[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
REVIEWING FDA'S IMPLEMENTATION OF FDASIA
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
FIRST SESSION
__________
NOVEMBER 15, 2013
__________
Serial No. 113-98
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
______
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COMMITTEE ON ENERGY AND COMMERCE
FRED UPTON, Michigan
Chairman
RALPH M. HALL, Texas HENRY A. WAXMAN, California
JOE BARTON, Texas Ranking Member
Chairman Emeritus JOHN D. DINGELL, Michigan
ED WHITFIELD, Kentucky FRANK PALLONE, Jr., New Jersey
JOHN SHIMKUS, Illinois BOBBY L. RUSH, Illinois
JOSEPH R. PITTS, Pennsylvania ANNA G. ESHOO, California
GREG WALDEN, Oregon ELIOT L. ENGEL, New York
LEE TERRY, Nebraska GENE GREEN, Texas
MIKE ROGERS, Michigan DIANA DeGETTE, Colorado
TIM MURPHY, Pennsylvania LOIS CAPPS, California
MICHAEL C. BURGESS, Texas MICHAEL F. DOYLE, Pennsylvania
MARSHA BLACKBURN, Tennessee JANICE D. SCHAKOWSKY, Illinois
Vice Chairman JIM MATHESON, Utah
PHIL GINGREY, Georgia G.K. BUTTERFIELD, North Carolina
STEVE SCALISE, Louisiana JOHN BARROW, Georgia
ROBERT E. LATTA, Ohio DORIS O. MATSUI, California
CATHY McMORRIS RODGERS, Washington DONNA M. CHRISTENSEN, Virgin
GREGG HARPER, Mississippi Islands
LEONARD LANCE, New Jersey KATHY CASTOR, Florida
BILL CASSIDY, Louisiana JOHN P. SARBANES, Maryland
BRETT GUTHRIE, Kentucky JERRY McNERNEY, California
PETE OLSON, Texas BRUCE L. BRALEY, Iowa
DAVID B. McKINLEY, West Virginia PETER WELCH, Vermont
CORY GARDNER, Colorado BEN RAY LUJAN, New Mexico
MIKE POMPEO, Kansas PAUL TONKO, New York
ADAM KINZINGER, Illinois JOHN A. YARMUTH, Kentucky
H. MORGAN GRIFFITH, Virginia
GUS M. BILIRAKIS, Florida
BILL JOHNSON, Ohio
BILLY LONG, Missouri
RENEE L. ELLMERS, North Carolina
7_____
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan
JOHN SHIMKUS, Illinois ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee JIM MATHESON, Utah
PHIL GINGREY, Georgia GENE GREEN, Texas
CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina
LEONARD LANCE, New Jersey JOHN BARROW, Georgia
BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin
BRETT GUTHRIE, Kentucky Islands
H. MORGAN GRIFFITH, Virginia KATHY CASTOR, Florida
GUS M. BILIRAKIS, Florida JOHN P. SARBANES, Maryland
RENEE L. ELLMERS, North Carolina HENRY A. WAXMAN, California (ex
JOE BARTON, Texas officio)
FRED UPTON, Michigan (ex officio)
(ii)
C O N T E N T S
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Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 2
Hon. Phil Gingrey, a Representative in Congress from the State of
Georgia, opening statement..................................... 2
Hon. Leonard Lance, a Representative in Congress from the State
of New Jersey, opening statement............................... 3
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 4
Hon. John D. Dingell, a Representative in Congress from the State
of Michigan, opening statement................................. 5
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, opening statement.................................... 5
Prepared statement........................................... 6
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, opening statement............................... 6
Witnesses
Janet Woodcock, Director, Center for Drug Evaluation and
Research, Food and Drug Administration......................... 7
Prepared statement \1\....................................... 11
Answers to submitted questions \2\........................... 61
Jeffrey E. Shuren, Director, Center for Devices and Radiological
Health, Food and Drug Administration........................... 8
Prepared statement \1\....................................... 11
Answers to submitted questions............................... 139
----------
\1\ Ms. Woodcock and Mr. Shuren submitted a joint statement for
the record.
\2\ Ms. Woodcock submitted a partial response to questions for
the record.
REVIEWING FDA'S IMPLEMENTATION OF FDASIA
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FRIDAY, NOVEMBER 15, 2013
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:02 a.m., in
room 2322, Rayburn House Office Building, Hon. Joseph R. Pitts
(chairman of the subcommittee) presiding.
Members present: Representatives Pitts, Burgess, Whitfield,
Shimkus, Rogers, Murphy, Blackburn, Gingrey, Lance, Guthrie,
Griffith, Bilirakis, Upton (ex officio), Pallone, Dingell,
Engel, Capps, Green, Butterfield, Barrow, Castor, Sarbanes, and
Waxman (ex officio).
Staff present: Clay Alspach, Chief Counsel, Health; Sean
Bonyun, Communications Director; Noelle Clemente, Press
Secretary; Brad Grantz, Policy Director, Oversight and
Investigations; Sydne Harwick, Legislative Clerk; Robert Horne,
Professional Staff Member, Health; Carly McWilliams,
Professional Staff Member, Health; Andrew Powaleny, Deputy
Press Secretary; Chris Sarley, Policy Coordinator, Environment
and the Economy; John Stone, Counsel, Oversight; Ziky Ababiya,
Democratic Staff Assistant; Eric Flamm, Democratic FDA
Detailee; Karen Nelson, Democratic Deputy Committee Staff
Director for Health; Rachel Sher, Democratic Senior Counsel;
and Ryan Skukowski, Democratic Staff Assistant.
Mr. Pitts. The subcommittee will come to order. The Chair
will recognize himself for an opening statement.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
The Food and Drug Administration Safety and Innovation Act,
FDASIA, was signed into law on July 9th, 2012. The purpose of
the bill was to bring predictability, consistency, and
transparency to FDA's regulation of drugs and devices. To that
end, FDASIA reauthorized two successful user fee programs, the
Prescription Drug User Fee Act, PDUFA, and the Medical Device
User Fee Act, MDUFA, scheduled to expire at the end of fiscal
year 2013. It also authorized two new user fee programs, for
generic drugs, GDUFA, and biosimilars, BSUFA. In each case the
industry negotiated a level of user fees to be paid to FDA in
return for the agency meeting agreed-upon performance and
accountability metrics.
Additionally, FDASIA permanently reauthorized the Best
Pharmaceuticals for Children Act and the Pediatric Research
Equity Act; reformed both the drug and medical device
regulatory processes; addressed drug supply chain and drug
shortage issues; and incentivized the development of new
antibiotic drugs, among other provisions. The bill represents a
bipartisan success not only for our committee, but for Congress
as a whole. It passed the House by a voice vote and passed the
Senate by a vote of 92-4.
Now, over a year later, we are here to examine whether the
law has been a success for the American people, resulting in
safer drugs and devices, faster approval times, and more
consistency and predictability in the process. There is great
congressional interest, not only in the overall implementation
of FDASIA, but also in the day-to-day operational challenges
and successes. And I would like to congratulate Dr. Woodcock
for what I understand is significant progress in the Center for
Drug Evaluation and Research.
I would like to welcome both Dr. Janet Woodcock and Dr.
Jeffrey Shuren to the subcommittee. I look forward to hearing
their testimony. And I yield 1 minute to Dr. Gingrey.
[The prepared statement of Mr. Pitts follows:]
Prepared statement of Hon. Joseph R. Pitts
The subcommittee will come to order.
The Chair will recognize himself for an opening statement.
The Food and Drug Administration Safety and Innovation Act
(FDASIA) was signed into law on July 9, 2012.
The purpose of the bill was to bring predictability,
consistency, and transparency to FDA's regulation of drugs and
devices.
To that end, FDASIA reauthorized two successful user fee
programs, the Prescription Drug User Fee Act (PDUFA) and the
Medical Device User Fee Act (MDUFA), scheduled to expire at the
end of fiscal year 2013.
It also authorized two new user fee programs for generic
drugs (GDUFA) and biosimilars (BSUFA).
In each case, industry negotiated a level of user fees to
be paid to FDA in return for the Agency meeting agreed upon
performance and accountability metrics.
Additionally, FDASIA permanently reauthorized the Best
Pharmaceuticals for Children Act and the Pediatric Research
Equity Act, reformed both the drug and medical device
regulatory processes, addressed drug supply chain and drug
shortage issues, and incentivized the development of new
antibiotic drugs, among other provisions.
The bill represents a bipartisan success, not only for our
committee, but for Congress as a whole. It passed the House by
voice vote and passed the Senate by a vote 92 to 4.
Now, over a year later, we are here to examine whether the
law has been a success for the American people, resulting in
safer drugs and devices, faster approval times, and more
consistency and predictability in the process.
There is great Congressional interest not only in the
overall implementation of FDASIA, but also in the day-to-day
operational challenges and successes. And, I would like to
congratulate Dr. Woodcock for what I understand is significant
progress in the Center for Drug Evaluation and Research.
I would like to welcome both Dr. Janet Woodcock and Dr.
Jeffrey Shuren to the subcommittee.
OPENING STATEMENT OF HON. PHIL GINGREY, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF GEORGIA
Mr. Gingrey. Mr. Chairman, thank you very much for
yielding. I, too, am pleased to see Dr. Woodcock and Dr. Shuren
again today. FDASIA looked to address the crisis of antibiotic
resistance with Title VIII, the GAIN Act, which I wrote with my
colleagues Mr. Green, Mr. Shimkus, Ms. DeGette, Mr. Whitfield,
and Ms. Eshoo.
By focusing on incentives to bring new drugs to market we
have seen renewed focus on the development of cutting-edge
drugs, antibiotic. However, even with the early success of this
program, I do believe that we do need to do more.
And so, Mr. Chairman, CDC had a September report, CDC in my
great capital center of Atlanta, Georgia, on antimicrobial
resistance, highlights 18 known resistance threats. It is
estimated that across the country more than 2 million people
are sickened every year with antibiotic-resistance infections
resulting in at least 23,000 deaths--23,000 deaths.
I look forward to continuing to work with the FDA to create
innovative pathways and processes. We must make sure that the
agency and drug developers have as many tools as possible to
navigate this emerging public health problem.
And I yield back.
Mr. Pitts. The Chair thanks the gentleman.
And now yields the balance of time to Mr. Lance.
OPENING STATEMENT OF HON. LEONARD LANCE, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Lance. Thank you, Mr. Chairman.
Today's hearing serves as a helpful pulse check of the
FDA's implementation of the user fee agreements for the
prescription drug, medical device, generic, and biosimilars
industry signed into law last year. In New Jersey alone the
life sciences support over 300,000 direct and indirect jobs and
contributes more than $25 billion to the State's economy.
Historically the user fee agreements have improved the
times of drug and devices, and today's hearing will help this
committee gain further insight on how the FDA is carrying out
these congressionally mandated responsibilities. It is
important that regardless of the challenges the agency faces it
remain committed to bringing innovative treatments to market
and in the hands of patients who need them the most.
Thank you, Mr. Chairman. I look forward to hearing from our
distinguished witnesses, Dr. Woodcock and Dr. Shuren, on these
issues. And I yield back to you, sir.
Mr. Pitts. The Chair thanks the gentleman.
Now yields 5 minutes to the ranking member, Mr. Pallone,
for an opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairman Pitts.
And thank you to our witnesses for being here today. I am
eager to hear your testimony about FDA's progress in
implementing the Food and Drug Administration Safety and
Innovation Act, or FDASIA.
