reviews have significantly contributed to the very important trend
toward personalized medicine through clearance of a test system that
can assist in assessing the risk of tumor recurrence and long-term
survival for patients with relatively high-risk breast cancer.
Other important devices that have become available to patients over
the course of MDUFA II include, for example, the Implantable Miniature
Telescope (IMT), used for monocular implantation to improve vision in
elderly patients with stable severe to profound vision impairment
associated with end-stage age-related macular degeneration (AMD) \3\;
the Infrascanner--infrared brain hematoma detector, a non-invasive
hand-held device that uses near-infrared spectroscopy to evaluate
suspected brain hematomas at the site of injury within the ``golden
hour'' (the period following head trauma when pre-hospital analysis is
needed to rapidly assess a patient's neurological condition) \4\; and
the NeuRx DPS--RA/4 Respiratory Stimulation System, an implantable
electronic device that stimulates the diaphragm and allows certain
spinal cord injury patients to breathe for at least 4 hours a day
without a mechanical ventilator.\5\
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\3\ See FDA News Release, ``FDA Approves First Implantable
Miniature Telescope to Improve Sight of AMD Patients'' (July 6, 2010),
available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm218066.htm.
\4\ See Office of Naval Research, ``Naval Technology Could be a
Lifesaver'' (Dec. 21, 2011), available at http://www.onr.navy.mil/
Media-Center/Press-Releases/2011/Infrascanner-brain-TBI-FDA-
approval.aspx.
\5\ See FDA News Release, ``FDA Approves Diaphragm-Pacing Device''
(June 18, 2008), available at http://www.fda.gov/ForConsumers/
ConsumerUpdates/ucm116914.htm.
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However, neither the FDA nor industry believe that the user fee
program has reached the level of performance, or produced the extent of
benefits, that it has the potential to achieve.
MDUFA II Performance
FDA has been meeting or exceeding goals agreed to by FDA and
industry under MDUFA II for approximately 95 percent of the submissions
we review each year. For example, FDA completes at least 90 percent of
510(k) reviews within 90 days or less. In the few areas where FDA is
not yet meeting its MDUFA goals, the Agency's performance has generally
been improving--despite growing device complexity and an increased
workload. FDA's performance over the course of MDUFA II has not been
limited to achieving quantitative goals for the timely review of
premarket submissions like PMAs and 510(k)s; we have also accomplished
a number of ``qualitative'' goals set by MDUFA II in 2007, including
issuing more than 50 new and updated guidances for industry. Guidance
documents are important resources for industry because they describe
the Agency's interpretation of, or policy on, regulatory issues, and as
such, are critical to support industry efforts to comply with the law
and develop new products that may benefit the public health.\6\ The
availability of guidance documents also facilitates regulatory
predictability and consistency.
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\6\ Guidance documents include documents that relate to: (1) the
design, production, labeling, promotion, manufacturing, and testing of
regulated products; (2) the processing, content, and evaluation or
approval of submissions; and (3) FDA's inspection and enforcement
policies. See generally, ``Food and Drug Administration Report on Good
Guidance Practices: Improving Efficiency and Transparency'' (issued
Dec. 2011), available at http://www.fda.gov/downloads/AboutFDA/
Transparency/TransparencyInitiative/UCM285124.pdf.
---------------------------------------------------------------------------
It is important to note that MDUFA metrics reflect FDA time only;
they do not reflect the time taken by device sponsors to respond to
requests for additional information. Overall time to decision--the time
that FDA has the application, plus the time the manufacturer spends
answering any questions FDA may have--has increased steadily since
2001. As the graphs below illustrate, while the time FDA spends
reviewing an application has improved (for both low-and high-risk
devices), average total days for the review of 510(k)s has been
increasing since 2005, and has been increasing for PMA applications
since 2004.
FDA bears some responsibility for the increase in total time to
decision, and we have been instituting management, policy, and process
changes to address this issue. As a result, we are starting to see
indicators of improved review performance. For example, the Agency has
currently completed review of 85 percent of the 510(k) submissions
received in fiscal year 2011. The graph below, illustrating average
time to decision during the last 5 years at this same point (85 percent
of 510(k)s reviewed), shows that progress was made, starting last year,
in stabilizing 510(k) review times.
In addition, in fiscal year 2011, CDRH for the first time began
reducing what previously was an increasing backlog of unresolved 510(k)
submissions, as indicated in the next chart--and that trend is clearly
continuing as we approach the mid-point of fiscal year 2012.
Likewise, there had been a continuous annual increase, since fiscal
year 2002, in the percentage of 510(k) submissions requiring an
Additional Information (AI) letter \7\ after the first review cycle,
which had contributed to the increasing total time from submission to
decision. As indicated in the chart below, however, in fiscal year
2011, the percentage of 510(k)s requiring an AI letter declined for the
first time since 2002.
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\7\ If, after reviewing an application, FDA determines that it
cannot approve or clear the application in its current form, FDA sends
a letter informing the sponsor of this decision. For 510(k)
applications, this is called an ``Additional Information'' (AI) letter.
Smart Regulation's Role in Facilitating Medical Device Innovation
FDA recognizes that, if the United States is to maintain its
leadership role in this area, we must continue to streamline and
modernize our processes and procedures to make device approval not just
scientifically rigorous, but clear, consistent, and predictable,
without compromising safety. We are committed to continued improvements
in the device approval process to address legitimate concerns raised by
industry and other stakeholders.
A little over 2 years ago, CDRH recognized that, given the growing
complexities of medical product development, we needed to re-evaluate
and modernize our regulatory review processes in order to ensure that
patients had timely access to safe and effective medical devices. At
that time, CDRH began to undertake a new systematic approach to device
regulation, moving away from the traditional misperception that safety
and effectiveness and innovation are incompatible. Rather than focus on
more regulation or less regulation, we began to focus on ``smart
regulation.''
Our goal has been to ensure that safety and effectiveness and
innovation are complementary, mutually supporting aspects of our
mission to promote the public health. As part of our process to improve
CDRH's internal systems, we first reached out to stakeholders to hear
their concerns and listen to their recommendations about our premarket
programs. This is what we heard: industry felt that inadequate
predictability, consistency, and transparency were stifling innovation
and driving jobs overseas; and consumer groups, third-party payers, and
some health care professionals believed that one of our premarket
pathways--the 510(k) program--did not provide adequate protection for
American patients and did not generate sufficient information for
practitioners and patients to make well-informed treatment and
diagnostic decisions. In turn, CDRH employees expressed concerns that
the 510(k) program had not adapted to the increasing complexity of
devices, and that poor-quality 510(k) submissions, poor-quality
clinical studies conducted in support of PMA applications, and an ever-
growing workload were straining already overburdened premarket
programs.
We also began two assessments of our premarket programs to identify
issues, their root causes, and the appropriate solutions. One
assessment focuses on the 510(k) program. The other looks at how we use
science in regulatory decisionmaking, touching on aspects of several of
our premarket review pathways, such as our clinical trials program. In
addition, we contracted with the Institute of Medicine (IOM) to conduct
an independent evaluation of our 510(k) program.
In August 2010, following extensive public input, we released two
reports that identified issues regarding our premarket programs and
proposed potential actions for us to take to address the underlying
root causes. The No. 1 problem we found was insufficient predictability
in our premarket programs, which can create inefficiencies, increase
costs for industry and FDA, and delay bringing safe and effective
products to market. We identified several root causes of these issues.
They include very high reviewer and manager turnover at CDRH (almost
double that of FDA's drug and biologics centers); insufficient training
for staff and industry; extremely high ratios of employees to front-
line supervisors; insufficient oversight by managers; CDRH's rapidly
growing workload, caused by the increasing complexity of devices and
the number of overall submissions we review; unnecessary and/or
inconsistent data requirements imposed on device sponsors; insufficient
guidance for industry and FDA staff; and poor-quality submissions from
industry.
While it is true that providing more user fee resources alone won't
solve the problems with our premarket programs, insufficient funding is
at the root of, or a contributing factor to, several of these problems.
Adequate and stable funding is one key component to our and industry's
success in bringing safe and effective devices to market quickly and
efficiently.
After considering extensive and varied public input on our
recommendations, in January 2011, FDA announced a Plan of Action that
included 25 specific actions that we would take in 2011 to improve the
predictability, consistency, and transparency of our premarket
programs. We continued to engage in dialog about issues of importance
to CDRH and to members of the public, including the medical device
industry, health care professionals, patients, and consumers,\8\ and
followed up the Plan of Action with eight additional steps we would
take. As of March 2012, 27 actions are already completed or well
underway.\9\ In February 2011, we announced our Innovation Initiative,
which included several proposals to help maintain the position of the
United States as the world's leader in medical device innovation,
including the creation of a new approach for important, new
technologies called the Innovation Pathway.
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\8\ Numerous public meetings and workshops, including three ``town
hall'' discussions with the Center Director and senior CDRH management,
were held in 2011; similar CDRH outreach to stakeholders is ongoing.
For more details, see http://www.fda.gov/MedicalDevices/NewsEvents/
WorkshopsConferences/ucm111051.htm.
\9\ More information about FDA's progress in implementing the CDRH
``Plan of Action for 510(k) and Science'' is available on FDA's Web
site at http://www.fda.gov/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm276 286.htm.
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Since then, we have announced additional efforts to improve our
premarket programs, including actions to improve our program for
clinical trials and the Investigational Device Exemption (IDE) program.
The actions we are taking can be grouped into three main areas of
emphasis. Overall, our actions seek to:
Create a culture change toward greater transparency,
interaction, collaboration, and the appropriate balancing of benefits
and risks;
Ensure more predictable and consistent recommendations,
decisionmaking, and application of the least-burdensome principle; and
Implement more efficient processes and use of resources.
Specific steps that we are taking include:
Issuing guidance clarifying the criteria used to make
benefit-risk determinations a part of device premarket decisions. This
will provide greater predictability and consistency and apply a more
patient-centric approach by considering patients' tolerance for risk in
appropriate cases (draft guidance issued August 15, 2011, and final
guidance issued on March 27, 2012);
Creating standard operating procedures for when a reviewer
can request additional information regarding a premarket submission and
identifying at what management level the decision must be made. These
steps are intended to provide greater predictability, consistency, and
the appropriate application of the least-burdensome principle by
reducing the number of inappropriate information requests (Standard
Operating Procedures issued November 10, 2011);
Developing a range of updated and new guidances to clarify
CDRH requirements for predictable, timely, and consistent product
review, including device-specific guidance in several areas such as
mobile applications (draft guidance released July 19, 2011) and
artificial pancreas systems (draft guidance released December 1, 2011);
Revamping the guidance development process through a new
tracking system, streamlined processes, and, to the greatest extent
possible within available resources, core staff to oversee the timely
drafting and clearance of documents (December 2011);
Improving communications between FDA and industry through
enhancements to interactive review (some enhancements are already in
place);
Streamlining the clinical trial (IDE) processes by
providing industry with guidance to clarify the criteria for approving
clinical trials, and the criteria for when a first-in-human study can
be conducted earlier during device development. These actions aim to
create incentives to bring new technologies to the United States first
(guidances issued November 10, 2011) (IDEs are required before device
testing in humans that involves significant risks may begin, and they
ensure that the rights of human subjects are protected while gathering
data on the safety and efficacy of medical products);
Implementing internal business process improvements to
ensure that decisions are made by the appropriate level of management,
that decisions are made consistently and efficiently, and that we
appropriately apply the least-burdensome principle. For example, CDRH
created the internal Center Science Council to actively monitor the
quality and performance of the Center's scientific programs and ensure
consistency and predictability in CDRH scientific decisionmaking
(Center Science Council established March 31, 2011);
Creating a network of experts to help the Center resolve
complex scientific issues, which will ultimately result in more timely
reviews. This network will be especially helpful as FDA confronts new
technologies (Standard Operating Procedures issued September 30, 2011);
Instituting a mandatory Reviewer Certification Program for
new reviewers (program launched September 2011);
Beginning a pilot Experiential Learning Program to provide
review staff with real-world training experiences as they participate
in visits to manufacturers, research and health care facilities, and
academia (to begin in April 2012);
Providing industry with specific guidance on how to ensure
the quality and performance of clinical trials while applying the
least-burdensome principle, so that industry conducts studies that are
more likely to support the approval of their products (guidance
released August 15, 2011); and
Streamlining the de novo review process, the pathway by
which novel, lower-risk devices without a predicate can come to market
(draft guidance released October 3, 2011).
Our efforts to improve the premarket review programs at CDRH are
ongoing. We recently released our Strategic Priorities for 2012,\10\ in
which we commit to completing or continuing the work we already started
in four priority areas: (1) Fully Implement a Total Product Life Cycle
Approach,\11\ (2) Enhance Communication and Transparency, (3)
Strengthen Our Workforce and Workplace, and (4) Proactively Facilitate
Innovation to Address Unmet Public Health Needs. Our plan for 2012
includes timeframes associated with each strategy and specific actions
we will take to meet those goals or make significant progress toward
achieving those goals, including, for example:
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\10\ CDRH, ``2012 Strategic Priorities,'' available at http://
www.fda.gov/AboutFDA/Centers
Offices/OfficeofMedicalProductsandTobacco/CDRH/CDRHVisionandMission/
ucm288735.htm.
\11\ A Total Product Life Cycle (TPLC) approach involves making
well-supported regulatory decisions that take into consideration all of
the relevant information available to CDRH at any stage of a product's
life cycle to assure the safety, effectiveness, and quality of medical
devices and the safety of non-device radiation-emitting products. The
Center's TPLC database integrates premarket and post-market data about
medical devices. For more information, see CDRH's Web site at http://
www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/
CDRH/CDRHTransparency/ucm199906.htm.
By April 1, 2012, begin the Triage of Premarket
Submissions Pilot to increase submission review efficiency and better
manage the premarket review workload;
By September 30, 2012, make recommendations on how to
adequately recognize good employee performance and address poor
performance;
By September 30, 2012, create processes and tools that
will improve the pipeline for innovative medical devices and transform
the way CDRH works with medical device innovators, such as the new
Entrepreneurs-in-Residence program;
By September 30, 2012, develop methods and procedures for
the systematic analysis and use of medical device recall information;
By October 31, 2012, develop a comprehensive strategy to
assess real-world device performance;
By December 31, 2012, conduct an evaluation of CDRH
staffing, infrastructure, policies, and practices pertaining to medical
device software;
By December 31, 2012, review remaining Class III pre-
amendment medical devices;
By December 31, 2012, fully implement the Experiential
Learning Program to enhance premarket reviewer knowledge of how medical
devices are designed, manufactured, and utilized by providing real-
world learning opportunities; and
By December 31, 2012, launch the CDRH Leadership
Enhancement and Development (LEAD) program to provide CDRH managers and
supervisors information and tools to ensure effective leadership.
We believe the actions that we've taken and plan to take in the
future will have a positive impact on the device review process by
providing greater predictability of data requirements through guidance,
reducing unnecessary data requests through training and policy and
process changes, implementing policies to appropriately balance
benefit-risk determinations, using external experts more extensively
(consistent with conflict-of-interest guidelines), creating incentives
to conduct clinical studies first in the United States, speeding up IDE
approval decisions, implementing the Innovation Pathway 2.0 (a priority
review program to expedite development, assessment, and review of
important technologies), and instituting efficiencies in the premarket
review process.
For example, I'm pleased to report that, consistent with our many
improvements to the 510(k) program, the recent increase in the ``not
substantially equivalent'' (NSE) rate \12\ appears to be turning
around. For manufacturers and FDA, NSE determinations often represent
an inefficient use of time and resources. NSE determinations require
significant Agency resources and time, yet fail to result in the
marketing of a new product. As shown in the next chart, from a peak of
8 percent in fiscal year 2010, the NSE rate has decreased to 4 percent
by the end of the first 5 months of fiscal year 2012. Just as
important, we also may be seeing a reversal in the trend of declining
rate in Substantially Equivalent (SE) decisions that clear a 510(k)
submission for marketing. After several years of declining percentages,
reaching a low of 73 percent in 2010, SE rates increased by 6
percentage points by the end of the first 5 months of fiscal year 2012,
as shown in the chart below.
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\12\ Among the reasons that 510(k) submissions result in NSE
determinations are: lack of a suitable predicate device; intended use
of the new device is not the same as the intended use of the predicate;
technological characteristics are different from those of the predicate
and raise new questions of safety and effectiveness; and/or performance
data failed to demonstrate that the device is as safe and effective as
the predicate. The vast majority of NSE decisions are due to the
absence of adequate performance data, sometimes despite repeated FDA
requests.
To best serve patients, both the medical device industry and FDA
must have the flexibility to be innovative and entrepreneurial. CDRH
must continue making critical improvements to our device program. At
the same time, the medical device industry and CDRH must continue to
work together to ensure that the Center receives high-quality
submissions that contain the information we need to make well-informed
and timely decisions. Finally, CDRH must have adequate and stable
resources to get the job done right and quickly. Timely reauthorization
of MDUFA, as well as the congressional appropriations process, is
critical to achieving these goals.
Moving Forward: Reauthorization of MDUFA
When MDUFA was reauthorized in 2007, Congress directed FDA to take
additional steps to ensure that public stakeholders would have adequate
opportunity to provide input to any program enhancements. In addition
to FDA receiving input from stakeholders during an initial public
meeting \13\ in September 2010, as directed by Congress, we met with
stakeholders, including representatives of patient and consumer groups,
between January 2011 and February 2012, and made the minutes of those
meetings available to the public.\14\
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\13\ A transcript of the September 2010 public meeting, and related
meeting materials, are available on FDA's Web site at http://
www.fda.gov/MedicalDevices/NewsEvents/Workshops
Conferences/ucm218250.htm.
\14\ The minutes of the stakeholder discussions on MDUFA III
reauthorization are available on FDA's Web site at http://www.fda.gov/
MedicalDevices/DeviceRegulationandGuidance/Overview/
MedicalDeviceUserFeeandModernizationActMDUFMA/ucm236902.htm.
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During that 13-month period, we also held discussions with
representatives of the medical device industry, as required under the
MDUFA II statute, in an effort to develop a package of proposed
recommendations for MDUFA reauthorization. Minutes of those
consultation meetings were also made available to the public.\15\
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\15\ The minutes of the industry discussions on MDUFA III
reauthorization are available on FDA's Web site at http://www.fda.gov/
MedicalDevices/DeviceRegulationandGuidance/Overview/
MedicalDeviceUserFeeandModernizationActMDUFMA/ucm236902.htm.
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We were pleased to announce last month that FDA and representatives
from the medical device industry reached an agreement on the proposed
recommendations for MDUFA III. That agreement, which would authorize
FDA to collect $595 million in user fees over 5 years (plus increases
based on inflation), strikes a careful balance between what industry
agreed to pay and what FDA can accomplish with the amount of funding
proposed. We believe that it will result in greater predictability,
consistency, and transparency through a number of improvements to the
review process. On March 15, 2012, FDA made public the package of
proposed recommend-
ations,\16\ requested written public comment on those proposed
recommendations, and announced that we would be holding a public
meeting on March 28, 2012, at which interested stakeholders could
present their views.
---------------------------------------------------------------------------
\16\ The proposed package of recommendations for MDUFA III is
available on FDA's Web site at http://www.fda.gov/MedicalDevices/
NewsEvents/WorkshopsConferences/ucm292860.htm.
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The proposed recommendations for MDUFA III address many of the
priorities and concerns identified by public stakeholders and the
device industry and many of the important challenges identified by FDA.
Some of the notable improvements to the MDUFA program in the MDUFA III
proposed recommendations include:
Review Process, Infrastructure, and Capacity Enhancements:
Facilitating earlier and more transparent and
predictable interactions between FDA and the applicant, both
during the early product development or ``pre-submission''
stage as well as during the review process, by implementing a
structured process for managing pre-submissions and continuing
to incorporate an interactive review process;
Providing more detailed and objective ``submission
acceptance criteria'' for determining when a premarket
submission is complete and when a premarket submission is
incomplete and should not be accepted for review;
Improving the process of developing, reviewing,
tracking, issuing, and updating guidance documents;
Recommending reauthorization of the third-party
review program and working with interested parties to
strengthen and improve the current program as resources permit;
Fully implementing guidance on factors to consider
when making benefit-risk determinations, meeting with patient
groups to better understand the patient perspective on disease
severity and unmet medical need, and increasing FDA's
utilization of Patient Representatives to provide patients'
views early in the medical product development process;
Identifying additional low-risk medical devices to
exempt from premarket notification requirements;
Working with industry to develop a transitional In
Vitro Diagnostics (IVD) approach for the regulation of emerging
diagnostics;
Enhancing scientific and regulatory review capacity
by hiring additional staff and reducing the ratio of review
staff to front line supervisors--FDA is seeking to obtain
streamlined hiring authority in order to accomplish this;
More Rigorous Review Performance Goals and Shared Outcome
Goals:
Adopting streamlined FDA review goals to provide
better overall performance and greater predictability,
including a commitment to meet with an applicant if FDA's
review of their submission extends beyond the goal date;
Eliminating the ``two-tier'' goal structure of MDUFA
II and adopting a more simplified structure, incorporating a
single, high-percentage goal for each performance metric;
Instituting more rigorous performance review goals:
increasing the percentage of 510(k) reviews that
are completed in 90 review days from the current 90 percent to
95 percent by fiscal year 2015;
increasing the percentage of PMA reviews that are
completed within 180 review days, from the current 60 percent
to 90 percent by fiscal year 2016, for PMAs not requiring
external advisory panel review--for PMAs that do undergo panel
review, FDA will complete 90 percent of the reviews within 320
review days by fiscal year 2017;
Instituting a Substantive Interaction goal for
several submission types to track the Agency's communication
with applicants at specified points during the review process;
A joint commitment between FDA and industry to
accomplish shared outcome goals to reduce the total average
calendar time to a decision for PMAs and 510(k)s so that safe
and effective devices reach patients and health care
professionals more quickly;
Enhanced Metrics for Improvements to the Premarket Review
Process:
Conducting a comprehensive independent assessment of
the premarket review process to identify potential enhancements
to efficiency and effectiveness, and incorporating those
findings and recommendations into management of the review
program;
More detailed quarterly and annual reporting of MDUFA
III review program performance.
