[House Hearing, 112 Congress]
[From the U.S. Government Publishing Office]

FDA USER FEES 2012: HOW INNOVATION HELPS PATIENTS AND JOBS

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HEARING

BEFORE THE

SUBCOMMITTEE ON HEALTH

OF THE

COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES

ONE HUNDRED TWELFTH CONGRESS

SECOND SESSION

__________

APRIL 18, 2012

__________

Serial No. 112-136

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
JOE BARTON, Texas HENRY A. WAXMAN, California
Chairman Emeritus Ranking Member
CLIFF STEARNS, Florida JOHN D. DINGELL, Michigan
ED WHITFIELD, Kentucky Chairman Emeritus
JOHN SHIMKUS, Illinois EDWARD J. MARKEY, Massachusetts
JOSEPH R. PITTS, Pennsylvania EDOLPHUS TOWNS, New York
MARY BONO MACK, California FRANK PALLONE, Jr., New Jersey
GREG WALDEN, Oregon BOBBY L. RUSH, Illinois
LEE TERRY, Nebraska ANNA G. ESHOO, California
MIKE ROGERS, Michigan ELIOT L. ENGEL, New York
SUE WILKINS MYRICK, North Carolina GENE GREEN, Texas
Vice Chairman DIANA DeGETTE, Colorado
JOHN SULLIVAN, Oklahoma LOIS CAPPS, California
TIM MURPHY, Pennsylvania MICHAEL F. DOYLE, Pennsylvania
MICHAEL C. BURGESS, Texas JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee CHARLES A. GONZALEZ, Texas
BRIAN P. BILBRAY, California TAMMY BALDWIN, Wisconsin
CHARLES F. BASS, New Hampshire MIKE ROSS, Arkansas
PHIL GINGREY, Georgia JIM MATHESON, Utah
STEVE SCALISE, Louisiana G.K. BUTTERFIELD, North Carolina
ROBERT E. LATTA, Ohio JOHN BARROW, Georgia
CATHY McMORRIS RODGERS, Washington DORIS O. MATSUI, California
GREGG HARPER, Mississippi DONNA M. CHRISTENSEN, Virgin
LEONARD LANCE, New Jersey Islands
BILL CASSIDY, Louisiana KATHY CASTOR, Florida
BRETT GUTHRIE, Kentucky JOHN P. SARBANES, Maryland
PETE OLSON, Texas
DAVID B. McKINLEY, West Virginia
CORY GARDNER, Colorado
MIKE POMPEO, Kansas
ADAM KINZINGER, Illinois
H. MORGAN GRIFFITH, Virginia
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 EDOLPHUS TOWNS, New York
MIKE ROGERS, Michigan ELIOT L. ENGEL, New York
SUE WILKINS MYRICK, North Carolina LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee CHARLES A. GONZALEZ, Texas
PHIL GINGREY, Georgia TAMMY BALDWIN, Wisconsin
ROBERT E. LATTA, Ohio MIKE ROSS, Arkansas
CATHY McMORRIS RODGERS, Washington JIM MATHESON, Utah
LEONARD LANCE, New Jersey HENRY A. WAXMAN, California (ex
BILL CASSIDY, Louisiana officio)
BRETT GUTHRIE, Kentucky
JOE BARTON, Texas
FRED UPTON, Michigan (ex officio)

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. Joe Barton, a Representative in Congress from the State of
Texas, opening statement....................................... 2
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, prepared statement........................ 3
Hon. John D. Dingell, a Representative in Congress from the State
of Michigan, prepared statement................................ 4
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, opening statement.................................... 5
Prepared statement........................................... 5
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 6
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, opening statement............................... 7

Witnesses

Janet Woodcock, M.D., Director, Center for Drug Evaluation and
Research, U.S. Food and Drug Administration.................... 8
Prepared statement........................................... 10
Answers to submitted questions............................... 200
Jeffrey E. Shuren, M.D., J.D., Director, Center for Devices and
Radiological Health............................................ 44
Prepared statement........................................... 46
Answers to submitted questions............................... 200
David E. Wheadon, M.D., Senior Vice President, Scientific and
Regulatory Affairs, Pharmaceutical Research and Manufacturers
of America..................................................... 113
Prepared statement........................................... 115
Sara Radcliffe, Executive Vice President of Health, Biotechnology
Industry Organization.......................................... 122
Prepared statement........................................... 124
David Gaugh, R.Ph., Vice President, Regulatory Sciences, Generic
Pharmaceutical Association..................................... 135
Prepared statement........................................... 137
Joseph A. Levitt, J.D., Partner, Hogan Lovells US LLP, on behalf
of the Advanced Medical Technology Association................. 157
Prepared statement........................................... 159
Allan Coukell, Director of Medical Programs, Pew Health Group,
The Pew Charitable Trusts...................................... 172
Prepared statement........................................... 174

Submitted Material

Statement of the National Alliance on Mental Illness, submitted
by Mr. Pitts................................................... 194
Statement of the California Healthcare Institute, submitted by
Mr. Bilbray.................................................... 198

FDA USER FEES 2012: HOW INNOVATION HELPS PATIENTS AND JOBS

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WEDNESDAY, APRIL 18, 2012

House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The Subcommittee met, pursuant to call, at 10:15 a.m., in
room 2123 of the Rayburn House Office Building, Hon. Joe Pitts
(chairman of the subcommittee) presiding.
Members present: Representatives Pitts, Burgess, Shimkus,
Rogers, Myrick, Murphy, Blackburn, Gingrey, Latta, Lance,
Cassidy, Guthrie, Barton, Bilbray, Upton (ex officio), Pallone,
Dingell, Engel, Capps, Schakowsky, Matheson, Eshoo, Markey, and
Waxman (ex officio).
Staff present: Clay Alspach, Counsel, Health; Gary Andres,
Staff Director; Nancy Dunlap, Health Fellow; Paul Edattel,
Professional Staff Member, Health; Debbee Keller, Press
Secretary; Ryan Long, Chief Counsel, Health; Carly McWilliams,
Legislative Clerk; Monica Popp, Professional Staff Member,
Health; Chris Sarley, Policy Coordinator, Environment and
Economy; Heidi Stirrup, Health Policy Coordinator; Alli Corr,
Democratic Policy Analyst; Eric Flamm, FDA Detailee; Karen
Lightfoot, Democratic Communications Director, and Senior
Policy Advisor; Karen Nelson, Democratic Deputy Committee Staff
Director for Health; and Rachel Sher, Democratic Senior
Counsel.

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

Mr. Pitts. The subcommittee will come to order, and the
chair recognizes himself for 5 minutes for an opening
statement.
Today's hearing addresses the FDA user fee package
discussion draft. This draft is the product of over a year of
hard work by various parties. While the individual industries--
prescription drugs, medical devices, generic drugs and
biosimilar drugs--represented in this draft were negotiating
with FDA on their user fee agreements, this subcommittee was
holding at least 10 hearings on subjects related to the draft.
After intense negotiation between both sides of the aisle, we
have arrived at a discussion draft that I hope all members of
the subcommittee will be able to support.
There are still some outstanding issues that staff
continues to work on, and I hope that they can be resolved
before next week's subcommittee markup.
This package is critical to patients. It will ensure that
FDA has the resources and reforms needed to speed new drugs,
devices and treatments to those who are ill. These user fee
agreements will make the approval process more transparent,
more consistent and more predictable, benefiting patients, but
also keeping the United States the preeminent leader in drug
and device development and manufacturing.
Good-paying jobs in the drug and device industries, like
those in my home State of Pennsylvania, will be critical to our
economic recovery, and we cannot afford to outsource them.
I look forward to hearing from our witnesses today, to get
their thoughts and reactions on the discussion draft. \*\
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\*\ The discussion draft is available at http://
energycommerce.house.gov/sites/republicans.energycommerce.house.gov/
files/Hearings/Health/20120418/BILLS-112HR-PIH-UFAreauthorization.pdf.
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[The prepared statement of Mr. Pitts follows:]

Prepared statement of Hon. Joseph R. Pitts

Today's hearing addresses the FDA user fee package
discussion draft. This draft is the product of over a year of
hard work by various parties. While the individual industries--
prescription drugs, medical devices, generic drugs, and
biosimilars drugs--represented in this draft were negotiating
with FDA on their user fee agreements, this Subcommittee was
holding at least ten hearings on subjects related to the draft.
After intense negotiation between both sides of the aisle,
we have arrived at a discussion draft that I hope all members
of the Subcommittee will be able to support.There are still
some outstanding issues that staff continues to work on, and I
hope that they can be resolved before next week's Subcommittee
markup.
This package is critical to patients. It will ensure that
FDA has the resources and reforms needed to speed new drugs,
devices, and treatments to those who are ill. These user fee
agreements will make the approval process more transparent,
more consistent, and more predictable, benefitting patients,
but also keeping the United States the preeminent leader in
drug and device development and manufacturing.Good-paying jobs
in the drug and device industries, like those in my home state
of Pennsylvania, will be critical to our economic recovery, and
we can't afford to outsource them.
I look forward to hearing from our witnesses today, to get
their thoughts and reactions on the discussion draft.

Mr. Pitts. I yield the remaining time to the chairman
emeritus of the committee, Mr. Barton.

OPENING STATEMENT OF HON. JOE BARTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS

Mr. Barton. Thank you, Mr. Chairman, and thank you for
holding this hearing today.
Put me down, as I said at the last hearing you had on this,
as undecided on this particular bill. I know that you have
worked very hard and your staff has worked very hard and the
minority staff and members have worked very hard on the bill.
My basic problem is that I am not sure the FDA deserves a large
increase in user fees given the amount of money that they have
been receiving in general fund increases.
As you know, under the Patient Protection and Affordable
Care Act, there is a new 2.3 percent gross sales tax on the
sale of all medical devices in the United States beginning in
the year 2013. This tax is supposed to raise $20 billion to
help offset the cost of President Obama's $1 trillion new
health bill. A 2.3 percent tax is imposed on revenues, as you
know, and not profits, so that the tax applies to devise
regardless of they are sold at a loss. This is on top of the
current federal tax rate of 35 percent on corporate profits and
all State and local taxes in addition. It is obvious that
companies have less incentive to stay in the United States than
they did before these bills became law.
This Administration has indicated that the increased tax
will have little to no negative effect on medical innovation in
the United States. That just begs credulity, Mr. Chairman. When
you increase taxes across the board and then throw these user
fee increases on top of it, that has to have a negative effect.
It is simply a law of physics, so to speak.
In any event, I do want to commend you and others for
trying to come together on a bipartisan bill. I think it is
obvious by my comments that I may be a no vote but I do want to
be a positive part of the process if at all possible.
I want to thank our witnesses for being here today, and
with that, Mr. Chairman, I can yield the remaining 1 minute to
someone else or yield it back to you.
Mr. Pitts. All right. The gentleman yields back. The chair
recognizes the ranking member of the Subcommittee on Health,
Mr. Pallone, for 5 minutes.

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

Mr. Pallone. Thank you, Chairman Pitts.
Today, the subcommittee is meeting to hear testimony about
the released discussion draft concerning the prescription drug,
medical device, generic drug and biosimilar drug user fee
agreements as well as several other FDA-related proposals
including programs to foster the development of prescription
drugs for children, administrative and regulatory reforms at
the FDA, and drug shortages.
I will note as a matter of process that each of these
issues has had its own hearing in the subcommittee over the
course of the 3 months, and I want to commend Chairmen Pitts
and Upton and the staffs on both sides. We have worked very
hard to cover a lot of ground, and I would also like to thank
all the subcommittee members for their participation in these
hearings and I welcome their comments and suggestions on the
discussion draft as we continue to move forward.
Let me state that we have not yet reached full agreement on
the discussion draft in time for today's hearing. As we will be
seeing, the bill contains language largely identical to the
March draft released by the Republicans except for the brackets
surrounding a majority of the text. These brackets indicate
that the bill is a work in process and we continue to make
headway.
There are many issues that have been worked out.
Specifically, we have been able to make substantive changes to
the FDA reforms in this draft would have led to many unintended
and unacceptable consequences to FDA's regulatory scheme. We
have also been working hard to include language that would
equip the FDA with the authority and the resources it needs to
address a growing global drug supply. That language has come a
long way, and I am optimistic that we can strengthen it
further.
It is important to note that there are still key concerns
remaining but the process has been a good one to date and I am
hopeful that we can come together to address those outstanding
issues and generate a consensus, a bipartisan product that both
sides can support.
I just wanted to quickly comment on the four user fee
proposals that are the impetus behind this legislation. The
discussion draft is largely based on the agreements between the
FDA and the industry. These programs represent a critical
opportunity to work alongside FDA, industry and other
stakeholders to build upon and improve these critical programs.
Together we can help give patients access to safe, effective
and breakthrough medical treatments while supporting the
advancement of science and promoting a thriving life science
industry in the United States.
A particular note of course is the new generic drug user
fee agreement, which will dramatically improve the median
approval times for generic applications. This program will
cause an influx of generic drug products onto the market and
into the hands of consumers, thereby significantly lowering
health care costs.
I just want to welcome back our witnesses here today. You
have been a great resource to our subcommittee throughout this
process. We are eager to hear your opinions and your
suggestions, and I look forward to working with you, Chairman
Pitts, leading up to next week's scheduled markup to improve
the discussion draft further. And again, thanks for the
continued bipartisanship.
I would like to yield my 2 minutes left to the chairman
emeritus, Mr. Dingell.

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

Mr. Dingell. Mr. Chairman, I thank you for holding today's
hearing and I thank my good friend, Mr. Pallone, for yielding
to me.
I am delighted that we are having this hearing and I am
happy to work together with my colleagues in a bipartisan
consensus effort to achieve a good piece of legislation on food
and appliance and other performance by the FDA.
FDA's authorities are not sufficient to protect our drug
supply chain. Investigations by this committee found the FDA
not only lacks knowledge of how many drug manufacturing
facilities are operating overseas, what entities are importing
drugs or when incidents like adulteration, theft,
counterfeiting, contamination or repeated manufacturing
failures are posing health risks. FDA has lacked the authority
to detain or destruct harmful drugs, to prevent medical product
from entering the country if the manufacturer prohibits
inspection or to require importers to provide compliance
information at the border.
Current law has unintentionally created an unlevel playing
field which hurts our domestic manufacturers. While FDA
inspects domestic manufacturers every 2 years, it may or may
not inspect foreign manufacturing facilities, although it
occasionally gets around to it about every 9 years. This
committee must address these critical gaps in FDA's authority
and the knowledge of our entire food chain from active
ingredients to the patient's medicine cabinet. FDA ought to
know the parties who are manufacturing, distributing or
importing drugs and should be able to take action against those
who are allowing harmful drugs into the United States market.
We have before us today an opportunity to deal with the
shortage of money and personnel and see to it that we stop
making Americans sick or killing Americans by having a failure
to have Food and Drug have the ability to carry out its
responsibilities. I thank you, Mr. Chairman.
Mr. Pitts. The gentleman yields back, and I now recognize
the chairman of the full committee, Mr. Upton, for 5 minutes.