Over 1 year ago, FDASIA was signed into law and, among
other things, was designed to promote timely FDA review of
drugs, medical devices, generic drugs, and biosimilar
biological products through the collection of user fees. It
both renewed existing FDA user fee programs for pharmaceutical
and medical device manufacturers and established new user fee
programs for generic drugs and for lower cost versions of
biotech drugs.
The user fees are an essential component of FDA's funding.
They help to ensure a predictable and efficient review process
so that the American public has access to safe and effective
healthcare products.
For generics, at the time of enactment there was a backlog
of over 2,500 applications for new generic drugs and a median
review time of 31 months. These essential products typically
cost 50 to 70 percent less than their brand name counterparts
and have provided an estimated $1 trillion in savings to the
Nation's healthcare system over the past decade. It is
important that American consumers have access to these safe,
effective, and low cost alternatives more quickly, which is why
the provisions in the generic drug user fee agreement were so
important, because it gave FDA the resources they need to make
sure that happens. So I am interested to hear in that progress
today.
FDASIA also gives FDA additional tools to ensure the safety
of the global drug supply chain, such as requiring registration
with the unique facility identifier for foreign and domestic
drug establishments, administrative detention for adulterated
or misbranded drugs, and increased penalties for counterfeit
drugs. The additional authorities in FDASIA allow FDA to
strengthen cooperation with foreign regulators as well.
These provisions were based on the ideas and proposals
contained in the Drug Safety Enhancement Act, which I
introduced with Mr. Dingell, Mr. Waxman, and Ms. DeGette. We
worked hard with our Republican colleagues during consideration
of this law to help FDA keep our medicines safer in this
complex and ever-growing global supply chain.
We also included provisions in FDASIA to address drug
shortages. FDASIA enhances early notification of supply
interruptions for certain medically important drugs and directs
FDA to establish a task force and submit a strategic plan on
drug shortage mitigation, which FDA submitted to Congress last
month. Early notification started as a result of an executive
order in 2011 and was codified into law by FDASIA, and it has
helped FDA to prevent shortages and to decrease the number of
new shortages.
I will close by saying that FDASIA is the product of strong
bipartisan collaboration and compromise that strengthens FDA's
ability to safeguard the public health. What I outlined here
today was only a snapshot of the promising provisions of the
law. We strengthened both the agency and the public health by
its passage while allowing companies to innovate in the
process. And I am proud of the work we did in passing FDASIA,
and I look forward to hearing about FDA's progress so far in
implementing this law.
So I would like to yield the remainder of my time to Mr.
Dingell.
OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Dingell. I thank my good friend for that.
This legislation is a fine example of the great work this
committee can do when we put politics aside and work together
in a bipartisan manner. I hope the committee will return to
this spirit when considering a lot of other issues that will
lie before us today and in following times.
One year ago, President Obama signed the Food and Drug
Administration Safety and Innovation Act into law, the law
[audio gap] user fee programs FAD. Big bold steps to improve
supply chain safety, amongst other things. FDA now needs new
innovative tools to deal with increasingly globalized supply
chain [audio gap] succeed in their mission keeping the American
people safe from harm from food, drugs, cosmetics, and other
things.
I look forward to hearing from our witnesses today about
the progress made by FDA and I commend you for having this
hearing, and look forward to hearing from Food and Drug about
what it is they are doing, how the matter is proceeding and how
much more this committee must do to see to it that they are
able to carry out their responsibilities.
Dr. Woodcock, welcome.
I yield back to my good friend Mr. Pallone the time that he
so graciously yielded to me.
Mr. Pallone. I yield back the balance of my time.
Mr. Pitts. The Chair thanks the gentleman.
Now recognize the chair of the full committee, Mr. Upton, 5
minutes for an opening statement.
OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Upton. Well, thank you again, Mr. Chairman. And I
appreciate this morning's hearing on the implementation of the
FDA Safety and Innovation Act.
You know, as many of us know, this was one of the
committee's most significant bipartisan achievements in the
last Congress, it really was. I particularly want to thank Dr.
Woodcock, who is with us, and Dr. Shuren for coming today to
provide an update on that implementation, something that we
said we would do when it passed.
Last Congress this committee held at least 10 hearings on
subjects related to the legislation, and at these hearings we
focused on improving the predictability, consistency, and
transparency of FDA's regulations of drugs and medical devices.
Improving FDA regs is essential to fostering innovation which
brings life-saving and life-improving drugs and medical devices
to American patients and boosts job creation across the
country, including southwest Michigan, most importantly.
I was very proud of the bipartisan work that we did in the
last Congress, and I am pleased to hear that initial reports on
implementation, especially at the Drug Center, are promising.
Today is an opportunity to get an update on whether the FDA is
meeting its commitments related to the various user fees that
we authorized, as well as the independent assessment of the
device center.
It also is a chance to hear about how the FDA is
implementing provisions related to rare diseases, drug
shortages, an important provision that we wrote in,
prescription drug abuse, and drug imports. These were
provisions important to Republicans and Democrats, Americans
across the country, and we look forward to working with the FDA
on these issues. Our drug and device makers are global leaders
in innovation and job growth, and we will continue working to
ensure that they remain on top.
And I am prepared to yield to any of my Republican
colleagues. Seeing none, I yield back the balance of my time.
[The prepared statement of Mr. Upton follows:]
Prepared statement of Hon. Fred Upton
Mr. Chairman, thank you for holding today's hearing on the
implementation of the Food and Drug Administration Safety and
Innovation Act. As many of you know, this was one of the
committee's significant bipartisan achievements last Congress,
and I thank Dr. Woodcock and Dr. Shuren for coming today to
provide an update on implementation.
Last Congress, the committee held at least 10 hearings on
subjects related to thelegislation. At these hearings, we
focused on improving the predictability, consistency and
transparency of FDA's regulation of drugs and medical devices.
Improving FDA regulation is essential to fostering innovation,
which brings lifesaving, life-improving drugs and medical
devices to American patients and boosts job creation across the
country, including southwest Michigan.
I am very proud of the bipartisan work we did last
Congress, and I am pleased to hear that initial reports on
implementation, especially at the Drug Center, are promising.
Today is an opportunity to get an update on whether FDA is
meeting its commitments related to the various user fees we
reauthorized, as well as the independent assessment of the
device center. It also is a chance to hear about how FDA is
implementing provisions related to rare diseases, drug
shortages, prescription drug abuse, and drug imports. These
were provisions important to Republicans and Democrats, and we
look forward to working with FDA on these issues. Our drug and
device makers are global leaders in innovation and job growth,
and we will continue working to ensure that they remain on top.
Mr. Pitts. The Chair thanks the gentleman.
Now recognize the ranking member of the full committee, Mr.
Waxman, 5 minutes for an opening statement.
OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Mr. Waxman. Thank you, Mr. Chairman. I am pleased we are
holding this oversight hearing on the legislation that we
passed last year on a bipartisan basis, bipartisan, bicameral,
and with the close working relationship with the Food and Drug
Administration.
The bill had a number of important provisions. It
reauthorized FDA's drug and medical device user fees programs,
providing resources to enable the efficient review of
applications and give patients access rapidly to new therapies.
It reauthorized two pediatric programs which foster the
development and safe use of prescription for children.
Established two new user fee programs to help FDA speed up the
review of new generics and biosimilars. It gave FDA new
authorities to address a wide array of issues with respect to
drugs and devices, new incentives for the development of
antibiotics to treat serious and life-threatening infections.
This was designed to ensure that the drugs we most need to
protect us from dangerous resistant pathogens are the ones that
are developed as quickly as possible.
This law also includes provisions to modernize FDA's
authorities with respect to our increasingly globalized drug
supply chain. Today 80 percent of the active ingredients in
bulk chemicals used in U.S. drugs come from abroad and 40
percent of finished drugs are manufactured abroad. This law
gave FDA new and improved tools to police today's dramatically
different marketplace. The legislation addressed the crisis of
drug shortages that has caused many problems for access to
medicines in our country.
There are provisions relating to medical devices. I had
some concerns about many of the device proposals, but we worked
together to address these concerns with the goal of assuring
that nothing in the House-passed bill took us backwards in
terms of patient safety. And I hope Dr. Shuren will tell us
today whether we succeeded in that goal or if there have been
unintended and detrimental facts of this legislation.
Mr. Chairman, I thank you for holding this hearing. It is
an important part of the job of Congress not just to work
together to pass legislation, but to continue our review and
oversight. I hope FDA will share with us whether there are any
refinements or improvements to any of the law's provisions that
we need to pass through the Congress. Our goal was and still is
to ensure that the American public benefits from this
legislation by getting access to safe and effective drugs and
medical devices at the earliest possible time. I look forward
to the testimony.
I do notice that I do have a couple of minutes left and if
any member on our side of the aisle wants that time I would be
happy to yield to them. And if not, I will offer the time to
anybody on the other side of the aisle who wants to make any
further comments. If not, I yield back the time.
Mr. Pitts. The gentleman yields back. Chair thanks the
gentleman.
That concludes the opening statements.
On our panel today we have two witnesses from the U.S. Food
and Drug Administration, Dr. Janet Woodcock, Director of the
Center for Drug Evaluation and Research, and Dr. Jeffrey
Shuren, Director of the Center for Devices and Radiological
Health.
Thank you for coming. Your written testimony will be made a
part of the record. We ask that you summarize your opening
statements to 5 minutes. And at this time the Chair recognizes
Dr. Woodcock for 5 minutes for an opening statement.
STATEMENTS OF JANET WOODCOCK, DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION; AND
JEFFREY E. SHUREN, DIRECTOR, CENTER FOR DEVICES AND
RADIOLOGICAL HEALTH, FOOD AND DRUG ADMINISTRATION
STATEMENT OF JANET WOODCOCK
Ms. Woodcock. Thank you and good morning. I am Janet
Woodcock, head of the center for drugs at FDA.
The FDASIA legislation was really landmark legislation for
drug regulation. It authorized two new user fee programs, one
of which was critically needed to fix a problem, the problem of
the backlog of generic drugs, a program that had become
burdened by its own success and the massive filing of new
generic drug applications that we had. And another one, which
is more or less preventive, the biosimilars user fee program,
hopefully will help us promptly review biosimilar drugs and get
them on the market as we receive applications.
It also made two pediatric pieces of legislation permanent.
And I am happy to say we passed a landmark of 500 labels that
have been revised and updated with pediatric information
because of this legislation. So 500 drug labels have
information now for children that didn't before.
Additional pressing problems that were addressed included
the lack of new pipeline for antibiotics, particularly for
drug-resistant organisms, the drug shortage problem, and the
supply chain safety issues. In addition, the legislation
included a breakthrough designation program that has been very
enthusiastically taken up, both by the industry and by the FDA,
and many other provisions of course.
Congress laid out a very ambitious agenda and timeframe for
our accomplishment of all of this, and we have been working
hard, we have been very successful in implementing provisions.
However, I brought our spreadsheet. This is two-sided, OK,
tracking of all the obligations that we have under this
legislation. And this isn't all of them, but it is certainly
the ones that have hard deadlines. So we are trying to work
against all these deadlines and make all of our timeframes and
so forth.
I am happy to discuss this year's progress with you, and I
look forward to working with the committee. Thank you.
Mr. Pitts. The Chair thanks the gentlelady.
Dr. Shuren, you are recognized 5 minutes for an opening
statement.
STATEMENT OF JEFFREY E. SHUREN
Mr. Shuren. Thank you. Mr. Chairman and members of the
subcommittee, I am Dr. Jeff Shuren, Director, Center for
Devices and Radiological Health, or CDRH, at the Food and Drug
Administration.