Additional details regarding the proposed recommendations for
reauthorization of MDUFA, including the draft MDUFA III commitment
letter and legislative language, are available on FDA's Web site at
http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/
ucm292860.htm.
The public comment period for review of the proposed
recommendations for MDUFA III began on March 15, 2012. After the
conclusion of the public comment period on April 16, 2012, FDA will
consider the public's views and comments, revise the proposed
recommendations as necessary, and transmit a final package of
recommendations to Congress, along with a summary of the views and
comments that were received and any changes that were made to the
proposed recommendations in response to the public's views and
comments. As we continue to work with all interested stakeholders and
Congress toward reauthorization of MDUFA in order to provide adequate
and stable funding for the program, we will also be moving forward with
our ongoing CDRH program improvements, focusing on smart regulation
that will facilitate device innovation. As these new policies and
processes continue to be implemented, we expect to see notable
improvements in the consistency, transparency, and predictability of
our premarket review programs.
Smart Regulation's Role in Assuring Patient Safety
As we continue to look for ways to improve our ability to
facilitate innovation and to speed safe and effective products to
patients, we must not lose sight of the benefits of smart regulation to
the medical device industry, to patients, and to society. Smart
regulation of medical devices results in better, safer, more effective
treatments as well as worldwide confidence in, and adoption of, the
devices that industry produces.
We at FDA see daily the kinds of problems that occur with medical
devices that are poorly designed or manufactured, difficult to use,
and/or insufficiently tested. We appreciate the concern that some
devices come on the market in the European Union (EU) before they do in
the United States. While we want devices to be available to American
patients as soon as possible, consistent with U.S. law, they need to be
both safe and effective. The U.S. system has served patients well by
preventing devices from entering the U.S. market that were later shown
to be unsafe or ineffective.\17\
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\17\ See, e.g., D. Cohen and M. Billingsley, ``Europeans Are Left
to Their Own Devices,'' British Medical Journal, 342:d2748 (2011),
available at http://www.bmj.com/content/342/bmj.d2748.
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There are significant differences between the EU and the U.S.
medical device review systems. In the EU, manufacturers must
demonstrate safety and performance, while in the United States, the
standard for approval is safety and effectiveness.\18\ In the EU, more
than 70 private, non-governmental entities called ``Notified Bodies''
review and approve devices by giving them a ``CE mark.'' These
decisions are kept confidential and are not released to the public or
to EU regulatory bodies. In fact, the EU does not have one centralized
regulatory body. Instead, each country can designate an entity as a
Notified Body, yet the decision of one Notified Body applies to all EU
countries.
---------------------------------------------------------------------------
\18\ See ``Recast of the Medical Devices Directives: Public
Consultation,'' available at http://ec.europa.eu/consumers/sectors/
medical-devices/files/recast_docs_2008/public_consultation
_en.pdf; European Commission, ``Guidelines on Medical Devices: Clinical
Evaluation: A Guide for Manufacturers and Notified Bodies'' (Dec.
2009), at p. 4, available at http://ec.europa.eu/health/medical-
devices/files/meddev/2_7_1rev_3_en.pdf.
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Because of these factors, it is impossible to track medical device
approvals, adverse events, or recalls in the EU, since there are few to
no publicly accessible, centralized systems for collecting and
monitoring information about medical device approvals or safety
problems. The use of Notified Bodies has been criticized as encouraging
``forum shopping'' by sponsors to identify those Notified Bodies with
the most lax operating standards, and the varying levels of expertise
among Notified Bodies has been critiqued.
Some have suggested that the United States adopt the medical device
regulatory system of the EU. Yet, outside the United States, pressure
is growing toward greater premarket scrutiny of medical devices. A June
2011 report from the Belgian Health Care Knowledge Centre (a
governmental agency that produces studies to advise policymakers when
deciding on health care and health insurance) \19\ concluded that
``[f]or innovative high-risk devices the future EU Device Directive
should move away from requiring clinical safety and ``performance''
data only to also require pre-market data that demonstrate `clinical
efficacy,' '' and ``[t]he device industry should be made aware of the
growing importance of generating clinical evidence and the specific
expertise this requires.'' \20\
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\19\ Additional information about the Belgian Health Care Knowledge
Centre, and its mission and activities, is available at https://
kce.fgov.be/content/about-the-kce.
\20\ Belgian Health Care Knowledge Centre, ``The Pre-market
Clinical Evaluation of Innovative High-risk Medical Devices,'' KCE
Reports 158 (2011) at p. vii, available at http://www.kce.fgov.be/
index_en.aspx?SGREF=202677.
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In May 2011, the European Society of Cardiology (ESC) issued a
``case for reform'' of the European medical device regulatory system:
that body's recommendations included creating a unified regulatory
system, imposing stronger clinical data requirements, and requiring
more accountability for notified bodies.\21\ The ESC cited examples of
several different cardiovascular technologies that were implanted in
patients in the EU that were later proven to be unsafe and/or
ineffective through clinical trials required under the U.S. system and
were subsequently removed from the European market.
---------------------------------------------------------------------------
\21\ See ``Clinical evaluation of cardiovascular devices:
principles, problems, and proposals for European regulatory reform,''
Alan G. Fraser, ET al., European Heart Journal, May 2011.
---------------------------------------------------------------------------
Also in May 2011, a series of feature articles was published in the
British Medical Journal, criticizing the opacity of the European
medical device regulatory system, and raising concerns about the
regulation of high-risk devices and how well they are tested before
coming on to the European market.\22\ Several of the featured articles
cited the FDA system's transparency as helping physicians to make
informed decisions about which devices to use and providing patients
with access to information about the devices that will be used on them.
---------------------------------------------------------------------------
\22\ ``The Truth About Medical Devices,'' British Medical Journal,
vol. 342, at PP. 1115-30 (May 21, 2011), available at http://
www.bmj.com/content/342/7807/Feature.full.pdf (Deborah Cohen, ``Out of
Joint: The Story of the ASR,'' British Medical Journal 2011; 342:d2905;
Deborah Cohen and Matthew Billingsley, ``Medical Devices: European
Patients Are Left to Their Own Devices,'' British Medical Journal 2011;
342:d2748); see also Fiona Godlee, ``Editorial: The Trouble With
Medical Devices,'' British Medical Journal 2011; 342:d3123, available
at http://www.bmj.com/content/342/bmj.d3123.full; Carl Heneghan, ET
al., ``Medical-Device Recalls in the UK and the Device-Regulation
Process: Retrospective Review of Safety Notices and Alerts,'' BMJOpen
(May 2011), available at http://bmjopen.bmj.com/content/early/2011/05/
12/bmjopen-2011-000155.full.pdf.
---------------------------------------------------------------------------
Most recently, France's Directorate General for Health and its
consumer safety body AFSSAPS \23\ issued a report \24\ urging stronger
national and European regulation and monitoring of medical devices. In
an accompanying statement, France's Minister of Health, Xavier
Bertrand, said that EU rules on regulating and monitoring medical
devices ``must be radically overhauled.'' \25\
---------------------------------------------------------------------------
\23\ Agence francaise de securite sanitaire des produits de sante,
France's Agency for the Safety of Health Products.
\24\ See AFSSAPS, ``Poly Implant Prothese: remise d'un rapport de
la DGS ET de l'Afssaps aux ministres charges de la sante--Communique,''
available at http://www.afssaps.fr/index.php/Infos-de-securite/
Communiques-Points-presse/Poly-Implant-Prothese-remise-d-un-rapport-de-
la-DGS-et-de-l-Afssaps-aux-ministres-charges-de-la-sante-Communique.
\25\ See ``France Calls for Europe-wide Control on Prosthetics
following PIP Breast Implant Scare,'' The Telegraph (Feb. 1, 2012),
available at http://www.telegraph.co.uk/health/women_shealth/9054282/
France-calls-for-Europe-wide-control-on-prosthetics-following-PIP-
breast-implant-scare.html.
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FDA continues exploring ways to get medical products to patients
with serious and life-threatening diseases or conditions faster, but
lowering U.S. approval standards isn't in the best interest of American
patients, our health care system, or U.S. companies whose success
relies on the American public's confidence in their products. We are
pleased that a U.S. medical device industry trade association, AdvaMed,
has stated that it supports maintaining our current rigorous standards
of safety and effectiveness for marketing medical devices: ``The
medical technology industry has long recognized that a strong and well-
functioning FDA is vital to maintaining America's pre-eminence in
medical technology innovation, and we support the current regulatory
framework in the United States.'' \26\
---------------------------------------------------------------------------
\26\ Advanced Medical Technology Association (AdvaMed), ``AdvaMed
Statement on the House Energy and Commerce Subcommittee Hearing on FDA
Device Regulation'' (July 20, 2011).
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conclusion
Over the course of MDUFA II, and especially during the last 2
years, CDRH has been working, with extensive input from industry and
other stakeholders, to take concrete actions toward creating a culture
change toward greater transparency, interaction, collaboration, and the
appropriate balancing of benefits and risks; ensuring predictable and
consistent recommendations, decisionmaking, and application of the
least-burdensome principle; and implementing efficient processes and
use of resources. These actions--geared toward a system of smart
regulation--have already started to have a measurable, positive impact
on our premarket programs, and we fully expect that positive trend to
continue as we proceed to implement the improvements we have committed
to make.
While we work with industry, other stakeholders, and Congress in
the statutory process toward the reauthorization of medical device user
fees, in order to ensure adequate and stable funding of the program, we
are also continuing to move forward with CDRH program improvements.
MDUFA II is scheduled to expire on September 30, 2012, and FDA is ready
to work with you to ensure timely reauthorization of this critical
program. If we are to sustain and build on our record of
accomplishment, it is critical that the MDUFA reauthorization occurs
seamlessly, without any gap between the expiration of current law and
the enactment of MDUFA III. At the same time, we must remain mindful
that, unlike the PDUFA program in which fees fund more than 60 percent
of drug review costs, user fees under MDUFA III (as described in the
recently announced agreement) will fund about a third of the total cost
of the medical device premarket review process, making it important to
keep these resources focused on the performance goals identified in the
MDUFA agreement.
Mr. Chairman and members of the committee, I share your goal of
smart, streamlined regulatory programs. Thank you for your commitment
to the mission of FDA, and to the continued success of our medical
device program, which helps to ensure that patients and practitioners
have access to safe and effective innovative medical technologies on a
daily basis. I am happy to answer questions you may have.
The Chairman. Thank you very much, Dr. Shuren.
We will begin a round of 5 minute questions. We have a good
turnout here today, so we will try to move right along.
Starting with you, Dr. Shuren, we hear a lot about speeding
up the review times for devices, applications.
Referring back to your testimony, which I had gone over
last evening, you said, ``Our goal is not more regulation or
less regulation, but smart regulation.'' You said, ``Our goal
has been to ensure that safety and effectiveness and innovation
are complementary,''--complementary--``mutually supporting
aspects of our mission to promote the public health.''
We hear a lot about speeding up review times, but how will
user fees be used to ensure that devices are safe for patients?
Safe.
Dr. Shuren. What is critical in the user fee agreement
along those lines is we are not changing the standards for a
product to come to market.
These fees are going to allow us to put in place process
improvements, and have the staff to make well-informed and
timely decisions assuring that those products are safe and
effective when they are coming to market. We will not
shortchange the quality of our decisions. What we will do is be
able to speed up those decisions, but still assure the safety
and effectiveness of devices coming forward.
The Chairman. The same question I will ask of Dr. Woodcock
is how would patients be affected if we did not reauthorize
this on time? How would your patients be affected, both of you,
Dr. Shuren, on your devices and then Dr. Woodcock?
Dr. Shuren.
Dr. Shuren. We would have to let go staff and it is more
than just that. Our program will actually be in a death spiral
because our good people will leave the program, it will go
down. There will be delays in reviewing products. There will be
disincentives for innovation and that will lead to new
technologies, jobs, all going overseas. That is not in the best
interest of patients. It is not in the best interest of
industry. It is not in the best interests of the U.S.
Government.
The Chairman. Thank you. Dr. Woodcock. How would patients
be affected if we did not get the prescription drug user fees?
Dr. Woodcock. The Prescription Drug User Fee Act, if
terminated, would require us to begin to layoff a large number
of staff involved in review, and also probably some involved in
managing drug safety post-marketing.
We would go back to the point, unfortunately, where
innovative products are reaching American patients last in the
world instead of first in the world.
But in addition, the other user fee programs also provide,
for example, the generics. We need a robust generic drug
industry because 80 percent of prescriptions dispensed in this
country are generic drugs, and our patients rely upon those
drugs: their safety, their quality, and their affordability. So
that program needs more support to keep building on its
success.
The Chairman. Dr. Woodcock, let me followup with another
question. I have heard from many members of the rare disease
community about the unique challenges that this community faces
in getting drugs developed and approved to treat their serious
ailments.
How does PDUFA-V, as we are calling it, enhance focus on
orphan drugs for rare diseases?
Dr. Woodcock. The program includes enhancements of our
ability to support those companies that are developing a rare
disease--their specific support added will be able to add staff
because often, these are small companies that need a great deal
of advice.
There is also a provision for assisting small companies
where we will be adding significant staff that will be able to
help small companies or new companies through the review and
approval process.
The Chairman. Very good. That is all I have for right now
unless I have another second round.
Senator Enzi.
Senator Enzi. Thank you, Mr. Chairman.
I will begin with Dr. Shuren. The proposed medical device
user fee agreement will give you resources to hire and train
more reviewers, more managers, and more technical writers.
What effect can we expect and how will you make that
happen? What kind of training?
Dr. Shuren. We have already put in place a new reviewer
certification program. Every new reviewer that comes in the
door, now goes through standardized coursework, oversight of
the applications that they are reviewing.
We are going to follow that up this year, and actually in
the next few weeks, with a pilot for what we call an
experiential learning program. We are going to let our staff go
out to manufacturer facilities, healthcare facilities, and get
real world experience.
We are also putting in place core curriculums for each of
the critical roles in our center in premarket review and
elsewhere. This includes for managers, medical officers, lead
reviewers, engineers, and on down the line.
Senator Enzi. Thank you.
Dr. Woodcock, the proposed prescription drug user fee
agreement addresses issues concerning the Risk, Evaluation, and
Mitigation Strategies, or REMS. REMS was intended as a tool to
let the FDA ensure that the benefits of a drug or biological
product outweigh its risks, but implementation resulted in some
delays and confusion.
Can you describe the challenges of implementing REMS over
the past few years and how this agreement addresses the
outstanding concerns?
Dr. Woodcock. Certainly. We think the REMS are a good tool
because some drugs have to have additional safety measures to
be on the market because they have some severe safety risk.
However, the original implementation of the REMS was not
standardized, and it was one off for each REMS that was
implemented. This caused difficulties for the manufacturers,
but it also caused tremendous difficulties for the health care
system.
We had a public meeting about this, and we heard, believe
me, very clearly that we need standardized tools. We need one
way to do this. It has to be convenient, both for the
physicians, healthcare professionals, and the pharmacists in
particular who have to implement these REMS. And the user fee
program will provide us with the goals and the resources to do
that.
Senator Enzi. Thank you.
This question will be for both of you because I see that
the proposed, both fees, have provisions concerning the patient
perspective on benefit-risk decisions.
What does that mean to each of you? Let's start with Dr.
Woodcock.
Dr. Woodcock. We are very excited about these provisions
because taken as a whole, we think they will move toward
patient-centered drug development because, actually I hate to
tell you, but drugs are not really safe. Most drugs have
liabilities. They have risks, and so the benefits are taken
into account with those risks.
But we need to understand what tradeoffs a patient is
willing to take. What risks might they be willing to receive in
order to get the benefits? And that tradeoff, we need to hear
from patients. It turns out that doctors, or regulators, we do
not really know, we do not really speak with a patient's voice.
The agreement proposes that we get 20 diseases, that we go
through a process to elicit the patient's point of view, and we
are piloting that now in obesity, and we are learning a great
deal, even with this pilot we are doing.
We also are developing a standardized benefit-risk
framework, which we would publish for each drug, that would go
over the benefits, the risks, the uncertainties, and the
alternative therapy, and let people know how the new therapy
stacks up.
Then we hope to incorporate patient-reported outcomes into
the trials, so we hear from the patient point-of-view how they
experienced the disease and the drug, and how the drug
mitigated the disease, as well as how the side effects burdened
the patient.
This would really revolutionize, I think, our understanding
when taken together of how therapies actually impact patients.
Senator Enzi. I will probably have a couple of followup
questions, but I will go to Dr. Shuren first.
Dr. Shuren. I share Dr. Woodcock's perspective, as does my
center, how important it is to take into account what a patient
perceives as a risk and what they are willing to take. As I
tell my reviewers, they are not the ones who are getting these
devices; the patients are and the patients have to make a
choice.
We, too, under MDUFA-III have committed to develop a
benefit-risk determination framework that takes into account
patient's tolerance for risk. I am pleased to say that,
actually, it was something we were pursuing. We put out a draft
proposal in August of this year and we just issued the final
framework on the 27th, this week. It will go into effect
starting on May 1st. We are going to begin to do training of
our staff, and it will move forward.
We, too, have committed for engagements with the patient
community to better understand their perspective. We already
have developed a survey tool that we are going to be piloting.
We are also looking in the obesity context. We will be
leveraging the meetings that CDHR is putting together and we
think, together, this will actually move the program in a very
positive direction.
Senator Enzi. Encouraging. My time has expired. Thank you,
Mr. Chairman.
The Chairman. Thank you, Senator Enzi. I remind members of
the committee that we have another panel of five after this
panel. Also, it looks like we are going to have a vote here
sometime soon, so we will have to take a break, so I ask all
Senators to please respect the 5 minute time.
I have in order now, Senator Murray, Senator Roberts,
Senator Mikulski, Senator Burr, and then Senators Whitehouse,
Bennett, Murphy, Hagan, and Blumenthal.
Senator Murray.
Statement of Senator Murray
Senator Murray. Thank you very much, Mr. Chairman.
I really want to thank all of our witnesses for being here
to talk about this really important issue. The medical device,
pharmaceutical, and biotechnology industry is really working
hard to find cures for diseases that affect millions of
Americans and their families. Companies in this industry are
also really critical to our local economies.
In my home State of Washington, biotech companies employ
about 18,000 workers directly and almost 50,000 more through
their economic activity. Medical device companies employ about
9,000 people and supports the employment of another 20,000.
These are not just any jobs. These are high-skilled, stable
jobs that pay good wages. I think they are exactly the kind of
21st century careers we are all working hard to create here in
America.
I am very encouraged by the success and growth of this
industry, and that is why I am very focused, Mr. Chairman, on
making sure the Federal Government is doing what it can to make
sure they are successful, and why this important discussion is
happening today. I am really pleased that we are working
together to strengthen the FDA user fee system.
Dr. Woodcock, Dr. Shuren, you have answered my questions,
and I know we have another panel. I just wanted to mention, Dr.
Woodcock, you said, ``If we do not reauthorize this, we will go
from first to last,'' which is frightening, I think, for a lot
of patients in this country, who really depend on the FDA. I
really appreciate you pointing that out.
Dr. Shuren, I wanted to quickly ask you, can you give us an
idea of some of the products or disease categories where FDA is
currently leading the world in advancing innovation that would
be impacted should we not reauthorize the user fees
legislation?
Dr. Shuren. I think you can actually go down the list of
any innovative technology we want to get to patients here in
the United States first.
If the program goes down, that will not even be a dream. It
will be an impossibility.
Senator Murray. Thank you very much.
I do know you have another panel, Mr. Chairman, so I will
wait to hear their testimony. Thank you.
The Chairman. Thank you, Senator Murray.
Senator Roberts.
Statement of Senator Roberts
Senator Roberts. Thank you, Mr. Chairman, for a very timely
hearing. Thank you for your leadership.
And to all of the five witnesses, we always have
obligations, and I apologize for not being here. But you have
really put together an excellent panel following this panel.
I particularly want to thank Sara Radcliffe, who is
speaking for BIO and its 1,100 members. She says in her
testimony, ``Given the recent establishment of the biosimilars
at the FDA, only modest appropriations are currently allocated
to the program.'' So, of course, they have agreed to, ``An
equitable balance of fees and appropriations,'' and that is
what we are facing here in terms of user fees.
I do not like user fees, but under the circumstances, there
is not any real alternative, and it is a challenge we face, I
think, in almost every program that we have here before the
Senate, regardless of what committee it is. But she sort of hit
the nail on the head and I thank her for her testimony.
Then I would like to move, still on the second panel, a
farmer points out that, ``America in 2009. We are talking about
674,192 direct jobs, $918 billion for the total economic
sector.'' So that is why this reauthorization is such an
important factor, and this agreement holds.
I would also like to thank Dr. David Gaugh, I hope I am
pronouncing that right, I apologize if I am not. But he says,
and he is here to represent the generics,
``By designing the programs to spread fees across
multiple stakeholders and sources to keep individual
amounts as low as possible, the programs will help
assure that American consumers continue to receive a
significant cost savings from generics,''
ET cetera, etc. My question is, how do we do that?
After all of that, I would like to ask our two witnesses,
in terms of user fees, who really pays? Who really pays?
Dr. Shuren. In reality, it is probably the American public
who pays. They pay through----
Senator Roberts. Exactly, that is right.
Dr. Shuren [continuing]. Appropriations and then the cost
for user fees.
Senator Roberts. Yes, I know the appropriations.
Dr. Shuren. Right.
Senator Roberts. And I know that we would like to have more
appropriations, so would the Chairman, so would the Ranking
Member, but it is going to be the public that pays the user
fees. Now, with all of that, I do not need to ask you, Doctor,
the exact same thing.
Dr. Woodcock, how exactly does the FDA plan to meet the
commitments outlined in the agreements? How do we plan to meet
these deadlines because, as you know, FDA has missed time and
time again?
Dr. Woodcock. FDA is currently exceeding the vast majority
of its PDUFA goals, and over the 20-year history of the
program, we have met those goals consistently, except for
immediately after the FDA Amendments Act, where we had the REMS
and multiple other assignments.
Senator Roberts. Right.
Dr. Woodcock. We have crafted this very carefully to make
sure that the goals will work for industry, but that are also
achievable by us. And I have every confidence that we will meet
the goals of the drug user fee programs that are proposed.