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

Mr. Upton. Thank you, Chairman Pitts, for today's hearing
on the reauthorization of the FDA user fees and the impact of
innovation on American patients and jobs.
Since the beginning of February, this subcommittee has held
six hearings on the FDA, and during these hearings, we have
heard from witnesses from around the country on how Congress
can help FDA become more predictable, consistent and
transparent and how that will foster innovation here in the
United States. I have heard this back home from my constituents
as well. I think we all agree that fostering innovation does
help American patients and aids in creating American jobs. As
part of our efforts to foster that innovation, we need to fix
the recent problems with the investigational device exemption
approval process and the medical device modifications guidance
document. Recent FDA policy changes have created some problems,
and we intend to use the user fee legislative process to
rectify them.
I really want to thank Mr. Waxman and Mr. Pallone and Mr.
Dingell and other members of this committee for their
constructive and bipartisan work to reauthorize these user
fees. During the past couple of months, we have had a number of
productive conversations on ways to improve the regulatory
process at FDA. As I said at the start of this process, we need
to reauthorize the user fees by the end of June to assure
continuity at the FDA and increase predictability for America's
medical innovators and job creators. We still have work to do
but because of the bipartisan commitment from members on both
sides of the aisle, I am convinced that we are on track to do
that, and I appreciate all the hard work, particularly from the
staff as they have spent countless numbers of hours working to
make sure that we can have a productive bill, and I yield the
balance of my time to the vice chairman of the subcommittee,
Dr. Burgess.
[The prepared statement of Mr. Upton follows:]

Prepared Statement of Hon. Fred Upton

I'd like to thank Chairman Pitts for holding today's
hearing on the reauthorization of the Food and Drug
Administration user fees and the impact of innovation on
American patients and jobs.
Since the beginning of February, this subcommittee has held
six hearings on the FDA. During these hearings, we've heard
from witnesses from around the country on how Congress can help
FDA become more predictable, consistent and transparent and how
that will foster innovation here in the United States. I have
heard this back home from my constituents too.
I think we all agree that fostering innovation helps
American patients and aids in creating American jobs. As part
of our efforts to foster innovation, we need to fix the recent
problems with the investigational device exemption approval
process and the medical device modifications guidance document.
Recent FDA policy changes have created major problems, and we
intend to use the user fee legislative process to rectify them.
I'd like to thank Ranking Member Waxman, Ranking Member
Pallone, Mr. Dingell and the other Democratic members of the
Energy and Commerce Committee for their bipartisan work on
reauthorizing the user fees. During the past few months, we've
had productive conversations on ways to improve the regulatory
process at FDA.
As I said at the start of this process, we need to
reauthorize the user fees by the end of June to assure
continuity at the FDA and increase predictability for America's
medical innovators and job creators. We still have work to do
but because of the bipartisan commitment from members on both
sides of the aisle, we are on track to do that.

OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS

Mr. Burgess. I thank the chairman for yielding. I want to
thank the chairmen of the full committee and subcommittee as
well as the ranking members of the full committee and
subcommittee for moving this legislation forward. I think the
manner that this has been approached is one that has been
constructive and certainly been respectful of individual member
concerns. We have been sensitive to patient concerns and we are
focused on finding an end product that is workable for the
agency and for the patients that it serves.
The impact of these areas, the medical device, the
pharmaceutical, the biologic and generic industries of the
United States certain reaches farther than the patients that
benefit from them, and we will hear a lot about job creation
and help to the economy, but the patient concerns must remain
our primary focus. And these industries do affect commerce.
They affect technology. They do affect the economy and they
provide quality jobs to Americans, which range from the
scientific to the highly skilled and technical and those
involved in their manufacturing.
The Food and Drug Administration has one of the most
important missions of any federal agency to ensure that medical
products are safe and effective. They are also the gateway to
providing patients with products that help them maintain their
health, perhaps help them live with a chronic condition. We
have to be certain that that gateway does not become a
bottleneck. I think there are constructive updates that can be
made and I appreciate so much the discussion draft now being
out there for all of us to reflect and offer our thoughts.
Again, I want to thank the chairman for his approach to the
process, thank our witnesses for their willingness to come
before this committee multiple times, for the transparency that
they have exhibited and the fact that this has come through
under regular order and that the chairman has worked to a
product which I think both sides of the dais can justifiably be
proud, and I----
Mr. Shimkus. Will the gentleman yield?
Mr. Burgess. Yes, I will be happy to yield.
Mr. Shimkus. Thank you. I want to just take a minute and
talk about this process and some of the reforms that are
proposed and just make the point, especially in two areas that
I have been interested in, the investigative device exemption
and the 510(k) modifications.
The attempt is really to remedy through public policy
changes in the operation that the FDA has done in the last
couple years. So it is an attempt to return back to a day when
these two areas were working and we weren't losing innovation
and jobs and folks moving overseas to get these approvals. And
so I hope that you all will when we get into that part of the
discussion receive it in the attempt that we are trying to
portray it. We really want to get back to where we don't have
this backlog and we are the innovators, we are the producers
and we lead the world again.
I yield back my time.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the ranking member of the full committee, Mr.
Waxman, for 5 minutes for an opening statement.

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

Mr. Waxman. Chairman Pitts, thank you for holding this
hearing today.
Although we were not able to come to full agreement in time
for the discussion draft released yesterday, I am pleased with
the progress that we have made on this user fee package thus
far. I am optimistic that we will get to full agreement soon.
We all know how important it is to reauthorize the underlying
user fee programs in a timely way. No one is served by adding
controversial proposals to the bill. That would only serve to
slow the process.
So far, we have worked together to avoid weighing down this
critical legislation with extraneous policies about which we
cannot agree. This will ensure that we get the work on these
critically important bills done in time.
I am particularly hopeful about the progress we have made
in the area of drug safety as it relates to the increasingly
globalized supply chain. Mr. Dingell has a strong bill that has
served as a template in this area, and I appreciate all the
work that Mr. Upton and Mr. Pitts have done to incorporate
provisions modeled on that bill.
I want to note however that I continue to have strong
concerns with respect to devices. We have all heard the
increasing rhetoric that FDA is slowing innovation and forcing
jobs abroad, but that does not justify the troubling provisions
that could compromise patient safety that are under
consideration. There are numerous examples of unsafe medical
devices that have been permitted on the market and have caused
incalculable suffering for victims. And that occurs under the
current system with the powers FDA has today. Now is not the
time to go backwards and take away important authorities from
the FDA that it needs to help ensure the safety and
effectiveness of devices. I will continue to oppose any
addition of any provisions that would prevent FDA from doing
what it feels necessary to protect patients from unsafe and
ineffective devices.
Let me turn now to the area of antibiotics. The discussion
draft includes the GAIN Act, which is a good first step toward
creating incentives for the development of new antibiotics,
which we all agree we desperately need. I remain concerned that
the bill does not narrowly target antibiotics that treat
dangerous infections for which we don't have adequate
treatments. The bill should also include provisions to ensure
that the efficacy of these newly developed antibiotics is
preserved once they are on the market. These are goals we
should all share and I am optimistic that we will fix the bill
to achieve them.
I also look forward to learning more today about the
proposal put forward by the Infectious Disease Society of
America, the Limited Population Antibacterial Drug, or LPAD--it
sounds like a new technical device sold by Apple--approval
mechanism. This proposal would establish a more rapid
regulatory pathway for new antibiotics targeted at the most
serious infections.
The concept appears to have great promise at speeding
important new antibiotics to the market, but I think we need to
be assured that these drugs will not be inappropriately used.
If we cannot get that assurance, we should all be concerned
about moving forward with this kind of proposal.
Strengthening and improving FDA is in the interest of all
Americans. I look forward to continuing to work with all of my
colleagues on this committee to reach bipartisan agreement on
this critically important legislation, and I yield back the
balance of my time.
Mr. Pitts. The chair thanks the gentleman.
We will now to go to panel one. We have two panels today.
Our first panel will have two witnesses: Dr. Janet Woodcock,
Director of the Center for Drug Evaluation and Research at the
FDA; and Dr. Jeffrey Shuren, Director, Center for Devices and
Radiological Health. We are happy to have both of you here
today.
Dr. Woodcock, you are now recognized for 5 minutes for your
opening statement.

STATEMENTS OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, U.S. FOOD AND DRUG ADMINISTRATION; AND
JEFFREY E. SHUREN, M.D., J.D., DIRECTOR, CENTER FOR DEVICES AND
RADIOLOGICAL HEALTH

STATEMENT OF JANET WOODCOCK

Dr. Woodcock. Thank you. Mr. Chairman, members of the
subcommittee, thank you for the opportunity to testify about
the three important drug user fee proposals that are laid out
in the discussion draft. Each of three drug user fee programs
is important for the public, and will, if enacted, impact
positively on patients, industry and on biomedical innovation.
The fifth iteration of the prescription drug user fee
program contains important advances for regulatory science and
patient-centered drug development as well as maintaining
consistent and predictable review process for the innovator
industry. The biosimilars user fee program will support the
growth of a new industry and will help provide more affordable
biological drugs to the public. Both I think are very important
public goals.
The generic drug user fee program as proposed would
represent a historic agreement to maintain a high and uniform
level of drug quality no matter where the drug is sourced in
the world. It also will ensure a robust and predictable path to
market for generic drugs that should invigorate the industry.
That said, implementation of these three new programs if
enacted will create a significant body of work for the agency.
We are eager to undertake this but we are wary of additional
provisions, unfunded provisions. The experience after the FDA
Amendments Act I think is illustrative. While FDA implemented
the many needed safety programs that were stipulated in the
Amendments Act, we had to miss a number of user fee goals under
the prescription drug user fee program and slow down our review
process, and while that was a worthy tradeoff, we have to
recognize that any additional provisions will have tradeoffs on
workload.
I understand that there are other policy issues and
development challenges that are unaddressed by the user fee
proposals, which are really about process and procedures, and I
am happy to answer questions about these issues and I really
look forward to the discussion. Thank you.
[The prepared statement of Dr. Woodcock follows:]

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Mr. Pitts. The chair thanks the gentlelady.
Dr. Shuren, you are recognized for 5 minutes for your
opening statement.

STATEMENT OF JEFFREY SHUREN

Dr. Shuren. Mr. Chairman and members of the committee,
thank you for the opportunity to testify today.
As you know, on February 15th, FDA and representatives from
the medical device industry reached an agreement on proposed
recommendations for the reauthorization of the Medical Device
User Fee Act, or MDUFA, the details of which we provided to you
on March 16th. As required by law, we held a public meeting on
March 28th and sought public comment on the proposal package.
We plan to send the final package to you by the end of this
week.
When I came to CDRH in 2009, in response to concerns
expressed by industry and others, we initiated a review of our
device premarket review programs. The following year, we
released two reports that concluded as I have testified before
that we had not done as good a job managing the review programs
as we should have. The number one problem we found was
insufficient predictability, which was leading to
inefficiencies, higher costs for industry and FDA, sometimes
delays in bringing safe and effective products to market.
In January 2011, we announced a plan with 25 specific
actions that we would take that year to improve the
predictability, consistency and transparency of our premarket
programs. We announced additional steps since then. As of
today, 30 actions have been completed or well underway. They
are intended to create a culture change toward greater
collaboration, interaction, transparency and the appropriate
balancing of benefits and risk. They focused on assuring
predictable and consistent decision making and application of
the least-burdensome principle and implementing more efficient
regulatory processes.
Preliminary data indicate that the actions we have taken
have started to bear fruit. For example, the backlog of 510(k)
submissions that had been steadily increasing from 2005 to 2010
decreased for the first time last year and are continuing to
decline in 2012. The backlog of PMA submissions that had been
steadily increasing from 2007 to 2011 has decreased this year
for the first time, and average total time for review appears
to be decreasing for the first time as well.
However, we still have much work to do. Reauthorization of
MDUFA will provide the resources that CDRH needs to continue
improving the device review programs and help reduce the high
staff turnover that has adversely affected review
predictability and consistency. The proposed MDUFA
recommendations we have agreed upon with industry includes
several important process improvements. For example, if a
performance goal on a device application is missed, the MDUFA
proposal would require FDA and applicants to work out a plan to
complete the work on the submission, ensuring that no
submission would be left behind, and requiring a new
substantive interaction between FDA and an applicant would help
assure sufficient time for the applicant to properly respond to
appropriate questions. These and other proposed enhancements
are intended to achieve a shared outcome goal of reduced
average total time to decision, which both we and industry
believe is an important indicator of a successful premarket
review program.
The agreement we have reached with industry strikes a
careful balance between what industry agreed to pay and what
FDA can accomplish with the amount of funding proposed.
However, we have concern that even if device user fee resources
are increased under MDUFA III, additional new legislative
mandates imposed on CDRH could divert resources and undermine
FDA's ability to achieve the new performance goals. We are very
willing to work with Congress on initiatives that complement
the user fee agreement. However, just as FDA and industry
mutually agreed that some initiatives would be part of the
formal agreement, we also agree that some initiatives would not
be part of the agreement. Additional legislation to codify
initiatives the agency and industry chose not to devote
resources to risks diverting resources from achieving MDUFA
goals and could undermine the user fee agreement entirely.
When PDUFA was last reauthorized in 2007, as you heard, the
addition of new policy-related requirements ultimately resulted
in FDA's drug review program having to temporarily suspend
meeting its PDUFA review goals in order to meet the statutory
mandates. We want to avoid such a situation so that CDRH can
focus on meeting the ambitious new proposed MDUFA program goals
and achieving timely patient access to safe and effective
devices, which is an objective that we share with industry,
health care practitioners, patients, consumers and you.
Mr. Chairman, we share your goal of timely reauthorization
of MDUFA. We look forward to working with you toward enactment
of this critical legislation. I commend the subcommittee's
efforts and am pleased to answer any questions the subcommittee
may have. Thank you.
[The prepared statement of Dr. Shuren follows:]