FDASIA includes a third authorization of the Medical Device
User Fee Act, or MDUFA III. Reauthorization of the medical
device user fee program has helped to speed innovative new
products to market without compromising safety and
effectiveness. It did so by establishing new policies,
procedures, and performance goals, and by boosting review
capacity. It represents our commitment to increase the
predictability, consistency, and clarity of our regulatory
processes.
In exchange for the additional user fees, we work with
stakeholders to develop much enhanced performance goals. We are
committed to meeting those goals, and preliminary data
indicates that we are on track to meet or exceed all of our
fiscal year 2013 performance goals, and that includes a new
shared goal with industry of average time to decision.
Since the early 2000s, CDRH's performance on several key
measures had been steadily declining each year, reaching its
lowest point in 2010. In 2010 we conducted an extensive
assessment of our premarket programs, identified the problems,
proposed solutions, sought extensive public input, and then
issued a plan of action in January 2011, with some corrective
action starting in 2010. Since 2010, due to the reforms we put
in place in MDUFA III, we have seen improvement in these key
measures. For example, our backlogs of 510(k) submissions and
PMA applications are each down by about one-third. Our average
total time to decision of PMA applications is down 37 percent.
The percent of 510(k)s cleared and percent of PMAs approved are
back up, in the case of PMAs back to where it was about a
decade ago.
To provide greater transparency we are would providing
substantially more detailed reporting on our progress in
implementing performance goals. These reports are publicly
available online and are discussed at quarterly meetings with
industry.
FDASIA also includes provisions to streamline the de novo
pathway for novel devices of low to moderate risk. Since
passage of FDASIA, we have seen the number of de novo requests
roughly double. We have also implemented process improvements
and are seeing our review times for de novos trending downward
as a result. As part of our MDUFA III commitments we agreed to
implement our benefit-risk determination guidance we issued in
March 2012. For the very first time and with public input we
described the factors we would use in determining whether or
not the benefits of the device outweigh its risk.
The framework we developed is flexible and patient-centric.
For example, one factor we may take into account is patients'
tolerance for risk and perspectives on benefits. Because
patient viewpoints matter and to further implementation of the
framework, earlier this year we launched our Patient
Preferences Initiative. The initiative seeks to identify and
validate tools for assessing patient preferences, establish an
approach when incorporating those preferences into our device
approval decisions, and then communicating that information
publicly so that patients and practitioners can make better-
informed decisions.
CDRH implemented the FDASIA provisions relating to
investigational device exemptions, or IDEs. We have trained our
staff and modified our decision letters to align them with
FDASIA's requirement that FDA may not disapprove the clinical
investigation on the basis that it would not support approving
the device.
We have also taken several steps to facilitate first-in-
human studies in the U.S. and to streamline our clinical trials
program. As a result, the mean time for giving approval for
manufactures to proceed with clinical studies of their devices
has been cut almost in half.
We also recently announced a final rule for unique device
identification, or UDI system, which will provide a
standardized way to identify medical devices. The UDI reflects
substantial input from the clinical community and from the
device industry during all phases of its development. Once
fully implemented the UDI system will provide improved
visibility for devices as they move through the distribution
change to the point of patient use, greatly enhancing our post-
market surveillance capabilities and offering a way of
documenting device use in electronic health records. We have
also made good progress on classifying the remaining pre-
amendment devices. Since passage of FDASIA we have issued 13
proposed orders.
Implementing the device-related provisions of FDASIA is a
massive undertaking, but we are committed to doing it in a way
that provides lasting improvement to public health. Mr.
Chairman, I commend the subcommittee's efforts and am pleased
to answer any questions.
[The prepared statement of Ms. Woodcock and Mr. Shuren
follows:]
[GRAPHIC] [TIFF OMITTED]
Mr. Pitts. The Chair thanks the gentleman. That concludes
the opening statements. We will now begin questioning. I will
recognize myself 5 minutes.
Before I begin, Dr. Woodcock, would you submit that
spreadsheet for the record?
Ms. Woodcock. I will confer with my folks and see what I
can send you. We definitely will give you something.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. All right. And I have a number of questions for
both of you that I will submit for the record. Would appreciate
that you respond promptly.
Dr. Woodcock, we enacted FDASIA in order to bring greater
predictability, consistency, and transparency to FDA's
regulation of medical devices and drugs. FDASIA included some
significant changes to the review process on the device and
drug side. How have you translated the FDASIA policy changes
into the regulatory review process? And how have you
communicated these changes to your staff? How are you ensuring
that your staff implements the law correctly?
Dr. Woodcock, you want to begin?
Ms. Woodcock. Well, some of the primary changes that we
received, we negotiated with the industry under the PDUFA
agreements for a new review program for new molecular entities.
They are the most innovative drugs. We are now having midcycle
meetings during the review process. So this mainly changes how
we run the review process, allows for more communication
between industry and the review staff during the review
process. And it is hoped we can clear up any confusion, answer
questions and so forth, and get to a complete response that
includes all the issues at the end of the day.
So we are running that as a pilot. We are going have an
independent assessment of that. We have had a number of new
molecular entities that have been approved. I believe six have
been approved that have gone through that program. So it is in
its early stages, though, because we are going to run several
years of the program and then evaluate its success.
And the other major change, of course, has been the
breakthrough designation program, and I could talk about that
if you want. So we have received almost up to 100 applications
for designation under this program. We have designated more
than 25 different products for a range of different diseases as
potential breakthrough products. And we have just approved two,
one last week and one on Wednesday. On Wednesday we approved a
drug for mantle cell lymphoma, which is a rare kind of immune
system or blood tumor.
So we feel this program has been fairly successful so far
in bringing greater attention to drugs that are potential game
changers for people with serious diseases.
Mr. Pitts. All right. Thank you.
Dr. Shuren, under MDUFA III industry and the FDA agreed to
have an independent two-phase assessment and program evaluation
to objectively assess the FDA's premarket review process. Can
you explain how FDA was involved in setting the parameters of
this assessment?
Mr. Shuren. Certainly. We have put out calls for an
independent contractor to perform the work, and that was
assigned to--oh, my apologies.
We have put out a call to have an independent contractor
perform the assessment, and Booz Allen Hamilton is that
contractor. We worked on a draft statement of work which we put
out to the public for comment. We had discussions with industry
on what should go into that statement of work.
And then finally we have been overseeing the process for
the contractor. We get updates on the progress they make. But
it is independent, so we don't know what they are actually
going to report to us. Our understanding is they have gone out,
they have had conversations with stakeholders, particularly
industry, they have conducted focus groups. And we are
expecting to get their first report very soon, and we have a
public commitment to make that available to the public in
December, which we will do. And that first phase includes their
at this point preliminary findings, a lot of their more of the
low-hanging fruit. Six months thereafter, so in May, they will
have the second phase, where we will get all of their
recommendations. At that point, too, we have a public
commitment to issue our plan for implementation of the
recommendations.
Mr. Pitts. Would you agree to submit a detailed accounting
of the agency's involvement with the contractor relating to the
review and any recommendations or directions you provided them?
Mr. Shuren. Yes, we can provide you with information.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. And would you agree to submit a compiled list of
recommendations in its entirety to the committee upon its
completion?
Mr. Shuren. We are going to make it available to the entire
public.
Mr. Pitts. OK.
Mr. Shuren. But we will include you on that, too.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. All right.
Dr. Woodcock, the President's Council of Advisors on
Science and Technology's September 12th report included
specific recommendations on how the Federal Government might
propel innovation in drug discovery and development. PCAST
expressly recommended, quote, ``It could be valuable for the
Congress to establish that encouraging innovation and drug
development is a clear component of the FDA mission,'' end
quote.
Do you agree with the President's advisors that including
innovation in the mission statement would be valuable?
Ms. Woodcock. Well, I think it is a double-edged sword. We
don't encourage innovation for innovation's sake. OK?
Innovation can end up being bad as well as being good, right?
But innovation is essential to treat current unmet medical
needs. So absolutely we should foster innovation and be open to
it and allow new methods of both treating patients and
manufacturing drugs to have progress. So I think it is really
how you state that support for innovation that is important.
Mr. Pitts. All right. My time has expired.
The Chair recognize the ranking member, Mr. Pallone, 5
minutes for questions.
Mr. Pallone. Thank you, Mr. Chairman.
My questions of Dr. Woodcock--first, welcome back. I can
guess you have had quite a busy year. And I wanted to start
today talking about the new Office of Generic Drugs. I was glad
to see the decision FDA made last year to elevate the Office of
Generic Drugs to a ``super office'' on equal footing with the
Office of New Drugs within the agency. And as you know, I
introduced a bill last year that included a provision to do
just that and I have long been an advocate for the structural
change within FDA to enhance the role of the Office of Generic
Drugs.
I would like to ask you, Dr. Woodcock, whether the Office
of Generic Drugs has officially been set up in its new elevated
position? And how is it structured? What kinds of changes have
been made? And when do you expect the change to be finalized?
Ms. Woodcock. The organizational change has been not
finalized. We are in the final stages of that, and I hope it
would occur very soon. What it will do is recognize the fact
that generic medicines treat most people in the United States.
Eighty-four percent of dispensed prescriptions are for generic
drugs. And so the new generic drug office will have a much more
clinical focus. We will have more doctors there, more clinical
staff, very much focused on therapeutic equivalents, the
adverse event reporting, making sure those generic drug labels
are up to date and so forth.
So as a super office it is proposed to have a
bioequivalence office, a research office, because under GDUFA
we negotiated and received money so that we can do research to
get new categories of drugs like inhalers to become generics,
right? So they have a research office and then an office that
will run the operations, including a clinical safety staff.
Now, as part of this, what we are proposing, though, is
that quality regulation, drug quality regulation be reorganized
and that we centralize that, and that is a plan that I am
working very intimately on. And this would ensure that generic
drugs, new drugs, over-the-counter drugs, any kind of drug we
regulate have the exact same quality expectations across the
industry.
Mr. Pallone. OK. Then I wanted to speak about the FDA's
progress in implementing GDUFA. I commend the FDA on meeting
its GDUFA hiring goals for the fiscal year, and I know the
difficulties associated with implementing a brand-new program.
But how many FTEs have you hired to date and how many do you
plan to hire in the first two quarters of next year? And given
the backlog of pending ANDAs, can you give the committee an
estimate on how many of these new hires will be dedicated to
ANDA review? I have others, but let's start with that.
Ms. Woodcock. OK. We have hired upward of 300 people. I
mean, that number changes every day. We are aggressively
hiring. And we exceeded our GDUFA goal, which was 25 percent of
the total number of people that were to be hired. OK?
We have acted on 900, I think, of ANDAs in the backlog in
different ways, so we have reduced that pending backlog, but it
is still formidable. I wouldn't diminish that. And we have done
a lot of things to try and aggressively address this backlog.
So your other question?
Mr. Pallone. Well, I was going to ask you if the government
shutdown affected the progress for those 2 or 3 weeks?
Ms. Woodcock. Well, the major effect on our review
programs, because we were able to continue to operate under the
user fees. However, the inspections stopped for those several
weeks. So the inspectional programs were not operating. And of
course that is one of the things that we really need to ramp up
under GDUFA, is to increase the number of facility inspections
that we do if we are going to tackle this backlog and get into
a steady state.
Mr. Pallone. And the last thing, it is my understanding
that FDA recently advised sponsors that it has restricted
communications with sponsors during the ANDA process.