Senator Roberts. Good. And I hope the committee stands
behind you in your endeavors, I am sure.
Now, I am concerned by comments I have heard recently that
the culture at the FDA has changed and folks feel that FDA is
moving away from working in a collaborative way with industry
to more of a regulatory enforcement kind of culture.
Is that the case? Are we going to tell this committee about
any improvements that are being made to the culture at FDA?
Dr. Woodcock. CDHR went through an entire culture effort
over the last 4 years. And I think that we are not changing our
approach to our standards of drug regulation.
The issues I have heard are that we are not able to
interact with the industry as often as the industry would like,
and we are not as transparent. I have looked into this, and it
really is a workload issue.
In fact, the user fee, the prescription drug user fee
program proposal that is before you explicitly addresses this
issue.
Senator Roberts. OK.
Dr. Woodcock. And it puts a negotiation discussion----
Senator Roberts. OK. I am out of time and the Chairman is
going to bang the gavel. So you are telling, basically us, if
we do our job and get this done, you can do your job, and then
industry will not complain about this issue.
I have one other question for Dr. Shuren, but I am out of
time. I will just submit that for the record. Thank you for
coming by my office, sir, and paying me a courtesy call. We had
a good visit.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Roberts.
Senator Mikulski.
Statement of Senator Mikulski
Senator Mikulski. Mr. Chairman, thank you for organizing
this hearing as we are on the brink of an actual mark up of a
variety of user fees. I am going to welcome our panel.
Mr. Chairman and colleagues, Maryland is the home of life
science jobs. We are very proud of our innovation corridor and
a substantial number of the jobs in that corridor are in
research. NIH is an international icon and Hopkins speaks for
itself.
But after the research, you have to deal with the valley of
death, which is taking all the great research and converting it
into products that people can use to have a better life and a
sustained life. This is why I am excited about moving the user
fees process forward.
I am proud of the 5,000 people who work at FDA at all
levels. I am often dismayed about the harassment and hazing
that these employees go through from the public--cheap
political shots and cutesy one-liners at town hall meetings.
Despite this harassment, we expect them to show up every day
with an attitude of, ``Hoo-rah, hoo-rah!'' and be ready to work
with us. So I think we need to get real, as we have very real
expectations of them.
Now let me move on to my questions.
In regard to this whole user fee process, I have been
involved in every user fee since 1992. I thought this version
had intellectual rigor and had a process that was open and
transparent. That process actually engages with industries in
conversation and, even taken corrective action with the
certification program. This authorization is welcoming everyone
to the table.
Having said that, however unlike other authorizations, we
have sunsets on the user fees. If we do not act in light of
these sunsets, what would be the consequences to the workforce
in FDA?
Dr. Shuren. We would lose all the positions being supported
by user fees and more because----
Senator Mikulski. Because you would have to give RIF
notices?
Dr. Shuren. We would have to give RIF notices.
Senator Mikulski. When would you have to give RIF notices?
Dr. Shuren. As a matter of regulations, it would start
around July, about that time. We are required to give at least
60 days advance notice, and then start to wind down the
program.
Senator Mikulski. Approximately how many employees would
that involve?
Dr. Shuren. It would involve approximately 250. The problem
is once people know that is happening, more people leave, and
that is a problem.
Senator Mikulski. So I say, Mr. Chairman and colleagues, if
we are talking about RIF notices in July, we know that people
will begin to worry in May and April. We need to really adhere
to your mark up schedule in a very rigorous way. A mark up in
April would keep the process and morale going as we work out
our legislative issues.
Am I correct in thinking that?
Dr. Shuren. Yes.
Senator Mikulski. In summary, we should have a sense of
urgency and adherence to our own timelines and compliance
issues?
Dr. Shuren. I have to tell you that message alone would be
very welcome by the staff at FDA. They are really looking for
help, and knowing the commitment of this committee, and the
process is moving quickly and help is on the way, and this
program will survive, and will mean a lot. And it will help us
move things forward.
Senator Mikulski. That is heartening to hear, and I think
we need to take it to heart.
Now, lets talk about all the bipartisan agreements and
letters of agreement with the industries. I am sure both of
you, have participated in and read these agreements. Do you
feel that the agreements offer guidance? Further, do you feel
satisfied with the three drug agreements in existence, and also
the two new agreements in generic and biosimilar? I know these
agreements contain pretty sophisticated science and complicated
regulatory measures, but do you feel if we follow any of those
five agreements you have flashing yellow lights?
Dr. Woodcock. For the drug agreements, we feel very
confident about all three of them that they will accomplish our
mutual goals of getting these products through in a timely and
sound way, and also supporting the safety of products for the
United States.
Senator Mikulski. What about biosimilar and generic?
Dr. Woodcock. The same. The generics are, as you know,
directed partly at improving and assuring the quality and
safety of the generics no matter where they are sourced in the
world. We regard this as a critical issue.
Senator Mikulski. Oh, I know. We could talk about that
issue as a whole separate hearing.
Dr. Woodcock. And the biosimilars, we are very confident
that we can enact a biosimilars program and we are doing that
now. However, as these applications really start to roll in, we
will need the staff to support this program. We will need
additional resources.
Senator Mikulski. And the training.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Mikulski.
Senator Burr.
Statement of Senator Burr
Senator Burr. Mr. Chairman and my colleagues, the proposed
reauthorization is an unprecedented level of user fees. There
is going to be on our part the need for an unprecedented level
of oversight, transparency, and accountability as part of these
reauthorizations, and I hope my colleagues will remember that.
Dr. Coburn and I are releasing a GAO report today that
confirms a disturbing trend: the FDA is taking longer and
longer to make final decisions on life-saving medical devices.
GAO also confirms that the FDA is not meeting some of its
performance goals.
I would like to take this opportunity today to share some
of the key findings of this report with my colleagues because I
think it is crucial and critical that we consider these
findings as we work through the user fee reauthorizations.
Let us start with the findings that relate to PMA's, and I
quote their GAO report,
``The FDA was inconsistent in meeting performance
goals for PMA submissions. The average time to final
decision for original PMA's increased from 462 days for
fiscal year 2003 to 627 days for fiscal year 2008,
which is the most recent year for which complete data
was available.''
I go on to quote,
``This report shows that the average number of review
cycles increased for certain PMA's, while the
percentage of PMA's approved after one review cycle
generally decreased.''
Now, let us look at the 510(k)'s, and I quote,
``Even though FDA met all medical device performance
goals for 510(k)'s, the elapsed time from submission to
final decision has increased substantially in recent
years from fiscal year 2005 through fiscal year 2010,
the average time to final decision for 510(k)'s
increased 61 percent.''
It goes on to quote,
``The average number of review cycles in FDA's
request for additional information for 510(k)
submissions also increased.
``Clearly, reporting only on the user fee performance
goals negotiated by the industry and the FDA does not
paint a full picture of the FDA's performance and how
well the agency is fulfilling its public health
mission. The proposed user fee agreements have been
sent to Congress for reauthorization. The goal of the
user fees is to ensure timely review and action on
medical products.
``This is why increasing times are so concerning.
Patients rely upon FDA to make sound medical decisions
in as timely a manner as possible. Increasing
regulatory uncertainty and unnecessary delays are
stifling investment in the development of lifesaving
medical devices.
``If Congress fails to ensure consistent oversight
and transparency at the FDA, we risk continuing to
drive medical innovation and job creation overseas,
jeopardizing American patients' access to the most
cost-cutting medical devices created.''
So where do we go from here? I know you are probably going
to tell us a little more about all the new initiatives that the
FDA has committed to put in place, and there are some good
concepts. I commend you for some of the changes that you have
made within CDRH.
Comments were made 5 years ago and they have not been met.
A doubling of user fees is not going to guarantee the agency
meets its goal. If we are going to fix what is not working that
well at the FDA, these commitments have to be fulfilled
consistent with the law.
My question to you, Dr. Shuren, is at the end of the day,
what are the clear matrix by which CDRH will be held to ensure
that the qualitative and quantitative goals agreed to under
this proposed agreement are fulfilled? In other words, what are
the metrics Congress and the American people can use to measure
if the commitments made in this agreement and the steps FDA is
proactively taking to address concerns are actually translating
into more predictable and consistent day-to-day action across
CDRH?
Dr. Shuren. In our commitment letter, we have two pages of
metrics that we are committing to. In fact, the largest section
in the commitment letter goes to our reporting on metrics and
transparency.
In MDUFA-II, we have reported over the 5 years on about
157,000 data points in our quarterly reports and 180,000 data
points in our annual reports. In MDUFA-III, it will be 10 times
the amount. By the end of the 5 years, we will have reported on
over 3 million data points. That is more than you will see for
any other country.
We are being very transparent in what we do, and we are
putting in tough metrics. I will say what we are putting in
this time is a metric for total time. This is a shared goal. It
requires work on our part. It requires work on industry's part
and that is reflected in the commitment letter.
I will note in the GAO report, that they also talk about
the actions we are taking to address the challenges facing the
program. They, too, have acknowledged that the actions we are
taking are directed, and it looks like they will address those
challenges. I am very glad to see that reflected in the report
as well.
Senator Burr. Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Burr.
Senator Whitehouse.
Statement of Senator Whitehouse
Senator Whitehouse. Thank you, Chairman.
Kenny Sparks from Little Compton, RI was diagnosed 6 years
ago with a disease called frontotemporal dementia. He died last
year on August 30, 2011 and his wife Cheryl said that it was a,
``Difficult and lonely journey.''
One of the reasons it was a difficult and lonely journey
was because this was a rare disease and there were few
treatments and no cure. So I would urge you to continue to
press forward in every way you can to make sure that the orphan
drugs, as the Chairman mentioned, are pursued so that that
journey for these families becomes a little less lonely.
My question to you, however, is about foreign manufacture
of pharmaceuticals. Things have changed in this industry. What
used to be very much a home built industry is now reliant on
international supply chains. We do not inspect international
factories.
How much has this problem grown recently? How urgent is
this problem? And do you think the steps we have taken to
address it are adequate?
Dr. Woodcock. There are two issues here. One is FDA's
ability to inspect those foreign facilities, and the generic
drug user fee program squarely addresses that, and will level
the playing field, and make sure that the intensity of
inspection, domestic, foreign, no matter where, will be the
same. We will be able to use a risk-based approach to
inspection.
The other issue, though, is the tools that we might have to
keep counterfeit or improperly manufactured drugs out of the
U.S. drug supply. There, of course, we do not have modern
tools, probably because the statute was written at a time when
domestic manufacture was really the norm and was considered.
For example, we really do not have the ability based on our
suspicions to stop drugs at the border if we have suspicion. We
have a burden of proof that we have to prove something is
wrong, and I find that shocking, and I think that American
consumers would find that shocking as well.
There are additional tools, I think, that other countries
certainly have to stop products at their border that are
suspicious and other enforcement tools that we currently lack.
Senator Whitehouse. Thank you very much.
Do you care to add anything else, Doctor? Do you care to
add anything?
Dr. Shuren. Regarding shortages, we had to deal with a
slightly----
Senator Whitehouse. No. The question was regarding the
international supply chain and its integrity, and what that
means for American consumers.
Dr. Shuren. Yes, I was just going on the shortage side with
the supply chain for devices, but we do have concerns about
assuring the integrity of the supply chain.
On the device side, we deal with certain different kinds of
challenges, but we also have issues with foreign sourcing. Many
of the companies do just-in-time production, and because
devices are becoming increasingly complex, as they rely on
foreign suppliers, just a problem with one component in a
device can hold up the manufacturing and the availability of
that technology even when all the different parts and
components may be available.
Senator Whitehouse. Thank you, Chairman.
The Chairman. Thank you, Senator Whitehouse.
Senator Isakson.
Statement of Senator Isakson
Senator Isakson. Mr. Chairman, I will defer. I just walked
in the room, and I would probably be repetitive. So I will
defer to the next questioner.
The Chairman. Thank you, Senator Isakson.
Senator Bennet.
Statement of Senator Bennet
Senator Bennet. Thank you, Mr. Chairman.
I want to start by saying how grateful I am and Colorado is
for your leadership here.
The Chairman. Thanks.
Senator Bennet. And for the Ranking Member's leadership in
producing this bipartisan basis for this legislation going
forward.
It is not only important for all the reasons Senator
Mikulski said and the urgency of getting this done, I think it
sets a model for what the rest of Congress should be doing. I
am very proud to have the chance to work with both of you on
this, and with my democratic and republican colleagues on a
series of important bills here.
I wanted to ask Dr. Woodcock, in that context, about drug
innovation. This area of drug and biotech innovation is of
great interest to me because Colorado has a growing bioscience
community with cutting edge researchers. They are desperate
that this not move overseas, and I know the FDA does not want
that either.
In an effort to work across the aisle, Senators Hatch,
Burr, and I have introduced a bill that would provide certainty
when drugs show promising prospects or even dramatic results
early on. And I know you have been a strong advocate of having
a more formal designation for breakthrough therapies.
Can you talk to us about how you see this working at FDA,
and give us some examples of products where this would be a
helpful designation, where today there is none?
Dr. Woodcock. Certainly, and I thank you for your
leadership and the other members for their leadership on this
issue.
Today, with modern science, we are seeing something that we
rarely saw before with therapeutics, which is sometimes very
early in human testing. Sometimes it is the very first low
doses that are carefully given to people, we see responses to
the treatment that we have never seen before. And this might be
for a serious and life threatening disease such as a dementia,
where no treatment exists, it is effective.
When that happens, we need what I call, ``all hands on
deck.'' Everybody needs to sit up straight, get together, and
figure out how to evaluate that therapy as rapidly as possible,
so that if it actually has the promise that it shows in that
early testing, it can be moved to patients as quickly as
possible.
Some of these may fail. However, the fact that some of them
may work and actually be a breakthrough for patient and offer
treatment that has never been seen before, a benefit, means
that we have an ethical obligation to work as rapidly as
possible.
The designation process, I believe, would get everyone's
attention. There would be an obligation to get that development
path as efficient as possible. We also can run into ethical
problems.
If you had a serious or life threatening disease, and there
was a tremendously promising therapy, would you want to be on
the placebo group for 6 months?
We need to design trials and evaluations that also take
those issues into account. As soon as we lose what is called
``clinical equipoise,'' and as soon as we think the therapy is
much more likely to be better than anything out there, we need
to take the appropriate steps.
That is what this is about. It is different than Fast
Track, which is actually a designation about review and
working, rolling review and working with the company, and so
forth. This is for those exceptional therapies which, we hope
with the new science, we are going to be seeing more often
where we really have to pay attention.
Senator Bennet. I think it is a critical component of
trying to create a patient-centric approach here. So I
appreciate very much your words.
Dr. Shuren, I do not have a lot of time left, and you and I
have gone over some of this before, and you have been kind
enough to visit Colorado, which I deeply appreciate.
I wonder if you could talk specifically about how the user
fees, in your view, are going to help smaller and mid-size
companies that may not have the same resources as larger ones
navigate the FDA?
Dr. Shuren. There are a number of improvements and
enhancements that we will see under MDUFA-III, and I will just
highlight a few.
One of them is in the pre-submission process. That is where
now a company can come to us before they have actually even
done the testing, or a lot of testing on their product, to get
advice from us. This will be a much more rigorous process where
we provide that advice. We write it down. We stand behind it,
unless we wind up generally getting new information that is
raising new issues. That is a big deal for these companies to
have that kind of advice.
The second is we are getting some additional people. It is
only five. But you know what? Five can help a lot for putting
out more guidance documents. We think putting out guidance is
critical. It provides clarity, transparency, and predictability
for companies. And this will help us get there.
I will make one comment on that, though. On the drug side,
a much bigger program, they have about 82 people in their
office who handles those regulatory issues, guidance in those
rules. We are at 18; the 5 will put us up to 23. It will help,
but we have a way to go.
Senator Bennet. Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Bennet.
Senator Merkley
Statement of Senator Merkley
Senator Merkley. Thank you, Mr. Chair.
And thank you all for your testimony. I am going to try to
keep my questions short because I want to get through several
of them.
The first, Dr. Woodcock and Dr. Shuren, I wanted to ask
about the issue of developing the Unique Device Identifier,
UDI, in the context of medical devices, particularly
implantable devices in order to be able to track the results
and close the feedback loop.
How important is that to accomplish?
Dr. Shuren. Unique Device Identifiers are a game-changer.
That number now on the device, being able to now either track
or to link to information about that device or experience, is
critical for things like recall, rapidly identifying the
product, more robust adverse event reporting, taking advantage
of insurance claims data, electronic health records to identify
safety problems.
But also to reduce the cost for some companies on doing
their postmarket studies because we can have a more rigorous,
robust postmarket surveillance system, and use that information
to maybe reduce the evidentiary needs on premarket review.
Senator Merkley. This would be included in the Sentinel
Postmarketing Studies?
Dr. Shuren. To actually participate in Sentinel in any
meaningful way, we cannot do without a UDI.
Senator Merkley. Dr. Woodcock.
Dr. Woodcock. Yes, we feel that electronic health records
and electronic health data provide tremendous benefit in order
to find out what is actually happening with patients with all
these new technologies.
The Sentinel program right now has 125 million lives in it.
In none of these are the patient data sent to FDA. They stay
with the provider, but they are able to perform analyses. We
hope to increase that so that we are looking at what most
Americans experience, and we would love to have the device
program robustly participate in that.
Senator Merkley. I believe that the UDI rule is currently
stalled at OMB. Any insights on how we can get that rule
accomplished in order to have these benefits?
Dr. Shuren. I will say any kind of help to try to get a UDI
system in place would be most welcome by the agency. And I
think expressing the importance and maybe even the expectations
for having a UDI system in place.
Senator Merkley. Maybe we should raise it in a hearing like
this and shine a light on it?
Dr. Shuren. Would be helpful and then some.
Senator Merkley. All right. Great, great.
Also, I am working with some other folks to develop a bill,
if necessary, to basically put a deadline on getting this rule
accomplished so we can try to benefit from this. There are a
host of issues associated with this, including the 510(k)
process in which a device is approved based on a predicate
device that is substantially equivalent.
There is something interesting that occurs, that even if
there is a recall of a device in that it can still serve as a
predicate for other devices under 510(k).
How is it possible that we allow a device that has been
recalled, by the manufacturer, to be utilized as the foundation
for other, similar devices to bypass by the regular pre-market
approval system?
Dr. Shuren. That is one challenge in the 510(k) program. I
will say the real issues occur very infrequently, and that is
where you have a device that has a design flaw that affects
safety and effectiveness, and gets recalled. Then a new device
comes, and they replicate that design flaw.
Senator Merkley. Yes, exactly.
Dr. Shuren. Under the law, it can be substantially
equivalent. We try to work with companies, but oftentimes it is
issues about labeling. The burn does not flip the other way to
say either the design flaw is not there, so we do not worry, or
adequate mitigations have been taken to assure that that device
is, in fact, safe and effective.
Senator Merkley. It does seem like using a flawed design as
a foundation for approving another device under 510(k) is
something that we need to wrestle with. It does not make sense
to patients who have these implanted devices, and are not too
happy to find out the device that was implanted in them, was
based on a design that has been recalled.
Dr. Shuren. Yes, agreed.
Senator Merkley. Last, I wanted to raise the issue of drug
shortages and drug scalping. My understanding, Dr. Woodcock, is
you have not found much evidence of drug scalping. But I keep
hearing from practitioners in Oregon of being offered drugs at
10, 20 or even 100 times the price.
So I am trying to figure out, how is it I can hear all
these examples from practitioners, but the agency cannot seem
to find any evidence that it is a problem?
Dr. Woodcock. We have referred to the Department of Justice
a compilation of the complaints which is more than 100 drugs in
shortage, and we would encourage your constituents to report
any of these instances to the FDA, so that we can forward them
to the Department of Justice for appropriate investigation.
Senator Merkley. OK. We will try to channel as many as
possible. It does seem like there is an issue here with
middlemen buying up drugs, and then reselling them, and it is
such an easy market to corner, when there is a small amount of
drugs available in the system.
One of my colleagues referred to the international flow of
ingredients, and sometimes that causes shortages that in its
moment, that a scalper can capitalize.
I am really hoping we can try to solve this problem because
when patients are told, ``Well, we are partway through your
cancer treatment, and we cannot get the drugs.'' Or, ``We are
partway through the cancer treatment and we can only get the
drugs at many multiples of what they should cost,'' something
is fundamentally wrong.
Thank you.
The Chairman. Thank you very much, Senator Merkley.
I understand the votes are going to start at 11:15. Let us
see how far we can go. We have Senator Hagan. Senator
Blumenthal.
Statement of Senator Blumenthal
Senator Blumenthal. Thank you. Thank you, Mr. Chairman.
If I may ask you, Dr. Woodcock first, how many drugs are in
shortage today in the United States?
Dr. Woodcock. In 2010, there were 178. We have seen an
increasing number. There were 250 shortages tracked in 2011,
some of those have been mitigated, but additional ones. So I
cannot tell you a summary, but there are over 200 drugs in
shortage.
Senator Blumenthal. What is the FDA doing to mitigate those
shortages?
Dr. Woodcock. We have taken multiple actions, including
allowing importation of drugs that are not approved in the
United States.
Senator Blumenthal. What is the FDA doing to mitigate those
shortages by addressing problems with the manufacturing
process?
Dr. Woodcock. We work very carefully with manufacturers who
are having manufacturing problems to try and keep them in
production of the drugs in shortage.
Senator Blumenthal. Have cases of drug shortages and black
market issues been referred to the Department of Justice?
Dr. Woodcock. Absolutely. Any time we receive any
information, we do refer either of price gouging or, of course,
when there is an issue of counterfeits.
Senator Blumenthal. Can you tell me which, in the last 3
months, have been referred to the Department of Justice?
Dr. Woodcock. We can get that information to you. I do not
have it.
Senator Blumenthal. Can you give it to me within the last
year?
Dr. Woodcock. We certainly can get that to you. Absolutely.
Senator Blumenthal. What steps are being taken to notify
the public more expeditiously about those shortages, including
the medical community?
Dr. Woodcock. We have a Web page. We really try, as much as
possible, to both work with the associations and also reach out
to the affected communities.
Senator Blumenthal. Have you considered steps that can be
taken beyond the way the working group has proposed, or will be
proposing within the next few days?