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Mr. Pitts. The chair thanks the gentleman.
I will begin the question period and recognize myself for 5
minutes for that purpose. Dr. Woodcock, we will begin with you.
In your testimony, you say that FDA is expediting manufacturing
change submissions to help with drug shortages. In the
discussion draft, we include a section on expediting
manufacturing changes that will alleviate a drug shortage. In
talking with patients and manufacturers and providers, they
tell me it is one of the best parts of the discussion draft and
it will really help with shortages. Do you agree with those
patients, providers and manufacturers that expediting
manufacturing changes that will alleviate drug shortages is a
good idea? I would like your comments on that section.
Dr. Woodcock. We are currently able to expedite
manufacturing changes and we do to alleviate shortages or to
prevent them if we hear about them in advance. So we do not
need authority authorities to expedite a review of
manufacturing changes or implementation by manufacturers.
Mr. Pitts. All right. What is the latest on medical gases?
We had a hearing on this issue. Will you have a proposal to
share with the committee by the end of the week on this?
Dr. Woodcock. Well, both parties will have to. We are in
active discussions with the association. I have had personal
meeting with the association and my staff and there have been
multiple additional discussions. I think we are in substantial
agreement but we are continuing to go back and forth and make
sure we have all the details nailed down, so I can't guarantee,
because it is only my side of it, that it will done by the end
of the week but we certainly are working very hard on bringing
this to a conclusion.
Mr. Pitts. The user fee discussion draft includes language
to enhance FDA performance reporting in the drug space by
including division-level data. I believe there is great value
in regularly gathering and analyzing the best possible data in
order to understand where there are working and where they need
improving. Collecting more granular information at the review
division level will allow FDA management, patients, industry
and Congress to better identify where things are working and
where improvements are needed. As an example, in November of
2011, the agency issued a report citing the approval of 35
innovative drugs that represented advances in treatment for
many serious disorders. If we had division-level data, we could
better understand what practices led to such an accomplishment
and how we could apply those lessons in other areas. Do you
agree that collecting, reporting this information is a good
idea given that it will help us understand how we can apply
these best practices in other parts of the drug center and
agency? Would you comment on that, please?
Dr. Woodcock. Certainly. We have calculated the
requirements for personnel and investment in generating
additional formal reports. We really do believe in transparency
of all our processes, and I believe I as a manager am
accountable to you and to the public to make sure that we
review particularly lifesaving or life-altering drugs as
rapidly as possible. It is one of my highest priorities.
However, setting up additional reporting systems, we calculate
would cost us $4.7 million based on what is laid out in the
draft and would require 15 FTEs, or full-time equivalents, of
people to work on that. Those people would be diverted from
working on reviewing the applications.
Now, the division-by-division variability in how many
applications come out and how many of those are approved and so
forth is primarily a function of the input. So right now, if
you looked at it sort of naively, you would say our cancer
group is like the most productive group and they do the best
job. But they get--right now there is a renaissance of cancer
therapies based on the molecular knowledge of cancer that has
been generated and so they are able to approve--we are seeing a
lot of very good applications and we are able to approve those
rapidly.
So I don't think you can make a cause-and-effect link
between what comes out in a given disease area and their
particular productivity. For example, I think our neurology
division is wonderful and does a fantastic job but we haven't
been able to approve a lot of new drugs for Alzheimer's because
those drugs have failed in development.
Mr. Pitts. The chair thanks the gentlelady. My time is
expired.
I yield to the ranking member, Mr. Pallone, for 5 minutes
for questions.
Mr. Pallone. Thank you, Mr. Chairman.
I am going to start with Dr. Woodcock and may able to get
to Dr. Shuren if there is time. Well, first, welcome back, and
I appreciate your being with us again today. I wanted to focus
on review times for Abbreviated New Drug Applications, or
ANDAs. Under current law, what is the length of time in which
the FDA is required to review generic drug applications?
Dr. Woodcock. This is like a quiz. I think it might be----
Mr. Pallone. At least it is not yes or no.
Dr. Woodcock. I think it is 180 days.
Mr. Pallone. OK. And what is the median review time for
ANDAs today?
Dr. Woodcock. Currently, the average or median or
approximately average review time is 30 months.
Mr. Pallone. And how long do you think it will take to
significantly reduce the review times for generic drug
applications?
Dr. Woodcock. I believe if the proposed user fee program
that is put within the discussion draft is enacted, within
several years we will be seeing a greatly improved performance.
Mr. Pallone. And then can we expect to see any meaningful
reduction in review times in year one or year two of the
generic user fee program?
Dr. Woodcock. We will certainly try. However, we have a
backlog that comprises almost--there are 2,600 applications in
the queue that we have to clear out, and that would be our
first priority.
Mr. Pallone. Chairman Pitts just asked and referred to the
discussion draft on PDUFA, and I guess on pages 18 and 19 there
is some bracketed language that will require FDA to report to
Congress on various statistics about the agency's drug reviews,
and I wanted to ask you about this language. Was this part of
the negotiated user fee agreement?
Dr. Woodcock. Could you repeat the question?
Mr. Pallone. Sure. I'm talking about PDUFA, and the
chairman asked and referred to the discussion draft. On pages
18 and 19, there is some bracketed language that would require
the FDA to report to Congress on various statistics about the
agency's drug reviews. I don't think that was part of the
negotiated user fee agreement, correct?
Dr. Woodcock. Yes, that was not part of what we negotiated
with the public and with industry, and it was not accounted for
in the resource calculations for the user fee.
Mr. Pallone. So that was my question. I am concerned about
putting a burden on the agency that is not funded by user fees
and could result in an unwarranted reshuffling of resources
that Congress intended to be dedicated to other activities, and
I think we need to be careful when we start opening up the
PDUFA agreement. I don't know if you wanted to comment on that
a little more.
Dr. Woodcock. Yes. I believe, as I said, very highly
believe in transparency and accountability of the new drug
review program to the public, to Congress and to any of our
stakeholders. However, we feel these additional tracking
requirements when unfunded will divert us from actually
accomplishing the objectives that are laid out by Congress in
the user fee agreement.
Mr. Pallone. Now, let me go to Dr. Shuren for a question. I
have a couple minutes or less. I wanted to ask you about one of
the provisions in the discussion draft related to devices,
specifically Section 706 would change the standard for when
device manufacturers are required to submit a new 510(k)
application for changes to their already cleared devices. It
might seem like an arcane issue, but I know it is an extremely
important one. Permitting companies to make changes to their
devices without first obtaining FDA clearance could result in
devices on the market over which the FDA had had very little
oversight and knows very little about. Industry of course would
say that if they are just making small changes to the device,
there is no need to go through the 510(k) process again. But I
wanted to get a better sense from you about what is going on
here. Is there a need for any change here? Can you speculate on
why the language of 706 is being included in the draft, and
basically does the FDA have concerns about the language in
Section 706?
Dr. Shuren. We believe the existing standard that we have
for modifications is a good one. Most modifications made to a
device do not come to the FDA for review. The only ones that
come are those that could significantly affect safety or
effectiveness. The issue right now is about a guidance we put
out on modifications that we did not put out with the intention
of increasing in any significant way the number of 510(k)s
coming in but provide greater clarity in places that have been
gray zones and emerging technologies. We recognize there are
many concerns with the guidance. That is why we have had lots
of meetings with industry. We have even had two all-day
meetings with a group of companies, trade associations coming
in the door and raising their issues and working it through.
Our intent is to get that guidance right, and we know because
of the concerns, our plan is, we would actually put out a new
draft guidance and make sure we work it out.
Our concern with what has been proposed in the legislation
is it would change the existing approach that we had that had
been working for many years, and instead changes it to only
submit if it does significantly affect safety and
effectiveness. If it does affect safety and effectiveness, you
don't submit a 510(k). The product wouldn't come on the market.
So essentially companies will be making changes to their
devices and none of those changes will be coming to the FDA for
review. That causes significant concern. You have devices like
linear accelerators that blast radiation at patients to treat
cancers. You can now make modifications that can impact that
technology, and we won't see it, and we have plenty of cases
where companies made changes, they did some testing, and there
were big problems that but for the FDA review, those unsafe
technologies would have gotten to patients, and that is what we
worry would happen with this change in the law.
Mr. Pallone. All right. Thank you, Doctor.
Mr. Pitts. The chair thanks the gentleman and now yields to
the vice chairman of the committee, Dr. Burgess, 5 minutes for
questions.
Mr. Burgess. Thank you, Mr. Chairman.
Dr. Shuren, we might come back to the issue of
modifications if I have time, but let us talk for a minute
about the 510(k) process. It is my understanding that when the
Food and Drug Administration clears a device through the 510(k)
process, it tells the company that they have received a
substantial-equivalence determination and then the FDA sends a
letter to the company that expressly states, please be advised
that the FDA's issuance of a substantial-equivalence
determination does not mean that the FDA has made a
determination that your device complies with other requirements
of the act, that being the Food, Drug and Cosmetic Act. Is that
a correct statement?
Dr. Shuren. As a paraphrase, and then the company is
responsible for assuring they have met what we have called
general controls, things that pertain to reporting requirements
or labeling or meeting our quality systems or Good
Manufacturing Practices.
Mr. Burgess. If there is a device that is found to be
defective that has been approved under a 510(k) authority and
another device is found to be substantially equivalent, because
of the defect that you discovered in the predicate device, you
would do something to prevent that follow-on device from going
to the market. Is that not correct?
Dr. Shuren. What we do in those cases, and there are
limited cases, we try to--within our authority we might put
explanations in the labeling, try to address it as best we can.
The challenge is that those may be ineffective. Right now,
there is not a responsibility on the part of the manufacturer
to show that if they replicate a design flaw, for example, that
they have put in appropriate mitigations to make sure that does
not affect patient safety or effectiveness. It has been
proposed by some in industry what we would do is, well, you
would clear it. They could go to market and then you would
build a legal case to say it is misbranded and then take an
enforcement action against the company, which kind of puts the
cart before the horse. In reality, what we do is clear a
device, then maybe take an enforcement action, and what they
would have to do is actually come back in the door with another
510(k). So we do what we can with the authorities that we have
but it is not a perfect solution. There is a way of solving it
that focuses very narrowly----
Mr. Burgess. Please let me ask a question so I am sure that
I understand it. Right now you are compelled to approve an
unsafe device under the 510(k) program?
Dr. Shuren. Well, compelled to determine that there is
substantial equivalence between the predicate and the new
product.
Mr. Burgess. Right. So substantial equivalence, but then
that does not necessarily infer that there is approval to
market the device under the Food, Drug and Cosmetic Act. Is
that correct?
Dr. Shuren. The terminology, just so we have it right, is
clearance. The manufacturer is then responsible for meeting the
other requirements of the law to then put it on the market but
they do not wait for any other affirmative determination by the
agency to go to market.
Mr. Burgess. This is important, and I am not trying to be
argumentative, but has the FDA allowed products that they know
to be harmful to reach the market?
Dr. Shuren. We believe that we have tried to take the best
actions we can to assure that the devices that come to market
are safe.
Mr. Burgess. Well, why didn't you just immediately say
these are misbranded and must not be marketed?
Dr. Shuren. So in the few cases where this has happened, we
have tried to either address it with labeling and it is our
hope that that will be an adequate mitigation. What we don't
have in a normal case in premarket review is the data to
support that it would be an adequate mitigation.
Mr. Burgess. Can you provide this committee--you keep
saying there are a limited number of examples. We actually need
to see those cases. I have to tell you, that concerns me
greatly that the Food and Drug Administration for all of the
heft that you have has allowed devices to come to the market
that may be inherently unsafe that you knew were unsafe before
they were marketed. So can you please--how many cases do we
have like that? You say there are a few but is it like three or
five or nine?
Dr. Shuren. There are a handful. We will get you some of
them. We would be happy to do so.
Mr. Burgess. All of them, Dr. Shuren. We need all of them
because we have to make a determination about where the process
is not working because clearly this is--I don't believe you
want it and I certainly don't want it where the FDA is
approving, because of a finding of substantial equivalence,
allows a device to come to market that is inherently unsafe. I
don't understand, why would you not issue a mandatory recall
immediately?
Dr. Shuren. Well, first of all, a mandatory recall, if
there is a problem, first of all, that we find the problem
thereafter. We tend to work with the company for a voluntary
recall. A mandatory recall winds up taking--can actually take
several years because it involves a formal hearing, and
oftentimes we work with the company----
Mr. Burgess. All I know is, in a medical staff situation,
if you know you have a provider, a doctor, who presents a clear
danger to patients, I mean, there is an immediate revocation of
that person's privileges. I don't see why the same should not
apply within your agency in the device world.
Dr. Shuren. No, I appreciate that, and if folks think that
we actually have the authority to do that right now and
immediately stop it from going to market, it would be helpful
to us then to provide that clarity in legislation.
Mr. Burgess. Well, and part of the clarity is providing us
the cases because that is--Mr. Chairman, I think we may need to
involve the Subcommittee on Oversight and Investigations to
look into this because this is a fundamental issue of patient
safety, and if the primary federal agency charged with
providing that drugs and devices are safe and effective is not
meeting that first goal, that is a serious, serious problem,
and I will yield back my time.
Mr. Pitts. The chair thanks the gentleman and now recognize
the ranking member of the full committee, Mr. Waxman, 5 minutes
for questions.
Mr. Waxman. Thank you very much, Mr. Chairman. The point
Mr. Burgess raised is an important one, and if you feel you
need stronger or clearer legislation in that area, let us know
because we are concerned about whatever, even a handful of
devices that may be harmful.
Dr. Woodcock, I would like to ask you about two proposals
designed to help get new important antibiotics to market. One
is GAIN and the other is LPAD. First of all, on GAIN, we know
the pipeline for new antibiotics is essentially dry. It is a
serious public health threat and it is clear that we need to
look at ways to incentivize the development of these lifesaving
drugs. One way to do that, of course, is to provide additional
exclusivity. I think whenever we talk about adding new
exclusivity, we need to ensure that it is truly necessary, and
in this case, I think a good case can be made that it is, but
then it should be narrowly targeted so that only the drugs we
need to have developed are rewarded with this generous prize,
and exclusivity is often very generous and you never get it
back even when it is no longer valid or useful.
I am concerned that the language in the discussion draft
does not adequately target, and I want to get your views on
that subject. As I read it, the legislation would provide 5
years additional exclusivity to an antibiotic that received FDA
approval based only its ability to treat or prevent essentially
any antibiotic-resistant bacterial pathogen. I think this
legislation should be narrowly targeted and only apply to
antibiotics approved for serious or life-threatening diseases
for which there is an unmet medical need. I would like to know
whether you agree. If so, how would that work in practice? Is
that a standard FDA could easily apply?
Dr. Woodcock. We do apply a standard on approval on review
called the Priority Review, and we determine whether or not a
product would be an advance in its class or is simply yet
another option amongst multiple options, so we do have some
experience in applying some standard like that. I think of
course it is up to Congress how you weigh these different
tradeoffs as far as the affordability of drugs versus their
availability. You don't want to set up an incentive program, in
my opinion, that drives developers toward the broadest market
and thus to neglect potentially those challenging areas of,
say, drug-resistant organisms, which is where we have the
greatest need for new antibiotics. But because that is a narrow
market, if you do an incentive program, often the desire is to
apply that to the broadest market possible to gain the most
obviously profit from doing that. So I think Congress needs to
think about what incentive you are offering and how is that
incentive going to operate, and will it operate to solve the
problem that has been identified. There are several problems.
One problem is, we don't have antibiotics----
Mr. Waxman. Let me--it is very helpful but then I think
about all the things I still want to ask. So you agree that we
ought to be sure to narrowly focus this incentive because
otherwise an incentive becomes just very beneficial to those
who get it but not really solving the main problem that we
have. Is that correct?
Dr. Woodcock. I believe that Congress ought to define the
problem that you are trying to address and make sure you design
an incentive that incentivizes drug development to solve that
problem.
Mr. Waxman. I want to ask you about the LPAD approach. This
has been discussed by the Infectious Disease Society of
America, and as I understand it, this approach is intended to
establish a more rapid regulatory pathway for new antibiotics
targeted at the most serious infections. The risk-benefit ratio
for such antibiotics will often support more narrowly tailored
clinical trials that are needed for other antibiotics. A
fundamental aspect of this proposal is that it would require
that any antibiotic approved under this pathway bear a strong
label statement describing the limited population of patients
with serious or life-threatening infections for which the drug
had been approved and noting that its safety and effectiveness
had not been established beyond this limited population.
Companies would have to provide their promotional materials to
FDA before distributing them. It seems this kind of approach
could really get help critically important antibiotics on the
market more rapidly than otherwise possible. However, for it to
work as intended and for it not to lead to lowering of the
approval standard, it has to have effective mechanisms for
ensuring that antibiotics approved for small populations are
indeed used by those small populations. I would like to hear
your views on whether you think LPAD maintains that balance.
Specifically, do you think that it will facilitate the more
rapid approval of important new antibiotics for limited
populations, and do you think that there are adequate controls
to prevent widespread off-label use in a much broader
population than for which it was tested and approved?
Dr. Woodcock. Yes, and yes. I believe that probably a
narrow development program, and we could offer, we believe, a
radically smaller development program than for an antibiotic
intended for broad uses is a stronger incentive than
financial--than exclusivity, number one. And number two, we
believe that particularly if Congress were to make a statement
about the antibiotic stewardship of this class of products,
good stewardship in the market, that that would have the effect
of limiting the use.
Mr. Waxman. Thank you.
Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Illinois, Mr. Shimkus, for 5 minutes for
questions.
Mr. Shimkus. Thank you, Mr. Chairman. Thank you all for
coming.
Dr. Woodcock, I agree that Congress needs to define a
problem we want to address, and that is part of this process of
the hearing and also some of the bills that have been
introduced. So I couldn't agree more, and of course, I will
focus mine on the IDE and the 510(k) issue.
First of all, Dr. Shuren, you said that the number of
applicants is down. Is that what you said in your opening
statement?
Dr. Shuren. No, the backlog, so the number of 510(k)s that
are still under review at the end of the year has gone down. It
had been going up for 510(k)s since 2005 every single year.
Mr. Shimkus. OK. Let me follow up then. According to
companies who I have talked to, your draft guidance could
increase 510(k) submissions by 300 to 500 percent. Do you agree
with that? And do you have the capability to respond to that if
that is the case?
Dr. Shuren. So first of all, we don't know if that number
is correct.
Mr. Shimkus. Have you heard that number before?
Dr. Shuren. We have heard that number before. But putting
aside whether data support that or not, we agree there are
concerns with the policy we put out, which is why we are
working with industry to make adjustments and try to get it
right. Our intent is not to see----
Mr. Shimkus. And that is what we are trying to do
legislatively also in response to what Dr. Woodcock said that
we should define a problem we want to address and we are trying
to legislatively address that problem.
Let me go to the IDE real quick, and you have also--a
couple concerns. First of all, one is that we do have an issue
that we think disregards the Administrative Procedures Act in
that it acts as--the guidance contradicts regulation so concern
one on that. It also--we do think it also could be not in
compliance with the Federal Food, Drug and Cosmetic Act and a
former IDE administrator says, and I quote, ``It does not look
like the authority is there to disapprove an IDE based upon the
fact that FDA doesn't anticipate that it would support a