Specifically, rather than providing ongoing status updates, the
FDA has a new policy of only providing approval answers. Can
you explain the reasoning behind this, why you feel the need to
have less communications than before, given that we have the
user fee funds available?
Ms. Woodcock. We have upward of 8,000 items pending in the
generic drug review program. The previous practice was
companies would call all over the place to try to find their
status. If every chemist and bioequivalence reviewer is
answering questions from 8,000 different sites asking them what
is the status, we are never going to get done.
So we are trying to bring order to this process, like we
have for PDUFA, and what we want to do is have predictable
deadlines so that every company knows their application is on
track and going to get out of the agency and they are going to
get a complete response within the timeframe that has been
established under GDUFA.
So I think some of this is a transition issue where we are
going from one state to another and we are going to have to get
through this period. We are doing everything we can and we are
considering additional steps to notify industry as their
application approaches an action so that they can prepare, say,
for launch or whatever they need to prepare for. We understand
that need. However, we can't have companies' thousands of calls
to reviewers or we are not going to get this program done.
Mr. Pallone. All right, thanks a lot.
Mr. Pitts. The Chair thanks the gentleman.
We are presently voting on the floor. We will try to get
through a couple more members. The Chair recognize Mr.
Whitfield for 5 minutes for questions.
Mr. Whitfield. Well, thank you very much, and thank you all
for joining us this morning.
Last April I attended a meeting with a group of
dermatologists and they were talking about the approval process
for over-the-counter in general and sunscreen in particular.
And they had indicated that there were, like, eight sunscreen
applications that had been at FDA waiting for a decision for,
like, 10 years. Some of these have been used in Europe.
We all are very much aware that you all have a very heavy
workload and you have limited resources. And I know in
conversations with Congressman Dingell, and I know on the
Senate side Senators Reid and Isakson have been discussing this
issue, and Congressman Dingell and I have draft legislation to
try to expedite the process and we had submitted to you all for
technical assistance. And I was going to ask, one, are you,
with the multitude of issues you deal with, are you even aware
of legislation that we have submitted? And if you are, could
you give us any idea of maybe when we could expect a response
from you?
Ms. Woodcock. We hope you would get a prompt response.
Mr. Whitfield. OK.
Ms. Woodcock. This is a very intractable problem. I think,
if possible, we are more frustrated than the manufacturers and
you all are about this situation. We have to do regulations to
get these ingredients into the monographs. That is the problem.
And they are backlogged and they are slow to get through, and
we have to do a proposed regulation, sometimes we have to do
advanced notice of proposed regulation, then do a proposed
rule, and then do a final rule, which can take 6 to 8 years.
And we have multiple categories of these over-the-counter
products that we have to handle. But the sunscreens, there is a
public health issue here.
Mr. Whitfield. Right. And who on your staff specifically
can we be in contact with on the technical assistance?
Ms. Woodcock. Well, I think that our lead in this is Dr.
Sandra Kweder, who is acting head right now of the office that
oversees this, but, of course, work through our legislative
staff and we will provide any assistance needed.
Mr. Whitfield. OK.
Mr. Dingell. Would the gentleman yield?
Mr. Whitfield. I would be happy to yield.
Mr. Dingell. Briefly. First of all, I want to thank the
gentleman. Second of all, I want to commend him. And third of
all, I want to note that this is important. This matter has
been dawdling by prodigious overlong delay, and it has simply
got to come to a halt. Your assistance would be extremely
important. I want to work with my good friend. And I urge you
to resolve this problem. It is a significant problem that does
do the Food and Drug Administration no credit whatsoever.
Mr. Whitfield. I yield back the balance of my time.
Mr. Pitts. The Chair thanks the gentleman.
I think we can get one more in. We will reconvene shortly
after the second vote. There are two votes. That will be about
11 o'clock. The Chair recognize the gentleman, Mr. Dingell, 5
minutes for questions.
Mr. Dingell. Mr. Chairman, I would like to defer. I move
rather slowly.
Mr. Pitts. All right. Then we will at this point recess the
committee until after the second vote, and hope you will be
patient with us. We will get back as soon as we can. Thank you.
The committee is in recess.
[Recess.]
Mr. Pitts. The time for our recess having expired, the
subcommittee will reconvene. And the Chair recognize the
gentleman from Texas, Mr. Green, for 5 minutes for questions.
Mr. Green. Thank you, Mr. Chairman, for holding the
hearing.
And, Dr. Woodcock and Dr. Shuren, thank you for taking time
to be here today.
One of my top priorities is fostering a regulatory
environment that would promote the development of the new
antibiotic drugs to address the growing public health threat of
drug-resistant bacteria. I am proud to have worked with leaders
on this committee, Dr. Gingrey and a coalition of other
members, to advance the GAIN Act last year. We have always said
that this was a good first step, but more must be done. And I
know from your testimony today that is true. Thank you for your
leadership on the GAIN Act, Dr. Woodcock, and also promoting
the new antibiotic development.
In April, CDC released a report on drug-resistant bacteria.
In that report, CDC states that antimicrobial resistance is one
of the most serious health threats to our country. Dr.
Woodcock, does the FDA agree with the CDC on the nature of this
threat?
Ms. Woodcock. Absolutely. We are very concerned about this.
Mr. Green. In this report, the CDC highlights a handful of
strategies to address this threat. One of the main methods they
suggested was to develop new antibiotics. As I understand it,
part of the challenge of the new developing antibiotics is that
drug resistance oftentimes begins in limited populations and
approving a drug through the FDA for use in a limited
population can be difficult.
Dr. Woodcock, on June 4th of this year you were quoted by
the National Public Radio as saying that you hope Congress
would pass legislation soon to make it easier for FDA to
approve new antibiotics. What type of legislation were you
referring to when you made those statements on NPR?
Ms. Woodcock. Well, there have been discussions, and the
PCAST report referred to earlier--I am sorry. There have been
discussions, and the PCAST report referred to earlier have
talked about a program for limited use that is specifically
directed where there is subpopulation of broader population.
Because one of the problems we have with the antibiotics, as
you well know, is overuse. And what we are concerned about if
we approve an antibiotic for a limited use, just for drug-
resistant organisms, that there would be temptation to use it
more broadly and thus lose its effectiveness. And so we feel
that it should be explored that Congress could make some kind
of program that would really send a signal about limited use
and then good antibiotic stewardship.
Mr. Green. Well, I am working on legislation with my
colleague Dr. Gingrey, and meant to be the next step from GAIN,
focused primarily on promoting antibiotics meant to be used in
limited populations. Is there anything that you believe we
should keep in mind as we draft this legislation?
Ms. Woodcock. Well, I feel that a strong signal from
Congress to the healthcare community about stewardship would be
extremely important. FDA frequently approves drugs for limited
populations, but usually there isn't that sort of, let's say,
an orphan population, there isn't that sort of temptation or
ability to use it broadly in a much broader population.
So one of the main things is a signal from Congress that it
is fine to do limited populations out of a broader disease with
a very small development program, but then there should be that
stewardship by the healthcare community to not use it more
broadly.
Mr. Green. Well, and I know if you deal with any of the
infectious disease specialties, they talk about that. And can
we statutorily, because I know in medical practice a doctor can
make that decision on their own, and that may be part of the
problem. But you can't limit it to just, for example, people
who deal with infectious diseases, I guess.
Ms. Woodcock. We feel that there shouldn't be an overt
limitation like that, because it is not feasible. Patients come
in, they have infections, there is a resistant strain
circulating in the community, doctors should have the
discretion to use appropriate antibiotics. However, I think a
signal of prudence and stewardship would be a mechanism I think
would be very effective.
Mr. Green. And I am almost out of time, but the other issue
on that is we need to make sure we keep this, because what may
be successful a year from now or 10 years from now, we will
still have people who develop those resistance, so we need to
keep that pipeline going for these new levels of antibiotics
and other ways to treat these terrible illnesses.
As health care gets more advanced and threats to our health
get more complicated, it is important that both Congress and
the FDA be responsive to this changing world. Many of the
processes at FDA are decades old. Drug resistance, medical
software, and personalized medicine are going to strain the
limits of the outdated statute. I hope we can work together and
have FDA as an active partner when we are drafting this and
protect not only public health, but foster that innovation we
need for that long term.
So, Mr. Chairman, thank you for your time.
Mr. Pitts. The Chair thanks the gentleman.
Now recognize the vice chair of the committee, Dr. Burgess,
for 5 minutes for questions.
Mr. Burgess. Thank you, Mr. Chairman. I apologize I wasn't
here earlier. I had some obligations on the House floor.
I do want to take this opportunity just to recognize the
fact that this subcommittee, and in fact the Energy and
Commerce Committee as a full committee, did its work in what
was sometimes a very difficult election year of 2012. Food and
Drug Administration reauthorization of user fee agreements was
going to expire. All of the people who write in the important
papers around town said we couldn't do it. And you and Mr.
Upton did it. The bill went through regular order, passed the
subcommittee, passed the full committee, went over to the
Senate, conference with the Senate, and the President signed it
into law on July 9th of 2012. No one knows that because there
was no signing ceremony and there was no press present. But
Congress, when pressed, can actually function in a very
reasonable way.
Dr. Woodcock, as you will recall, during the
reauthorization discussion, actually I worked with Ranking
Member Pallone on the concept of the advisory committees to
make certain that they were staffed with the very best experts
to serve patients well, serve you and your agency well, and
reduce backlogs and save resources. And so it looks to me like
the initial thing, reports I am getting are good. Do you have
any updates for the committee today?
Ms. Woodcock. Yes. We have been able to remove several
steps that were very time consuming within the vetting of the
advisory committee process for members for a specific
committee. That has helped us streamline that program. Of
course, all advisory committee members are still subject to the
broad Federal conflict of interest requirements, and that is,
you know, fairly stringent as well. But the additional steps
have been removed, and that has been helpful.
Mr. Burgess. And sometimes it is helpful to have someone on
an advisory committee who actually has some knowledge of the
pathophysiology that might be involved in the disease under
which we are contemplating treatment? Would that be a fair
statement?
Ms. Woodcock. I would say it is essential.
Mr. Burgess. I think so, too.
Now, there is going to be a rare disease meeting in January
of this year. Is that correct?
Ms. Woodcock. I believe so.
Mr. Burgess. And looking forward to improving the
regulatory process for approving drugs for rare diseases. You
held a similar meeting in 2010 and issued a report with
recommendations. Can you kind of update us as to the
implementations of those recommendations made 3 years ago in
advance of this next meeting in January?
Ms. Woodcock. Well, I think we are doing extremely well on
rare diseases. We have established a rare disease staff. We are
tracking all the rare diseases. In 2013 we approved a large
number of products for rare diseases. Every one of them was
approved based on a surrogate in fiscal year 2013. That is 1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 were products for rare
diseases. And then one was approved on an animal rule without
human efficacy testing. So we do have a robust program, and we
are going to try to take it to the next level as we have more
meetings, public meetings.
Mr. Burgess. Dr. Shuren, as you know, for some time I have
been interested in the research use only application. And there
is recent guidance put out by your department that only
products that could significantly restrict patient access and
restricting sales of these products. Is there any evidence out
there of patients being harmed by research use only products?
Mr. Shuren. Well, we do have evidence of companies who are
putting those products out for research use only, but actually
promoting them for clinical diagnosis in cases where those
research use only, because they are research use only, haven't
been shown necessarily to be accurate. And in times where we
have taken action, it is predominantly where there is an
already available approved or cleared test that would be there
as an alternative.