Dr. Woodcock. No. I would refer you to the HHS analysis of
the root causes of drug shortages by the Assistant Secretary
for Planning and Evaluation, which I think has the most in-
depth analysis of what caused these shortages and----
Senator Blumenthal. Let me just say that I think that the
response of the FDA so far has been inadequate. I have said it
before at a hearing, I am not sure whether you were here or
not, I feel that working group's proposals are a small step, a
baby step, a tiptoe that also fails to address this issue.
I think that the American people will be justly outraged,
not just angry and impatient, but outraged when they understand
both the causes and the impacts of drug shortages in this
country. I will be very disappointed if this Congress fails to
do much more than is contemplated right now in addressing these
problems in the course of reauthorizing these agreements.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Blumenthal. Again, let me
just thank you for your diligence in this area, and your focus
on this whole area of the drug shortages, what is causing them,
and its impact on our economy and people. I thank you very
much.
Senator Blumenthal. Thank you, Mr. Chairman, and I will
look forward to receiving that additional information from the
FDA.
The Chairman. Absolutely.
Senator Franken.
Statement of Senator Franken
Senator Franken. Thank you, Mr. Chairman.
Dr. Shuren, it is good to see you again. Thank you for
being so willing to meet with me, and for coming to Minnesota a
number of times, and meeting with our medical device industry
there.
You and I share a goal of patient safety, and as you
acknowledge in your testimony as Director of the office that
approves medical devices at the FDA, your job is to make sure
that patients are safe.
As you also acknowledged in your testimony, part of patient
safety is getting treatments to patients who need them in a
timely manner. If a patient with a disease or a condition
cannot get a device that would help them stay healthier or even
alive, we are failing at keeping that patient safe.
When I talk with medical device manufacturers in Minnesota,
they tell me how frustrated they are, that they are developing
innovative and potentially lifesaving devices, but they cannot
get them to patients because the FDA has not approved them yet,
and you certainly referenced that in your testimony.
I know that you have been working with Minnesota's
LifeScience Alley, which just so happens to be the largest life
sciences trade association in the Country, on an initiative to
develop a regulatory science initiative. I want to thank you,
again, for reaching out to Minnesota's biotech industry to work
together on this. I hope that initiatives like this one will
lead to a real change in the way that you and the industry
communicate.
Can you update me on the status of that partnership? And
what are your next steps?
The Chairman. Before you answer, Dr. Shuren, I just want to
note that the vote has started at 11:16. It is my intention
that after we finish with Senator Franken's round, that we will
recess, and then we will come back and start the second panel.
Dr. Shuren. We have been working with LifeScience Alley to
start to identify the specific projects that we would begin to
work on together as first steps, and we have actually gotten it
to a short list. Our goal is in the coming weeks to finalize on
a set of activities that we will be doing jointly together.
That will include on the research side. It will include on the
education side as well.
Senator Franken. OK.
Dr. Shuren, my bill, the Patient Access to Medical
Innovation Act, will help get treatments to patients who need
them. As you know, my bill has two provisions.
The first part will help patients with rare diseases get
them new and innovative treatments. The second part will remove
red tape that keeps the FDA from consulting with the experts in
health care and biotechnology which, I think, dovetails with
the goals you have with your regulatory science initiative with
LifeScience Alley.
I am happy to say that both of these provisions have been
included in the bipartisan health committee consensus draft
legislation that will be attached to the user fee legislation
later this year.
As Director of the office that reviews devices, do you
believe that the added flexibility that my bill gives you to
consult with experts will help you get safe devices to the
market faster? How do you think this flexibility would help
you, if that is the case?
Dr. Shuren. I do think this is helpful. This will allow us
to more quickly and with broader scope include critical experts
in our pool of special Government employees who can be on our
advisory committees, and provide us with advice and
recommendations. That is very important to us.
Senator Franken. My other provision will reward innovators
who develop devices to treat rare conditions, and Senator
Whitehouse talked about the importance of pharmaceuticals for
that.
Do you believe that my bill will help patients with rare
diseases? And how will it help patients, do you think?
Dr. Shuren. I do and actually, I want to commend you on
this particular provision because you have tried to strike that
balance of preserving the incentive already in place for
developing devices for pediatric conditions, while extending
that incentive for developing devices for other rare
conditions.
There are some technical things we would like to work with
the committee on for that provision, but this can be an
important step forward for getting and incentivizing
development of devices for rare conditions.
Senator Franken. I would be happy to work with you on that
and with the Chairman. Thank you both for your testimony.
Now I guess we should go vote.
The Chairman. The committee will be in recess for about 10
minutes, then we will come back.
Thank you both very, very much. Appreciate it, Dr. Shuren
and Dr. Woodcock.
[Recessed.]
The Chairman. I'll ask our panelists to come up and take
their respective seats.
As I said to all of you at the beginning when I made my
opening statement, when I introduced you and who you are
representing, I thank you for being here. Your statements will
all be made a part of the record in their entirety. We will go
from left to right and I ask if you would sum up your testimony
in 5 minutes or so, we would be most appreciative.
We will start with Dr. David Wheadon, senior vice president
for Regulatory Affairs at PhRMA.
Dr. Wheadon, please proceed.
STATEMENT OF DAVID E. WHEADON, M.D., SENIOR VICE PRESIDENT OF
SCIENTIFIC AND REGULATORY AFFAIRS, PHARMACEUTICAL RESEARCH AND
MANUFACTURERS OF AMERICA, WASHINGTON, DC
Dr. Wheadon. Thank you. Chairman Harkin, Ranking Member
Enzi, members of the committee, good morning.
I am David Wheadon, senior vice president of Scientific and
Regulatory Affairs at the Pharmaceutical Research and
Manufacturers of America, better known as, PhRMA.
PhRMA appreciates this opportunity to testify today, and
share our views on the fifth reauthorization of the
Prescription Drug User Fee Act, PDUFA, and the authorization of
the Biosimilars User Fee Act, BsUFA.
The PDUFA-V performance goals letter is the result of
extensive negotiations between the U.S. Food and Drug
Administration and the innovative biopharmaceutical industry,
and is intended to improve FDA's ability to conduct thorough
and efficient reviews of new medicines for patients.
FDA's process in negotiating these performance goals
included unprecedented transparency and input from all
stakeholders, including patient advocates, healthcare
professionals, consumers, and academia.
PhRMA, as the representative of the country's leading
pharmaceutical research and biotechnology companies, strongly
supports the original intent and goals of PDUFA. Namely, to
provide patients with faster access to innovative medicines; to
preserve and strengthen FDA's high standards for safety,
efficacy, and quality; and to advance the scientific basis for
the agency's regulatory oversight.
PhRMA strongly endorses the recommendations of the PDUFA-V
performance goals letter and urges Congress to reauthorize
PDUFA in a timely manner, based on the PDUFA-V agreement. This
agreement will provide FDA with the resources and tools
required to further enhance the timeliness, completeness, and
efficiency of the drug review process.
As you have heard this morning, failure to authorize PDUFA
in a timely manner would have catastrophic effects on the FDA's
ability to carry out its important role in bringing new
medicines to patients with debilitation diseases.
PDUFA-V will improve the review process for new molecular
entity drug and biologic applications, which will be
particularly significant for patients because NME's are novel
compounds that have the potential to address unmet medical
needs in advanced patient care. The enhanced NME review process
addresses the increasing complexity of reviewing new drug
applications and biological license applications, and provides
for increased communication between FDA and drug sponsors prior
to and during the drug review process.
As a result, the NME review program is expected to improve
the efficiency of the review process and reduce the overall
time until new medicines become available to patients. The
success of the new review program and of the agency's ability
to achieve its drug review goals will be independently assessed
and publicly reported in 2015 and 2017.
Several new provisions in the PDUFA-V performance goal
letter afford FDA with appropriate staffing and resources to
develop, through public input, new tools and methods to
integrate emerging scientific data and techniques into the drug
development and review process.
Provisions to enhance FDA's regulatory review capabilities
include, but are not limited to, the use of pharmacogenomics
and biomarkers to decrease drug development time by helping
demonstrate therapeutic benefits more rapidly, and identifying
patients who are likely to benefit from treatment, as well as
those at increased risk for serious adverse events.
Avenues for accelerating drug development for rare and
orphan diseases, and providing FDA with the necessary
regulatory flexibility to encourage and advance research into
novel treatments for patients with significant unmet needs
today. And forming a public process to help standardize Risk
Evaluation and Mitigation Strategies, or REMS, with the intent
to assess and reduce burden on healthcare providers and
patients.
PDUFA has advanced public health by accelerating the
availability of innovative medicines to patients who are
helping to insure patient safety. PDUFA-V will continue to
provide FDA with the resources and tools that are essential to
support patient safety and promote medical innovation through
enhanced timeliness, completeness, and efficiency of the drug
review process.
PhRMA urges Congress to reauthorize PDUFA in a timely
manner based on the negotiated PDUFA-V performance goals, and
to minimize the inclusion of additional provisions that may
have the unintended consequence of distracting from the Act's
original intent.
I will just briefly comment on BsUFA, but I know my
colleague will be focusing on that. But the BsUFA performance
goals are consistent with congressional intent to create a
unique user fee program to meet the needs of biosimilar product
applicants, and to provide FDA with the means necessary to
build, essentially from scratch, its capacity for science-based
review for biosimilar applications.
Among the key aspects of the proposed BsUFA performance
goals is the expectation for FDA in fiscal year 2013 to review
and act on 70 percent of original biosimilar application
submissions within 10 months of receipt, and to review and act
on 70 percent of resubmissions within 6 months of receipt. As
the agency's review capacity for biosimilar products develops,
review performance goals will gradually increase.
In summary, PhRMA and our managed member companies are
committed to working closely with FDA and all stakeholders to
ensure the continued success of PDUFA in bringing safe,
effective, innovative medicines forward to address unmet
medical needs for all patients.
PhRMA stands ready to work with the FDA and other
stakeholders in establishing a science-based approach to the
development and review of biosimilar and interchangeable
biological products.
We therefore urge Congress to reauthorize PDUFA in a timely
manner based on the negotiated PDUFA-V agreement and to
authorize BsUFA with congressional appropriations allocated in
support of this program for fiscal years 2013 through 2017.
Thank you, and I would be happy to answer any questions.
[The prepared statement of Dr. Wheadon follows:]
Prepared Statement of David E. Wheadon, M.D.
summary
The Prescription Drug User Fee Act (PDUFA) has been a great success
for patients since its initial passage in 1992. The PDUFA user fee
program provides FDA with the additional staffing and resources it
needs to significantly reduce the timeframe for the review of new
medicines, while protecting public health by assuring the safety of
these products.
The PDUFA-V performance goals letter is the result of
extensive negotiations between the FDA and the innovative
biopharmaceutical industry. FDA's process for negotiating these
performance goals included unprecedented transparency and input from
all stakeholders, including patient advocates, healthcare
professionals, consumers and academia.
A number of important new commitments are detailed in the
PDUFA-V performance goals letter, including provisions to make the
regulatory review of new medicines more efficient and timely, advance
regulatory science and modernize drug development, improve benefit/risk
decisionmaking, and further strengthen FDA's focus on patient safety.
PhRMA urges Congress to reauthorize PDUFA in a timely
manner based on the negotiated PDUFA-V performance goals and to
minimize inclusion of additional provisions that may distract from the
Act's original intent--faster access to innovative medicines while
preserving and strengthening the FDA's high standards for safety,
efficacy and quality.
Failure to reauthorize PDUFA in a timely manner would not
only have an extraordinarily disruptive effect on the FDA and impede
patients' access to new and innovative treatments, but such a failure
would also endanger biopharmaceutical innovation.
The Biologics Price Competition and Innovation Act of 2009 (BPCIA)
established an abbreviated pathway for biosimilar products and
interchangeable biological products. PhRMA was a participant in the
technical negotiations with the FDA that, together with input from
patient and healthcare provider groups, resulted in the Biosimilars
User Fee Act (BsUFA)performance goals letter.
The BsUFA performance goals are consistent with
congressional intent to create a unique user fee program to meet the
needs of biosimilar product applicants, and to provide FDA with the
means necessary to build, essentially from scratch, its capacity for
science-based review of biosimilar applications.
PhRMA believes that the review process for biosimilar and
interchangeable biological products must be scientifically rigorous,
timely, and above all, protective of patient safety. Achieving these
objectives will require a clear and formalized regulatory pathway for
biosimilar products, quality standards equal to standards for
innovative products, and adequate preclinical and clinical testing to
ensure that biosimilars are both safe and effective.
PhRMA urges Congress to authorize BsUFA with congressional
appropriations allocated in support of this program for fiscal years
2013-17.
______
Chairman Harkin, Ranking Member Enzi, members of the committee,
good morning. I am David Wheadon, senior vice president, Scientific and
Regulatory Affairs at the Pharmaceutical Research and Manufacturers of
America (PhRMA). PhRMA appreciates this opportunity to testify today
and share our views on the fifth reauthorization of the Prescription
Drug User Fee Act (PDUFA) and the authorization of the Biosimilars User
Fee Act (BsUFA).
reauthorization of the prescription drug user fee act (pdufa-v)
PDUFA has been a great success for patients--the tens of millions
of Americans who rely on innovative drugs and biologics to treat
disease and to extend and improve the quality of their lives. The PDUFA
user fee program has provided FDA with additional staffing and
resources it needed to significantly reduce the timeframe for review of
new medicines, while protecting public health by assuring the safety of
these products. Furthermore, PDUFA has helped to improve America's
competitiveness around the world. Since the passage of the original
Prescription Drug User Fee Act in 1992, the United States has become
the world leader in bringing new medicines to patients first.
The PDUFA-V performance goals letter is the result of extensive
negotiations between the U.S. Food and Drug Administration (FDA) and
the innovative biopharmaceutical industry and is intended to improve
FDA's ability to conduct thorough and efficient reviews of new
medicines for patients. FDA's process for negotiating these performance
goals included unprecedented transparency and input from all
stakeholders, including patient advocates, healthcare professionals,
consumers and academia.
PhRMA and its members, the country's leading pharmaceutical
research and biotechnology companies, strongly support the original
goals of PDUFA, namely--to provide patients with faster access to
innovative medicines, to preserve and strengthen FDA's high standards
for safety, efficacy and quality, and to advance the scientific basis
for the Agency's regulatory oversight.
PhRMA strongly endorses the recommendations of the PDUFA-V
performance goals letter. This agreement will provide FDA with the
resources and tools required to further enhance the timeliness,
completeness, and efficiency of the drug review process. Failure to
reauthorize PDUFA in a timely manner would have catastrophic effects on
the FDA's ability to carry out its important role in bringing new
medicines to patients suffering from debilitating diseases.
The Role of PDUFA in Encouraging Innovation and Economic Growth.
Ensuring that the United States maintains a policy and regulatory
environment that encourages an efficient, consistent and predictable
drug review process is key to keeping America competitive in today's
global economy. A 2011 report by Battelle \1\ found that the U.S.
biopharmaceutical industry ``is well recognized as a dynamic and
innovative business sector generating high quality jobs and powering
economic output and exports for the U.S. economy.'' According to the
report, nationwide the sector supported a total of 4 million jobs in
2009, including 674,192 direct jobs. The total economic output from the
sector's direct, indirect, and induced impacts was $918 billion.
Because PDUFA has injected greater consistency, transparency and
predictability into the FDA's drug review process, its reauthorization
is an important factor in ensuring that biopharmaceutical companies
maintain this level of job creation and economic growth. Failure to
reauthorize PDUFA in a timely manner would not only have an
extraordinarily disruptive effect on the Agency and impede patients'
access to new and innovative treatments, but such a failure would also
endanger biopharmaceutical innovation.
---------------------------------------------------------------------------
\1\ Battelle Technology Partnership Practice. The U.S.
Biopharmaceuticals Sector: Economic Contribution of the Nation. July
2011. Battelle Memorial Institute. Prepared for the Pharmaceutical
Research and Manufacturers of America.
---------------------------------------------------------------------------
There are a number of important new commitments in the carefully
negotiated PDUFA-V performance goals letter, including provisions to
make the regulatory review of new medicines more efficient and timely,
to advance regulatory science and modernize drug development, to
improve benefit/risk decisionmaking, and to further strengthen FDA's
focus on patient safety.
Below I discuss these significant enhancements of the PDUFA-V
performance goals letter.
Enhanced NME Review Program. PDUFA-V will improve the review
process for new molecular entity (NME) drug and biologic applications
which will be particularly significant for patients, because NMEs are
novel compounds that have the potential to address unmet medical needs
and advance patient care. The enhanced NME review model addresses the
increasing complexity of reviewing new drug applications (NDAs) and
biologic license applications (BLAs), and provides for increased
communication between FDA and drug sponsors prior to and during the
drug review process. A validation period will help FDA plan activities
such as inspections and advisory committee meetings, and will
accommodate iterative interactions between sponsors and the Agency. As
a result, the NME review program is expected to improve the efficiency
of the review process and reduce the overall time until new medicines
become available to patients. Specifically, it is anticipated that
earlier and more comprehensive communication between the Agency and
drug sponsors will improve the rate of ``on-time, first-cycle''
successes--that is, the number of new medicines that are fully reviewed
and for which definitive regulatory action is taken within the target
timeframe following initial submission. The success of the new review
program and of the Agency's ability to achieve its drug review goals
will be independently assessed and publicly reported in 2015 and 2017.
Advancements in Regulatory Science. Several new provisions in the
PDUFA-V performance goals letter will afford FDA with appropriate
staffing and resources to develop, through public input, new tools and
methods to integrate emerging scientific data and techniques into the
drug development and review process. These advancements in regulatory
science will rely on engagement with industry, academia and other
stakeholders to identify best practices so the Agency can provide
appropriate guidance to stakeholders involved in drug development.
Provisions to enhance FDA's regulatory review capabilities include:
The use of pharmacogenomics and biomarkers to decrease
drug development time by helping demonstrate therapeutic benefits more
rapidly, and identifying patients who are likely to benefit from
treatment, as well as those at increased risk for serious adverse
events.
Avenues for accelerating drug development for rare and
orphan diseases and provide FDA with the necessary regulatory
flexibility to encourage and advance research into novel treatments for
patients with significant unmet needs today.
Standards for and validation of patient-reported outcomes
and other assessment tools that may assist regulators in evaluating
treatment benefits and potential risks from the patient's point of
view.
And the evaluation of the use of meta-analyses in
regulatory review and decisionmaking, highlighting best practice and
potential limitations.
Systematic Approach to Benefit-Risk Assessment. A key provision in
the PDUFA-V performance goals letter recognizes that the drug review
process could be improved by a more systematic and consistent approach
to benefit-risk assessment that fairly considers disease severity and
unmet medical needs. During PDUFA-V, the Agency will implement a
structured benefit-risk framework, and hold public meetings to assess
the application of such frameworks in the regulatory environment. In
addition, over the course of PDUFA-V the Agency will hold a series of
public meetings with the patient advocacy community to identify disease
states that--from the patient perspective--have considerable unmet
needs. Development and implementation of a patient-focused, structured
framework for evaluating benefits and risks of new treatments will help
inform the drug development process as well as ensure that regulatory
decisions are consistent, appropriately balanced, and based on best
science.
Modernizing the U.S. Drug Safety System. Finally, further
enhancement and modernization of the FDA drug safety system under
PDUFA-V will ensure that patient safety remains paramount. The PDUFA-V
performance goals letter provides for a public process to help
standardize risk evaluation and mitigation strategies (REMS), with the
intent to assess and reduce burden on healthcare providers and
patients. Additionally, FDA will continue to evaluate the feasibility
of using the Agency's Sentinel Initiative to actively evaluate post-
marketing drug safety issues.
PDUFA has advanced public health by accelerating the availability
of innovative medicines to patients while helping to ensure patient
safety. The PDUFA program has strengthened the scientific basis of
FDA's regulatory review process through the development and application
of new tools, standards, and approaches that facilitate assessment of
the safety and efficacy of innovative drugs and biologics. PDUFA-V will
continue to provide FDA with the resources and tools that are essential
to support patient safety and promote medical innovation through
enhanced timeliness, completeness, and efficiency of the drug review
process. PhRMA encourages Congress to reauthorize PDUFA in a timely
manner based on the negotiated PDUFA-V performance goals, and to
minimize the inclusion of additional provisions that may have the
unintended consequence of distracting from the Act's original intent--
to provide patients with faster access to innovative medicines, to
preserve and strengthen FDA's high standards for safety, efficacy and
quality, and to advance the scientific basis for the Agency's
regulatory oversight.
authorization of a user fee program for biosimilar biological products
under the biologics price competition and innovation act of 2009
(bsufa)
An abbreviated approval pathway for biosimilar products and
interchangeable biological products was established in the Biologics
Price Competition and Innovation Act of 2009 (BPCIA) and PhRMA has been
supportive of FDA's ongoing efforts to implement BPCIA in a manner that
ensures patient safety and encourages biopharmaceutical innovation.
PhRMA was a participant in the technical negotiations with the U.S.
Food and Drug Administration (FDA) that, together with input from
patient and healthcare provider groups, resulted in the Biosimilars
User Fee Act (BsUFA) performance goals letter.
The BsUFA FDA performance goals are consistent with congressional
intent to create a unique user fee program to meet the needs of
biosimilar product applicants, and to provide FDA with the means
necessary to build, essentially from scratch, its capacity for science-
based review of biosimilar applications. PhRMA believes that the BsUFA
performance goals will benefit patient safety and public health as
biosimilar products will be required to meet FDA's high standards for
safety, purity, and potency.
Several of PhRMA's member companies for many years have been
actively engaged in the development of innovative biological products.
In addition, some of PhRMA's member companies have expressed their
intent to develop biosimilar products. PhRMA therefore supports the
development of a robust user fee program for biosimilar products to
provide FDA with the resources needed to review biosimilars without
diverting resources from the review of innovative medicines. PhRMA is
further supportive of the appropriation of congressional funds for this
purpose, a feature common to existing user fee programs, to ensure that
user fees supplement, rather than replace, appropriations.
PhRMA believes that the review process for biosimilar and
interchangeable biological products must be scientifically rigorous,
timely, and above all, protective of patient safety. Achieving these
objectives will require a clear and formalized regulatory pathway for
biosimilar products, quality standards that meet standards for
innovative products, and adequate preclinical and clinical testing to
ensure that biosimilars are both safe and effective.