marketing approval or clearance.'' So the question is, how have
innovators reacted to your policy change?
Dr. Shuren. There have been concerns raised of what we
would not consider truly a policy change. Our IDEs, we will not
approve if it doesn't provide sound science or if the
investigational plan is inadequate. Now, what we said in the
guidance is, if it is a pivotal clinical trial and a pivotal
clinical trial is intended to demonstrate safety and
effectiveness----
Mr. Shimkus. The question is, how have the innovators
reacted? What have the innovators told you? I can tell you what
they have told me.
Dr. Shuren. So their concern is whether or not this will
actually lead to our not approving more clinical studies than
before. We think the language may not have articulated clearly
what we are talking about. That is namely that if you submit a
study that is producing sound science for its intended purpose,
what it is intended to do. In case of a pivotal trial----
Mr. Shimkus. Let me--I only have a minute and 40 left. One
innovator told me that in 2012, he will only have been in the
United States for 5 weeks prior to the first 5 months of the
year because he had to do clinical trials overseas. That is
what we are hearing from innovators based upon this policy, and
I think if the policy is questionable that it is against the
Administrative Procedures Act and legally may be against the
Federal Food, Drug and Cosmetic Act, I think that would raise
some concerns as to the policy which is new and implemented
under the last couple of years.
Let me go to funding. In the last hearing, you did talk
about funding and the like. Is it true that even under the
agreement which doubles the user fees that FDA gets from
industry, you will still get about 70 percent of your CDRH
budget from appropriations?
Dr. Shuren. About 65 to 70 percent of funding will come
from----
Mr. Shimkus. So you will have other non-user fee funds that
are appropriated by Congress?
Dr. Shuren. That is correct.
Mr. Shimkus. Shouldn't Congress be able to give direction
on how these funds are spent?
Dr. Shuren. Congress has broad authority to weigh in on how
we should actually use our funds.
Mr. Shimkus. Thank you. Isn't it true that the FDA
undertook activities during the life of MDUFA II that were
significant resource investments and outside the agreement? And
you probably know what I am talking about, the Institute of
Medicine report that was unfinished and not totally accurate?
Dr. Shuren. First of all, the IOM report, we didn't pay out
of any user fee dollars.
Mr. Shimkus. Right, and $1.3 million of taxpayer funds went
to the IOM report.
Dr. Shuren. Well, there were concerns raised on the 510(k)
program, how well it was operating to meet the----
Mr. Shimkus. But there was obviously concern about the
accuracy of the IOM report also.
Dr. Shuren. Well, we did disagree with one of their
recommendations regarding the 510(k) program. We actually
agreed with most of their other recommendations.
Mr. Shimkus. Thank you, Dr. Shuren. I appreciate your time.
Dr. Shuren. But I do want to make the point on clinical
trials, because it is an important one, and we don't want
innovators going overseas, but quite frankly, if we are
approving a clinical trial and we are putting our name on it
saying that this study is good enough to show safety and
effectiveness but it doesn't and it is not going to then
support that product coming to market, then we have put
patients at risk because they are----
Mr. Shimkus. But they are going overseas.
Dr. Shuren. And then the companies come in the door, and
this is exactly what was happening, with studies that then they
weren't getting their products approved, and that is the worst
thing for the company and it is the worst thing for patients.
So the policies we have put out have actually tried to address
the real problem, which is reviewers who are coming back to ask
for a study that quite frankly they believe is the better study
but that is not the point. It is the least-burdensome
principle. They need to put out the study that is least
burdensome and approve it. And the second is that they were
holding up approvals trying to address questions that were not
relevant at that time for making a decision and so draft policy
we put out in the fall was meant to readjust that so that we
were freeing up and making decisions and approving products. In
fact, we are now seeing that first cycle approvals for clinical
trials are going up.
Mr. Shimkus. And I would just end by saying what I think we
have done is moved our innovators overseas, and I yield back my
time.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the ranking member emeritus, Mr. Dingell, for 5
minutes for questions.
Mr. Dingell. Mr. Chairman, thank you. I commend you for
this meeting of the committee and for your fine cooperation in
framing this legislation and working with the minority. I also
want to express the same commendations to our distinguished
chairman.
These questions go to Dr. Woodcock. Please respond yes or
no. The heparin incident made it clear that there needs to be
robust communications between drug manufacturers and FDA
regarding unsafe or compromised drugs. Currently, does the
Food, Drug and Cosmetic Act require manufacturers to notify FDA
if they have reason to believe that their products have been
adulterated, contaminated or misbranded prior to distribution?
Yes or no.
Dr. Woodcock. No.
Mr. Dingell. Are drug manufacturers currently required to
notify FDA if their drug has been stolen, counterfeited, lost
or there have been repeated manufacturing quality incidents?
Yes or no.
Dr. Woodcock. My understanding is that they do have to
notify us for quality problems under field alert reports. The
rest is no.
Mr. Dingell. OK. Now, would requiring drug manufacturers to
report such information to FDA confer benefit on the public
health?
Dr. Woodcock. Yes.
Mr. Dingell. As FDA continues to regulate an increasingly
globalized market, the ability of FDA to work and share
information with trusted foreign regulatory counterparts is
critical. Do you believe that, and is that a correct statement?
Dr. Woodcock. Yes.
Mr. Dingell. Doctor, is it true that FDA only shares
commercial confidential information with State, local or
trusted foreign regulators when FDA has written assurance that
the agency will not disclose? Yes or no.
Dr. Woodcock. Yes.
Mr. Dingell. Doctor, can FDA currently share trade secret
information with State, local or trusted foreign regulators?
Yes or no.
Dr. Woodcock. No.
Mr. Dingell. Now, would authority to share this information
with other regulators help monitor FDA's efforts to protect the
American public with regard to today's globalized drug supply?
Yes or no.
Dr. Woodcock. Yes.
Mr. Dingell. Now, would this authority help FDA to have
better information to assess risk and target oversight? Yes or
no.
Dr. Woodcock. Yes.
Mr. Dingell. Doctor, if given this authority, FDA would
commit to only sharing such information with trusted foreign
regulators when they have proper and satisfactory assurances
that the foreign agency will not disclose. Is that correct?
Dr. Woodcock. Absolutely yes.
Mr. Dingell. Is that necessary for us to do?
Dr. Woodcock. Yes.
Mr. Dingell. I happen to think so. Now, Doctor, so then the
agency would not share proprietary commercial information like
the formulation of Coca-Cola with China or any foreign country.
Am I correct on that?
Dr. Woodcock. Yes.
Mr. Dingell. And FDA would protect that concern and that
policy. Is that right?
Dr. Woodcock. That is correct.
Mr. Dingell. Now, Doctor, I have a concern. We have the
ability to regulate to some degree the shipment into this
country of food, drug, cosmetics and devices. How about the raw
materials or the components of this? What is FDA's ability to
regulate? Do you have a statutory ability to regulate or not?
Dr. Woodcock. We have very limited ability to regulate the
supply chain of components.
Mr. Dingell. Now, I must assume that being able to regulate
that kind of activity and that kind of product would be
extremely important to assure the safety of American consumers.
Is that right?
Dr. Woodcock. Yes.
Mr. Dingell. We found that out in the heparin case, did we
not?
Dr. Woodcock. We did.
Mr. Dingell. Now, this committee looked at this problem
over the years of safety and that sort of thing, and one of the
things that we found is that nobody seems to be able to keep
out the admission of illegal substances, unsafe, counterfeits
and things of that kind including some controlled substances,
and I sense that a part of that, although not all, is the
inability of Food and Drug to have the money, the personnel and
the necessary cooperative agreements with other regulatory
bodies that deal with entry of commodities and people into this
country. Am I correct in that?
Dr. Woodcock. Yes.
Mr. Dingell. Do you need additional authority there?
Dr. Woodcock. Yes.
Mr. Dingell. Mr. Chairman, I notice I have used all my
time. I thank you for your courtesy.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the gentleman from Michigan, Mr. Rogers, for 5
minutes for questions.
Mr. Rogers. Thank you, Mr. Chairman.
Dr. Woodcock, I want to thank you and your staff for
working with us on the permanent reauthorization of BPCA and
PREA. Thank you very much for doing that. I think it has been
productive. I introduced that legislation with my friend, Ms.
Eshoo from California, and Mr. Markey, and I think it is
representative of good bipartisan work, which is included in
the committee's draft today, so I am hoping that other members
will join us in supporting that effort. I think they will, and
I am proud to say the bill has support of numerous
stakeholders, as you know, including the American Academy of
Pediatrics, BIO and PhRMA. So I think we are in a good place.
We will do good things. And again, I want to thank you and your
staff for that. While making these laws permanent, the bill
also includes important reforms to encourage earlier submission
of pediatric plans, give the FDA new enforcement tools to make
sure sponsors meet their PREA commitments and improve FDA's
ability to track pediatric studies. I believe our bill strikes
that right balance and will improve pediatric drug research,
and I hope all members on the committee can support it.
Dr. Woodcock, as you know, there was some language actually
authored in 2007 that began the process of developing a
standard numerical identifier, or SNI, to help the tracking and
tracking of prescription drugs. However, the FDA currently does
not have the authority to require the use of SNIs throughout
the supply chain. Is that correct?
Dr. Woodcock. That is correct.
Mr. Rogers. So you are familiar with the proposal put
forward by a broad group of stakeholders in the drug supply
chain on this particular issue?
Dr. Woodcock. Yes.
Mr. Rogers. Great. So if you agree that additional
statutory authority is needed to protect the drug supply chain,
and I assume you aren't comfortable waiting another 5 years, at
least I hope you are not, for the next UFA reauthorization, to
create a system that protects patient safety, I would encourage
you to roll up your sleeves and sit down with this coalition,
and I hope you can do that soon. I think it would be highly
productive, and I believe there is a solution here that
provides FDA with more authority than it has today but does so
in a reasonable, thoughtful way that balances costs and
enhancements to patient safety and the supply chain, so I am
hoping that we can get a commitment that you will sit down with
that coalition and begin that process.
Dr. Woodcock. I would be happy to do so, and we obviously
need to make advancements in this area. We are seeing, as we
saw recently with the counterfeit Avastin and others, we are
seeing more incursions of actual drugs that are totally fake
into the U.S. drug supply.
Mr. Rogers. Which is highly concerning, and concerning for
you as well. So I look forward to hearing reports on those
coalition meetings. Hopefully they will happen soon.
Dr. Shuren, I have some concerns about that new proposal,
and I know Mr. Shimkus talked about it a little bit on the
510(k) submissions. It is my understanding that they would have
to submit these submissions under your new rules for small
manufacturing issues like changing suppliers. Is that correct?
Dr. Shuren. In a number of cases, it depends. The supplier
change may be something that actually doesn't get reported to
us.
Mr. Rogers. But apparently there has been some confusion,
but in some cases it would and in some cases it would not. Is
that correct?
Dr. Shuren. Yes, and we can actually get back to you with
more details.
Mr. Rogers. So there are details, so if I read that in
total, as a manufacturer I would understand when exactly I have
to report or when I do not have to report. Because my
understanding is, there is confusion in the way it is written,
and if you are on the manufacturing side of that, you are going
to have to err on the side of reporting.
Dr. Shuren. So there are a number of parts in that guidance
where confusion has arisen. We recognize that. Our intent in
the guidance was to clarify circumstances for submitting a
modification because we had guidance out there beforehand and
manufacturers were then running into circumstances where we
have never addressed the question. They didn't know what to do.
Our intent was to actually clarify those circumstances. We
recognize there still is a lot of confusion, which is why we
have taken the effort to try to work with industry and we will
continue to do so to provide clarity that will be most helpful
to them, but our goal is not to suddenly raise up the bar and
see many more 510(k)s getting in the door.
Mr. Rogers. But unfortunately, the reality is, that is what
is happening and they are going through these processes now
believing that they have to do it, so having future
conversations aren't really all that helpful.
Dr. Shuren. Well, it is a draft guidance, so nothing has
changed, and that is the whole point of the guidance process.
We go out there, we get public comments and we can work this
through. That happens all the time. If you actually look at the
guidances we put out last year, it is about 44. We heard
concerns about maybe three of them in any big way, and that
kind of shows the process ultimately works.
Mr. Rogers. I hear you, but that is the difference between
not having to meet a payroll, meeting a payroll, meeting the
guidelines for the government that regulates you. They will
start to make adjustments based on those guidelines. It will
cost them money. They are doing it today, which is exactly why
we are hearing from innovators, this isn't worth it anymore, it
is easier for me to head overseas than it is to try to deal
with what is an untenable regulatory environment. That is what
concerns me, and this notion that it is all just fine and it is
only guidance and nobody should worry about it is absolutely
incongruent with the real world. That worries me greatly, and I
hope you will take a hard look at this and come back, and if
that is the case, then start making serious indications to the
folks who are actually under the gun for this investment to
save kids' lives or devices or fill in the blank that you will
make that early. Otherwise they are going to have to make these
adjustments, and I think that is what you are missing and that
is where the frustration is coming from. And I see my time is
done, and I thank you, Mr. Chairman. I look forward to hearing
about your progress in the coalition's effort to bring
manufacturing and clinical trials back to the United States.
Dr. Shuren. We would be happy to do it. We would actually
be happy to come and talk to you in more detail on what is
going on with clinical trials. In fact, some of the policies,
if you really want to get technology to this country and keep
it here, you focus on the very first clinical studies because
the innovators have said loud and clear, if there is a good
opportunity to start clinical studies here, we bring the
technology here, we keep it here, because we keep going back to
the same doctors and we put out policy in November to actually
make it easier to start those early studies and start it
earlier in device development than ever before. The feedback
was very positive. In fact, companies have wanted to act under
a draft policy, and we have allowed them if they wanted to
because they like that policy so much, and we have heard very
good feedback from the innovators on that.
For modifications, it is a draft policy, it is not in
effect, and we will work with companies and we are happy to
come back and give you updates on it to finally get it right,
and as I said, this is one where we anticipate we would go out
with another draft before even moving to final.
Mr. Rogers. Thank you, Doctor.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the gentlelady from California, Ms. Capps, for 5
minutes for questions.
Mrs. Capps. Thank you very much, Mr. Chairman, and to our
guests, thank you very much for being here today. I appreciate
your testimony, Dr. Shuren.
A couple of months ago at our hearing on medical device
user fees, I had asked you about the Sentinel system for
postmarket surveillance. The PDUFA V agreement allows for
postmarket surveillance of prescription drugs through the
Sentinel system. However, the same progress has not been made
on the device side and the bill draft before us does not
address this issue, and that is why I am working on language
that would start the process of adding devices to the Sentinel
program. I believe this would be a win-win for patients and the
industry because patients would gain the security that
potential device issues would be found early and recalls
targeted to only those devices at risk. Similarly, industry
would have the knowledge that data, not newspaper articles,
would drive safety decisions. So I am going to have a question
for Dr. Woodcock as well, but I would like you to discuss,
please, the opportunities for Sentinel in the device base as
you see them.
Dr. Shuren. We think greater engagement for devices in
Sentinel could be of tremendous value for not only patients but
also for companies as we can identify if there is a problem
more quickly so we don't get those big newspaper articles, and
even more robust systems that we might be able to leverage in
terms of informing for premarket review and ease some of the
burden there. The barriers right now, the biggest one is, we
don't have there a unique device identifier as we have on the
drug side and therefore it is hard to link an actual device
with a patient's experience with the device, and we have
developed proposed legislation that--regulation--we can't do
legislation yet--a regulation that is currently under review by
the Administration that will help, and it was helpful when
Congress said that Sentinel should be there, should be for
drugs, because it gave a push for people to engage. We don't
have quite the same push on the device side.
Mrs. Capps. Well, so if we could get some language in this
bill that would give you that push, if you will, would that be
a value to you and do you see that it is not a one-to-one
corollary, I am sure, but there are ways to make it possible
for a direct connection to be made, at least some kind of
connection to be made from the device to the patient's
experience?
Dr. Shuren. Yes, we do think that could be helpful.
Mrs. Capps. I appreciate that. Thank you very much.
Dr. Woodcock, I appreciate your testimony as well. Back in
February at our hearing where you testified on generic drug
user fees, you and I had discussed the drug shortage problems
this country is facing. It is still facing them. It is a very
important issue that affected then and continues to affect a
great number of people including many of my constituents, and I
had shared one story at that hearing. Given the gravity of this
situation, I am pleased to see that current legislation now
before us includes measures to try to address this problem, but
I am concerned that the way the draft is written, it could
preclude some health care providers from being involved.
Currently, in three separate sections of the FDA user fee
discussion draft, the bill lists stakeholders to be consulted
with in regards to drug shortages. However, it doesn't specify
what kind of stakeholders and health providers like nurse
practitioners and physician assistants are notably absent from
these lists, despite the fact that the work they do have been
affected by drug shortages, in some ways even more directly
because they are so much on the front lines. This is evident,
for example, in a nurse anesthetist's difficulty in finding
anesthesia drugs or an oncology nurse practitioner who is the
actual person who dispenses the medication under the doctor's
direction and they see firsthand the cancer drug shortages, so
would you share with us your thoughts on the kinds of
stakeholder engagement with regard to drug shortages?
Dr. Woodcock. Well, we believe that we need to hear from
the whole prescribing community, which includes a wide range of
individuals. Also, the entire pharmacy community is a very
important resource for us. So the stakeholders are almost
anyone who uses, dispenses, prescribes or manages drug supply
in this country and so it is a very broad group of people.
Mrs. Capps. And I thank you for that. I believe there is an
easy fix here, which I am sort of saying to our committee
members to ensure participation and then just including the
phrase ``all relevant health professionals'' not just doctors
and hospitals, and that is something you would then agree with?
Dr. Woodcock. Yes.
Mrs. Capps. That would be useful language to include?
Dr. Woodcock. Yes.
Mrs. Capps. I appreciate that. Thank you, and I yield back
the balance of my time.
Mr. Pitts. The chair thanks the gentlelady and now
recognizes the gentlelady from North Carolina, Ms. Myrick, for
5 minutes for questions.
Mrs. Myrick. Thank you, Mr. Chairman, and I thank both of
you for being here.
Dr. Woodcock, as you know, the discussion draft at hand
makes an effort to further address the drug shortage issue, and
I know the FDA is playing close attention to shortage issues as
well as working with DOJ on issues of price gouging and
stockpiling, but it recently came to my attention that there
appears to be a growing problem with drug shortages for trauma
and critical-care patients so I have got two questions for you.
Does the FDA have a sense of how widespread the shortage is for
drugs often used in trauma and critical-care settings, and how
do the FDA and DEA need to work together to prevent further
shortages in controlled substances used in the critical-care
field? For example, are there changes that need to be made to
the DEA number assignment system for controlled substances that
are being substituted in the event of a shortage or are there
other interagency solutions that could alleviate the shortage
problem for DEA-controlled drugs, you know, short of an act of
Congress, something that you could do internally or with the
other agencies?
Dr. Woodcock. Well, on the first question, we are well
aware that both critical-care settings and trauma settings are
being impacted by drug shortages. The shortages are for sterile
injectable products, products that are injected directly into,
say, a vein or your IV line primarily, and these actually are
used in a wide variety and unfortunately very important medical
illnesses, very serious and life-threatening illnesses. They
are used in ICUs and emergency rooms as well as in cancer
treatment, and we are aware of these shortages. We have heard
from the professional societies, I have heard personally, and
we are doing everything we can. This year we have averted 22
shortages already because we have heard early notification.
However, shortages do remain and they are causing serious
consequences for the public.
As far as the DEA, we work closely with the DEA. They have
a system of allocating materials to companies based on--we
provide information to the DEA on projected use for each year
as part of their process, and we work with them on shortages,
informing them and so forth, but I believe that further
discussion of this might require going into more detail, and we
would be happy to work with you on that.
Mrs. Myrick. I would appreciate it very much if you could
get back to us because that is an issue I think that there may
be some solutions as other people have said with other things.
I have got a second question too. Your testimony goes into
some detail about FDA's calculation of risk and benefit when it