We have recognized some of the concerns, I will tell you,
with the guidance. And one of the things in there was about
putting on the makers of research use only that they should
reasonably know about the people they are selling it to and
their intentions. That is something we heard loud and clear. I
want too tell you we have heard those comments. That will come
out of the final guidance. And that final guidance will come
out probably by the end of this month, and we will get you a
copy of that, too.
Mr. Burgess. And I appreciate that. But specifically, do
you have evidence that patients have been harmed by using the
research use only designation?
Mr. Shuren. I am not aware of a specific patient for one of
those. I don't know. We can look a little bit further.
Mr. Burgess. Thank you. And I would appreciate your further
investigation of that.
Finally, Dr. Woodcock, I just have to ask a question.
January 1st of 2012 I lost access to a low-cost over-the-
counter asthma inhaler. When am I going to get it back?
Ms. Woodcock. Well, I can't talk, as you know, publicly
about applications that might be pending and so forth. But
certainly that monograph status remains. And we certainly heard
your concern.
Mr. Burgess. Thank you.
Mr. Pitts. The Chair thanks the gentleman.
And now recognize the gentlelady, Ms. Castor, for 5 minutes
for questions.
Ms. Castor. Well, thank you, Mr. Chairman.
And welcome. Dr. Woodcock, in September, in Tampa we had
the BioFlorida Conference with researchers and device
manufacturers and folks that are developing drugs come from all
across the State. And FDA was kind enough to send Dr. Richard--
--
Ms. Woodcock. Moscicki.
Ms. Castor. Moscicki, thank you, from the Center for Drug
Evaluation and Research. And I want to thank you very much,
because it is, I know, the budgets are very tight, but to have
folks that are leaders at FDA be able to interact directly with
the folks in my State was greatly appreciated. So thank you.
And the conference focused a lot on the future of drug
approvals.
So we are pleased that the Federal laws are working well. I
think the number one fear of everyone, the topic of this
conference turned to sequestration, because people are rather
surprised that even though FDA relies a lot on user fees, the
user fees are subject to sequestration. This is not smart.
Some of the analysis I have seen, and tell me if these
numbers are right, that to your budget, I don't know if this is
the entire FDA budget or just your section, that in fiscal year
2013 you were subject to sequestration of $209 million. And on
top of that, $85 million in private funding, the user fees,
were sequestered at the same time. And then in fiscal year
2014, if the sequester is not replaced, you are looking at a
cut of $319 million. And $112 million of that, or you can
explain that, on top of that or as part of that is the private
funding user fees.
I mean, this has got to have a harsh impact on development
of new therapies, on review of devices, on review of innovative
drugs. Tell us what you are facing now in your shop.
Ms. Woodcock. Well, the sequestration has been very
difficult. Of course, it cuts the appropriated support for
these programs as well as where there are use fees, some of the
user fee programs have been subject. My understanding is that
total for user fees has been $79 million in the last fiscal
year. But, frankly, how these are calculated is above my pay
grade, all right? But what certainly has happened, there are
user fees that we are not able to access, across the device and
the PDUFA program, and that would continue.
And what happened with PDUFA, we negotiated and the bill
was passed. It recognized the new agreements on rare diseases,
patient-focused drug development, and these other programs. And
then the sequester removed practically the whole amount that
was negotiated for these new programs, these patient-focused
programs, and other programs.
Now, we have put on the patient-focused drug development
meetings regardless, but our implementation of our rare disease
staff has been delayed because of the sequester, and similarly
with a number of the other programs that we agreed to.
Ms. Castor. So that is not good news for families across
the country, families with rare diseases that rely on your
agency. It seems like we have taken a step forward with the
Federal laws that have given you certain authorities and
expanded user fees, but then it seems like on the other hand
sequestration, brought by the Congress, is going to handicap
you. I mean, this is a bad time to shortchange FDA. Can you
characterize what it means, where you are very concerned? And I
would assume you would recommend that sequestration be replaced
going forward.
Ms. Woodcock. Well, as I said, the whole financial issues
are above my pay grade. That is really up to Congress. However,
we are in a threshold, and I think with devices, too, of a
revolution in biomedicine, and we are starting to see the
benefits of that. And we need to have the programs that can
respond to that, and also programs that can get for those older
drugs, get low cost, affordable generics out on the market
promptly, and at the same time, shepherd those innovations,
both devices and drugs, that are going to make a difference for
people who are still suffering from untreatable diseases.
And we really, I passionately feel we have to deliver this
to the public. We have to make sure our regulatory programs are
up to the task of dealing with drug-resistant organisms, of
dealing with the new science that is coming forward.
And we are always close to the bone, as you know, in FDA.
We have to shepherd our resources very carefully. More is at
stake here than just having our staff. What is at stake is are
we going to translate these innovations into benefit for the
public.
Ms. Castor. Thank you.
Mr. Pitts. The Chair thanks the gentlelady.
Now recognize the gentleman from Illinois, Mr. Shimkus, 5
minutes for questions.
Mr. Shimkus. Thank you, Mr. Chairman. I am glad to follow
my colleague from Florida, because obviously history, it is
interesting in that this was the President's proposal to go
into sequestration. It was passed by the House. I voted for it.
And the real way to solve sequestration is understand debt,
deficits, and our entitlement programs, and get those reforms.
My fear for any agency, that without that the expansion of
our entitlement programs is going to squeeze out the
discretionary budget, whether that is the military, whether
that is your agency. And the sooner we as a Nation own up to
that, then we wouldn't be having this debate.
One of the great things I love about the job of being a
Member of Congress is working with our constituents. So right
during votes I had one of my constituents go, and we measured
the Ohio clock, because I have a constituent who is building a
replica. So we were tape measuring and stuff. So that is an
example of kind of the things that we do.
And it is just lucky that you are testifying when I was
approached by a constituent, a member of my church. And so I am
going to get a privacy release statement and we are going to
follow up with the FDA, but he was supposed to be in clinical
trials in September. They have not been called. He has asked me
to ask why. So if you all would just be prepared for when we
get involved with that, I would appreciate that on behalf of my
constituent.
So having said that, really my questions are to Dr. Shuren
on the 510(k), some issues revolving with that, which I have
been trying to follow closely. Many companies are providing us
feedback that they are experiencing a significant shift in
requirements for various 510(k)s. Particular concerns have
arisen about new requirements being communicated by the FDA
during the 510(k) review that go beyond previously sufficient
data requirements.
If true, this concerns me because in many instances FDA has
not issued any new guidance on public communication regarding
policy changes. So the question is, has the FDA changed its
data requirements for submission types without issuing updated
guidance documents? And if so, can you tell me why the change
in consistency?
Mr. Shuren. Well, first of all, I will say that oftentimes
if we are asking a company for additional data, sometimes it is
in response to the data they provided to us, that there may
have been issues in what was submitted.
One thing I will ask you is, if you have companies who
believe that something has been changed and changed
inappropriately, you are very welcome to send them to me
directly, and I promise you I will look into it.
Mr. Shimkus. Thank you.
At hearings in this committee prior to the enactment of
FDASIA you acknowledged that in some cases the CDRH reviewers
were asking for data to support product applications that they
should not be asking for. You also indicated in an October 2011
document that you planned to work on training reviewers to
avoid these sorts of data requests. Can you give us an update
on this and what steps have you taken to address this?
Mr. Shuren. So we have taken a variety of steps to assure
that the questions that we ask are need to know rather than
nice to know. And I will tell you even from our own analysis it
is not common, but it happens, and it concerns us.
So one of the things we have done is we have been
reorganizing in our premarket review offices, and thanks to
MDUFA III we have been bringing in additional managers for more
oversight of the process. We have changed policies and
procedures to put more checks into the system.
Under MDUFA III, we have also put in a back check. So with
our high-risk devices, we actually have a dedicated staff who
will review any and all major deficiency letters that go out
for accuracy and appropriateness. We have biweekly premarket
review rounds, where if issues get raised we are dealing with
them with the reviewers and the managers at that point. And of
course we have done training for everyone for starters.
Mr. Shimkus. And I will end up on this. What, if any,
consequences are there for reviewers who ask questions beyond
what is appropriate? And are those annotated on their
performance review evaluation so that if it happens numerous
times? Many of us have been managers of personnel. And, you
know, the reality is you have got to document, document,
document, especially on a Federal employee who may not be
responding to the proper directions.
Mr. Shuren. Well, I will first say, and I am going to put
this in because my folks get sometimes a hard rap, they are a
great group of people. They are very smart, they are dedicated,
and they have been working exceptionally hard to implement
FDASIA and to make changes. And I think it is reflected, quite
frankly, in our premarket review numbers. The bottom line is
our performance is getting better, and it is getting better for
the first time in a decade of worsening, and that is a lot of
credit to them.
Making changes is hard when it is a large organization, and
there are going to be blips along the way. And it is our
responsibility to keep good oversight in the center. And when
things do arise, we do engage with the individual. We try to
educate and work with them and keep on top of it.
Mr. Shimkus. If the chairman would for just a follow-up, of
course, annotating if there is numerous examples and writing it
down is part of a good personnel status. So I hope you would
consider and do that.
Mr. Shuren. Yes. And I will say for anyone who is not
performing appropriately, and that goes for anything, then
appropriate documentation in the file, and also discussions
with the employee, because you always want to, if an employee
isn't doing well, to try to help them to get back on par with
performance.
Mr. Pitts. The Chair thanks the gentleman.
And now recognize the gentlelady from California, Ms.
Capps, for 5 minutes for questions.
Mrs. Capps. Thank you, Mr. Chairman.
And thank you to our witnesses for being here today. I am
so pleased that we were able to reschedule what I consider to
be a very important hearing. And I am very pleased that FDASIA
included parts of my Sentinel Assurance for Effective Devices
Act, also known as the SAFE Act, in its final form.
One section of that bill was to ensure swift release of the
UDI, the unique device identifier rule, for public comment to
improve device tracking and aid in any potential recalls. So,
Dr. Shuren, I want to commend you for getting the final rule
out on UDI. I know it has been a long time coming, and I am
glad that you finalized it so things can finally move forward.
One concern we have heard from consumer groups has been
that the final UDI, unique device identifier--I want to make
sure people know what I am talking about--rule does not require
the identifier to actually be on the individual product itself.
Can you explain the decision to not require the UDI to be on
each one of these products?
Mr. Shuren. One of the principal drivers was cost, cost to
the companies. And we want to make sure that in implementing
and putting forward this important regulation that we keep in
mind what the burdens may be for companies to try to comply. So
that was the major reason.
We do still keep in marking the devices in really one
exception, and that is if you make a device that is going to be
used more than once and it is going to be reprocessed. Because
in that case, the labeling that came along with the product
that had the UDI got thrown away, now it is moving over to
someone else, and you wouldn't know what that device is unless
you marked those devices. And that is a requirement in the
rule.
Mrs. Capps. OK. OK. That is good to know.
My SAFE Act also built upon the existing Sentinel program
at FDA, a program that enables FDA to actively query automated
healthcare data to evaluate possible drug safety issues quickly
and securely. The SAFE Act, and section 615 of FDASIA, both
broadened that usage to the medical device space, which will
benefit producers and consumers alike by catching problems
early and ensuring that data, not conjecture, but data
determine our device safety policies.
Unfortunately, the rollout of Sentinel on the drug side has
taken many years, more than many in the field think is
necessary. So I hope that expansion to the device side will not
be plagued with the same delays. And can you each give me a
brief update on where the agency is with Sentinel? I would
appreciate a longer update for the record.
[The information appears at the conclusion of the hearing.]