PhRMA recognizes that, for the purpose of this first authorization,
the biosimilar user fee program must be structured differently from
other user fee programs. It will be necessary, for example, to collect
fees earlier in the biological product development process, until fees
from licensing applications can provide sufficient ongoing revenues to
support the Agency's activities. It must be understood, however, that
the proposed user fee program for biosimilar products--and, in
particular, the provision for payment of a portion of the application
fee at the time of an Investigational New Drug (IND) submission and
yearly thereafter--is a stop-gap measure, subject to review at the time
of BsUFA reauthorization in 2017.
Among the key aspects of FDA's proposed BsUFA performance goals is
the expectation for FDA, in fiscal year 2013, to review and act on 70
percent of original biosimilar application submissions within 10 months
of receipt and to review and act on 70 percent of resubmissions within
6 months of receipt. As the Agency's review capacity for biosimilar
products develops, review performance goals will gradually increase.
The BsUFA performance goals further provide for specific FDA/
sponsor meetings to facilitate the biosimilars development phase. This
provision includes a special protocol assessment mechanism for clinical
study protocols that are intended to establish biosimilarity and/or
interchangeability with a reference biological product, to help ensure
that the study design is adequate to meet scientific and regulatory
requirements for approval.
The proposal also calls for FDA to issue guidance on procedures for
meetings between the Agency and sponsor prior to submission of a
biosimilar licensing application, and PhRMA urges the Agency to
accelerate its guidance development in this area. Eventually, the
biosimilar application process should be codified in regulations
similar to all other approval pathways.
Additionally, user fees will be applied to enhance patient safety
through implementation of measures to reduce medication errors related
to similar sounding proprietary names, unclear labeling, and confusing
package design.
PhRMA supports the proposed BsUFA performance goals agreement as a
means of advancing public health by making adequate resources available
to FDA to build a capacity for regulatory review of biosimilar
products, consistent with the Agency's high standards for patient
safety and scientific rigor.
PhRMA and its member companies are committed to working closely
with FDA, and all stakeholders, to insure the continued success of
PDUFA in bringing safe, effective innovative medicines forward to
address unmet medical needs for all patients. Additionally, PhRMA
stands ready to work with the FDA and other stakeholders in
establishing a science-based approach to the development and review of
biosimilar and interchangeable biological products. PhRMA therefore
urges Congress to reauthorize PDUFA in a timely manner based on the
negotiated PDUFA-V agreement and to authorize BsUFA with congressional
appropriations allocated in support of this program for fiscal years
2013 through 2017.
Thank you for the opportunity to testify today and I welcome any
questions you may have.
The Chairman. Thank you very much, Dr. Wheadon.
Now we turn to Miss Radcliffe representing the
Biotechnology Industry Organization.
Miss Radcliffe, welcome.
STATEMENT OF SARA RADCLIFFE, EXECUTIVE VICE PRESIDENT, HEALTH,
BIOTECHNOLOGY INDUSTRY ORGANIZATION, WASHINGTON, DC
Ms. Radcliffe. Thank you very much.
Chairman Harkin, Ranking Member Enzi, members of the
committee, it is my privilege to provide testimony before you
today.
My name is Sara Radcliffe and I am executive vice president
for Health for the Biotechnology Industry Organization. In that
role, I had the opportunity to manage BIO's involved in the
Biosimilars User Fee, or BsUFA, technical discussions with FDA
as well as lead BIO's engagement in the Prescription Drug User
Fee Act technical discussions.
BIO represents over 1,100 members involved in the research
and development of innovative healthcare, agricultural,
industrial, and environmental technologies.
The U.S. biotechnology industry is poised to be a major
driver in an innovation-driven economy. Biotechnology offers
real solutions to our most pressing healthcare needs, curing
disease, reducing costs, increasing quality, and insuring that
people enjoy not only longer lives, but also better and more
productive lives.
I am here today primarily to express BIO's strong support
for the authorization of the biosimilars user fee program as
part of FDA's ongoing implementation of a well-constructed,
science-based pathway with the approval of biosimilar
biological products that protects patient safety and preserves
incentives to innovate.
Throughout both the legislative consideration of the
Biologics Price Competition and Innovation Act of 2009 and
ongoing FDA implementation of the pathway, BIO articulated a
number of principles that will promote the development of an
effective regulatory framework for biosimilar biological
products including: that patient safety be insured, that the
scientific differences between drugs and biologics be
recognized, that incentives for innovation be preserved, that
transparent statutory and regulatory processes be established
and followed, and that FDA would continue to prioritize the
review and approval of innovative therapies and cures.
BIO believes that the proposed standalone user fee program
is consistent with these principles. BsUFA will provide FDA
with dedicated user fee resources and review capacity to
facilitate the development and evaluation of biosimilar,
biological products while also continuing to prioritize the
review of innovative drugs and biologics under PDUFA.
I would like to mention a few key features of the BsUFA
program. First, the biosimilars user fee program establishes a
unique product development fee, which is ultimately deducted
from the sponsor's application fee. Because there is currently
no established biosimilar industry to form a stable funding
source for activities that occur before submission of
applications, it is important to front load the fees through
this product development fee so that the agency has resources
available to meet with sponsors during development to provide
scientific advice and feedback.
We note, however, that this situation with respect to
biosimilar biological products should not establish any
precedent for investigational new drug or IND fees under the
PDUFA program. Additionally, an IND-associated fee should
sunset permanently in fiscal year 2018 when both PDUFA and this
new user fee program would sunset.
PDUFA also promotes robust postmarket safety for biosimilar
biological products by establishing a lifecycle approach to
product evaluation and directing resources to FDA's postmarket
pharmaco vigilance activities in alignment with approach to
drug safety that has been adopted by innovative sponsors.
BIO also recognizes that historically most FDA user fee
programs have been established on a preexisting base of
appropriations. However, only modest appropriations are
currently allocated to biosimilars review processes. To
facilitate an equitable balance of fees and appropriations, FDA
and industry support a trigger provision similar to the
established appropriations triggers in other user fee programs
that would ensure FDA allocates at least $20 million per year
to the program.
BIO encourages Congress to recognize the importance of a
well-resourced and viable biosimilars pathway at FDA, and we
request that adequate new funding be appropriated for the
program.
I would also like to address briefly the Prescription Drug
User Fee Act or PDUFA reauthorization. We have addressed the
elements of the PDUFA-V technical agreement in detail in our
written testimony. In short, BIO believes that the PDUFA
program represents a critical element of our Nation's overall
innovation ecosystem. The set of PDUFA-V enhancements that were
agreed by FDA, BIO, and PhRMA seek to reinforce FDA's review
program and get back to basics for patients.
Timely PDUFA reauthorization will enhance the drug
development and review process through increased transparency
in scientific dialog, advanced regulatory science, strengthen
postmarket surveillance, and help establish best practices for
timely interactive dialog between sponsors and the agency
during drug development. Most importantly, our hope is that
PDUFA-V will provide patients and doctors with earlier access
to important new therapies.
In conclusion, a transparent, predictable, and balanced
regulatory framework for the review and approval of biosimilars
accompanied by reasonable performance goals and a dedicated
independent funding stream will ensure that FDA can facilitate
the development and evaluation of biosimilars products. Both
user fee programs, BsUFA and PDUFA, will enhance FDA's ability
to protect and promote the public health, and we strongly
encourage Congress to enact them in a timely manner.
Thank you.
[The prepared statement of Ms. Radcliffe follows:]
Prepared Statement of Sara Radcliffe
summary
BIO supports swift enactment of the Biosimilars User Fee Agreement
(BsUFA). The funding and goals contained in this proposal, along with a
well-constructed, science-based, transparent pathway for the approval
of biosimilar products, will ensure that FDA can facilitate the
development and evaluation of biosimilars products.
BIO recognizes that 351(k) applications will raise novel and
complex questions of science and law, requiring substantial time,
expertise, and additional resources to ensure a thorough regulatory
review. BIO believes that one of the principal goals of this new user
fee program must be to ensure that workload associated with biosimilar
applications does not harm the Agency's ability to efficiently review
innovative drugs and biologics, and that new treatments continue to
have the highest review priority. Accordingly, we agree with FDA's
principle that the Agency needs sufficient review capacity and
dedicated user fee resources for 351(k) applications to assure that
resources are not redirected from innovator reviews.
Additionally, BsUFA promotes robust post-market safety for
biosimilar products by establishing a life-cycle approach to product
evaluation and directing resources to FDA's post-market
pharmacovigilance activities. Because biologics are complex and
challenging to characterize, and the nature of a biologic is closely
dependent on the starting materials and processes used to make that
product, minor changes made by a manufacturer to starting materials or
to manufacturing processes can lead to changes in the product that may
not be detectable by current technologies. Therefore, a carefully
designed pharmacovigilance effort is important.
BIO also recognizes that, historically, most FDA user fee programs
have been established on a pre-existing base of appropriations.
However, given the recent establishment of the biosimilars program at
FDA, only modest appropriations are currently allocated to the program,
and this funding is inadequate to meet the anticipated workload
demands. To facilitate an equitable balance of fees and appropriations,
FDA and industry support a trigger provision--similar to the
established appropriations triggers in other user fee programs--that
would ensure that FDA allocates at least $20 million per year to the
program. BIO encourages Congress to recognize the importance of a well-
resourced and viable biosimilars pathway at FDA and we request that
adequate new funding be appropriated for the program.
The biosimilars user fee program also establishes a unique
biosimilar product development fee, which is ultimately deducted from
the sponsor's application fee. The assessment of a product development
fee is unique to this situation with respect to biosimilar products and
should not establish any precedent for investigational new drug (IND)
fees under the PDUFA program. Additionally, any IND-associated fee
should sunset permanently in fiscal year 2018 when both PDUFA and this
new user fee program would sunset.
A key to the success and the future of the U.S. biotechnology
industry is a reliable, predictable, and science-based regulatory
environment, and the PDUFA program represents an important element of
our Nation's overall innovation eco-system. While establishing a sound
BsUFA was a priority for BIO, so too is reauthorizing PDUFA. The
principles which guided BIO in our technical discussions with FDA
regarding PDUFA reauthorization were that a science-based, transparent,
and well-managed review process that appropriately balances benefits
and risks can enhance public trust and increase patient access to new
medicines. With these principles in mind, BIO, PhRMA, and FDA agreed
upon a set of enhancements under PDUFA-V that seek to reinforce FDA's
review performance and get back-to-basics for patients. These proposals
have also been informed by an unprecedented level of public input
through workshops, meetings, and stakeholder outreach, which further
strengthened the technical agreement.
Under the PDUFA-V agreement, industry has reinforced its commitment
to a well-funded drugs and biologics review program that supports
sound, science-based regulation consistent with FDA's public health
mission. However, user fees are intended to support limited FDA
activities around the drug review process and were never intended to
supplant a sound base of appropriations. User fees currently account
for nearly two-thirds of the cost of human drug review. We urge
Congress to support FDA's mission and fund the Agency at the
Administration's fiscal year 2012 requested levels.
Finally, it is critical for PDUFA to be reauthorized well in
advance of PDUFA-IV's expiration in September 2012, to avoid a
reduction in force at the FDA. Even the threat of a downsizing at the
FDA would be devastating to the Agency's public health mission and its
ability to review new drugs and biologics.
______
Chairman Harkin, Ranking Member Enzi, members of the committee, it
is my privilege to provide testimony before you today. My name is Sara
Radcliffe and I am executive vice president for Health for the
Biotechnology Industry Organization (BIO). In that role, I have had the
opportunity to manage BIO's involvement in the biosimilars user fee
(BsUFA) technical discussions, as well as lead BIO's engagement in the
Prescription Drug User Fee Act (PDUFA) technical discussions with the
Food and Drug Administration (FDA).
BIO represents over 1,100 members involved in the research and
development of innovative healthcare, agricultural, industrial, and
environmental technologies. The U.S. biotechnology industry is poised
to be a major driver in an innovation-driven economy. Biotechnology
offers real solutions to our most pressing health care needs: curing
disease, reducing costs, increasing quality, and ensuring that people
enjoy not only longer lives, but better and more productive lives.
I am here today to express BIO's support for the establishment of
the biosimilars user fee program as part of FDA's ongoing
implementation of a well-constructed, science-based pathway for the
approval of biosimilar products that protects patient safety and
preserves incentives to innovate. BsUFA will provide FDA with the
resources and capacity to facilitate the development and evaluation of
biosimilars products, while also continuing to prioritize the review of
innovative drugs and biologics under PDUFA so that safe and effective
new treatments--many for currently untreatable and serious diseases--
can be made readily available to patients.
BIO also supports timely reauthorization of PDUFA, which we believe
will enhance the drug development and review process through increased
transparency and scientific dialog, advance regulatory science, and
strengthen post-market surveillance. Most importantly, our hope is that
PDUFA-V will provide patients and doctors with earlier access to
important new therapies.
i. bio supports passage of the biosimilars user fee program
BIO supports FDA's ongoing implementation of a well-constructed,
science-based pathway for the approval of biosimilar products. A
transparent, predictable, and balanced regulatory framework for the
review and approval of biosimilars, accompanied by reasonable
performance goals and a dedicated, independent funding stream, will
ensure that FDA can facilitate the development and evaluation of
biosimilars products.
Throughout both the legislative consideration of the Biologics
Price Competition and Innovation Act of 2009 (BPCIA) and ongoing FDA
implementation of the pathway, BIO has articulated several key
principles that will promote the development of an effective regulatory
framework for biosimilar products:
Ensuring Patient Safety
Recognizing Scientific Differences Between Drugs and
Biologics
Maintaining the Physician-Patient Relationship
Preserving Incentives for Innovation
Ensuring Transparent Statutory and Regulatory Processes
Continuing to Prioritize FDA Review and Approval of New
Therapies and Cures
BIO believes that the proposed user fee program is consistent with
these principles and supports congressional enactment of the program.
The establishment of a stand-alone, independent biosimilars user
fee program is consistent with congressional intent and precedent
established under other user fee programs. BIO recognizes that 351(k)
applications will raise novel and complex questions of science and law,
requiring substantial time, expertise, and additional resources to
ensure a thorough regulatory review. BIO believes that one of the
principal goals of this new user fee program must be to ensure that
workload associated with biosimilar applications does not harm the
Agency's ability to efficiently review innovative drugs and biologics,
and that new treatments continue to have the highest review priority.
Accordingly, we agree with FDA's principle that the Agency needs
sufficient review capacity and dedicated user fee resources for 351(k)
applications to assure that resources are not redirected from innovator
reviews.
Additionally, BsUFA promotes robust post-market safety for
biosimilar products by establishing a life-cycle approach to product
evaluation and directing resources to FDA's post-market
pharmacovigilance activities. Because biologics are complex and
challenging to characterize, and the nature of a biologic is closely
dependent on the starting materials and processes used to make that
product, minor changes made by a manufacturer to starting materials or
to manufacturing processes can lead to changes in the product that may
not be detectable by current technologies. Therefore, a carefully
designed pharmacovigilance effort is important.
BIO also recognizes that, historically, most FDA user fee programs
have been established on a pre-existing base of appropriations.
However, given the recent establishment of the biosimilars program at
FDA, only modest appropriations are currently allocated to the program,
and this funding is inadequate to meet the anticipated workload
demands. To facilitate an equitable balance of fees and appropriations,
FDA and industry support a trigger provision--similar to the
established appropriations triggers in other user fee programs--that
would ensure that FDA allocates at least $20 million per year to the
program. BIO encourages Congress to recognize the importance of a well-
resourced and viable biosimilars pathway at FDA and we request that
adequate new funding be appropriated for the program.
The biosimilars user fee program also establishes a unique
biosimilar product development fee, which is ultimately deducted from
the sponsor's application fee. Because there is no established
biosimilars industry, facility base, and product base to form a stable
funding source for activities that occur before submission of
applications, it is important to ``front-load'' the fees through the
product development fee so that the agency has resources available to
meet with sponsors during development to provide scientific advice and
feedback. It should be noted, however, that the assessment of a product
development fee is unique to this situation with respect to biosimilar
products and should not establish any precedent for investigational new
drug (IND) fees under the PDUFA program. Additionally, any IND-
associated fee should sunset permanently in fiscal year 2018 when both
PDUFA and this new user fee program would sunset.
ii. pdufa-v: getting back to basics for patients
A key to the success and the future of the U.S. biotechnology
industry is a reliable, predictable, and science-based regulatory
environment, and the PDUFA program represents an important element of
our Nation's overall innovation eco-system. Since 1992 Congress, FDA,
and the biopharmaceutical industry have supported this carefully
structured user fee program to help fund FDA's human drug review
activities. The program has contributed to the approval of more than
1,200 new medicines and, initially, reduced review times for the
newest, most innovative drugs by more than a year.
While establishing a sound BsUFA was a priority for BIO, so too is
reauthorizing PDUFA. The principles which guided BIO in our technical
discussions with FDA regarding PDUFA reauthorization were that a
science-based, transparent, and well-managed review process that
appropriately balances benefits and risks can enhance public trust and
increase patient access to new medicines. With these principles in
mind, BIO, PhRMA, and FDA agreed upon a set of enhancements under
PDUFA-V that seek to reinforce FDA's review performance and get back-
to-basics for patients. These proposals have also been informed by an
unprecedented level of public input through workshops, meetings, and
stakeholder outreach, which further strengthened the technical
agreement. These enhancements include:
New Molecular Entity (NME) Review Program: Historically,
nearly 80 percent of all NME applications submitted to FDA are
ultimately approved, but fewer than half are approved on the first
submission.\1\ Sponsors and FDA can and must do better for patients. By
strengthening scientific dialog and transparency between FDA and
Sponsors under the proposed review program for novel drugs and
biologics, we can minimize the potential review issues that can delay
patient access to needed treatments. Increased FDA-Sponsor scientific
dialog and transparency, such as a mid-cycle communication, exchange of
discipline review letters and advisory committee information, and a
significant new late-cycle meeting, will help to identify and resolve
issues earlier in the review. This represents a significant paradigm
shift in FDA's review process while maintaining FDA's high standards
for safety and efficacy. An additional 2-month validation period
preceding the review period will help to ensure FDA has all the
information it needs at the beginning of the process to perform a
complete review. Finally, a robust third-party evaluation will provide
data on whether we have been successful in this program of leading to
fewer review cycles, shorter approval times, and earlier patient access
to needed treatment.
---------------------------------------------------------------------------
\1\ Fiscal year 2010 PDUFA Performance Report, p. 4, http://
www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/
UserFeeReports/PerformanceReports/PDUFA/UCM
243358.pdf.
---------------------------------------------------------------------------
Enhanced Communication during Drug Development: To help
advance American innovation and promote the development of the next
generation of modern medicines, FDA has also committed to a philosophy
under PDUFA-V that timely, interactive communication with biotechnology
and life science companies during drug development is a core Agency
activity.
FDA's recent report on driving biomedical innovation highlights
that ``the private sector is the engine of innovation, and much of this
innovation begins with small business.'' \2\ Indeed, many small
biotechnology companies operate on the cutting edge of biomedical
science to develop new therapies for devastating diseases. Yet we must
acknowledge that the scientific method does not operate in a vacuum,
and it is critical to promote interactive, scientist-to-scientist
communication between FDA and Sponsors. In the course of drug
development, Sponsors sometimes have simple or clarifying questions,
the responses to which could have a significant impact on the
development program, but which are not extensive enough to warrant
formal meetings. To obtain timely responses to such questions, Sponsors
currently often have to engage in a lengthy exchange of multiple formal
letters with FDA, which is an inefficient and cumbersome use of both
FDA's and the Sponsor's time. For small biotechnology companies reliant
on limited venture capital, these delays can create significant
impediments to development programs.
---------------------------------------------------------------------------
\2\ FDA, Driving Biomedical Innovation: Initiatives for Improving
Products for Patients, October 2011, http://www.fda.gov/downloads/
AboutFDA/ReportsManualsForms/Reports/UCM274464
.pdf.
---------------------------------------------------------------------------
Additionally, independent reports commissioned by FDA have
demonstrated that enhanced communication during drug development
ultimately results in higher quality applications, which can improve
efficiency for FDA reviewers.\3\
---------------------------------------------------------------------------
\3\ Booz Allen Hamilton, Independent Evaluation of FDA's First
Cycle Review Performance--Final Report. July 2008, http://www.fda.gov/
ForIndustry/UserFees/PrescriptionDrugUserFee/ucm127117.htm.
---------------------------------------------------------------------------
BIO fully supports the PDUFA-V proposal to promote innovation
through enhanced communication between FDA and Sponsors during drug
development, which will establish best practices for this type of
interactive dialog, train staff on communication practices, and provide
the Agency with additional staff capacity to respond to sponsor
inquiries in a timely manner.
Modernizing Regulatory Science: Additionally, the PDUFA-V
agreement makes new resources available to modernize regulatory
science, for example, in the areas of personalized medicine and rare
disease drug research. Modern approaches to drug development and
evaluation, such as the application of new tools for rare disease drug
development, flexibility with regard to creative study designs and new
endpoints, and greater utilization of biomarkers and patient-reported
outcome measures, will introduce new efficiencies in the drug
development enterprise and provide FDA with additional tools to
evaluate the benefits and risks of pharmaceutical products. These
proposals will also integrate more structured and systematic approaches
to assessing benefits and risks of therapies, and allow FDA to conduct
outreach to patients and hold workshops to understand better patient
perspectives on disease severity and unmet medical need.
Robust Drug Safety and Post-Market Surveillance Capacity:
PDUFA-V continues industry's commitment to a lifecycle approach to
product evaluation by strengthening FDA's post-market surveillance and
benefit/risk management capacity. Earlier discussion of risk management
strategies, standardized approaches to REMS, and further validation of
the Sentinel Network will promote patient confidence in drug and
biologics.
Under the PDUFA-V agreement, industry has reinforced its commitment
to a well-funded drugs and biologics review program that supports
sound, science-based regulation consistent with FDA's public health
mission. However, user fees are intended to support limited FDA
activities around the drug review process and were never intended to
supplant a sound base of appropriations. User fees currently account
for nearly two-thirds of the cost of human drug review. We urge
Congress to support FDA's mission and fund the Agency at the
Administration's fiscal year 2012 requested levels.