comes to approving treatments for fatal diseases, and you list
a recently approved metastatic-melanoma drug as an example of
this risk-benefit approval calculation. It is stated it poses
severe and even fatal autoimmune reactions in 12.9 percent of
the patients treated yet the drug was approved. The drug is not
a cure but, you know, patients successfully treated live much
longer than with others. My question is, was this drug approved
in tandem with a screening test to distinguish the patients who
might respond well from those who might suffer serious
autoimmune responses?
Dr. Woodcock. No. I think scientifically we aren't there
yet to be able to predict that. I am a rheumatologist, and I
can tell you our understanding of rheumatic diseases and
autoimmunity is still not as advanced as it should be.
Mrs. Myrick. Well, would it not be helpful to do some
screening test to try and figure out in addition to what you
are doing on this issue?
Dr. Woodcock. Absolutely, and we support at FDA the concept
of personalized medicine. It is simply that scientifically we
don't have the tools to develop such a test, and because the
patients can develop a wide range of autoimmune symptoms, and
to predict each one of those and whether people would develop
autoimmunity against their thyroid or their brain or their
vessels, we don't have the technology to do that right now. But
in the future, that is the future of medicine.
Mrs. Myrick. Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentlelady and now
recognizes the gentlelady from Illinois, Ms. Schakowsky, 5
minutes for questions.
Ms. Schakowsky. Thank you, Mr. Chairman, and I want to
thank both of you for your testimony.
Dr. Shuren, I want to revisit a topic we discussed at the
February 15th MDUFA reauthorization hearing. There had been
suggestions that FDA's mission statement should be changed to
include things like job creation and innovation, and in fact,
the draft House user fee bill does include those changes to the
FDA mission statement. And when you testified in February, you
spoke about the ``unintended consequences'' that could lead to
``troublesome changes'' at the agency, changes that could
actually slow down or complicate the review process, not to
mention change the standard of evidence for product approvals.
You also said that changing the mission statement could even
force the FDA to expose confidential industry information,
something industry was telling you please don't do, and could
require the FDA to review commercial financial records. So I am
asking if you could comment on the implications of revising the
FDA mission statement to include things like promoting
innovation, economic growth, competitiveness, and I am
particularly interested in whether you think these should be a
part of the core mission of a public health agency. I would
also like to know whether these and other requirements in the
mission statement might be the basis for lawsuits or other
challenges against the agency.
Dr. Shuren. Well, we do have concerns about some of the
changes that would be made to our mission statement, and the
highlighted economic growth or job creation is of concern. If
this now becomes a part of what we take into account in making
decisions, think about approval decisions. Whose jobs are we
talking about, the job of the companies coming in with a
product and they may get some more jobs or the competitors who
may lose jobs? In fact, when there is disruptive technology,
many of the competitors, there are shakeups in the market and
some of the companies, their product lines go and people's jobs
may go. Are we talking about foreign companies? Are we talking
about U.S. companies? Are we now taking into account financial
considerations in terms of those companies' anticipated market
growth or not? Those are things our scientists shouldn't be
dealing with. We should focus on science in assuring that the
products that come on the market are safe and effective, and
that is protecting public health and we are also promoting
public health, which is already in our mission statement.
Regarding lawsuits, just within the past few months we have
had two lawsuits where the mission was cited as one of the
bases for that lawsuit, and we do see that coming. So if there
are changes to the mission statement, yes, people will use that
as a basis for lawsuits.
Ms. Schakowsky. Thank you. Those changes concern me very
much as taking away from the core mission that you have, and I
would also like to ask Dr. Woodcock, because the dramatic
changes to the FDA mission statement would apply across all
product areas including drugs, I wonder if you could also
comment on those proposed changes.
Dr. Woodcock. I agree with Dr. Shuren. We neither have the
expertise to figure out the economic consequences and parse
them finally nor--our primary public is the people who take
medicines and the people prescribing give those medicines. To
them we owe our central obligation of making sure those drugs
are safe and effective and they reach them as rapidly as
possible. So I see this could have negative consequences.
Ms. Schakowsky. And you are suggesting that those negative
consequences could be patients, industry, the agency. What are
your main concerns? I mean, would you view this as a
distraction from what you are currently doing?
Dr. Woodcock. Yes, and it would be primarily that we would
have challenges of our approval decisions based on factors that
most people would consider extraneous to whether the product
will really help people. That has to be our main consideration,
is it effective in the population, is it safe, and if we are
asked--that is what I believe we should be focused on: impact
on patients.
Ms. Schakowsky. Well, I agree. I think this would be a
dramatic shift in focus and one that really the agency has no
historical expertise nor in my view should it. So I thank you
and yield back.
Mr. Pitts. The chair thanks the gentlelady and recognizes
the gentleman from Pennsylvania, Dr. Murphy, for 5 minutes for
questions.
Mr. Murphy. Thank you very much.
Dr. Woodcock, welcome back. I always appreciate your candor
and information to us. I also want to thank my colleague, Mr.
Dingell, for working with us on some of the issues involving
GDUFA. And finally, in your testimony, I want to thank you for
working on the accelerated approval of Kalydeco for cystic
fibrosis. Many of the patients I know in my area are grateful
for that. I know it is a small step but it is a significant
step, and I think it is an example of why we need to be moving
on some things with accelerated action here.
At a recent Senate hearing, you stated--you were talking
about the challenges in international factory inspections. Here
is your answer. You said there are two issues here. One is the
FDA's ability to inspect to inspect those foreign facilities
and the generic drug user fee program squarely addresses that,
and I will level the playing field and make sure that the
intensity of inspection, domestic, foreign, no matter where,
will be the same and will be able to use a risk-based approach
to inspection. Now, under the GDUFA goals letter, the FDA says
it wants to achieve biannual inspection of foreign plants
within 5 years, so here is my two-part question. First, is your
answer from the Senate hearing still true, and two, can the FDA
achieve parity between foreign and domestic facility
inspections within the 5-year $1.5 billion time zone outlined
in GDUFA?
Dr. Woodcock. Yes, we believe that the answer is true. I
was at a meeting yesterday where we were discussing this with
our field organization and the Center for Drugs how we would
implement this inspectional program, and we would really look
forward to having that global safety net in place.
Mr. Murphy. Thank you. Now, I should disclose an important
generic drug manufacturer, Mylan, is headquartered in my
district, and we want to make sure that any inspections they
have to go through are equivalent to what takes place overseas.
Now, my understanding is that based on the current statute, the
FDA inspects domestic plants more frequently because they are
looking for so-called ``known risks'' even if the plant has no
history of problems but inspectors don't have the same body of
knowledge about foreign factories because they haven't been
there, and sometimes not in the last decade. So Dr. Woodcock,
will you agree that inspectors have a certain comfort level
visiting domestic factories because there is a record of
inspection history that helps to identify known risks to these
factories?
Dr. Woodcock. My understanding is that we have a statutory
requirement to inspect domestic facilities every 2 years, and
that is partly what drives the frequency of inspection. It is
also that there is considerable logistical challenges to
covering the globe. But the Center for Drugs has a risk-based
approach to inspecting facilities. We try to identify the
facilities that pose the most risk including the fact that we
don't very much about them and try to target out inspections
based on those risks. In addition, we do preapproval
inspections, so that drives quite a few inspections because
before a drug is released on the market, we want to know that
the facility that is producing it and often it is multiple
facilities are in compliance.
Mr. Murphy. Thank you. I am just concerned here that if you
go to a domestic factory, you see a problem, you can follow up
or even a suspicion something might have happened but if we
have long time delays--and I understand the global problems
there but it is a concern that there is not the same follow-up.
If Congress directs the FDA away from a statutory requirement
to inspect facilities once every 2 years and instead allows the
agency to adopt a risk-based approach, what factors might the
agency consider using to determine what is a facility in need
of inspection versus one that may not be?
Dr. Woodcock. Well, we currently have a model. Obviously
one of them is how recently have we been to the facility and
how much do we know about it, and really, the less we know, the
more important it is to know more and to visit the facility but
also, for example, parenteral drugs that have to be sterile are
a higher bar of manufacturing than tablets or capsules or
creams, so that is a factor. The number of products that are
produced in a facility ups the ante of risk, so to speak,
because it is harder. There are more changes for mix-ups and so
on if you have a lot of products made on the line. We have
multiple factors like that that are technical on the challenges
of manufacturing that go into the calculation as well as the
history of the firm--have they been having problems, has that
facility had problems in the past. That should prompt more
frequent visits.
Mr. Murphy. Well, thank you. I know that I am just about
out of time but I wanted to also note that I am exploring
putting guidance into the FDA for placing higher priority on
inspecting foreign plants that have not been visited within the
last 4 years. I could see this is beneficial for public safety
because I think it would establish something of a psychology
for plants that haven't been visited in the past 4 years that
the FDA might be visiting soon, and I welcome your thoughts on
that too, and also, in the goals letter for GDUFA, the FDA
estimates that are 2,000 finished dosage form and active
pharmaceutical ingredients manufacturing facilities that are
associated with generic drug applications. I hope you can get
to me in the future and let us know if this estimated all
included the FDF and API facilities and does the FDA believe
that there are other registered facilities under its
jurisdiction that solely support branded applications. I will
get you those questions in writing and I appreciate some
feedback. Again, Doctor, thank you for your candor. I really
respect your comments. I yield back.
Dr. Woodcock. Thank you.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Utah, Mr. Matheson, 5 minutes for questions.
Mr. Matheson. Thank you, Mr. Chairman. And Mr. Chairman, I
want to acknowledge how you have been working in a bipartisan
manner on the reauthorization of this. I really appreciate
that.
Over the past several years, I have worked with drug supply
chain stakeholders in crafting legislation to develop a
national system to better protect our Nation's drug supply
against counterfeiting threats. Last year, I introduced
legislation along with my colleague, Mr. Bilbray, to address
this issue, and I certainly want to thank him for all the work
he has done with me on that bill. Recently, a consortium of
stakeholders from all sectors of the supply chain have come
together to craft a proposal to address counterfeiting and
supply chain safety. I am pleased to see that many of the
elements of the legislation that I have worked on were included
in this RxTEC proposal. I am supportive of this proposal, and I
hope to see its inclusion in this year's user fee
reauthorization, and I would like to note that the last time
this committee attempted to work on a national track-and-trace
system, we failed because there was no consensus among the
supply chain stakeholders. The FDA has raised concerns over
this proposal because it does not mandate a unit-level system
by a date certain.
Dr. Woodcock, in your written testimony, you note that
Congress should provide FDA with the authority to require a
``cost-effective track-and-trace system in order to improve the
security and integrity of the drug supply and show transparency
and accountability in product manufacturing and distribution.''
However, many in the supply chain have raised concerns that a
date-certain mandate approach would be cost-prohibitive and
create a logistical challenge that could actually endanger the
drug supply chain. So the question that I have for you, Dr.
Woodcock, first, how do we ensure that a date-certain approach
is in fact cost-effective and does not have unintended
consequences such as job loss or further exacerbating the
growing drug shortage problem in this country?
Dr. Woodcock. Well, to start with, I would like to say
again that we need to look at the problem we are trying to
solve and make sure that any interventions we take will solve
the problems that we are trying to address. My understanding
with track and trace is, we are trying to deal with
counterfeits, stolen drugs that are reintroduced, recalls,
substandard drugs and so forth and prevent them from actually
reaching patients and harming people. Our concern about the
current proposal by the coalition, we have talked to them. As I
said, I am happy to meet with them but that it will not meet
the objectives of preventing those problems. It may help--in my
analysis, it may help in reconstructing what went wrong after
the fact, but if you want to interdict counterfeits and
tampered drugs and so forth from reaching patients, then you
have to be able to recognize it at the time it is introduced
into the system, and so any system, any new requirements that
don't accomplish that may not be worth the cost because they
may be additional things that people have to do, but if they
don't accomplish the objectives of protecting patients, they
may not be worth it.
Mr. Matheson. I am all for looking for the objective but
you just mentioned cost, it may not be worth the cost, so I am
suggesting that the concerns raised that if you want a date-
certain mandate that that is going to have negative cost
consequences, and so my question is, how do we evaluate, how do
you intend to look at if there is going to be--the cost effect
is not going to be a problem here?
Dr. Woodcock. Well, we have been looking at this. We plan
to develop and are developing voluntary standards that we would
put out that people could use and hoping that the technology
which many products in the market are tracked this way already,
not pharmaceuticals, so hoping that the technology will reach a
state where it will be cost-effective and not excessively
burdensome.
Mr. Matheson. I have to admit, hoping technology gets there
and seeing date certain, those things in my mind are in
conflict. I don't actually think that matches well.
Noting some of the challenges that the California law is
facing, I am trying to understand why this date-certain
approach would work at a federal level when it has caused
difficulties at the State level in California, and should we
not look at the types of systems that are feasible across the
supply chain system before we decide what and when to mandate?
Dr. Woodcock. Well, I do believe that we should look at
feasibility, absolutely. However, many of the stakeholders have
told us they are worried about having 50 different systems.
Mr. Matheson. That is why I introduced my bill. I hear you.
We need a national standard. I am just trying to figure out how
we are going to manage it.
Dr. Woodcock. But that means we have to settle on the
technology if we do that, and what is going to be tracked and
how it is going to be tracked, and that has been difficult
because right now the costs have been fairly significant to
some of the stakeholders because they don't do this now. They
don't electronically track the products as they move through
the supply chain and all the way to the patient. So I agree,
there are tradeoffs here, and it will cost money to put such a
system into place.
Mr. Matheson. I will just close by saying I think the RxTEC
proposal represents a consensus of a lot of the stakeholders.
It does agree on a one-size-fits-all for the country and not 50
different State approaches. And I think we ought to continue
this discussion about looking for if there is a way to
accommodate this proposal without mandating a date-certain
approach.
With that, Mr. Chairman, I will yield back.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Ohio, Mr. Latta, for 5 minutes for
questions.
Mr. Latta. Thank you, Mr. Chairman, and welcome back to the
committee. Great to see you again.
Kind of going in a little bit different direction here. Dr.
Woodcock, I know of a number of hospital systems that are
coping with the hospital drug shortage by repackaging those
drugs into smaller dosages, and these hospitals have also noted
that the current law does not allow for the hospital to
repackage a drug for use in another hospital within their own
system, and we have quite a few systems, of course, not only in
Ohio but across the country, and this appears to be an older
regulation dating back to when hospitals were typically only in
one building before they became the hospital systems. Has the
FDA looked at updating this requirement to allow for
repackaging within the same hospital system?
Dr. Woodcock. I would have to get back to you on that. I do
not think that we would object to such practices if they would
help alleviate shortages but whether there is a law on the
books that is being interpreted as prohibiting that, I am not
aware of that.
Mr. Latta. And again, I am glad to hear that because again,
it seems a logical way to help solve it, because again, if one
hospital has it, they could get it out to one or others in the
same locale. That would be helpful because, again, it would
help alleviate those shortages.
Dr. Woodcock. If I may interject?
Mr. Latta. Absolutely.
Dr. Woodcock. We allow pharmacy compounding. Usually the
hospital pharmacy would be handling these products and they
would be the ones to put it into smaller vials or whatever. So
that is why I am confused about why they feel that that isn't
allowed, and we will get back to you on that.
Mr. Latta. I appreciate that. And over time, it would help
alleviate the problem, because again, we are talking about
these shortages, I know you have been here before. We have
quite a bit of discussion about that as to how to alleviate it,
and when you have the situation that at least in the chain that
one of the hospitals has the ability to supply the other ones,
it would be very helpful, and so I look forward to your
response on that. I would like to get back to these hospitals
to be able to say that they can get this done and help
alleviate that problem.
And with that, Mr. Chairman, I yield back.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Louisiana, Dr. Cassidy, for 5 minutes for
questions.
Dr. Cassidy. I always enjoy both your testimonies. Thank
you. And as a practicing physician, I respect what you said
earlier, Dr. Shuren, that the FDA's obligation is to protect
patients' health. I thank you for that too.
I would like to build upon, Dr. Woodcock, our conversation
last time which was very good. The last time, I think we agreed
that a valid prescription would be important to have, not just
for controlled substances as currently but also for non-
controlled drugs. So I just wanted to state that for the
record.
Dr. Woodcock. I agree.
Dr. Cassidy. Secondly, we also spoke a lot about
illegitimate online pharmacies. Now, you had mentioned the
VIPPS program, which I had mentioned as a practicing physician
married to a physician we did not know about, but since then we
have kind of looked at it. I gather that this, although a good
effort, only has about 30 pharmacies listed even though it is
estimated there are about 1,500 legitimate pharmacies and just
an explosion of illegitimate pharmacies. And secondly, that we
still have, despite our conversation last time, there continues
to be reports of adulterated drugs causing harmful effects to
patients here in the United States. So with that said,
Representative Ross and I in a companion bill to something that
Senators Feinstein and Cornyn and others have introduced on the
other side have an online pharmacy bill requesting that FDA
compile a registry of legitimate online pharmacies so that I as
a doc or I as a patient or I as a dad of a patient could log on
and see, is this a legitimate online pharmacy. I gather FDA has
some objections to that. Could you kind of go through those
objections?
Dr. Woodcock. Certainly. Basically there are practical
difficulties in us doing that. As you said, there is a huge
plethora of pharmacies that are probably not legitimate that
consumers do order their drugs from and often they have no
assurance that those are actual drugs.
Dr. Cassidy. That is why we have the bill.
Dr. Woodcock. Yes, so we are in agreement on the problem.
We have trouble certifying Internet sites that would be
legitimate. We have difficulties----
Dr. Cassidy. But see, the National Association of Boards of
Pharmacy, the NABP, currently does that.
Dr. Woodcock. Yes.
Dr. Cassidy. So why can they do it and the government
cannot, or why could you just not contract with them to ask
them to do it?
Dr. Woodcock. I think it is worth discussion on how to
establish a broader list of legitimate pharmacies. It is
another work stream that we don't actually understand how we
could accomplish very well.
Dr. Cassidy. Now, in our bill, we allow you to contract
that. I mean, I can tell you, Google can tell you who is
legitimate and who is illegitimate, you know, Google, the big
Internet----
Dr. Woodcock. I know Google but we are talking about a
pharmacy here and so----
Dr. Cassidy. But they advertise via Google, and so I
suspect that--I mean, it is not an impossibility to do it. You
may not have expertise nor I but I promise you, NAPB has that
expertise, and our bill allows you to contract out to them. Why
not?
Dr. Woodcock. Well, we are not sure that a certification by
the federal government could--it would have to be very frequent
inspection of the distribution center because you have a web
page but there is not necessarily a brick-and-mortar entity
behind that.
Dr. Cassidy. Now, in there we do require to have some sort
of U.S. asset, and we have spoken with NABP. Obviously, we
weren't concerned if someone could come in as legitimate and
flip to being rogue.
Dr. Woodcock. Exactly. That is one of our concerns.
Dr. Cassidy. NABP says that has never occurred in their
experience.
Dr. Woodcock. Of course, they only have 15 in there.
Dr. Cassidy. Thirty. That said, at some point we have to
move beyond existential fear, oh, my gosh, we don't know all
the unknowns, and say if we are going to protect patient safety
and we know this is an incredible problem, let us embrace the
fear, if you will. Again, why do we allow existential fear to
paralyze our efforts to protect our patients?
Dr. Woodcock. I don't think it is existential fear. I
believe that we are having difficulty conceiving of how we
would add this program to our existing programs. So we would be
very happy to work with you on this and talk to you about it.
Dr. Cassidy. I would love it if you would support the bill