But just quickly, can you also explain for us how UDI fits
into FDA's postmarket surveillance of medical devices? Will it
be good for patients and for providers and for manufacturers?
Mr. Shuren. So the UDI is absolutely essential. It is a
condition precedent for having Sentinel for medical devices.
And the reason is right now it is very hard to link a device
with a patient's experience with that device in electronic
health information, electronic health records. Unlike drugs,
which had a new drug code that they could use right away, we
didn't have anything for devices. So the UDI we need to have in
place. And that is going to take a few years.
But in the interim, what we are also doing is the
following. We are identifying, helping to develop new and
validating tools for active surveillance, being able to go
through information to find out what are better understanding
of benefits, risks, and problems with devices, And we are
working with our conflicts in CDER on that.
Also, Sentinel will be part of a broader National Medical
Device Postmarket Surveillance System. So electronic health
information and registries will be the backbone. And we view
this not so much as an FDA system, but truly a national system
to meet the needs of industry, healthcare providers, insurers,
FDA.
So moving forward, the Brookings Institution is very soon
going to call for the creation of a multistakeholder planning
board to start to lay out the governance structure, policies,
and procedures for such a surveillance system, which we think
is important not only for identifying problems, but being able
to use postmarket information to help lower burden and better
inform decisions on premarket approval, help products get to
market, help doctors and patients make better-informed
decisions.
Mrs. Capps. Thank you very much.
And finally and briefly, another piece of FDASIA was a key
component of my HEART for Women Act, bipartisan legislation
that focused on doing all we can to address women's heart
health and address health disparities. Section 907 of the
FDASIA required an examination of the extent to which data on
how approved medical products affect women, minorities, and
ethnic groups be collected, analyzed, and publicly reported.
This is an important step, but concerns persist I know, and I
will be submitting many questions for the record, and I
appreciate your team's attention to this matter.
And I don't think there is much time for you to respond. I
just wanted to put that out. We will follow up with you. Thank
you.
Mr. Pitts. The Chair thanks the gentlelady.
And now recognize the gentleman from Pennsylvania, Dr.
Murphy, 5 minutes for questions.
Mr. Murphy. Thank you, Dr. Shuren and Dr. Woodcock. I
appreciate you for being here today.
I would like to take just a moment to ask you about an
important medical device issue, although it was not part of
FDASIA. The FDA has regulations about proper maintenance of
complex medical devices such as radiation therapy and imaging
equipment, and manufacturers are required to recommend
maintenance standards to hospitals and physicians and collect
data on how that equipment is kept and serviced.
My understanding is that the Center for Medicare and
Medicaid Services may issue guidance telling hospitals they are
free to vary from the manufacturer's maintenance recommendation
on these types of devices. But we are not dealing with an
automobile or refrigerator here. These are highly specialized
pieces of equipment. And when a medical device is improperly
serviced, the consequences can be pretty deadly, as you know.
When a New York Times series in 2010 raised concerns about
patient deaths from improperly calibrated diagnostic and
therapeutic equipment, this committee held hearings in the
matter. I am concerned that weakening of equipment maintenance
standards could have some severe consequences for patient
safety, and the party responsible for that device is the
manufacturer. If something goes wrong, it is that company's
name on the label, even though they are not the ones that made
the maintenance changes. I believe the FDA has weighed in on
this possible action by CMS. Is that true, Dr. Shuren?
Mr. Shuren. Yes, that is true.
Mr. Murphy. Can you discuss the FDA's position on this and
you concerned about anything there?
Mr. Shuren. Our concern is that the maintenance schedule is
really part of assuring that that device remains safe and
effective. And we work with the companies on what is the
appropriate maintenance schedule to assure just that. And as
you mentioned, these are technologies that may be emitting
radiation, and we want to make sure not only are you getting
accurate images of patients, you want to make sure they are
also getting the right amount of radiation, not too much. And
so a good maintenance schedule is essential. And that is why we
had raised certain concerns and shared those with our
colleagues at CMS.
Mr. Murphy. OK. Let me ask another issue here. And I will
gave you a little briefing material on this a little bit ago,
but I want to make sure we have it in the record. We are all
concerned about hospital-borne infections. E. coli, MRSA, and
other infections which spread in hospitals are particular risks
for people in hospitals, particularly in an ICU, or people who
are immuno-compromised, et cetera, in transplant patients, et
cetera, and that people use substances that are put into paints
and plastics and clothing to try and reduce infections. But
there also is the element of copper, which in research I
understand has shown that basically E. coli, MRSA, and some
other diseases are killed in minutes, whereas those same
diseases can last for weeks on plastics and stainless steel.
The EPA has said that any sort of regulation on this is in
the FDA's hands and they are not going to do anything about it,
even though they have other jurisdiction over copper. I wonder
how this will work at the FDA in terms of expediting this. I
mean, it is obviously not a new element. It has been around for
billions of years. And it seems to me it ought to be something
we can use, copper itself, or copper-nickel alloys and other
alloys which we know that can be on handles, on trays, on other
equipment and supplies where these diseases can be killed right
away.
Can you comment on the procedures you could take on this?
And could anything be sped up on this process?
Mr. Shuren. So we are happy to look into it. If it is a
medical device and it has copper on it, if it has an anti-
infective, that is something that my center would generally
take care of. If it is not on the medical device, so it is just
the anti-infective, it tends to work by a chemical action,
becomes a drug issue. And that is why if there is a company or
companies dealing with it, it is important that we connect so
we figure out exactly what we are trying to do and help them as
best we can.
Mr. Murphy. Just help me understand this, because I want to
make sure we handle it in the right way. So if it is a door
handle or a touch plate entering an ICU, if it is a switch
plate in a hospital room, would those be medical devices or
would they be------
Mr. Shuren. So a lot of those basics oftentimes are not.
Mr. Murphy. What category would they be in?
Mr. Shuren. If you are talking about surgical instruments,
you are now getting into------
Mr. Murphy. I understand that. I understand that. So what
category would they be in? Because the EPA is saying that FDA
has to approve them.
Dr. Woodcock, do you have------
Ms. Woodcock. They would only considered a drug if they
actually had a disease claim in humans. And we don't usually
regulate door knobs as drugs, all right. I think we are talking
about some jurisdictional, like, murkiness here that we would
need to sort out.
Mr. Murphy. Well, I would just hope. Let's put that on the
record. We will get you the information on it. But I hope that
is something that you and the EPA can discuss fairly quickly.
Obviously, the 100,000 people who die every year from hospital-
borne infections and the fifty billion dollars we spend, if
this can be reduced by several, then we ought to work together.
Thank you so much. I appreciate it.
Mr. Pitts. The Chair thanks the gentlemen.
Now recognize the gentleman from New York, Mr. Engel, 5
minutes for questions.
Mr. Engel. Well, thank you very much. And welcome to both
of you. Followed both of your work. And thank you for your
service.
I believe that the good work done by this committee on the
Food and Drug Administration Safety and Innovation Act was
likely the best healthcare-related legislating done by Congress
last year. A little more than a year after its passage, I am
pleased that this hearing is taking place so we can continue to
monitor the implementation of this important bipartisan law.
I have always fought for those with rare and orphan
diseases. I am the author of the ALS Registry Act, and both the
Paul D. Wellstone Muscular Dystrophy Community Assistance
Research and Education Amendments of 2008 and 2013, which I
have done with Congressman Burgess. I am particularly
interested in the development and approval of drugs for rare
diseases.
Therefore, one of the aspects of FDASIA I am most
interested in is the improvements made to the accelerated
approval pathway as part of the law. To me, diseases like
muscular dystrophy are why the accelerated approval pathway is
so important. Duchenne muscular dystrophy is the most common
lethal genetic disorder of children worldwide, affecting one in
every 3,500 live male births. There is no cure. It is always
fatal. And the best hope for those with Duchenne is to treat
the symptoms and delay its progression. I have a group of
people in my district that called this disease to my attention.
However, in recent years the Duchenne research pipeline has
held much promise, as potentially life-saving therapies appear
on the horizon, making elements of FDASIA particularly relevant
to this research community. Earlier this week, the FDA informed
Sarepta Therapeutics that its experimental drug for Duchenne
muscular dystrophy was not a candidate for the accelerated
approval pathway at this time. I recognize that since Sarepta
has not filed its new drug application most of the discussions
between Sarepta and the FDA are confidential. But I hope that
Sarepta will continue to pursue their treatment for Duchenne
muscular dystrophy, and I hope that the FDA will continue to
provide clear feedback to the company as they move through
their various clinical trials.
So, Dr. Woodcock, can you elaborate on how you envision the
enhanced accelerated approval pathway working?
Ms. Woodcock. Certainly. As I said, in fiscal year 2013 we
approved a large number of rare diseases, and all of them were
based on surrogate end points, which is the foundation for
accelerated approval. However, we granted a number of them full
approval because we felt enough information had been provided
that a confirmatory trial would not be necessary.
So we certainly are using the accelerated approval in rare
diseases. And what the FDASIA instructed us to do was to really
consider additional end points, including intermediate clinical
end points, in other words clinical end points that are
reasonably likely to predict clinical benefit, and we intend to
do that.
Mr. Engel. Thank you. Let me ask you another question.
Recognizing the challenges in developing therapies within the
rare disease space, how is the FDA working with companies to
ensure proper parameters for success and failure are being
established through the clinical trial process in order for
experimental medications to possibly be considered under the
accelerated approval pathway?
Ms. Woodcock. We try to work one by one, because of course
each one of these diseases is different. One of the most
important things that can be done by the patient communities is
to establish a natural history of the disease through data so
that we understand and can predict what will happen. If there
is an intervention, you can calculate how many patients you
need in your trial and so forth.
And this hasn't been done before. And so we have really
been pressing on that, and I think we have seen a lot of
progress. But we work with the companies one by one to help
them design their trial. And as I said, we have set up a rare
disease staff, although that has been inhibited because some of
that money has been influenced by the sequester.
Mr. Engel. Well, thank you. And let me talk about the
sequester and building on what Ms. Castor asked. I didn't vote
for the Budget Control Act of 2011, thankfully, which created
this huge sequestration mess. I am very frustrated that the
user fees paid as part of agreements reached in FDASIA are
being sequestered. So why don't I ask Dr. Shuren, can you talk
about how sequestration impacts the ability of the FDA to meet
goals agreed upon as part of FDASIA?
Mr. Shuren. It is making it challenging. I mean, we are
meeting the goals now. But in 2013, we saw about an 8 percent
cut. Critical funding for training of our staff, of our review
staff who we want to be on top of cutting-edge technology. Saw
a 15 percent cut in our ability to recognize national and
international standards, which provides predictability for
industry. We had a 50 percent cut in our investment in
regulatory science to have better tools for assessing medical
devices faster and at lower cost, which is a big deal for
industry. And I had to shift 50 percent of my operating dollars
into payroll in order to hire the people I committed to hire
under MDUFA III.
So most of my extra money, if you will, beyond paying for
employees, is to pay for the rent, keep on the lights, put
money in the photocopier. I have very little to actually put in
to really improve a program that still needs a lot of help. And
if we go into 2014 and this continues, I am not going to have
the money to be able to hire and maintain the people we
committed to hire and maintain under MDUFA III. It is a big
deal for us.
And sequestration, it is important on user fees. Most of
our program is still funded by appropriated dollars. And those
cuts, they are killing us. And we are a program, like drugs,
where years before trying to actually turn the program around,
and this is making it very challenging for us to do that.
Mr. Pitts. The gentleman's time has expired.