Additionally, it is critical for PDUFA to be reauthorized well in
advance of PDUFA-IV's expiration in September 2012, to avoid a
reduction in force at the FDA. Even the threat of a downsizing at the
FDA would be devastating to the Agency's public health mission and its
ability to review new drugs and biologics.
BIO looks forward to working with Congress and FDA to fully
implement these enhancements under PDUFA-V.
iii. conclusion
In conclusion, BIO supports enactment of the proposed biosimilars
user fee program, which will provide FDA with adequate resources and
promote predictability in FDA's biosimilars review process, while
continuing to promote the development and evaluation of innovative
therapies for unmet medical needs under PDUFA. Both user fee programs
will enhance FDA's ability to protect and promote the public health,
and we encourage Congress to enact both legislative provisions in a
timely manner.
The Chairman. Thank you very much, Miss Radcliffe.
Senator Enzi. Mr. Chairman, I apologize.
I am going to leave. I want to thank Dr. Woodcock and Dr.
Shuren for staying to hear this testimony, and my staff will be
staying to hear the testimony, and I will have questions to
submit.
The Chairman. I appreciate that.
Senator Enzi. Thank you.
The Chairman. Thank you very much, Senator Enzi.
I thank you very much, Miss Radcliffe.
Now we turn to David Gaugh, the vice president for
Regulatory Sciences at the Generic Pharmaceutical Association.
Did I pronounce that name right?
Mr. Gaugh. Gaugh.
The Chairman. Gaugh.
Mr. Gaugh. Yes.
The Chairman. Thank you very much, Mr. Gaugh.
STATEMENT OF DAVID R. GAUGH, R.PH., VICE PRESIDENT FOR
REGULATORY SCIENCES, GENERIC PHARMACEUTICAL ASSOCIATION,
WASHINGTON, DC
Mr. Gaugh. Good morning, Chairman Harkin, Ranking Member
Enzi, and members of the committee.
Thank you for asking me to participate in this timely and
important hearing. I am David Gaugh, vice president for
Regulatory Sciences at the Generic Pharmaceutical Association
and a licensed pharmacist.
GPhA represents the manufacturers, distributors, and
finished dose generic pharmaceuticals, both pharmaceutical
chemicals and the suppliers of goods and services to the
generic industry. Generic pharmaceuticals account for 80
percent of all prescriptions dispensed in the United States,
but consumed as 25 percent of the total drug spending for
prescription medicines.
I would like to begin today by commending the committee for
your continued focus on this important issue that we are going
to examine today. As someone who has worked in and around the
generic industry for more than two decades, I witnessed
firsthand the industry's remarkable growth and the vital role
it plays in the lives of Americans every day.
This growth in the generic industry has also served to
underscore the critically important role of the Food and Drug
Administration. As I will highlight, the levels of cooperation
between the industry and the FDA have never been greater, and
it is our hope that this collaboration will continue, and
extend throughout all of the interactions with the agency.
However, the agency remains underfunded and the
responsibility of insuring access to safe and affordable
medicines is shared by one that rests on the entire
pharmaceutical industry and not just the FDA. That is why the
generic industry has stepped up to help provide the FDA with
additional resources to address the ongoing challenges caused
by an increasingly global drug supply chain.
Currently, more than 2,700 generic drug applications are
awaiting approval from the FDA's Office of Generic Drugs and
the average approval time for an application is now stretching
beyond 30 months, more than five times longer than the
statutory 6 months that were required by Hatch-Waxman.
Unfortunately, this backlog keeps safe, low-cost generics off
the market and reduces competition that may drive drug prices
down even further.
The proposed Generic Drug User Fee Act, or GDUFA, that we
are discussing today, will help alleviate this backlog and
expedite consumer access to generic drugs.
GPhA also recognizes, however, that while providing early
access to effective medicines is critical and the key aim of
all the existing user fee programs, an equally important pillar
of FDA and industry mission is insuring drug safety. This is
why GDUFA takes the unprecedented step of holding all players
contributing to the generic U.S. drug system, foreign and
domestic, to the same inspection standards, and enhances FDA's
ability to identify and require the registration of active
pharmaceutical ingredient and finished dose foreign
manufacturers involved in each generic drug product sold in the
United States.
It is paramount that as we work to shape the future of our
country's generic industry, we also work to bring the FDA into
the 21st century, and ensure that the agency's authority to
achieve its mission in this global age are up to date.
This is further exemplified by the other user fee program
we will discuss today for generic biologic drugs or
biosimilars. Biologic medicines are often the only lifesaving
treatment for many of the most severe diseases encountered by
patients today. In many respects, they represent the future of
medicine. Their high price tag, however, can keep them out of
the reach of many patients.
During biosimilar user fee negotiations, GPhA expressed its
support for user fees funding to provide FDA with the adequate
resources to apply consistent regulatory standards to all
biologics, and review new applications as they are filed. Both
industry and patients will benefit from the user fee program by
gaining a higher degree of certainty and timeliness in the
applications that are reviewed.
We applaud the FDA for recognizing the importance of
biosimilars and the need to apply state-of-the-art science in
all agency activities governing and reviewing the approval of
these important drugs.
By designing both of these user fee programs to spread fees
across multiple stakeholders and sources to keep individual
amounts as low as possible, the programs will help assure that
the American consumers continue to receive significant cost
savings from generics that, over the past 12 years, have
provided more than $1 trillion in savings to the national
healthcare system.
It is also important to emphasize that the funding provided
by both of these user fee agreements is in addition to, and not
a substitute for, congressional appropriations.
In conclusion, Mr. Chairman, this is truly an historic time
for GPhA, the user fee proposals are the culmination of months
of negotiation between the FDA and the industry, and the final
product as transmitted to Congress represents a careful balance
among all the stakeholders involved.
We respectfully urge the committee to approve GDUFA and
BsUFA as negotiated by the FDA and industry, and without
changes to the underlying agreements.
Thank you, and I will take any questions.
[The prepared statement of Mr. Gaugh follows:]
Prepared Statement of David R. Gaugh, R.Ph.
summary
I am David Gaugh, vice president for Regulatory Sciences at the
Generic Pharmaceutical Association and a licensed pharmacist. GPhA
represents the manufacturers and distributors of finished dose generic
pharmaceuticals, manufacturers and distributors of bulk pharmaceutical
chemicals and suppliers of other goods and services to the generic
industry. Generic pharmaceuticals fill 80 percent of the prescriptions
dispensed in the United States but consume just 25 percent of the total
drug spending.
Thanks to the efforts of the Food and Drug Administration (FDA),
the U.S. drug supply remains the safest in the world, and the FDA's
drug approval and inspection processes represent the gold standard for
regulatory agencies worldwide. However, the agency remains underfunded,
and the responsibility of ensuring access to safe and affordable
medicines is a shared one that rests with the entire pharmaceutical
industry, not just the FDA.
That is why the generic industry, through the negotiation of two
new user fee agreements, has stepped up to help provide the FDA with
additional resources to address the ongoing challenges faced by the
agency. The Generic Drug User Fee Act (GDUFA) and the Biosimilar User
Fee Act (BsUFA) will help ensure U.S. drug safety, establish a more
level playing field among all participants in the U.S. pharmaceutical
supply chain, and make certain that all Americans receive timely access
to safe, effective and affordable generic drugs. We urge the committee
to approve GDUFA and BsUFA as negotiated by FDA and industry in a
timely manner, so that patients, the FDA, and generic manufacturers can
begin to see the many benefits of these agreements.
landmark user fee programs will provide additional resources
Currently, more than 2,700 generic drug applications are awaiting
approval from the FDA's Office of Generic Drugs (OGD), and the average
approval time for an application is now stretching beyond 30 months.
The Generic Drug User Fee Act (GDUFA) will help alleviate the backlog
and expedite consumer access to generic drugs, while also enhancing
drug quality and safety. FDA will receive $299 million per year over
the 5-year GDUFA program, or about $1.5 billion in total. The new user
fee program will also establish performance goals for the FDA. The
agreement's performance goals call for FDA to complete, by the end of
year five, the review of 90 percent of all ANDAs that are pending on
October 1, 2012--effectively eliminating the current application
backlog. By the end of the program's fifth year, GDUFA calls on the FDA
to review 90 percent of ANDAs within 10 months after they are
submitted--almost 2 years faster than today's average review time.
GDUFA also takes the unprecedented step of holding all players
contributing to the U.S. generic drug system, foreign or domestic, to
the same inspection standards, and enhances FDA's ability to identify
and require the registration of API and finished dosage form
manufacturers involved in each generic drug product sold in the United
States.
biosimilar user fee act
The Biosimilar User Fee Act (BsUFA) will benefit both patients and
industry by providing a higher degree of certainty in the timeliness of
application reviews. The program creates a separate review platform for
biosimilar sponsors that will be jointly financed annually by industry
and the FDA through $20 million in congressional appropriations and
then supplemented by user fees equivalent to those under the
Prescription Drug User Fee Act. The program's performance goals call
for FDA, by the end of the program's fifth year, to review 90 percent
of the original biosimilar applications it receives within 10 months of
their submission.
______
Good morning Chairman Harkin, Ranking Member Enzi and members of
the Senate Committee on Health, Education, Labor, and Pensions. Thank
you for asking me to participate in this timely and important hearing.
I am David Gaugh, vice president for Regulatory Sciences at the
Generic Pharmaceutical Association and a licensed pharmacist. GPhA
represents the manufacturers and distributors of finished dose generic
pharmaceuticals, bulk pharmaceutical chemicals, and the suppliers of
other goods and services to the generic industry. Generic
pharmaceuticals now fill 80 percent of all prescriptions dispensed in
the United States, but consume just 25 percent of the total drug
spending for prescription medicines.
According to a recent analysis by IMS Health, the world's leading
data source for pharmaceutical sales, the use of FDA-approved generic
drugs in place of their brand counterparts has saved U.S. consumers,
patients and the health care system more than $931 billion over the
past decade--$158 billion in 2010 alone--which equates to $3 billion in
savings every week.
Prior to joining GPhA, I was vice president and general manager for
Bedford Laboratories, the generic injectable division of Ben Venue
Laboratories, I have also served as senior director, Pharmacy
Contracting and Marketing, for VHA/Novation, one of the largest Group
Purchasing Organizations in the United States, and was system director
of pharmacy for a regional referral tertiary-care healthcare system in
the Midwest.
introduction
I would like to begin today by commending the committee for your
continued focus on the important issues we will examine today. As
someone who has worked in and around the generic industry for more than
two decades, I have witnessed firsthand the industry's remarkable
growth and the vital role it plays in the lives of Americans every day.
By providing consumers access to safe and effective medicines at an
affordable price, the generic industry fills an essential role not only
for patients, but for our health care system and, indeed, our national
economy.
This growth in the generic industry has also served to underscore
the critically important role of the Food and Drug Administration
(FDA). As I will highlight, the level of cooperation between industry
and the FDA has never been greater. The two historic user fee
agreements we are discussing today represent only a small measure of
our ongoing collaboration. It is our hope that this collaboration will
continue and extend throughout all of our interactions with the agency.
As evidenced by these accomplishments, the FDA's work during this
period of growth for the generic industry has been extraordinary.
Thanks to their efforts, the U.S. drug supply remains the safest of
anywhere in the world, and the FDA's drug approval and inspection
processes represent the gold standard for regulatory agencies
worldwide.
However, the agency remains underfunded, and the responsibility of
ensuring access to safe and affordable medicines is a shared one that
rests with the entire pharmaceutical industry, not just the FDA. That
is why the generic industry has stepped up to help provide the FDA with
additional resources to address the ongoing challenges caused by an
increasingly global drug supply chain, the increase in the agency's
workload and the regulation of new and complex technologies.
Throughout much of last year, GPhA and our member companies worked
closely with the FDA to negotiate two separate user fee programs
designed to help the agency obtain additional resources to ensure all
participants in the U.S. generic drug system, whether U.S.-based or
foreign, comply with all of our country's strict quality standards.
Most importantly, the programs will make certain that all Americans
receive timely access to safe, effective and affordable generic drugs.
Let me provide some more details.
landmark user fee programs will provide additional resources
Currently, more than 2,700 generic drug applications are awaiting
approval from the FDA's Office of Generic Drugs (OGD), and the average
approval time for an application is now stretching beyond 30 months,
more than five times longer than the statutory 6-month review time
called for by Hatch-Waxman. Unfortunately, this backlog keeps safe,
low-cost generic drugs off the market and reduces competition that may
drive drug prices down further.
The proposed Generic Drug User Fee Act, or GDUFA, that we are
discussing today will help alleviate the backlog and expedite consumer
access to generic drugs, while also enhancing drug quality and safety
by ensuring inspection parity among both foreign and domestic
manufacturing sites.
Specifically, FDA will receive $299 million per year over the 5-
year GDUFA program, or about $1.5 billion in total. Of that funding, 80
percent, or about $240 million, will come from finished-dose
manufacturers, and the remaining 20 percent will be paid by
manufacturers of active pharmaceutical ingredients. Thirty percent of
the funding will stem from application fees and 70 percent will be
derived from fees on manufacturing sites, or facility fees.
Splitting the fees in this manner will provide the FDA with a
predictable source of annual income, as the number of facilities
manufacturing generic drugs on a yearly basis provides a more
consistent figure than the number of generic drug applications
submitted. Finished dose facilities that manufacture both generic and
brand medications will be required to pay both a Prescription Drug User
Fee Act facility fee and a GDUFA facility fee.
The new user fee program will also establish performance goals for
the FDA. As part of these goals, GDUFA calls for the agency to
complete, by the end of year five, the review of 90 percent of all
generic drug applications--commonly referred to as Abbreviated New Drug
Applications, or ANDAs--that are pending on October 1, 2012--the
proposed start date for the program. By achieving this goal, the GDUFA
agreement will effectively eliminate the current application backlog.
In addition, by the end of the program's fifth year, GDUFA calls on
the FDA to review 90 percent of ANDAs within 10 months after they are
submitted--almost 2 years faster than today's average review time.
These are great strides that will go a long way toward ensuring
patients have timely access to safe and effective generic medicines for
years to come. But GPhA also recognizes that while providing earlier
access to effective medicines is critical--and the key aim of all other
existing user fee programs--an equally important pillar of FDA's and
industry's mission is ensuring drug safety.
Since the enactment of the Federal Food, Drug and Cosmetic Act in
1938, the core public health mission of the FDA has been to protect and
promote the public's health. As part of that mission, the FDA has a
critical responsibility to ensure the safety, efficacy and security of
the entire U.S. drug supply, both brand and generic. Ensuring a safe
and effective drug supply, however, is significantly more challenging
today than it was in 1938 due to the increasing globalization of drug
manufacturing, supply and testing and an increase in FDA-regulated drug
products.
GPhA has long-maintained that, in light of this increasing
globalization and with nearly 40 percent of all the prescription drugs
in the United States being imported, the FDA needs more resources to
ensure adequate oversight of the Nation's drug supply.
A 2010 Government Accountability Office (GAO) report found that FDA
was able to conduct Good Manufacturing Practice, or GMP, inspections at
only 11 percent of the foreign establishments in its database, compared
to 40 percent of the domestic sites it inspected. According to the GAO,
in the absence of a paradigm shift, it would take FDA 9 years to
inspect all foreign facilities.
That is why GDUFA takes the unprecedented step of holding all
players contributing to the U.S. generic drug system, foreign or
domestic, to the same inspection standards, and enhances FDA's ability
to identify and require the registration of active pharmaceutical
ingredient and finished dosage form manufacturers involved in each
generic drug product sold in the United States. The program will
significantly improve the resources the FDA has to do this important
work, ensuring that it can be done with increasing speed, but without
any sacrifice to today's high quality standards.
It is paramount that, as we work to shape the future of our
country's generic drug industry, we also work to bring the FDA into the
21st century and ensure that the agency's authorities to achieve its
mission in this global age are up to date.
In many ways, this process is already underway. Perhaps the best
and most immediate example rests with the other user fee program we
will discuss today--for generic biologic drugs, or biosimilars.
biosimilar user fee act
Biologic medicines are often the only lifesaving treatments for
many of the most severe diseases encountered by patients today. In many
respects, they represent the future of medicine. Their high price tag,
however, can keep them out of reach for many patients. The cost of
biologics is increasing annually at a faster pace than almost any other
component in health care. As proven with chemical prescription drugs,
competition from generic biologic drugs will be the most important
factor in holding down the future costs of these lifesaving medicines.
With the FDA still working to determine the process by which these
products will be approved, GPhA continues to stress the importance of
creating a workable regulatory mechanism that does not serve as a
barrier to competition, but rather ensures the robust competition
needed to lower costs and spur future innovation. If such a system is
not put in place, it is our fear that the exponential growth of
biologics over the next 10 to 20 years, without adequate generic
alternatives, could bankrupt our health care system and the national
economy. Moreover, the lack of lower-cost generic biologics will keep
vital treatments away from the patients who need them most.
Within our organization, we represent manufacturers who currently
produce high-quality, safe and effective biosimilars approved in Europe
and other regulated markets around the world. These member companies
are dedicated to bringing the same level of access and affordability
for these critical medicines to U.S. patients.
During the biosimilar user fee negotiations, GPhA expressed its
support for user fee funding to provide FDA with adequate resources to
apply consistent regulatory standards to all biologics, and review new
applications as they are filed. Both industry and patients will benefit
from this user fee program by gaining a higher degree of certainty in
the timeliness of application reviews.
The proposed program creates a separate review platform for
biosimilar sponsors, to be financed annually through $20 million of the
funds appropriated to the FDA and supplemented by user fees equivalent
to those under the Prescription Drug User Fee Act. A portion of the
application fee paid during the biosimilar development phase will be
used to support earlier resourcing for product reviews. Similar to
GDUFA, the program also includes performance goals for the FDA, which
calls for the agency, by the end of the program's fifth year, to review
90 percent of the original biosimilar applications it receives within
10 months of their submission.
We applaud the FDA for recognizing the importance of biosimilars,
and the need to apply state-of-the-art science in all agency activities
governing the review and approval of these important drugs.
Through both of these user fee agreements, the generic industry has
truly stepped up to do our part to help ensure U.S. drug safety,
establish a more level playing field among all participants in the U.S.
pharmaceutical supply chain and significantly reduce the time needed to
commercialize a generic drug.
By designing the programs to spread fees across multiple
stakeholders and sources to keep individual amounts as low as possible,
the programs will help assure that American consumers continue to
receive the significant cost savings from generics that, over the past
dozen years, have provided more than $1 trillion in savings to the
Nation's health care system.
additional measures are needed to ensure access to affordable medicines
It is important to emphasize that the funding provided by both of
these user agreements is in addition to, not a substitute for,
congressional appropriations. And while the programs provide an
excellent framework for industry to help support the growing global
needs of FDA and speed the entry of generic drugs to market, they do
not completely solve the problem. As the user fee legislation moves
forward, we urge Congress to address additional areas--currently
outside the scope of the user fee acts--that would further increase
access to safe and effective generic medicines.
For example, a concern related to Hatch-Waxman that warrants
Congress' attention involves the law's ``Section viii'' process. Under
a Federal court's interpretation of current law, brand-name drug
manufacturers are able to block generic competition by providing the
FDA with misleading and overbroad descriptions of their patents.
While ``Section viii'' allows generic manufacturers to market their
products for FDA-approved uses not covered by any patent, brand
manufacturers have circumvented this process by changing their
product's ``use code''--a description of the patent required to be
filed by the FDA. Because the FDA is not institutionally equipped to
question brands' use codes by reading their patents, the agency has had
no choice but to deny the approval of generic competition in such
cases. And the Federal Circuit held that there is no judicial remedy
for the problem. Though the U.S. Supreme Court is now considering
reversing that ruling, clarity of the legislative language is needed
and would be beneficial even if the appellate ruling is overturned.
Additionally, as noted previously, GPhA strongly supports the
unprecedented steps taken in GDUFA to ensure that all contributors to
the U.S. drug system, both foreign and domestic, are held to the same
quality standard.
GPhA further supports a ``risk-based'' model for inspections that
prioritizes inspections according to a company's safety and compliance
track record. This system would ensure that questionable or problematic
facilities receive a comprehensive review and evaluation sooner, rather
than later, or not at all as can be the case under the current system.
Facilities with strong records of compliance and positive inspections
would be placed further down on the inspection schedule, allowing the
agency to prioritize its immediate attention on facilities that have
never had an inspection or that have a history of compliance issues.
GPhA recommends that Congress adopt a Federal drug tracking system
with uniform standards across all States. Given that products are
distributed throughout interstate commerce and across State lines,
having multiple standards will be problematic. The challenge to
implementation will be to ensure that the technology is reliable and
feasible in light of numerous economic, technical and logistical
factors, so that the end product delivers patient safety and does not
result in increased costs to consumers and payers.
As a member of the Pharmaceutical Distribution Security Alliance
(PDSA), a multi-stakeholder group working to develop a national model
for drug tracking, GPhA, in consensus with other supply chain partners,
supports the RxTEC model, which will increase patient safety and help
to achieve the goals we share with the FDA.
We believe this model will help prevent the introduction of
counterfeit drugs, facilitate their identification, provide
accountability for the movement of drugs by supply chain participants
and improve the efficiency and effectiveness of recalls. Establishing a
national uniform drug-tracking system, as opposed to a system based on
a patchwork of State laws and regulations, is critical to achieving
these goals.
conclusion
In conclusion, Mr. Chairman, this truly is an historic time for
GPhA. The user fee proposals are the culmination of months of
negotiations between FDA and industry, and the final product as
transmitted to Congress represents a careful balance among all the
stakeholders involved. We respectfully urge the committee to approve
GDUFA and BsUFA as negotiated by FDA and industry, without any changes
to the underlying agreements. It is also vital that the agreements be
approved in a timely manner so that patients, the FDA, and generic
manufacturers can begin to see the many benefits of these agreements.
Nothing is more important to our industry than ensuring patients have
access to the lifesaving generic medications they require, and these
historic agreements provide a critical step toward accomplishing this
goal. Thank you and I would be happy to address any questions you may
have.
The Chairman. Thank you very much, Mr. Gaugh.