because we will contract this out and there is someone out
there that can do it, which I think is a logical thing. Someone
out there knows how to do it even if the federal government
doesn't. When I go through TSA, they know everything about me.
To think that we can't figure who is legitimate and
illegitimate just seems not quite to make sense to me.
I have 2 seconds left but you have been giving everybody
slack. Can I quickly ask one more question?
Dr. Shuren, the unique identifier that has been suggested
for medical devices, it is my understanding it has been held up
at OMB for 5 years. That is what I was told. Maybe it not 5
years, maybe it is a shorter period of time. But even at the
glacial pace at which government works, that seems a way to
take a proposal and never get it out. Any thoughts about why
OMB is holding up a unique ID system which really could help us
improve safety of medical devices?
Dr. Shuren. It is probably a question best put to the
Administration. I will say the rule has been under review since
July of 2011, so not 5 years.
Dr. Cassidy. Oh, good. I am comforted by that.
Dr. Shuren. Well, sometimes when people hear that things
take longer, sometimes it is not always correct.
Dr. Cassidy. OK. So any idea? Is there ongoing discussion
or is it just a wall of silence? Do you have any sense of is
progress being made on this?
Dr. Shuren. We continue to engage with OMB. We certainly
believe it is important to have a unique device identification
system in place in the United States. It will be critical to
have a robust postmarket surveillance system. It will help in
terms of recalls and adverse-event reporting but can also allow
us to have a system in which we may get sufficiently good data
that can be used to support new products coming to market. So
it is not just about better understanding of benefit-risk
profile once out the gate. It may actually be able to help
companies in reducing the new evidence they need to generate to
bring a new device to the United States.
Dr. Cassidy. I yield back. Thank you.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Kentucky, Mr. Guthrie, for 5 minutes for
questions.
Mr. Guthrie. Thank you, Mr. Chairman, and first, Dr.
Shuren, I just have a comment. I know we have met in my office
over medical device approval processes. I thought that was a
very good, productive meeting, and you have talked today about
the first-time approvals or the innovators and the least
burdensome and getting it right, being safe and effective, but
also efficient. I think that is important. I appreciate that,
because it has been a big concern of mine that we are having
people go overseas to get their products approved but not going
to the least common denominator, going to the European Union
and other areas and trying to get approved. And so we are
interested as oversight monitor how that goes forward and
appreciate your openness in meeting on that.
Dr. Woodcock, there is a question I have. I talked to
anesthesiologists and anesthetists and of course in the
childcare cancer drugs of the shortages. When there is a
shortage in a drug, I guess you can go to an alternative source
if a manufacturer can't produce the drug. How does that process
work? How do you actually make that happen?
Dr. Woodcock. We hope usually we would get early
notification from a manufacturer that they may be having to go
out of production or reduce production and not meet the supply.
We will then look around to all other manufacturers who have
ever made that drug and see if they can ramp up so that we
would avert the shortage. If that doesn't happen, then we might
look outside the United States to people making a comparable
drug elsewhere and we would check with other regulatory
authorities to make sure their production was proper and the
history of the drug so make sure we are not introducing a
substandard drug into the United States, and then we would
allow importation of that drug to cover if a shortage actually
developed and we would talk to that manufacturer.
Mr. Guthrie. Is there a formal process for that?
Dr. Woodcock. A formal process?
Mr. Guthrie. A formal process. Does somebody have to notify
you when they know they are not going to make shipments and
things like that or it is something that you have to react to?
Dr. Woodcock. Well, there is some requirement to notify us
but of course there is interest in more formalizing that
notification process, and we think that would be helpful.
Mr. Guthrie. And I have had people talking about having to
delay surgeries for anesthesia and childhood cancers. Those are
the two I mentioned. I know there are others. But since you
have a handful that seem to be the bigger issue, do you have
like a list of the people that can come online when you need to
get them online?
Dr. Woodcock. We have done extraordinary efforts to try and
deal with this situation. The problem is that these are sterile
injectables. There were only a few facilities in the United
States that made these. They made large numbers of products so
hundreds of products, and they had problems that they had to
take their production offline and it almost sort of happened--
it was like a perfect storm of problems. So we are having to
look elsewhere and we are working with them as closely as
possible to try to bring them back up into production of these
medically necessary drugs.
Mr. Guthrie. Do you think it would be helpful to have some
kind of program that maybe manufacturers could voluntarily
participate in? I know there are some areas you are just going
to get blindsided because something happened in manufacturing.
I know sometimes things happen in a manufacturing facility. But
do you think if there would be a more formal program that maybe
companies could volunteer to participate in, manufacturers
could that could react quicker or do you think----
Dr. Woodcock. We have heard from the private sector, and
they are putting together some efforts on exchanging
information and providing better information to us, and we
think that things like that would help also. I would stress
that we already have the flexibility. We will allow the
manufacturers to continue in production even if they are having
manufacturing problems. Maybe they will release batch by batch.
We have even had manufacturers sent a filter with the product
that had particulates in it which can't go into your veins, but
we let them put a filter in after tests showed that would work
and shipped that with the product so that that product so
people could have anesthesia or they could have their cancer
drugs. So we have a lot of flexibility. We do a lot of things
now but it would probably help us to get more information
earlier.
Mr. Guthrie. OK. Thanks. I appreciate that very much, and I
yield back.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentlelady from Tennessee, Ms. Blackburn, for 5 minutes for
questions.
Mrs. Blackburn. Thank you, Mr. Chairman.
Dr. Shuren, I had a couple of questions for you. I really
wanted to follow up on a letter that some of my colleagues and
I sent to you earlier regarding the wireless medical devices
and the mobile medical applications. You have talked a little
bit about bringing technology and keeping technology-based jobs
here in the country, talking to innovators. So I wish that you
would take a couple of minutes and just detail what primary
activities related to wireless health services and health
devices are underway at the FDA including the independent and
jointly with the FCC and the ONC, if you will, if you will just
talk about what is underway there. And then I would also like
to know who is tasked, if you have got one person that is
tasked with overseeing the policy development in this area
looking at regulations, guidance, documents, etc.
Dr. Shuren. Certainly. For wireless technologies
specifically, we are working on guidance to provide greater
clarity to industry. We know this is a booming market and we
want to make sure that innovators have the information they
need to help bring those products to market. We have been
working with the FCC. We sort of have split responsibility
because they oversee what spectrum may be available and then we
assure that when we are dealing with medical devices that they
are safe and effective and so we have been getting together
periodically to assure this good coordination where there are
those areas in which we engage and to also make sure that we
stay out of each other's way.
Mrs. Blackburn. And do you have one specific point person
that is handling that?
Dr. Shuren. The person on our end who handles that
engagement is Bakul Patel, and he is in my office.
Mrs. Blackburn. OK. And then is he handling the intra-
agency coordination as well as the interagency?
Dr. Shuren. Yes, that is correct, so one person.
Mrs. Blackburn. So he is the guy in charge basically on
that?
Dr. Shuren. So to speak, yes.
Mrs. Blackburn. And then could we get a listing or a memo
that would give us more or less the primary activities related
to these wireless devices that are underway? Could you give us
a little bit more information or guidance on that? And you can
submit that in writing.
Dr. Shuren. We would be happy to do so. We can also provide
more information regarding medical apps, an area where I think
you know we took a position that while many of these apps could
be under FDA authority, we actually made the decision that you
know what, for the majority of these, they shouldn't come to us
even if they should as a matter of law and we are willing now
to----
Mrs. Blackburn. So are you traveling then with your
guidance to which--and this is one of my other questions for
you. Realizing that there is a difference between medical
devices and medical software, are you moving that direction to
being able to provide that guidance?
Dr. Shuren. So there is also guidance on clinical decision
support software. Some software has been regulated as medical
devices for years. What we are doing is going back for those
kind of software to say some of these things, you know what, we
shouldn't even look at even though they might fall under our
purview and a lot of things that otherwise we would, we are
going to come out with a policy that says we are leaving you
alone.
Mrs. Blackburn. So you are adjusting what would and would
not fall under the Drug and Cosmetics Act of 1970?
Dr. Shuren. We are going even further to say even if you
fall under it, we may go out and say we will exercise
enforcement discretion, don't worry about it, you don't have to
come to us. We are going to narrow actually our purview even
further than what the law may otherwise say. We are trying to
adapt to the emerging technologies and adapt our approach to
the business models for software, because we realize that even
in those cases where it comes to us, you can't apply a
traditional approach. There needs to be the ability to make
frequent updates and for us not to get in the way of that
technology.
Mrs. Blackburn. OK. Should we as legislators go in here and
update the definitions of devices and software based on those
advances in technology that you just touched on?
Dr. Shuren. We don't think there is a need for it, and, you
know, one of the challenges is, when you make the change in
statute, it winds up having broad ramifications. It is very
hard to put in something that applies the appropriate touch, if
you will, and that is why we are able to do through a public
process with policy changes where we can----
Mrs. Blackburn. OK. Let me ask you this then. You just
talked about some of the software updates. I get notices for
updates for different software packages all the time. I mean,
it seems like almost a daily occurrence. So would each update
that goes out, if it is under your jurisdiction, would each
update need a separate approval process, or how do you envision
that working?
Dr. Shuren. No, and in fact, we are kind of looking to have
an approach where you can make those kind of routine changes in
software and not have to bother coming to us. It would only be
certain things where you really change the technology itself
and what it was about where that is an issue, and even there,
the universe where we are going to be focusing is very, very
narrow, even though more things might fall under our purview,
so we are truly restricting where we would focus, and at the
end of the day there is the value added, but you will see that
the majority of the stuff out there, our intent is to just
leave it alone.
Mrs. Blackburn. OK. Thank you. I yield back.
Mr. Pitts. The chair thanks the gentlelady and recognizes
the gentleman from Georgia, Dr. Gingrey, for 5 minutes for
questions.
Dr. Gingrey. Mr. Chairman, thank you very much.
I will address my first question to Dr. Woodcock. First of
all, let me apologize for coming in at the last minute. We had
a concurrent hearing that I chaired, so I apologize for that.
In reference to antibiotic shortages in general and
specifically the GAIN Act in particular, I know that my
colleague on the other side of the aisle, the ranking member,
Mr. Waxman, had talked about that a little earlier this morning
in regard to this limited population antibiotic drug proposal.
Staff at FDA told my staff just this Monday that the FDA has
not officially endorsed the LPAD, if you can call it that, that
proposal. Has the FDA officially endorsed the Limited
Population Antibiotic Drug proposal as part of the GAIN Act or
in any way?
Dr. Woodcock. Well, the Commissioner, Dr. Hamburg, and I
have talked about this, a program like this to many different
stakeholders so we certainly feel that is something that should
be considered by Congress. But if course, there is nothing
specific in the GAIN Act right now that reflects this proposal.
So we do feel that it would be beneficial. The GAIN Act
provides long-term incentives for companies to move back into
the antibiotic space. A shortened development program, a very
narrow development program would provide that short-term
incentive. In fact, I have already heard from a company that
has written me a letter asking if they could be designated as
one of these products because they would be interested in
entering that space if they had a very clear development path
to market.
Dr. Gingrey. Well, I understand, and you said that you and
Dr. Hamburg have discussed it and certainly I am not saying
that the proposal does not have merit. I am just suggesting
that at this late date, industry has some concerns in regard to
making this part of the GAIN Act and subsequently of course
part of PDUFA. I wanted to very specifically ask, and I will do
that one more time. The FDA has not officially endorsed this.
Is that correct?
Dr. Woodcock. Well, the Administration has not put forth a
proposal.
Dr. Gingrey. Thank you very much, Dr. Woodcock.
Dr. Shuren, there is a line in the FDA industry agreement
that reads ``The FDA proposes to work with industry to develop
a transitional IVD, in vitro diagnostics, approach for the
regulation of emerging diagnostics.'' Dr. Shuren, explain to me
what this means exactly.
Dr. Shuren. Well, actually this is something that industry
put on the table, and they put it after 13 months of
negotiation back and forth. It actually came up in our second
to last meeting, so it was at the very end. And even though we
have committed in MDUFA III to talk about it, we have actually
already been meeting with industry on it. What we have seen is
to date a very broad brush proposal that needs a lot of work
but we will work with industry and MDUFA III in putting it
forward, and the broad brush strokes are for certain IVDs yet
to kind of be determined. Would they come on the market under a
lower standard than currently is in place for products to get
on the market in the United States with the requirement that
they provide the additional data to show that they are
ultimately safe and effective at a later date in time, and if
not, to then come off the market. Those are the broad
brushstrokes. One of the issues we will also have to wrestle
with are the implications for the FDA because even if we went
down that path, it involves two reviews and two decisions on
the part of the FDA for every single one of those devices going
through as opposed to the one review and the one decision, and
those kind of resource applications we didn't address in----
Dr. Gingrey. Let me ask you this, Dr. Shuren. I am about to
run out of time. I have one other question I wanted to ask.
Does the FDA see the benefit and support transitional pathway
approaches? Do you believe that such a pathway can benefit
patients and industry?
Dr. Shuren. Right now we need to work with industry on
exactly what this is and what the ramifications would be.
Dr. Gingrey. Will you keep the committee updated on the
talks with industry in these coming months?
Dr. Shuren. Yes.
Dr. Gingrey. I very much appreciate that. And real quickly,
Mr. Chairman, get it in under the line, and this is also Dr.
Shuren. A review of the Office of Device Evaluation's annual
report shows a decline in the percentage of IDEs approved on
the first IDE review cycle. They dropped actually from 76
percent approval in fiscal year 2000 down to 56 percent 9 years
later, 2009. What is the explanation for the huge drop in IDEs
approved on the first review cycle between 2009 and 2010? And
real quickly, is it true that with each new review cycle, a
company must pay an additional user fee for one product and
these multiple review cycles are a strain on the FDA's valuable
time and resources?
Mr. Chairman, thank you for your indulgence, if maybe Dr.
Shuren could quickly respond to that.
Dr. Shuren. Certainly. There are no user fees tied to the
review of IDEs, so we don't get any additional funding from
industry for that. What has happened over time, and this is
what we are addressing, is that we have got cases where we were
not consistently applying the least-burdensome principle. So a
decision was held up because a reviewer might be coming back to
say we think you should be doing a better study when in fact
the study was really good enough for its intended purpose
moving forward. And the second is where approvals were being
held up to get answers to questions that either did not need to
be answered at that time, it may be something for later on, or
there were questions that it would be nice to know but we don't
need to know it, and that is why we put out draft policy in
November of 2011 to sort of free that up to lay out very
clearly here are all the different circumstances where we
should approve that trial and these are other issues that can
be put off to later, in fact, allowing for some cases where we
never would have let the trial go through even in the past
where we might actually do a staged approval, let some patients
come in, make sure there is good data for safety and let it
move forward. That is the kind of flexibility we are trying
to----
Dr. Gingrey. Well, I am real encouraged to hear that
response, Dr. Shuren. Thank you.
Mr. Chairman, thank you for your indulgence.
Dr. Shuren. And if I can just add that the IDE first cycles
have dropped. This year in 2012, they have actually been going
upwards for the first time.
Mr. Pitts. The chair thanks the gentleman. That concludes
the subcommittee questioning. We have a couple of members on
the full committee who would like to ask questions. Without
objection, we will go to them at this time.
Mr. Markey from Massachusetts, you are recognized for 5
minutes for questions.
Mr. Markey. Thank you, Mr. Chairman and Ranking Member
Pallone, for allowing me to participate in today's legislative
hearing. I also thank you for including the bipartisan
Pediatric Research Equity Act and the Best Pharmaceuticals for
Children Act that I was proud to work on with Mr. Rogers and
Ms. Eshoo, and I look forward to continuing to work on these
important bills.
Dr. Shuren, I am concerned that the current discussion
draft misses an important opportunity to improve the safety of
medical devices. If a car is recalled because it had faulty
brakes, no consumer would want to purchase a new car with the
same brake problem. Yet when it comes to medical devices that
are implanted in patients' bodies, companies can and do base
their products on faulty predecessor technologies. The
definition of insanity is doing the same thing over and over
again and expecting a different result, but when it comes to
medical devices, we have an insane policy that makes no sense.
Devices have been recalled because they severely injured
patients and they are used again and again as models for new
devices with devastating, life-altering consequences for the
patients who are injured by them.
In fact, just last month, I issued a report that documented
this problem in detail and shared the stories of patients whose
lives were destroyed as a result of this federal loophole.
Under current law, the vast majority of medical devices are not
required to undergo clinical testing in humans before being
sold. Instead, companies need only prove that their new device
is substantially equivalent in technology in use to a device
that FDA has previously cleared, known as the predicate
technology. As we heard, Dr. Shuren, from your exchange with
Dr. Burgess, if the device proves to be substantially
equivalent to a device that is now known to be defective, the
FDA has no choice. The FDA is legally obligated to clear that
product for market. The law does not clearly provide the FDA
the authority it needs to protect patient safety so that new
victims are not created from a technology that we already known
is defective.
Dr. Shuren, if a new device proves substantial equivalence
to a predicate technology that has been voluntarily recalled
for a serious design flaw that could seriously injure people
who used it, would FDA have the legal authority to reject that
application?
Dr. Shuren. We would have to find that it is substantially
equivalent but we will then look for other opportunities to
clarify this, use other mitigations to address it and protect
the public. The challenge becomes more about having the ability
to just get information.
Mr. Markey. But if you found that it was substantially
equivalent, would you be able to reject it?
Dr. Shuren. Not for purposes of substantial equivalence
determinations.
Mr. Markey. You could not reject it even though you knew it
was defective. Is that correct?
Dr. Shuren. That is correct.
Mr. Markey. Well, what if the FDA had knowledge that the
new device repeated the same flaw as the predicate technology?
Would the FDA still be required to find it substantially
equivalent?
Dr. Shuren. We would have to find it substantially
equivalent. We oftentimes with the company at least try to look
for changes in labeling or other things that----
Mr. Markey. But that would be voluntary? You would not have
the legal authority to reject it. Is that correct?
Dr. Shuren. That is correct.
Mr. Markey. Now, the device industry argues that FDA has
complete authority to assure the safety and effectiveness of a
product including demanding clinical trails when they deem it
necessary. Is that true in a case where the product has been
shown is substantially equivalent to its defective predicate
technology?
Dr. Shuren. No.
Mr. Markey. You do not have that authority?
Dr. Shuren. We don't.
Mr. Markey. Does FDA currently have any authority to
invalidate defective predicate technologies?
Dr. Shuren. So to invalidate a predicate where there is a
problem, we would either rescind the 510(k) as a matter of law.
We could do that, a mandatory recall, or of by judicial order
the device is found----
Mr. Markey. So you can only do something after the fact,
labeling, etc. right? That is what you can do? But you can't
reject it. Is that correct?
Dr. Shuren. Yes, and the labeling we will do before the
product comes on the market.
Mr. Markey. Does FDA--some have argued that to get around
the lack of authority, FDA could just issue more mandatory
recalls, thereby invalidating the defective device as a
predicate. Why is that not a feasible response?
Dr. Shuren. If there is sufficient justification to do a
recall, we would actually work with the company on a voluntary
recall, and companies generally comply with it. To run to a
mandatory recall is profoundly resource-intensive, and because
there is a formal hearing that can actually take years to do.
Mr. Markey. You are saying it is a huge resource drain, not
often the best use of FDA's limited resources, but a device
recall voluntarily is still available to be cited as predicate.
Is that not correct?
Dr. Shuren. No, that is correct, and quite frankly, it is