Mr. Engel. Thank you.
Mr. Pitts. The Chair recognize the gentleman from Virginia,
Mr. Griffith, 5 minutes for questions.
Mr. Griffith. Thank you very much, Mr. Chairman.
Dr. Woodcock, greatly appreciate the passion you showed
earlier in your testimony. I would agree with you on that
passion, particularly about bringing innovative treatments for
rare and terminal diseases. I have a little bill that would
allow folks to get early access or early approval to those
drugs in order to help them, and what we believe will actually
lower the costs of some of that experimentation. We will talk
about that another time.
I do want to talk about a bill, I know what we are doing
here today is important, but I do want to talk a little about a
bill we have waiting over in the Senate. The House passed the
Drug Quality and Security Act. It was a bipartisan, bicameral
compromise to prevent another fungal meningitis outbreak like
the one associated with NECC's tainted sterile products, where
we had 64 Americans unfortunately died as a result of that
situation.
I am proud of the legislation that I worked on with
Congressmen Gene Green and Diana DeGette. Ultimately, although
we had a different package originally, we came to a compromise
with our Senate colleagues and with your agency, and I look
forward to the Senate getting around to it. It is held up for
other reasons, but I look forward to the Senate passing the
bill and it being signed into law.
And I am committed to engage in oversight to make sure that
patient safety is being properly protected. I also look forward
to the agency developing the notification system that
Congressman Green, Congresswoman DeGette, and I authored to
ensure that the FDA works more closely with those State boards
of pharmacy to prevent another public health crisis.
That being said, there were some areas that we thought we
might be able to get fixed that we didn't in that bill that
have raised some concerns. And I would like to ask you about
those in regard to that Drug Quality and Security Act. In its
previous draft guidance the FDA recognized the importance of
maintaining an office stock of compounded drugs that doctors
can readily access and administer to patients in their offices.
Can we rely on the agency to continue to allow doctors and
hospitals to order and keep compounded drugs on hand for office
use?
Ms. Woodcock. Well, we are going to have to see what is in
the final bill, if it is enacted. And then as I understand it,
it really removed the court disparity, which I didn't fully
understand, but was a problem. And so it leaves the previous
statute more or less intact, and we can implement it
aggressively. And obviously, that is one of the considerations
in there, is what are the four walls of what is Federal, what
is State, and what is permitted.
Mr. Griffith. And we didn't change anything in regard to
office use, and so there is some concern that maybe we should
have put it in. It was compromised that we would just leave it
silent. And I hope that we can count on the FDA. I know you
maybe can't answer that today. But I would hope that we can
count on the FDA to leave that part of it that was working very
well, which the FDA had previously done, leave that intact,
because I don't think there was any intention, certainly not on
our side, that that be changed in any way.
Likewise, repackaging of sterile drug products has
typically been regulated by the agency in the same fashion as
compounded drugs. Repackaged sterile drugs are vital for many
patients, especially those in ophthalmologic health issues.
Likewise, can we rely on the FDA not to go in and create chaos,
and to preserve the access to these repackaged sterile drugs
and limit the impact of burdensome regulations on that
practice?
Ms. Woodcock. Well, our intent certainly is not to create
chaos.
Mr. Griffith. Yes, ma'am.
Ms. Woodcock. All right? I think one of the goals, mutual
goals, is to prevent contaminated drugs. And that is really our
goal, and your goal as well, I believe.
Mr. Griffith. It is. There were some clarifications that
everybody decided to let go and hope that it works out. And so
I am just worried about those areas.
The last of the three that I have is the nuclear
pharmacists. They compound drug products that have a short
radioactive half life and must be quickly delivered to a
healthcare entity for administration to a patient. Sometimes
this must be done in advance of a patient-specific
prescription. Can we rely as well on the FDA to continue to try
to monitor that in the same fashion that they did before this
bill was passed? And I know that the Senate is either going to
pass it today or next week. But anticipating that, since it was
a compromise worked out between the two bodies and the FDA,
what are your thoughts on that?
Ms. Woodcock. Well, the nuclear pharmacies have not
represented a problem here. We have a scheme with them. We have
been very successful in implementing a regulation of positron
emission tomography facilities, and that has gone very well.
And so I think we should continue along that path.
Mr. Griffith. And I appreciate that greatly. And I would be
remiss, you know, it is good to see a witness with passion and
your dedication. We may not always agree on how to get there,
but I always appreciate the fact that you come in with honest
answers and a willingness to try to work things out, and I
appreciate that.
Ms. Woodcock. Thank you.
Mr. Griffith. With that, Mr. Chairman, I yield back.
Mr. Pitts. The Chair thanks the gentleman.
And recognize the gentleman from Maryland, Mr. Sarbanes, 5
minutes for questions.
Mr. Sarbanes. Thank you, Mr. Chairman.
I just want to pick up on the end of those comments, and
thank you, Dr. Woodcock, for being here, and say you are one of
the most professional and knowledgeable witnesses we have the
pleasure to bring before this committee from time to time. I
thank you for your testimony, and yours as well, Dr. Shuren.
And I want to thank the chairman for convening this panel
today and the committee hearing so we can get a sense of how
things are progressing. These days, sort of bipartisan
legislation that we all get behind is hard to come by, so it is
nice to have the opportunity to hear that good things are
already resulting from the passage of this reform, and we
appreciate your testimony in that respect.
I was going to ask as well about how the kind of user fee
resource has gotten caught in the switches of sequester, which
I think you have answered that. It is particularly jarring I
think to the industry, the notion that they are putting forward
through the user fees resources from the industry, and even
that gets implicated by the sequestration that has been put in
place. And hopefully, we can address that for all the reasons
that you have raised.
I don't have a lot of questions necessarily on the topics
you have been covering because I think you have done a good job
addressing them. I did want to ask something slightly off
topic, which is, as a result of redistricting in Maryland, I
now have the privilege of representing some portion of the
White Oak facility and had the opportunity to get a tour
recently and see the tremendous facilities that are provided
there. And I wondered if you could just speak to the benefits
of now being able to collocate so many of the FDA personnel and
have the labs there near each other and what that represents in
terms of the ability of the agency to function.
Ms. Woodcock. Well, we really appreciate this, because
CDER, when I took over CDER, first it was in 14 different
locations scattered around the metropolitan area here. We
expect a move this summer that will move the generic drug
program to the White Oak campus, and also move the biologic
therapeutics regulation, which has been located on the NIH
campus, with their associated laboratories, to White Oak. And
also our colleagues in the biologic center, with whom we work
on policy very closely.
So for the drug center, this is a tremendous advance, will
allow us both to have our new generic office on campus, as well
as build our quality regulation organization, which I spoke
about earlier, where we are going to have the same unit
regulate pharmaceutical quality across all different types of
drugs.
And also it will enable us to work with our colleagues at
CBER very closely. And the benefits of having the device center
right near us are tremendous, because there are many
combination products with this new technology that is coming
about that combine device elements and drug elements. So this
has been a tremendous advance for us.
Mr. Shuren. It has been a big deal for us as well. I would
also put a plug in on personalized medicine. So much of it
depends upon having the right diagnostics tied up with the
therapeutics, and we work very closely with our colleagues in
CDER. Having them down the hallway is essential.
And having the lab facilities to do absolutely critical
work. And that is work that also helps companies. Getting
product to market is so important. And one of the challenges we
face in the current budget climate is we are getting to the
point, getting very close to the point of starting to turn off
lights in some of those labs.
Mr. Sarbanes. Thank you very much. I yield back.
Mr. Pitts. The Chair thanks the gentleman.
Now recognize Mr. Guthrie 5 minutes.
Mr. Guthrie. Thank you. Thank you for coming. And this is a
good hearing. And it is one of those things that when you run
for Congress you don't think about these kind of issues. You
have other things that you more readily read about. But when
you get here, you realize they are vitally important to your
constituents. We have people come continuously, and they are
looking for devices, they are looking for approvals. And I
think Mr. Shimkus talked about one specifically that is in a
desperate situation. So it is important that we work together.
And I have a couple of questions. One is on the custom
devices. And, Dr. Shuren, this would be for you. Those that are
made by manufacturers for specific patients upon request by
their physician are critically important for patient care, but
are not viewed by many as efficient or lucrative. And so
therefore, in section 16 of the FDASIA, we established that
manufacturers could modify an existing device for which data
already existed instead of making an entirely new device.
The FDASIA language limits the manufacture or production of
five units per year of a particular device type. And some in
the industry have expressed concerns that the FDA may interpret
this to say it can only be for five patients per year versus
just five devices--only five patients who needed a custom
device. And I think that might render that kind of ineffective.
And so I just wonder how you interpret that provision.
Mr. Shuren. No, we are not putting such a strict limitation
on it. In the next few weeks we are going to put out draft
guidance to try to better clarify implementation of that
provision, which we think are very important provisions. And we
support custom devices, and we think it is so helpful that
Congress actually put in a much more clear standard for what is
a custom device. And we are going to provide that clarity then
in terms of interpreting it.
I would also add that companies do not need to come to us
in order to go out with a custom device. There is no premarket
review on it. They simply report to us annually. So hopefully
in the next few weeks we will have out that guidance so we can
have a fuller discussion with industry about it.
I will also say in those cases where they don't meet the
statutory definition of a custom device, there are other
mechanisms we have in place to help assure that patients who
need a device that isn't otherwise approved on the market can
get it. So many of those cases, even if the law doesn't allow a
custom device, could be for compassionate use and still get it
to the patient.
Mr. Guthrie. I know in the reporting that it makes it
quicker and better for the patient. I guess there was some
concern it might just be five patients. So in a couple weeks
you are going to have that guidance, and if you could keep us
informed, that would be fantastic.
I do want to point out that, I know we talked about
sequestration, and we are dealing with budget issues here, and
the budget conference committee is meeting as we speak through
December, but the FDA has experienced a dramatic increase in
appropriations over the past decade. And since the beginning of
MDUFA, CDRH has gone from approximately 1,000 MDUFA full-time
equivalents to over 1,400. And since 2004, CDRH has doubled its
budget from 179 to 385. That is from 2004 to fiscal year 2011.
And during this time PMA and 510(k) submissions have decreased.
However, studies have shown, and that is the CHI/BCG report
we are all aware of, that review times have gotten 43 percent
slower in the past few years and PMA 75 percent longer. So
sequestration does have an effect, I am not saying that it
doesn't, but there has been some substantial increase in the
budget at the FDA as well.
So, Dr. Woodcock, one of the central tenets of the
Prescription Drug User Fee program is to provide more certainty
and predictability on the timeline for FDA to make decisions to
approve a drug. And why is it important for companies in terms
of continued innovation and patient access to new medicines for
companies to have predictability on the FDA and when it will
make decisions on application?
Ms. Woodcock. Well, because these companies invest up to a
billion dollars in a development program, and then they need to
launch, and they have to do a lot of activities to get ready
for launch. They have to get their facility all ready,
distribution chain, all sorts of things. And so just knowing
what the sequence of events is going to be and when that time
on to market will be is extremely important to keep this
enterprise afloat.
Mr. Guthrie. I agree with you. And then do companies
receive patent term restoration based off the time it takes for
a company to go through the FDA process?
Ms. Woodcock. Well, I don't understand this very well. They
get restoration at the time of approval. So they get that. But
there can be things eating away at their patent in the interim.
Mr. Guthrie. OK. And it is important, because our
investment in research is second to none in the world. And I
know, we talked in my office, Dr. Shuren, on some of the device
companies that are going to other countries for better
opportunities to get approval of their processes. And I
appreciate the work that you have done on that, because we
don't want to lose our industry and our leadership in research,
and certainly not because of slow and unpredictable processes.