Next, we have Dr. David Nexon, senior executive vice
president for the Advanced Medical Technology Association, an
association representing manufacturers of medical devices and
diagnostics.
We also thank the representatives of the Medical Device
Manufacturers Association and the Medical Imaging Technology
Association who have coordinated with Dr. Nexon regarding his
testimony, so that it will reflect the full scope of the
medical device industry.
Quite frankly, it is rather a shock to my system to see Dr.
Nexon sitting there rather than here. I started out way down
there, Michael, down at that end and Dr. Nexon was our traffic
cop back here, but he always treated me well, and I appreciate
it very much.
Dr. Nexon, welcome back to the committee on this side of
the podium, I guess.
STATEMENT OF DAVID NEXON, Ph.D., SENIOR EXECUTIVE VICE
PRESIDENT, ADVANCED MEDICAL TECHNOLOGY ASSOCIATION, WASHINGTON,
DC
Mr. Nexon. Thank you very much, Mr. Chairman.
It is quite a pleasure to be back with the HELP committee,
although I must confess, as you pointed out, it feels a little
strange to be on this side of the witness table.
As many of you know, our industry has been a true American
success story for patients and for the U.S. economy. America's
medical technology industry truly leads the world, but our
leadership is slipping.
One key reason, and perhaps the most important reason that
our leadership is slipping is the significant decline we have
seen in FDA efficiency and consistency in recent years. I am
pleased that the FDA leadership and Dr. Shuren have recognized
the need to vigorously address the issues affecting the device
center, and we heard from Dr. Shuren this morning about a
number of steps that they are taking to turn the situation
around.
We believe that the new user fee agreement has the
potential to be a significant additional step in the right
direction. It is good for industry, it is good for FDA, and
most of all, it is good for patients.
The user fee agreement builds the conditions for success in
a number of major ways. For the first time ever, this user fee
agreement establishes average total time goals for FDA product
review. All previous agreements have set their goals in terms
of time on the FDA clock. But what matters to industry and
patients are the actual days on the calendar that it takes to
get a product from submission to final decision by FDA. By
setting in place this new goal, efforts will be focused on the
metric that is truly most important to everyone concerned.
Second, the agreement also established improved goals for
time on the FDA clock. These goals are a key management tool
for FDA and they work in concert with the total time goal to
produce better performance that either could achieve alone.
Third, the agreement includes process standards that we
anticipate will also improve the review process. These include
meaningful presubmission interactions between FDA and
companies. Agreements reached in these interactions will be
binding unless, of course, new information arises that requires
a change to protect the public health.
A mandatory substantive interaction between FDA and the
company midway through the review process is also included in
the agreement. This will assure that both companies and the FDA
identify any deficiencies in the application early so that they
can be corrected promptly.
The new procedure that we call ``no submission left
behind,'' that Dr. Shuren also referenced, will be instituted
so that if the FDA time target is missed, the company and the
FDA will meet to work out a schedule for resolving the
remaining issues so that the submission does not go to the
bottom of the pile and not get looked at again.
Fourth, the agreement provides for greater accountability.
Greater accountability means that FDA's success under this
agreement will be transparent to FDA, to FDA management, to
industry, to patients, and to Congress and the Administration
so that any problems that arise can be corrected promptly.
Under the agreement, there will be quarterly and annual
reporting on a wide variety of key metrics that both FDA and
industry agree are important.
In addition, the agreement requires an analysis of FDA's
management of the review process by an independent consulting
organization coupled with an FDA corrective action plan to
address opportunities for improvement.
Finally, to give FDA additional tools to meet the new
goals, the agreement provides $595 million in user fees over
the life of the agreement. Additional reviewers, lower manager
to reviewer ratios, enhanced training, and other resources
provided by the agreement will give FDA what it needs to
improve performance.
Overall, the agreement will allow FDA to hire approximately
200 additional FTE's and the vast majority of these new FTE's
will put in place where they are needed the most as additional
reviewers. This coupled with the additional supervisors who are
being hired this year should lead to more consistency and speed
in the review process.
Of course, and I want to emphasize this, no agreement no
matter how good on paper is self-executing. Making it work as
intended will require the full efforts of FDA's dedicated staff
and managers. Our industry has committed to work with FDA in
any way we can to make it a success. Continued oversight and
interest from the Congress will also be critically important.
Patients are really depending on all of us.
Finally, I should note that a number of legislative
proposals have been introduced with the goal of improving the
FDA's operations. We are appreciative of the efforts by all
members who seek to give the FDA the tools and structure it
needs to succeed. At the same time, I do want to emphasize that
we are strongly committed to the user fee agreement as
negotiated and we do not support any proposals that would
change the terms of the agreement or undermine its goals.
Just as this new user fee agreement has the potential to
help FDA move in a very positive direction for patients and
industries, the view I have emphasized, Mr. Chairman, and as
Ranking Member Enzi emphasized, failure to reauthorize this
program in a timely way would really be catastrophic for the
FDA, for industry, and for patients.
I thank the committee for the opportunity to testify and we
strongly support your efforts and urge the committee to do what
it is we know you want to do, which is to promptly reauthorize
this program, which is so critical to patients, to the FDA, and
to our industry.
Thank you very much.
[The prepared statement of Mr. Nexon follows:]
Prepared Statement of David Nexon, Ph.D.
The U.S. medical technology industry is an American
success story, directly employing more than 400,000 workers nationwide.
Success in our industry comes only from innovation. We are
very proud of our contributions to the U.S. economy and are even more
proud of our contributions to improving patient care.
FDA is a critical partner in our companies' efforts to
bring safe and effective medical devices to patients. Without a strong,
effective and efficient FDA, we cannot have a strong and competitive
industry.
While the FDA has consistently maintained a strong record
of assuring safety and effectiveness of the products it reviews, delays
in product approval, inconsistency in the review process, and the
resulting downstream effects on investment and innovation have
undermined the competitiveness of our industry and harmed patient
access to new treatments, diagnostics, and cures.
We are pleased that after extensive negations, FDA and
industry reached a user fee agreement that has the potential to help
achieve meaningful change in FDA performance through groundbreaking
accountability and transparency measures and enhanced FDA resources.
This user fee agreement establishes average total time
goals for FDA product review. Total time is the best indicator of
whether FDA is consistent and efficient in its review and is providing
sponsors with adequate information in advance of what data is needed
for different types of products. These total time goals are shared
performance goals, because industry also has an obligation to submit
good applications to FDA.
The agreement also establishes improved goals for time on
the FDA clock and the improved FDA goals and the total time goals work
together to encourage FDA to focus on a thorough but efficient review
of all product submissions.
The agreement includes process standards that we
anticipate will improve the consistency and timeliness of the review
process, including meaningful presubmission interactions, midway review
interactions, and a new process for submissions that are outside the
FDA time target.
The agreement provides greater accountability to industry,
patients and to Congress and the Administration, through regular
reporting on key metrics and an outside analysis of FDA's management of
the review process, coupled with an FDA corrective action plan to
address opportunities for improvement.
Last, to give FDA additional tools to meet the new goals,
the agreement provides $595 million in user fees for 2013-17.
Each of the provisions of this agreement has the potential
to make a difference in improving FDA performance, but the whole is
truly greater than the sum of its parts.
We urge the committee to act promptly to reauthorize the
MDUFA program and enact this agreement into law. Failure to act would
not only jeopardize the critical improvements made by the new agreement
but would have a devastating impact on our industry's ability to bring
improved treatments and cures to patients.
______
Thank you Chairman Harkin, Ranking Member Enzi, and members of the
committee for the opportunity to testify today.
My name is David Nexon, and I am senior executive vice president of
the Advanced Medical Technology Association (AdvaMed). My testimony
today on the MDUFA agreement is submitted on behalf of three of the
medical technology industry associations who participated in the MDUFA
negotiations--AdvaMed, MDMA, and MITA.
I want to thank you for convening today's hearing, and for your
interest in improving medical device regulation for patients and
industry. Over the course of the last year, members of this committee
have demonstrated their focus on improving the efficiency and
effectiveness of FDA regulation, and your outreach to the agency and
the policy proposals that have been introduced show your commitment to
this important issue.
the u.s. medical technology industry
The medical technology industry is an American success story. Our
industry directly employs more than 400,000 workers nationwide.
Typically, for every worker our industry directly employs, another four
workers are employed by businesses supplying components and services to
our industry and our employees, so that the total numbers generated by
our industry exceeds 2 million.
The jobs our industry provides are good jobs--the kinds of jobs
that allow employees to live the American dream. Industry pay levels
are 38 percent higher than average pay for all U.S. employment and 22
percent higher than other manufacturing employment. While the number of
manufacturing jobs was plummeting across the larger economy, even
before the recent economic downturn, employment in our industry was
expanding. Between 2005 and 2007, medical technology employment grew
20.4 percent, adding 73,000 jobs. During the recession, between 2007
and 2008, MedTech employment dropped 1.1 percent, compared to 4.4
percent for manufacturing as a whole.
Our industry is heavily skewed toward small companies--the kind of
companies that begin with a doctor, and engineer, and an idea to
improve patient care. Almost two-thirds of the 7,000 medical technology
firms in the United States have fewer than 20 employees. A high
proportion of the breakthrough products in our industry come from these
small, often venture-capital funded companies.
And whether the firm is large or small, success in our industry
comes only from innovation--the creation of diagnostics, treatments and
cures that extend and enhance lives. Our industry's investment in
research and development is more than twice the national average. Our
product life-cycle is only 18-24 months.
Our industry is so competitive that price increases have averaged
only one-quarter the rate of other medical goods and services and just
one-half the general CPI for almost 20 years.
With $33 billion in total exports in 2008, medical technology ranks
eleventh among all manufacturing industries in gross exports. Notably,
unlike virtually every other sector of U.S. manufacturing, medical
technology has consistently enjoyed a favorable balance of trade. With
the aging of both U.S. and foreign populations, the projected explosive
growth of large middle-class populations demanding modern health care
in developing countries like China and India, and the accelerating pace
of biomedical discovery, the potential for growth of our industry is
great.
While we are very proud of our contributions to the U.S. economy,
we are even more proud of our contributions to improving patient care.
For patients, medical progress has been remarkable. Between 1980 and
2000, medical progress added more than 3 years to life expectancy. The
death rate from heart disease was cut in half; the death rate from
stroke was cut by one-third, and the death rate from breast cancer was
cut 20 percent.
fda regulation of medical devices--mdufa-iii
While we are making progress in improving patient care and see
immense future opportunities to provide jobs and contribute to long-
term economic growth, we are also worried. Today, America is the world
leader in medical technology. But there are warning signs. As a recent
PriceWaterhouseCoopers report showed, our lead is slipping on a number
of dimensions of competitiveness. And a key factor in our loss of
competitiveness has been the decline in FDA's performance in ensuring
timely patient access to safe and effective medical devices.
Put simply, FDA is a critical partner in our companies' efforts to
bring safe and effective medical devices to patients. Without a strong,
effective, and efficient FDA, we cannot have a strong and competitive
industry. The predictability, consistency and efficiency of FDA
decisionmaking, as well as reasonable, risk-based standards of evidence
to assure the safety and effectiveness of medical technology products,
is essential to drive new innovations for patients and for the long-
term success of the medical device industry. While the FDA has
consistently maintained a strong record of assuring the safety and
effectiveness of the products it reviews, delays in product approval,
inconsistency in the review process, and the resulting downstream
effects on investment and innovation have undermined the
competitiveness of our industry and harmed patient access to new
treatments, diagnostics, and cures.
I am pleased to be able to report that after extensive
negotiations, the user fee agreement between FDA and industry has been
reached and is now awaiting your action. We believe this agreement has
the potential to help achieve meaningful change in FDA performance
through groundbreaking accountability and transparency measures and
enhanced FDA resources.
The FDA leadership and Dr. Shuren have recognized the need to
vigorously address the issues affecting the device center and are
already taking a number of steps that we believe have the potential to
bring significant improvements. The user fee agreement our industry
representatives just concluded with the agency has the potential to be
an additional step in the right direction. It is good for industry. It
is good for FDA. And most of all, it is good for patients. We urge this
committee and the Congress as a whole to act promptly to reauthorize
the user fee program and enact this agreement into law. Failure to act
would not only jeopardize the critical improvements made by the new
agreement but would have a devastating impact on our industry's ability
to bring improved treatments and cures to patients.
The user fee agreement builds the conditions for success in a
number of major ways.
total time goal
For the first time ever, this user fee agreement establishes
average total time goals for FDA product review. All previous
agreements have set goals in terms of time on the FDA clock. When the
FDA asks sponsors for additional information or data, the FDA clock
stops. The result was that while FDA may have been meeting the goals
for 510(k) submissions, the total time from submission to final
decision increased 43 percent between the average for 2003-7 and 2010.
Of course, what matters to companies and patients is not an artificial
construct like time on the FDA clock, but the time it actually takes to
get a decision from FDA.
FDA, of course, often has legitimate questions about an application
and it cannot control the amount of time it takes for a sponsor to
respond to questions about any individual application. But all sponsors
want to submit applications that meet FDA standards, and total time is
the best indicator of whether FDA is consistent and efficient in its
review and is providing sponsors with adequate information in advance
of what data is needed for different types of products. We refer to
this new standard as a shared performance goal, because industry also
has an obligation to submit good applications. Additionally, FDA will
have new authority to decline to begin review of an application that is
obviously deficient when it is submitted.
By setting in place this new goal, efforts will be focused on the
metric that is truly most important to all concerned.
improved fda day goals
Second, the agreement also establishes significantly improved goals
for time on the FDA clock. For example, for PMAs receiving panel
reviews--which tend to be the most innovative products. By the end of
this new agreement, 90 percent of PMA products will receive a decision
within 320 days. The improved FDA day goals and the total time goals
work together to encourage FDA to focus on a thorough but efficient
review of all product submissions.
process improvements
Third, the agreement includes process standards that we anticipate
will improve the consistency and timeliness of the review process
independent of the specific time goals.
The agreement provides for meaningful presubmission interactions
between FDA and companies where agreements reached will not change, so
that companies know what FDA expects and FDA is bound by its
commitments, unless, of course, new information arises that requires a
change to protect public health.
Additionally, there will be a substantive interaction between FDA
and the company midway through the review process. This will assure
that both companies and FDA identify any deficiencies in the
application early, so that they can be corrected promptly.
A new procedure that we call ``no submission left behind'' will be
instituted, so that if the FDA time target is missed, the company and
the FDA will meet to work out a schedule for resolving remaining
issues, so that the submission doesn't go to the bottom of the pile.
greater accountability
Fourth, the agreement provides for greater accountability. Greater
accountability means that FDA's success under this agreement will be
transparent to FDA management, to industry, to patients, and to
Congress and the Administration, so that any problems that arise can be
corrected promptly. Under the agreement, there will be quarterly and
annual reporting on key metrics, providing reliable and consistent
tracking of new performance indicators that both FDA and industry have
agreed are important.
In addition, the agreement requires an analysis of FDA's management
of the review process by an independent consulting organization,
coupled with an FDA corrective action plan to address opportunities for
improvement.
appropriate resources
Finally, to give FDA additional tools to meet the new goals, the
agreement provides $595 million in user fees for 2013-17. Additional
reviewers, lower manager-to-reviewer ratios, enhanced training, and
other resources provided by the agreement will give FDA what it needs
to improve performance. Overall, the agreement will allow FDA to hire
approximately 200 additional FTEs, the vast majority of which will be
put into place where needed most--additional reviewers. This, coupled
with additional supervisors who are being hired this year, should lead
to move consistency in the review process.
Each of the provisions of this agreement has the potential to make
a difference in improving FDA performance. But the whole is truly
greater than the sum of its parts. Each of the elements of the
agreement reinforces the others. For example, as I noted above, the
combination of total time goals and faster FDA time goals should result
in greater improvements than either one would achieve separately.
And, of course, no agreement, no matter how good on paper, is self-
executing. Making it work as intended will require the full efforts of
FDA's dedicated staff and managers. Our industry is committed to work
with FDA in any way we can to make it a success. Continued oversight
and interest from the Congress will also be important. Patients are
depending on all of us.
conclusion
Finally, I should note that a number of legislative proposals have
been introduced with the goal of improving the FDA's operations. We are
appreciative of efforts by all Members who seek to give the FDA the
tools and structure it needs to succeed. Legislative reforms that do
not alter the substance of the negotiated agreement between FDA and
industry and seek to improve consistency and predictability in the FDA
device review process hold the potential to create a legislative
reauthorization package that maximizes the opportunity for success at
the agency, which should be the shared goal of all involved.
For example, legislation has been proposed to streamline the de
novo process by eliminating the statutory requirement that a sponsor
receive a finding of ``not substantially equivalent'' before even
beginning the de novo process. FDA itself has recognized that the
current process is cumbersome, and FDA is looking at using its
regulatory discretion to improve that process. However, statutory
change may be the most effective way to address the problem, which will
help FDA, industry, and ultimately patients.
At the same time, I want to emphasize that we are strongly
committed to the user fee agreement as negotiated and do not support
any proposals that would change the terms of the agreement or undermine
its goals.
I thank the committee for the opportunity to testify and urge you
to act promptly to reauthorize this program which is so critical to
patients, to the FDA and to our industry.
The Chairman. David, thank you very much, again and thank
you for your 20 years of service to this committee too.
Mr. Nexon. Thank you, Mr. Chairman.
The Chairman. Next, we turn to Allan Coukell, the director
of Medical Programs at The Pew Health Group. In his current
role, he supervises programs related to pharmaceutical supply
chain safety, antibiotic development and stewardship, and
conflict of interest issues.
Mr. Coukell, welcome to the committee. Please proceed.
STATEMENT OF ALLAN COUKELL, B.SC.PHARM., DIRECTOR OF MEDICAL
PROGRAMS, THE PEW CHARITABLE TRUSTS, WASHINGTON, DC
Mr. Coukell. Mr. Chairman and members of the committee,
thank you for the opportunity to testify.
My name is Allan Coukell and I direct medical programs for
The Pew Health Group, which conducts research and analysis
aimed at improving the safety and well-being of American
consumers. As you mentioned, Pew has a number of initiatives
related to drugs, medical devices, and FDA.
Today, I would like to talk about how the user fee
agreements can promote innovation and help to ensure the safety
and effectiveness of medical products with the ultimate goal of
improving health.
Since 1992, PDUFA fees have given FDA significant and
sustained resources that allow the agency to review new
products quickly. Indeed, preliminary findings of a study that
Pew has funded show that FDA reviews new drugs faster than its
counterparts in the European Union and Canada.
PDUFA also established an accelerated review process for
drugs that offer major advances or provide treatment where no
adequate therapy exists, and FDA devotes extra resources to
reviewing those drugs.
This issue is especially important to Pew's Antibiotics and
Innovation Project, which is working to promote the development
of new antibiotics needed to treat serious and life threatening
bacterial infections.
Of the last 11 new antibiotics approved, four received
priority review and that meant faster approvals for drugs for
pneumonia, serious skin infections, and for C. difficile
diarrhea, which causes 14,000 U.S. deaths each year.
The Medical Device User Fee Program is similarly important,
and we are asking Congress to swiftly reauthorize it. The fees
that FDA collects under MDUFA would add 200 new staff and
nearly $600 million for the review of device applications, and
these new funds are important.
Pew recently commissioned an analysis of personnel at FDA
showing that the Device Center has higher attrition rates than
the centers for drugs and biologics, or the office of
regulatory affairs. Nearly 10 percent of staff in CDRH left in
fiscal year 2010, and the majority of device staff reported
that they did not have sufficient resources to get their job
done. To function effectively, CDRH must have adequate funding.
But it is critical to remember that true innovation is not
just about speed to market, but about developing products that
are safer or more effective than existing drugs and devices.
While more challenging to measure than review times, improving
health is the ultimate goal of the FDA.
User fees primarily support review of new products, but
some funds are available to support drug safety activities.
Five years ago, Congress created the Risk Mitigation Programs
known as REMS to help FDA and manufacturers manage the risk of
drugs. The current user fee agreement directs resources toward
insuring the effectiveness of these important programs.
The new Generic Drug User Fee Agreement also contains
important safety provisions, and this landmark measure will
enable FDA to inspect overseas generic drug plants more often.
As Pew's Drug Safety Project has noted, 80 percent of the
ingredients in our drug supply now comes from outside the
United States, yet FDA domestic inspections occur nearly every
2 years. And by way of contrast, inspections in China by the
FDA occur, on average, every 17 years. Addressing this
disparity will help protect patients from substandard drugs and
even the playing field for U.S. manufacturers.
GDUFA is an important step forward for safety, and PDUFA
funds will help evaluate drug safety. Medical devices are
different. In contrast with drugs, medical devices can come to
market with limited or no clinical data, and that makes it
especially important that we have a robust postmarket
surveillance system. And we urge Congress to allow FDA to apply
user fees to device safety initiatives, something not covered
to a great extent under the proposed agreement.
For example, PDUFA fees already support Sentinel for drug
adverse events. PDUFA fees should be used to support the
monitoring of devices in this program.
In closing, I would like to mention some of the other
crucial activities that user fees do not cover such as ongoing
inspections for brand name drugs, for example, and regulation
of food safety. As important as user fees are, they are not a
substitute for adequate appropriated funding.
The user fees, if they expire, would harm patients, public
health, and the industry. We urge Congress to move quickly to
pass these important bills and to ensure that FDA has continued
sustained funding for its vital public health mission.
Thank you, and I would welcome any questions.
[The prepared statement of Mr. Coukell follows:]
Prepared Statement of Allan Coukell, B.Sc.Pharm.
Based on data, science, and non-partisan research, the Pew Health
Group works to reduce risks to the health, safety, and well-being of
American consumers. Pew applies a rigorous, analytical approach to
improve public policy, inform the public, and stimulate civic life.
The user fee agreements can promote innovation, and help to ensure
the safety and effectiveness of medical products ultimately with the
goal of improving health. These agreements fund critical activities of
the Food and Drug Administration (FDA).
Since 1992, user fee agreements have given FDA significant and
sustained resources that allow the agency to review new products
quickly. Preliminary findings of a study Pew has funded show that FDA
reviews new drugs faster than its counterparts in the European Union
and Canada.