not a case of necessarily that predicate shouldn't be out there
to be used as a predicate but rather having the ability to
assure that if there was a problem, one, it is either not
replicated in the device, or if it is replicated, there is
adequate mitigation, and right now while we can try to work
with the company----
Mr. Markey. Final question. Would you like----
Dr. Shuren [continuing]. Having the ability to----
Mr. Markey [continuing]. The authority to reject certain
devices if they repeatedly had the same dangerous design flaws
as other previously recalled defective devices? Would you like
that authority?
Dr. Shuren. We would be happy to work with the committee on
what may be the best approach on how to deal with those----
Mr. Markey. Would you like to have the authority or not
have the authority?
Dr. Shuren. We would like to have appropriately tailored
authority.
Mr. Markey. OK. Great. I think I would like to work with
you to hopefully accomplish that goal so you do have that
appropriate authority.
I thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the gentleman from California, Mr. Bilbray, for 5
minutes for questions.
Mr. Bilbray. Following up on that line of questioning, Mr.
Chairman, if you had an inhaler, let us just say an insulin
inhaler, that was a new model that could be produced cheaper
and was smaller than the original but gave the same dosage,
same reliability, it was a different design but basically the
outcome to the patient was the same. Do we have the ability to
say yes, that is comparable, and thus you don't have to go
through the entire review process over again?
Dr. Shuren. It depends upon the changes you make. If those
changes made would not significantly affect safety and
effectiveness, then you don't have to----
Mr. Bilbray. Basically, my point is, you have two little
devices. One is this big and one is this big. Your doses are
the same, the same insulin is being used, it is just a
different--basically has been upgraded. You get a call from a
flip phone or you get a call from an iPhone, same product, same
delivery, different ways of doing it but the same deal. Do we
have the ability for you to say OK, this is comparable and thus
we can allow it to move forward or does the iPhone now have to
go through the whole thing, the review process all over again?
Dr. Shuren. So for some changes, size actually could affect
safety and effectiveness. If it does, that modification comes
to us. So you have things like certain joint replacements that
when you change the size, that can actually affect----
Mr. Bilbray. That is inside the body, though. I am talking
about an external----
Dr. Shuren. So some of the other things that may change in
size----
Mr. Bilbray. Like bringing an inhaler down from the size of
a liter bottle down to the size, you know, smaller than a
lighter. Do you have a comment on that?
Dr. Woodcock. Yes. We have a lot of experience in inhaled
drugs, regulating them, and----
Mr. Bilbray. Well, I have a lot of family members that have
that same problem, but that is a different issue.
Dr. Woodcock. So the problem with the inhalation devices is
that we do not have a good way to determine bioprevalance, and
that has hampered us in fact in improving generics of, say,
asthma drugs that are out there because we can't determine
whether they deliver the same dose as the innovator, so that is
the real question, OK. So if you move from one inhalation
device to another, it may be the same plume--we do plume
testing which is particle size, distribution, right? However,
the user interface is very important in inhaled devices because
some people--you know, we had some devices they were using
upside down or sucking on the wrong end, and so there are a lot
of issues with user interface with inhaled medicines that
influence whether or not how equivalent we can determine them
to be another version.
Mr. Bilbray. Dr. Woodcock, the question that us
Californians are talking about, and it has been a few years,
the State of California is going to start putting mandates on
the issue that had been talked about before, and that is the
pedigree issue or the tracing. The fact is, they are talking
about going to requiring every unit to be tagged and
identified, and we are hearing from a lot of manufacturers that
there is just no way they can follow that physically or cost-
effectively. What is the possibility of us working on a
compromise proposal with being able to trace lots and at least
start the process down the road sooner rather than waiting for
the crisis that is coming down the road in a couple years when
you have a State like California that controls over 12 percent
of the market, probably almost 20 percent of the market all at
once starting to have a standard that the rest of the country
doesn't have?
Dr. Woodcock. Well, number one, we agree that it is better
to have uniform standards than develop 50 different standards,
which would be a nightmare. Number two, you have to, I think,
determine what problem you are trying to solve and then see if
your solution will address the problem that you are trying to
prevent or solve, and then think about how much it would cost
to implement it and then you decide the tradeoffs between the
costs and the investment you have to make and the benefits that
it will bring. We are concerned that the coalition's proposal
doesn't provide enough benefits to justify doing that, but you
need to think about what else could be done, and I think we are
willing to work on that.
Mr. Bilbray. Are you willing to commit to work on that
within this year so that we get some definitive approach or at
least some unified strategy on this issue within the year?
Dr. Woodcock. I am certainly willing to sit down and work
with the coalition on this, absolutely.
Mr. Bilbray. Thank you very much, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman. That concludes
the questioning. We have one follow-up on each side. We will go
to Mr. Pallone for 5 minutes for follow-up.
Mr. Pallone. So Mr. Chairman, I would like to yield time to
Mr. Markey.
Mr. Markey. It would be just Dr. Shuren, if you could. I
had a woman that I brought to Washington and we had a press
conference about 2 weeks ago, and it was a bladder mesh that
she had surgically inserted into her body, and she was assured
that it was safe and had been FDA approved, and since then,
because of that faulty bladder mesh, she has lost her
livelihood as a truck driver, had to undergo multiple
corrective surgeries, and because of the medical bills is now
being foreclosed upon by the bank, and she has a mother who is
living with her, an elderly woman, and there are thousands of
other people who have had this faulty bladder mesh inserted in
them as well and it is all FDA approved because you cannot
reject something that is based upon this predicate technology.
So maybe you could explain a little bit about what happens
out there in the real world because the FDA does not have this
authority to protect women like that and thousands of others
like them that have FDA approval on a technology that has a
defect in it that you know about but you cannot take off the
market.
Dr. Shuren. First of all, we empathize with that patient
and for other people who may have had adverse effects from
medical devices. I will say in the case of surgical mesh,
generally the issues we are dealing with may be more of, are
they in the right regulatory framework, and we just went
through in the case of surgical mesh for pelvic organ prolapse
where in fact we held an advisory panel meeting to say should
these actually be 510(k) devices or should they be subject to
the more stringent requirements for a high-risk device or PMA,
and that is a process we are moving forward towards. If we make
that decision and if it is rulemaking, and that is the
challenge. If we change classification and we up-classify, it
is rulemaking.
Mr. Markey. What do you say to this woman? What can you do
for the thousands of other women out there? The device is still
out on the market, so what can you say to all these tens of
thousands of additional women who are being advised by their
doctors right now that it is an FDA-approved technology. I
mean, this is something that doesn't work and in fact it harms
women. What should we say to that woman?
Dr. Shuren. So I will tell you in the case of pelvic organ
prolapse, one, we have gone out with information communications
to patients. We have been working with the health care
professional community.
Mr. Markey. This woman is a truck driver, and her physician
in some town in Colorado told her it was safe. What can we say
to her in terms of other women who are just in the same
similarly situated predicament?
Dr. Shuren. Again, I empathize.
Mr. Markey. I understand. Empathy is important, and we
appreciate your empathy. But what can you say to her beyond
empathy in terms of she is concerned and she is like a Paul
Revere trying to warn these defective bladder meshes are
coming?
Dr. Gingrey. Would the gentleman yield?
Mr. Markey. Sure, I would be glad to yield.
Dr. Gingrey. And I appreciate the gentleman from
Massachusetts yielding to me. Of course, as he knows, I am a
physician member, and I am, like Dr. Shuren, certainly
tremendously empathetic to this individual's situation but
meshes have been used in surgery for years and years, and
whether it is an abdominal hernia situation where just a simple
repair and trying to stitch things back together is not
sufficient, you need that insert product to give a little
strength to the repair. You know, again, in this particular
situation, is it the product or could it have been an
improperly placed stitch to sew the product in place? Could it
have been an iatrogenic hospital-acquired infection that
occasionally happens that made the procedure unsuccessful or it
is really a defective product? Thank you for yielding. I just
wanted to----
Mr. Markey. Thank you, Doctor. In this particular case, it
is in fact a recurrence of a defect in the technology that had
already been identified and was in the original predicate
technology that the FDA did not have the ability to take off
the market as another company is making the same technology
with the same defect in it that was correctable but the new
company did not feel it had to correct it because the FDA was
still approving it. So that was where the problem originated,
and thousands of women are still having it inserted into them.
Is that not correct?
Dr. Shuren. Most of the issues we are dealing with with
surgical mesh are probably not a matter of replicating a
problem in the predicate. Many of the things we are seeing may
be issues about, are they in the right framework to begin with,
are we actually getting adequate assurances in the way they are
currently regulated generally that they are in fact safe and
effective.
Mr. Markey. But you do need authority here, don't you?
Don't you need stronger authority to protect women like this,
or what do you say to a woman like that? You need appropriate
authority here to make sure that a woman like this is not
victimized and thousands of others. Don't you agree?
Dr. Shuren. Again, in her particular case, I don't know
what happened, and I know people don't want to hear
``empathize'' but I do. I do think the case, if we wind up
making a change in surgical mesh, and again, we are looking at
pelvic organ prolapse but also urinary incontinence, the
challenge for us is, if we change classification, this is a
slightly different issue but an important one, we go through a
rulemaking process, and in those rare cases where that product
based upon new evidence should move to a different
classification, we have to take years to make that change. That
is a challenge that we do face. We are going through questions
now with metal-on-metal hips. You have raised it in terms of
pre-amendment devices. Our barrier is actually in those cases
statutory requirement to do rulemaking, and that makes it hard,
and you want to know something? I don't know what you tell
patients if you find a problem like that and you make a
decision to up-classify, what you do for all that time and all
those----
Mr. Markey. This woman's life is ruined, and the only thing
I could tell her is that her now ruined life in her own words,
will now pay dividends for other women who won't be facing the
same thing.
Mr. Pitts. The chair thanks the gentleman.
Mr. Markey. I thank you, Mr. Chairman.
Mr. Pitts. We will proceed for a follow-up to Dr. Burgess.
Mr. Burgess. I thank the chairman, and I have got some
other things I want to ask, but I just feel obligated. Once
again, substantial equivalence does not necessarily equate
clearance, and your own information that you sent to a company
that receives a substantial equivalence determination, ``Please
be advised the FDA's issuance of a substantial equivalence
determination does not mean that the FDA has made a
determination that this complies with other requirements of the
Act.'' They are referring to the Food, Drug and Cosmetic Act. I
think you have authority there. Now, this situation is perhaps
a little bit more ambiguous than an implantable pacemaker. I
would be happy to work with you too on this issue of
implantable mesh because I do think it is an important one. As
the baby boom generation ages, we are going to see a lot of
demand for these type of procedures, and as Mr. Markey points
out, it is important that we get it right because the problems
with defects down the road can be significant.
Dr. Woodcock, let me just ask you a question. I know we
visited drug shortages in these hearings, and I appreciate the
work that you have done, and while I wish there were some
single legislative product that would correct the defect, I am
not sure that there is, and then the problem is with
legislative products that we may make things worse if it leads
to hoarding and that sort of activity. But it also seems like,
you know, we brought specific examples in these hearings to
your attention--methotrexate, doxorubicin--and things have
happened then as a consequence, and I am very grateful for
that. I am sure the patients are grateful. But it also makes me
wonder if the problem isn't one of maybe if there were a little
more flexibility or creativity on the part of the FDA that some
of these shortages could be mitigated without having them
become a national crisis. You provided us a long list at
another hearing. Do you have someone on your staff who is
looking at that? There may be unique ways to mitigate some of
these shortages and perhaps we ought to get busy about doing
that rather than trying to find ideal legislation.
Dr. Woodcock. Well, we were working on methotrexate and
doxorubicin for quite a long time and we had different
solutions emerge for both of those. In every case, we are using
almost every tool we have. We don't make the drugs. The
manufacturers make the drugs, and we try to provide them with
encouragement and flexibility and lot release, like we said,
batch by batch. Even if their manufacturing isn't perfect, we
can mitigate many of these things. So I think we have tools to
do this. We think that additional notification may be helpful.
We think the proposals by the private sector for more
information sharing will be helpful. We feel that some of the
proposed discussion draft legislative might have unintended
consequences. For example, we have this expedited review. If we
have a lot of people requesting that and we know that other
companies are going to be able to come up and provide the
product, because we have talked to them, then we don't want to
be reviewing a lot of people or clamoring for expedited review
if we feel there is not going to be a shortage and the company
is in production. We think deeming compliance would be a
problem, all right? Because people are either in compliance or
not in compliance. If they are not in compliance with GMPs, we
have flexibility and they don't have to be in full compliance
to be producing these shortage drugs. They just have to be
producing drugs that are of good enough quality that we feel
comfortable with them going into the veins of our patients,
right?
Mr. Burgess. Right. Well, the only point I was trying to
make is, it does seem like there are sometimes out there that
if we just worked a little harder, we would come up with them,
and I just encourage you to keep doing that.
Dr. Woodcock. We are working very hard.
Mr. Burgess. But one specific instance, of course, a
shortage occurs right now today at any pharmacy across the
country that an asthmatic cannot walk into a pharmacy and buy
an over-the-counter asthma inhaler like they used to be able to
before January 1st. So there is a solution there, and that
would be to allow the manufacturer of the old CFC product to
sell what stock they have left. This product was not deemed to
be defective. It was an EPA requirement that they stop selling,
not an FDA requirement, and I appreciate the fact that you are
working through this problem with getting a new over-the-
counter preparation available, but as you pointed out, you have
difficulty with bioequivalency, and I will also readily admit
that HFA is not nearly as good a propellant as CFC, and don't
blame the victim. It was not because I was holding the thing
upside down. It is just not as good. But having said all of
that, could you help us with the EPA if you were to write
Administrator Jackson that because of the difficulties you are
having with assessing bioequivalence of these new products that
it would be helpful to allow the company to sell the product
that it already has manufactured. We are not asking them to
make a single vial. All the CFC that is going to be put into
vials has already been put in. The only problem is, we are
preventing asthmatics from having it accessible. Can I get your
help to write a letter to Administrator Jackson to let her know
of your problem so that maybe she can help us with the problem
that asthmatics are having?
Dr. Woodcock. We have been discussing and working with the
EPA on this matter.
Mr. Burgess. Yes, but this is something that people just
frankly do not understand why one federal agency and another
federal agency cannot come together on a reasonable solution.
That reasonable solution is, be able to sell the product as it
exists in warehouses today. Again, not one single molecule of
CFC is going to be produced that has not already been produced.
The hole in the ozone is not going to get one millimeter bigger
because we are allowing this product to be sold. Again, the CFC
has already been produced and it is already in the canisters.
One day it is going to come out by some mechanism or another. I
just think it would helpful to the patients of America. We
could eliminate this one drug shortage overnight if you could
get some cooperation with the EPA.
Mr. Pitts. The chair thanks the gentleman. Mr. Engel for 5
minutes for questions.
Mr. Engel. Thank you, Mr. Chairman.
Dr. Woodcock, I just have two quick questions. I want to
get back to the issue of drug shortages again because during
your last appearance before the subcommittee, I mentioned my
concerns about drug shortages of medications that overlap with
the DEA's controlled-substance jurisdiction, and I am pleased
to see in this discussion draft there are provisions for the
Attorney General to increase quotas as necessary within 30 days
of a request from a manufacturer. So let me ask you this. Do
you believe that the majority of drug shortages in the
controlled-substance category can be effectively prevented if
the Attorney General addresses this request within the 30-day
window or do you believe a shorter window would be necessary to
ensure patient access to needed medications?
Dr. Woodcock. I am not familiar enough with DEA procedures
to answer your question accurately. There are many causes of
drug shortages, and certainly not all shortages of controlled
substances may be related to DEA procedures or quotas or what
have you. So I think it is a complicated issue and we would be
glad to work with you.
Mr. Engel. OK. How about the 30 days, though? Do you think
that is sufficient? It might be a little too long if someone
really needs a medication.
Dr. Woodcock. Again, it is very difficult for me to put
that into--to understand what impact 30 versus a shorter time
would have on an unfolding shortage situation.
Mr. Engel. OK. Well, we will work with you on it.
During the last PDUFA reauthorization, I worked--this is a
couple years ago--I worked with Congresswoman Blackburn and
Congresswoman Giffords at that time to authorize critical path
public-private partnerships, and to date, the Critical Path
Institute in Arizona and the Clinical Data Interchange
Standards Consortium have worked under this partnership to
improve the regulatory science that FDA and industry depend on
when developing and improving new pharmaceuticals and medical
devices. So I am wondering if you could comment on that? It is
sort of loaded question, but I want you to be on the record,
because I feel strongly about the importance of the critical
path public-private partnerships and the FDA's work, so I would
like you to comment on that and what role you see for these
partnerships in the future.
Dr. Woodcock. Well, first of all, the Critical Path
Institute has done a number of projects that are essential. For
example, we have new biomarkers now being tested in the clinic
for drug-induced renal failure, something we don't have any
sensitive indicators for, and so this is a tremendous advance
in regulatory science if we can get these. We have qualified
them for animal studies. If we can use them in humans, that
would be a tremendous advance for drug development.
As far as the clinical data standards, as we move into
developing electronic health records for the public and so
forth, having unified standards for how you collect data in
clinical trials not only will help companies, it will help the
FDA and it will help all the investigators in efficiently
performing clinical trials. Right now, we have a tremendous
problem of loss of clinical studies from the United States and
going elsewhere, and harmonized standards within the United
States for clinical data are a tremendous requirement and would
really help both drug development and understanding the role of
medical products and their outcomes in our population. So this
type of regulatory science that is being done by the Critical
Path Institute and other public-private partnerships is really
building for the future, and we really endorse it.
Mr. Engel. Well, thank you. I couldn't agree with you more,
and you gave me the answer I wanted, so thank you very much.
Mr. Chairman, I yield back the balance of my time.
Mr. Pitts. The chair thanks the gentleman and yields to the
ranking member for a unanimous consent request.
Mr. Pallone. Thank you, Mr. Chairman. I just would like to
make a unanimous consent request that the statement of
Congresswoman Anna Eshoo as well as some questions that she is
promulgating to Dr. Janet Woodcock be entered into the record.
Mr. Pitts. Without objection, so ordered.
We will make sure you get all of the questions for follow-
up, if you would respond in writing.
That concludes our first panel. Thank you, Dr. Woodcock,
thank you, Dr. Shuren, for your testimony and your responses.
The committee will recess for 5 minutes as we change for panel
number two and we will reconvene in 5 minutes.
[Recess.]
Mr. Pitts. The 5 minutes having expired, we will reconvene
the subcommittee, and we now have panel number two. I would
like to thank all of you for agreeing to testify before the
subcommittee today. I would like to quickly introduce our
expert panel.
First, Dr. David Wheadon is Senior Vice President of
Scientific and Regulatory Affairs at Pharmaceutical Research
and Manufacturers of America. Dr. Sara Radcliffe is Executive
Vice President of Health at Biotechnology Industry
Organization. Mr. David Gaugh is Vice President of Regulatory
Sciences at the Generic Pharmaceutical Association. Mr. Joseph
Levitt is Partner at Hogan Lovells and is testifying on behalf
of Advanced Medical Technology Association. And Mr. Allan
Coukell is Director of Medical Programs of Pew Health Group at
the Pew Charitable Trust.
Again, thank you all for coming. We have your prepared
statements. They will be entered into the record. We ask that
you summarize your opening statements in 5 minutes. We are
scheduled to vote in about 20 minutes. We will try to get
through the presentations before having to go to the floor for
the vote.
So with that, Dr. Wheadon, we will begin with you. You are
recognized for 5 minutes to summarize your testimony.