So thanks for working to make that better.
And I yield back.
Mr. Shuren. Thank you. If you may, Mr. Chairman.
Mr. Guthrie. I have three seconds. Go ahead.
Mr. Shuren. And we are starting to see some changes. I just
got called this week by a company who said we were actually
going to conduct our first-in-human study overseas, and given
the changes at the FDA they were going to start it in the U.S.
And we are hearing that from other companies as well.
The numbers you gave in terms of our performance, they are
from a report from 2010. And that is actually what I would say
was the high point, the watershed mark for the program after
about a decade of worsening. And since that time those numbers
are actually down a fair bit. They are improving in review.
Mr. Guthrie. I understand. And I hope I didn't insinuate
that. But I was just saying the funding has doubled since 2004.
So there has been increased funding even though you are under
sequestration now. So I just want to make that point.
Mr. Pitts. All right. The gentleman's time has expired.
That concludes the first round of questionings. We will go to
one follow-up per side.
Dr. Burgess, you are recognized for 5 minutes for a follow-
up.
Mr. Burgess. Thank you, Mr. Chairman.
Dr. Woodcock, can I just ask you briefly about the decision
by the FDA to reschedule hydrocodone? Is there any update you
can provide us on that?
Ms. Woodcock. Well, let me explain the process. What we do,
we were asked, along with NIH, the National Institute for Drug
Abuse, to provide a recommendation to HHS, who then provides a
recommendation to DEA, who then go through a formal
notification and comment process. And DEA actually does
upscheduling. So what we announced was simply the fact that we
intended to recommend that the combination products be
upscheduled.
Mr. Burgess. Now, is there a report pending from FDA that
we have not yet seen or has not yet been made public?
Ms. Woodcock. Correct. What we need to do to actually any
scheduling action, we send something called an eight factor
analysis, which is stipulated under the Controlled Substance
Act, and findings based on that. And we write that up and send
that to HHS, who then will evaluate it and then send
recommendations to DEA. And that process, we should be moving
that process along fairly soon. We expect to.
Mr. Burgess. So we will have access to that report?
Ms. Woodcock. I don't know what point it becomes public. We
can get back to you on that part of it.
[The information appears at the conclusion of the hearing.]
Mr. Burgess. OK. Thank you. Well, you know, and it is a
concern, there being practicing physicians all over the country
who--sure, there are some things that require--State law
requires triplicate prescription in Texas, those things can't
be called in over the telephone in the middle of the night. But
someone who has run out of a postoperative medication and still
needs help, the doctor has the ability to get that help to that
patient without an emergency room visit. So it is important,
and it is something I don't want to see us lose.
We had a hearing here on, I guess it was on putting the
EpiPen over the counter, an over-the-counter Epinephrine
treatment for bee stings. And I don't remember now, quite
honestly, who was here from the Food and Drug Administration
that day, but I asked the question was there any thought to
putting Narcan over the counter, Naloxone, so people would have
the availability for that if they got into trouble abusing
drugs that either they got legitimately or illegitimately. And
then that was a feature of a story on Sanjay Gupta on CCN not
too terribly long ago.
So where are we in that process? We have gone to great
lengths to make levonorgestrel not just over the counter, but
down there with the Snickers bars in the front of the pharmacy.
Is there ever going to be any effort to make Narcan over the
counter?
Ms. Woodcock. We are certainly encouraging development of
forms of Naloxone. As you know, now it is compounded as nasal
sprays and so forth and used by paramedics. So we are certainly
encouraging development of sort of dosage forms that can be
used out in the field under emergency situations. And then we
would certainly consider whether over-the-counter access would
meet the criteria for over the counter and then would improve
emergency treatment of overdoses by friends and relatives, for
example.
Mr. Burgess. Well, thank you. Again, it was a pretty
startling film clip that Dr. Gupta showed on that series, and
again made me think again about the possibility that--again, no
one wants to condone the use of illicit drugs, but on the other
hand you hear about it where you lose--usually it is a teenager
in our community and it is a terrible tragedy when it happens.
And if there were another option maybe that would be a good
thing.
Ms. Woodcock. We totally agree with you, and if lives could
be saved that way then that is something we should really drive
toward, and we are very aggressively pursuing this.
Mr. Burgess. Don't misunderstand me, Mr. Chairman, it would
be better if they never abused the compounds in the first
place, but as a matter of first aid perhaps that is something
should be considered. Thank you for the recognition. I will
yield back.
Mr. Pitts. The Chair thanks the gentleman.
And now for follow-up, Mr. Sarbanes for 5 minutes.
Mr. Sarbanes. Thank you, Mr. Chairman.
Dr. Shuren, I know when last year we were debating the
various proposals around this reform one of the issues was
where to draw the line, what the proper balance should be in
terms of regulating medical devices. We wanted to make sure
that, you know, on the one hand we had sufficient regulation in
place and you had sufficient authority at the FDA to ensure
that these devices are safe and effective and so forth. At the
same time not have so much regulation that it becomes
burdensome on industry to a point of sort of quashing
innovation and investment.
And I would be curious generally for your thoughts on how
industry has responded to where we kind of put that line where
we struck the balance. And in particular I would be curious to
hear you talk about the new, more streamlined process you have
with respect to classification of devices from class 1 up to
class 3, where I gather now you can use a kind of
administrative process that doesn't necessarily involve full-
blown rulemaking and comment, so forth, in every instance. And
maybe you can give some examples of how you have used that
authority in an effective way.
Mr. Shuren. So, I mean, to answer the first part, I think
after much discussion that occurred last time around FDASIA
there was, I will say, general support for the U.S. standard of
reasonable assurance of safety and effectiveness. And the
question then becomes, what does that actually look like for
particular kinds of devices?
What we have done is put in place this new benefit-risk
strength work that is much more flexible and patient-centric to
try to set the needle, if you will, in the right place.
One of the things that we are going to be following up in
the coming months is to start talking about those circumstances
under which data we might otherwise collect premarket can be
shifted to the postmarket setting and not compromise patients,
but do an appropriate reduction of burden on companies and
address some of those cases in the postmarket setting. And that
will include some new pathways for high-risk devices as well,
and I think that is important.
Regarding classification, FDASIA provided some important
changes to the process. One is the fact that we can now issue
an order rather than a regulation. So in some respects it has
gotten a little easier, and it has been helpful.
But let me tell you one wrinkle we have, and that is where
if we do want to in fact reduce burdens on companies,
appropriately so because with more experience we realize we
should lower the classification, we should go from class 3 to
class 2, or class 2 to class 1, we actually now have more steps
to go through. We must hold an advisory committee meeting where
before we didn't have to do that. And that is actually making
it more challenging for us under appropriate circumstances to
reduce regulatory burden on companies.
Mr. Sarbanes. Thanks very much.
Mr. Pitts. The Chair thanks the gentleman.
We have had a couple of members detained on the floor and
missed the first round, so I will ask unanimous consent to
recognize them as they come in for 5 minutes.
Dr. Gingrey, you are recognized for 5 minutes.
Mr. Gingrey. Mr. Chairman, thank you for that courtesy.
Dr. Shuren, the Office of Combination was created to deal
with products that combine drugs, devices, or biologic
products. For instance, some companies are toying with the idea
of combining drugs and devices into solutions for antibiotic
infections, something that I care about personally, as you
know. However, the current approval method forcing companies
with a mainly device product to go through a drug pathway
because it induces a chemical reaction may discourage companies
from investing in new and breakthrough technologies because the
pathway is not best suited to what their product is.
The drug and device pathways were originally created
decades ago when the reality of combination products were not
yet realized. What steps is the FDA taking in light of its
current 1970s framework to work directly with these companies
who present the agency with 21st century technology like these
combination products?
Mr. Shuren. So the agency in setting up the Office of
Combination Products, which sits in the Office of the
Commissioner, is there to try to help determine what is the
appropriate pathway for those combination products to go
through. And they have been more recently trying to provide
clarification for when the primary pathway would be device or
drug.
But when it is a combination product there are needs that
would be met for both, let's say, if it is a device and a drug,
for the device side and for the drug side. So even if it is a
product that we have primary responsibility for, if it has a
biologic component, we go to our Center for Biologics for a
consult. If it has a drug component we go to our Center for
Drugs.
This is a very challenging area, I have to tell you this,
because given the way the law is we have been able to try to
minimize duplicative burden, if you will, and challenges on the
postmarket side for reporting, or on good manufacturing
processes, but when it comes to the standard for approving
products the law right now is very challenging for combination
product makers.
Mr. Gingrey. Dr. Shuren, thanks you very much.
Dr. Woodcock, the bipartisan GAIN Act took important steps
to encourage the new development of antibiotics by focusing on
incentives to new companies to keep companies in the
marketplace. At this time can you provide me the number of
qualified infectious disease products that have been designated
since the law was passed last year, what, last year?
Ms. Woodcock. Certainly. We have designated, as far as I
know, 27 products with 16 distinct active modalities. And that
number will continue probably to increase.
Mr. Gingrey. Well, I really have to commend the FDA on that
and realizing the desire and need for new antibiotics and
acting quickly to implement the program. I have received plenty
of positive feedback from companies, not just in my district,
who have been able to achieve benefits through the GAIN Act.
I think you would agree with me that more needs to be done
to combat resistance. One issue that needs attention involves
susceptibility tests, interpretive criteria or breakpoints.
Now, as you know, Dr. Woodcock, a breakpoint is criteria used
to determine a particular infection's susceptibility or
resistance to a specific antibiotic, and they are used by
physicians in clinical decision making.
With the growing public health threat of antibiotic
resistance, it is increasingly important to ensure that
physicians have these tools they need to prescribe the right
dose, of the right antibiotic, for the right patient, in the
right situation.
Given what we know about the science behind breakpoints and
our failure to keep pace with regulatory science in Europe, are
U.S. patients receiving the best medical care, using the most
up-to-date science, if the breakpoints for antibiotics are not
accurate?
Ms. Woodcock. Well, they would not be. We have updated
these criteria for about 121 of the 200 main antibiotic labels
that exist. However, we feel that it would remain more up to
date if we would not have this information remaining in the
drug labels but rather would be able to point to a Web page and
possibly to standard development organizations who are actually
out there on the ground in the communities and are getting the
information on an ongoing basis.
Even when we approve an antibiotic, we only look at a few
organisms. As you well know, physicians have to use diagnostic
criteria in the devices, the test for susceptibility, for a
wide range of organisms, many of which may not be in any drug
label. So we think we need a more dynamic and effective process
that reflects the ongoing experience in the community.
Mr. Gingrey. Dr. Woodcock, I have about 2 seconds. I want
to ask you to commit to me today to work with my office to fix
the breakpoint issue, as well as look toward other ideas to
address the epidemic of antibiotic resistance, one of the chief
threats to public health today.
Ms. Woodcock. We would be delighted to do that.
Mr. Gingrey. Thanks, Dr. Woodcock.
And I yield back, Mr. Chairman. Thank you.
Mr. Pitts. The Chair thanks the gentleman.
That concludes the questions for the members. I am sure
members will have follow-up questions. We would ask you to
please respond promptly once you get them.
I remind members that they have 10 business days to submit
questions for the record, and that means they should submit
their questions by close of business on Tuesday, December 3rd.
A very informative hearing. Thank you very much, and thank
you for your patience.
Without objection, the subcommittee is adjourned.
[Whereupon, at 12:17 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
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