The fees FDA collects under MDUFA provide the agency with
additional resources to review applications and add about 200 much-
needed staff members to the agency's Center for Devices and Radiologic
Health (CDRH). Under the proposed agreement, the total fees collected
over the 5-year period to 2017 are expected to reach $595 million. This
will help create a more efficient center that is sufficiently resourced
to better protect consumer safety and facilitate the introduction of
innovative devices.
Overall, the user fee programs have substantially sped up the
review of new drug applications. Review times are important insofar as
they speed patients' access to potentially important products. The user
fee agreements make review times a performance metric. However, true
innovation is not just about getting products to market faster; it is
about developing products that are safer or more effective than
existing drugs and devices. While more challenging to measure than
review times, improving health is the ultimate goal of the FDA.
the user fee agreements give fda more resources to ensure drug safety
While user fees primarily support the review and approval of
medical products, some funds are available to partially underwrite
certain product safety activities. The Generic Drug User Fee agreement
will enable FDA not only to review generic drug applications, but also
to inspect overseas drug manufacturing facilities more regularly.
Given the broad support for these agreements from Democrats,
Republicans, the business community, and consumers, we urge Congress to
move quickly to pass these important bills to ensure that FDA has
continued, sustained funding to carry out and expand its important
public health mission.
______
Chairman Harkin, Ranking Member Enzi, and members of this
committee, thank you for the opportunity to testify about the
importance of the user fee agreement legislation to patients and public
health.
Based on data, science, and non-partisan research, the Pew Health
Group works to reduce risks to the health, safety, and well-being of
American consumers. Pew applies a rigorous, analytical approach to
improve public policy, inform the public, and stimulate civic life.
Today, I would like to talk about how the user fee agreements can
promote innovation, and help to ensure the safety and effectiveness of
medical products ultimately with the goal of improving health. These
agreements fund critical activities of the Food and Drug Administration
(FDA), the Federal public health agency that regulates important, life-
sustaining products, such as drugs, vaccines, medical devices,
biologics, and food, as well as other products people use daily,
including cosmetics, vitamins, and, most recently, tobacco.
the user fee agreements promote innovation
Since 1992, user fee agreements have given FDA significant and
sustained resources that allow the agency to review new products
quickly. Preliminary findings of a study Pew has funded show that FDA
reviews new drugs faster than its counterparts in the European Union
and Canada.
The 1992 Prescription Drug User Fee Act also established an
accelerated regulatory review process for drugs that offer major
advances or provide treatment where no adequate therapy exists. FDA
devotes extra time and resources to drugs with priority review status.
This issue is particularly important to Pew's Antibiotics and
Innovation Project, which is working to promote the development of new
antibiotics needed to treat people suffering from serious and life-
threatening infections. Since 2000, FDA granted priority review to 4 of
the 11 new antibiotics (linezolid, daptomycin, tigecycline and
fidaxomicin) that it approved, quickly bringing much-needed treatments
for pneumonia, serious skin infections, and Clostridium difficile-
associated diarrhea to market.\1\ According to the Centers for Disease
Control and Prevention, Clostridium difficile, a bacterium that can
cause life-threatening infections, sickened 339,000 hospital patients
in 2009 and is responsible for 14,000 deaths per year.\2\
---------------------------------------------------------------------------
\1\ http://www.accessdata.fda.gov/scripts/cder/drugsatfda/.
\2\ Vital Signs: Preventing Clostridium difficile Infections. MMRW.
March 9, 2012/61(09);157-62. http://www.cdc.gov/mmwr/preview/mmwrhtml/
mm6109a3.htm?s_cid=mm6109a3_w.
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In 2002, Congress established a user fee program for medical
devices. We are asking that Congress swiftly reauthorize this program
as well.
The fees FDA collects under MDUFA provide the agency with
additional resources to review applications and add about 200 much-
needed staff members to the agency's Center for Devices and Radiologic
Health (CDRH). Under the proposed agreement, the total fees collected
over the 5-year period to 2017 are expected to reach $595 million, a
significant increase over the previous agreement. This will help create
a more efficient center that is sufficiently resourced to better
protect consumer safety and facilitate the introduction of innovative
devices.
The need for additional resources to boost the agency's capacity is
especially important at CDRH. An analysis commissioned by the Pew
Health Group examined CDRH, the Center for Biologics Evaluation and
Research, Center for Drug Evaluation and Research and the Office of
Regulatory Affairs. The report reveals that CDRH has the highest annual
attrition rate of the four centers, with nearly 10 percent of the
center's science, technology and engineering staff leaving in fiscal
year 2010. Resource issues may help explain the high attrition rates;
less than half of CDRH employees surveyed agreed that their workload is
reasonable and even fewer reported having sufficient resources to get
their job done. For it to function as efficiently and effectively as
possible, CDRH must have adequate funding.
Overall, the user fee programs have substantially sped up the
review of new drug applications. In the decade after the first user fee
agreement was passed, the median review time fell from 27.7 months to
13.8 months. Review times for drugs given priority status have also
fallen by half. Indeed, a standard review today is as fast as a
priority review a decade ago (13.9 months).\3\
---------------------------------------------------------------------------
\3\ http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/
speedingaccesstoimport
antnewtherapies/ucm128291.htm#compare.
---------------------------------------------------------------------------
Review times are important insofar as they speed patients' access
to potentially important products. The user fee agreements make review
times a performance metric. However, it is critical to remember that
true innovation is not just about getting products to market faster; it
is about developing products that are safer or more effective than
existing drugs and devices. While more challenging to measure than
review times, improving health is the ultimate goal of the FDA.
the user fee agreements give fda more resources to ensure drug safety
While user fees primarily support the review and approval of
medical products, some funds are available to partially underwrite
certain product safety activities. Five years ago, Congress created the
risk evaluation and mitigation programs, known as REMS, as a new tool
to help FDA and manufacturers manage the risks of drugs. The current
user fee agreement directs resources toward ensuring the effectiveness
of these important programs.
The new generic drug user fee agreement also contains important
safety provisions. This landmark measure will enable FDA not only to
review generic drug applications, but also to inspect overseas drug
manufacturing facilities more regularly. Eighty percent of the
ingredients in our pharmaceuticals come from foreign suppliers.\4\ Yet,
while FDA inspects American manufacturers every 2 years, it lacks the
resources to conduct effective inspections of facilities in places such
as China and India. In fact, FDA inspects overseas facilities on
average every 9 years.\5\ Addressing this disparity will help protect
patients from substandard drugs and will provide a level playing field
for generic drug makers that manufacture their products and source
their ingredients domestically.
---------------------------------------------------------------------------
\4\ U.S. Government Accountability Office (March 1998). Food and
Drug Administration: Improvements Needed in the Foreign Drug Inspection
Program (Publication No. GAO/HEHS-98-21).
\5\ U.S. Government Accountability Office (September 2010). Drug
Safety: FDA Has Conducted More Foreign Inspections and Begun to Improve
Its Information on Foreign Establishments, but More Progress Is Needed
(Publication No. GAO-10-961).
---------------------------------------------------------------------------
While GDUFA is a very important step forward in increasing drug
safety, and PDUFA funds will help evaluate certain drug safety
initiatives, we are disappointed that the draft MDUFA agreement does
not allow FDA to apply user fees to fund some important medical device
post-marketing surveillance activities. A robust post-market
surveillance infrastructure is critical to ensure the safety of these
products once they are on the market. Without adequate monitoring, it
is difficult to identify devices on the marketplace with unexpected
safety issues, which presents a threat to patient health. The user fee
agreement should recognize that creating an effective post-marketing
surveillance system is crucial to the willingness of the public and
regulators to see devices come to market quickly, with less clinical
data.
As a result, we urge Congress to allow FDA to apply user fees to
certain device safety initiatives. PDUFA already provides funding for
the agency's Sentinel Initiative, a proactive system for tracking drug
adverse events. We believe this program should be expanded to include
medical devices as well.
In closing, I would like to emphasize that as important as user
fees are to the efficient function of FDA, they cannot be a substitute
for adequate appropriated funding. User fees are not available for
critical activities such as enforcing good manufacturing practices,
most post-market safety activities, and for regulating non-drug
products, such as food, which are not covered by user fee agreements.
Furthermore, FDA is a public health agency that works to promote the
health of all Americans. Because of the public interest in a well-
performing FDA, the agency should receive public funds and be
accountable to the public, not just to the industries it regulates.
If the user fee agreements expire, patients, public health, and
industry will suffer. Given the broad support for these agreements from
Democrats, Republicans, the business community, and consumers, we urge
Congress to move quickly to pass these important bills to ensure that
FDA has continued, sustained funding to carry out and expand its
important public health mission.
Thank you and I look forward to answering any questions.
The Chairman. Thank you very much, Mr. Coukell.
To all of you, again, thanks for your testimony. I will
just take a few minutes here. I know time is progressing, but
this is must-do legislation. We are going to have to get this
done.
Around here, when there is legislation that must get
through, things start coming out of the woodwork as we say.
People have to hang something on it. They have something
vitally important, you know, that has got to be done, and since
there is no other, we will try to hang it on this. I have
already seen some of that happening when people know that this
bill must pass and has good bipartisan support.
I have heard from all of you and from FDA what would happen
if we did not pass it in time. But what I want to know is, will
your organization, each of you, I ask this of all of you, will
your organization help ensure that controversial policy
measures do not derail the user fee reauthorization package?
Sometimes we, here, need to count on all of you out there to
make sure that we keep this intact and we keep controversial
measures off of this.
Will your organization help ensure that that does not
happen? Dr. Wheadon.
Dr. Wheadon. Certainly, Chairman Harkin. We completely
agree with you. In fact, our original goal was a skinny PDUFA.
We moved to a lean PDUFA. We now recognize we have a PDUFA that
probably needs to go to Weight Watchers, but that having been
said, we stand ready to work to ensure that those additions are
kept to a minimum. And we will do our best to quickly
facilitate any additions so that you can meet your timetable.
The Chairman. Appreciate that.
Miss Radcliffe.
Ms. Radcliffe. BIO has been very committed to making sure
that controversial policy matters do not derail the PDUFA
reauthorization.
As has been mentioned here earlier this morning, it is
absolutely critical that PDUFA be reauthorized and well in
advance of its expiration in September 2012 to avoid a
reduction in force at the FDA. And even more, as I think was
mentioned this morning, even the threat of a reduction in force
at the FDA is extremely problematic for the agency, therefore
for our sponsors, and therefore for patients.
So, yes, we remain very much in agreement with you.
The Chairman. Thank you.
Mr. Gaugh.
Mr. Gaugh. To answer your question, yes.
The Chairman. Dr. Nexon.
Mr. Nexon. Ditto.
The Chairman. Ditto.
Mr. Coukell. Mr. Chairman, thank you.
I would like to thank you, the Ranking Member, and the
members of the committee for moving quickly to reauthorize
these important agreements. But also for the sustained
bipartisan work that has gone into three additional discussion
drafts that have been released or will be shortly on the drug
supply chain, on incentivizing new antibiotics, and on medical
device safety and innovation.
I think a lot of work has gone into hashing those out and
making sure they are not controversial, and it is our hope that
those will move with the reauthorization.
The Chairman. I appreciate all of that because this being a
campaign year and a lot of campaigns out there from the top
down, that I am concerned that things might try to interfere
with the passage of this legislation, not for substantive
reasons, but for political reasons.
That is why we need the industry out there, all of you who
have a stake in this, who have been involved in the drafting
and the putting of this together, and recognizing how necessary
it is that we pass it. That you will make sure that we have a
bill that has broad consensus and that we do not get involved
in controversial measures.
Senator Bennet.
Senator Bennet. Thank you, everybody, for all the work that
you have done and for your testimony today.
I hope, what I am about to raise, is not a controversial
measure. It is a complicated measure at the least, and a little
bit of a freighted questions, but I think it is an important
question to have, particularly in the context of all the
agreement that has been reached here.
As all of you know, we have seen countless tragedies
happen, tainted Heparin that made its way to patients killing
over 100 Americans. Heat-sensitive insulin that was stolen and
then redistributed to patients, millions of children's medicine
pills recalled and taken off the shelves, counterfeit Avastin
given to patients in need of chemotherapy, these issues really
do demand Congress's attention. Everybody has been talking
about having a uniform distribution system to increase the
safety of drug distribution chain for years; some of you have
talked about it for decades.
I believe that we can address the concerns and needs of the
regulated community, address concerns raised by pharmacists
about costs and provide the FDA with authority it says it needs
to implement a system effectively to protect the public health.
All of these are legitimate concerns that need to be reflected.
Pew has said before that they would like to see more effort
applied to authenticating these products so people know what
they believe they are taking corresponds to the actual products
they ingest. Right now, we can learn more from a barcode on a
gallon of milk than on a bottle of pills, pills that could be
the difference between life and death. And that just does not
seem right to people in Colorado, and I know other members of
the committee feel the same.
This is not an easy issue. Everybody has different and
legitimate concerns here whether it is the cost of
implementation, or whether it is really a meaningful system
that benefits the public health.
So my only question, this is the only one I am going to
ask, is whether there is an interest in trying to work together
to see if we can bridge this gap and create the kind of
tracking system we need, so our constituents can have
confidence in what they are ingesting.
That is for the whole panel or anybody that would like to
talk about it.
Dr. Wheadon. Certainly, Senator Bennet. Our industry has
stood ready and continues to stand ready to work with yourself,
your staff, and the many other members that are very focused
appropriately on this issue.
In terms of a system such as track and trace or a barcode,
it is important that whatever that system may be it is
uniformly adopted. It involves a number of other entities
beyond simply drug manufacturers, pharmacies, distribution
system, what have you. But that system needs to be uniform and
applicable across the entirety of the system.
Ms. Radcliffe. I would echo what Dr. Wheadon has said. It
is an issue that has been very important to BIO and its
members, and we have worked hard with the stakeholder community
to try and identify proposals that we all can stand behind.
I think we have made a tremendous amount of progress and we
certainly look forward to working on that more where there are
still some areas of disagreement, because the patchwork quilt
of requirements does not serve patients well, and it is
difficult for our members to comply with. So we do think that
that needs to be addressed.
Mr. Gaugh. Yes, to answer your question, GPhA does support
an alliance. And, in fact, is working with the PDSA, or the
Pharmaceutical Distribution Security Alliance, across multiple
stakeholders, and many of the stakeholders that you mentioned
to create a system through a serialization process. As you
said, bar coding on milk is known better and gives more
information than it does, in some cases, on the
pharmaceuticals.
So the PDSA group is working on a nationwide process, not a
State by State, but nationwide that would help resolve that and
we do support it.
Senator Bennet. Doctor, I will give you a pass unless you
want to. No.
Mr. Coukell. Senator, thank you for your leadership on this
issue, and for your work with the Chairman and the Ranking
Member.
I think consumers are surprised when they learn that we do
not now have a system that routinely checks to see if the drugs
they are about to get are counterfeit. Nor do we have a system
that is able to track the product as it moves through the
system, and a robust national system would be far preferable to
a patchwork of State laws.
Senator Bennet. Thank you.
The Chairman. I just want to say to my friend from Colorado
that I do not consider that controversial at all. We do need a
good tracking system all the way from the manufacturers
overseas, as we have said, with better inspections of those,
and a trace and track system that comes all the way down. I do
not consider that controversial.
I think most of the people here have said, and I agree with
them, that we need a national system so that we do not have
some hodgepodge of one State here, and one State there, and one
State doing this. We need a national system of tracking.
Senator Bennet. I appreciate that, Mr. Chairman. And I
think if we have the chance here, because of the good work that
is going on, to try to get through this so that we do not go
another decade, and another decade after that.
The Chairman. Absolutely.
Senator Bennet. I think that would be really welcome.
The Chairman. I look forward to working with you on that.
Senator Bennet. Thank you, Mr. Chairman.
The Chairman. Thanks.
Senator Blumenthal.
Senator Blumenthal. Thank you, Mr. Chairman.
I want to thank you and our Ranking Member, but
particularly you for your leadership in this whole area. A
difficult and certainly challenging one, particularly in this
political climate.
Mr. Coukell, if you could comment on one specific area that
you have mentioned, the development of new antibiotics, why it
is so critical, and why it should be part of this bill. As you
know, Senator Corker and I have introduced a separate measure,
which is largely incorporated in this bill, and your
organization has been absolutely instrumental and enormously
helpful and constructive in this effort.
I thank you and I invite you to comment on the need for
this measure.
Mr. Coukell. Thank you, Senator. And thank you and Senator
Corker for your work on the GAIN Act, which you referenced.
As you know well, antibiotics are unlike other drugs in a
couple of ways. A drug for high blood pressure will always be
as effective as it is today, but antibiotics will lose
effectiveness over time because the bugs will develop
resistance.
Dr. Woodcock, this morning, talked about the declining
pipeline for new drugs. That is especially acute in
antibiotics, and we have more and more resistant infections
emerging, and they tend to be small market drugs. We absolutely
agree with you that we need incentives to make this an
attractive play for companies to invest, so that we have a
continued flow of new antibiotics.
Senator Blumenthal. Thank you.
I want to ask a question for any member of the panel who
wants to comment on what you think can and should be done to
address the problem of drug shortages in this country. You
probably heard some of my comments earlier, and I could expand
on them now, but I think you got the drift of what my thinking
is, and invite you to comment.
Mr. Gaugh. From the GPhA perspective, we have been working
with the FDA on the drug shortage situation from a company, and
an FDA. As I said in my testimony, the FDA and the generic
industry has never been more collaborative than they are today.
We are, at GPhA, working on a system called Accelerated
Recovery Initiative, ARI. In fact, we have a meeting with the
FDA next week to discuss that model and how that can help
resolve some of the drug shortage issues that are occurring
today.
Senator Blumenthal. How would that happen?
Mr. Gaugh. It would work with the FDA, with the
manufacturers, through an independent third party, which would
help, we hope, at an even earlier pace to identify a drug
shortage that is occurring or about to occur. And then through
the independent third party and the FDA working with the
manufacturers separately to try to resolve the drug shortage as
it is happening, to make it a less lengthy drug shortage, or
maybe even to prevent it from happening.
Senator Blumenthal. What about preventing it from
happening? What can be done, for example, methotrexate, Doxil,
or the anesthesiology medicines?
This problem really is one, as I do not need to tell
anybody on the panel, or anybody in this room, of huge urgency
and immediacy to anybody who goes to a hospital each day,
anybody who talks to a doctor who treats patients. This is very
much on their minds, to say the least.
And I wonder whether the people in organizations like yours
share this sense of urgency?
Mr. Gaugh. Our hope and belief would be that the ARI can be
a more proactive solution to drug shortages. In today's
environment, it is pretty much a reactive. When the drug
company contacts the FDA, the FDA then goes into action to
resolve the situation. So it is a reactive. As you said,
methotrexate was one of those reactive situations.
So the ARI is our hope and our belief that working together
with the FDA and through an independent third party, we can
identify these at an earlier stage and help prevent them from
even occurring.
Senator Blumenthal. Before I conclude, anybody else on the
panel have any comments on this issue?
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Blumenthal.
Again, I thank all the panel for being here, and I thank
Dr. Woodcock and Dr. Shuren for remaining here for the duration
of this.
I request the record be kept open for 10 days for other
questions or submissions.
Again, I look forward to working with all of you to get
this legislation through in a timely manner this year.
With that, the committee will stand adjourned.
[Additional Material follows.]
ADDITIONAL MATERIAL
Prepared Statement of Senator Robert P. Casey, Jr.
Thank you to the panelists for your remarks today. I'd also
like to thank Chairman Harkin and Ranking Member Enzi for your
leadership in guiding this committee toward several substantial
and thoughtful bipartisan agreements on a variety of issues of
critical import to American patients. I am glad to have had the
opportunity to help to shape several of the agreements, and I
look forward to working with you to ensure they are included in
the upcoming Food and Drug Administration (FDA) Reauthorization
package to be considered by this committee.
I am proud to come from a State with a strong history of
leadership in medical discovery. During the past year, I have
been meeting with and working with many Pennsylvanians to bring
forward and support new proposals that will enhance rewards for
biomedical research and strengthen FDA's ability to protect
patient safety and at the same time improve access to medical
breakthroughs. I was glad to have played a role in helping to
advance bipartisan agreements in the HELP Committee to
modernize and strengthen the FDA's ability to respond, and pro-
actively address, significant public health threats such as the
unprecedented growth in prescription drug shortages, the surge
of antibiotic-resistant ``super bugs,'' and gaps in the current
FDA approval pathway with respect to novel low-to-moderate risk
medical devices.
Guaranteeing the safety and effectiveness of medical
products is a task of paramount importance to the American
public. It is also a responsibility that carries with it the
need to work diligently with critical health care industries,
such as pharmaceutical companies and medical device makers, to
drive progress in biomedical medicine and regulatory science
and help shepherd significant new cures and treatments to
patients with unmet medical needs.
Currently, the growing manufacturing, sourcing and rapid
dispersion of medical products from outside the United States
to the medicine cabinets and hospital beds of American patients
is a cause of great concern. Federal laws regulating such
activity have not been updated in decades and FDA is left
relying upon statutes from a time when the vast majority of
medicines were discovered, developed and distributed within the
United States. We cannot allow this to continue as the status
quo. Recent cases such as the counterfeit of Avastin and
Heparin showcase the life-threatening failings of our current
system.
It is crucial that, during this reauthorization, we update
our regulatory oversight and infrastructure at the FDA, and
give the FDA the appropriate authority and resources, so that
it can ensure that all products that reach American patients--
regardless of where they are made, or who distributes them--are
safe and effective. That is the public's expectation, and that
should serve as our North Star. In addition, I think that we
must not lose focus on the fact that, at the end of the day,
patients are depending on the FDA to not just review and
approve new products, but help to facilitate progress in
science and medicine that will lead to life-saving discoveries.
Historically, the FDA has done an outstanding job in
achieving all of these goals, but there is more work that
remains to be done. The onus rests on Congress to help provide
FDA with the guidance and wherewithal to meet the needs of an
increasingly diverse and aging population, and overcome the
unique challenges presented by our 21st century global economy.
Chairman Harkin and Ranking Member Enzi, I look forward to
working with you, and others on this committee, towards these
shared goals.
[Whereupon, at 12:24 p.m., the hearing was adjourned.]