STATEMENTS OF DAVID E. WHEADON, M.D., SENIOR VICE PRESIDENT,
SCIENTIFIC AND REGULATORY AFFAIRS, PHARMACEUTICAL RESEARCH AND
MANUFACTURERS OF AMERICA; SARA RADCLIFFE, EXECUTIVE VICE
PRESIDENT OF HEALTH, BIOTECHNOLOGY INDUSTRY ORGANIZATION; DAVID
GAUGH, R.PH., VICE PRESIDENT, REGULATORY SCIENCES, GENERIC
PHARMACEUTICAL ASSOCIATION; JOSEPH A. LEVITT, J.D., PARTNER,
HOGAN LOVELLS US LLP, ON BEHALF OF ADVANCED MEDICAL TECHNOLOGY
ASSOCIATION; AND ALLAN COUKELL, DIRECTOR OF MEDICAL PROGRAMS,
PEW HEALTH GROUP, THE PEW CHARITABLE TRUSTS

STATEMENT OF DAVID E. WHEADON

Dr. Wheadon. Chairman Pitts, Ranking Member Pallone and
members of the subcommittee, good afternoon. I am David
Wheadon, Senior Vice President, Scientific and Regulatory
Affairs, at the Pharmaceutical Research and Manufacturers of
America, better known as PhRMA. PhRMA appreciates this
opportunity to appear before you again today in order to share
our views on the 5th reauthorization of the Prescription Drug
User Fee Act and on the reauthorization of the Best
Pharmaceuticals for Children Act and the Pediatric Research
Equity Act.
PhRMA and its member companies strongly support the
original goals of PDUFA, namely to provide patients with faster
access to innovative medicines, to preserve and strengthen
FDA's high standards for safety, efficacy and quality, and to
advance the scientific basis for the agency's regulatory
oversight. PDUFA has advanced public health by accelerating the
availability of innovative medicines to patients while helping
to ensure patient safety. PDUFA has also played a role in
improving America's competitiveness around the world.
Since the passage of the original PDUFA in 1992, the United
States has become the world leader in bringing new medicines to
patients first, ensuring that the United States maintains a
policy and regulatory environment that encourages an efficient,
consistent and predictable drug review process is key to
keeping America competitive in today's global economy.
The PDUFA V performance goals letter was created with an
impressive inner transparency and involvement from diverse
stakeholders including patients, health care providers and
academia. This agreement will provide FDA with the resources
and tools required for further enhancing the timeliness,
completeness and efficiency of the drug review process
including provisions to advance regulatory science and
modernize drug development, to improve benefit-risk decision
making and to further strengthen FDA's focus on patient safety.
PhRMA strongly endorses the recommendations of the PDUFA V
performance goals letter and urges Congress to reauthorize this
important legislation in a timely manner based on the
negotiated agreement. Failure to reauthorize PDUFA in a timely
fashion would have catastrophic effects on the ability of FDA
to carry out its important role in bringing innovative
medicines to patients.
I would like to focus for a moment on one specific aspect
of PDUFA. The enhanced New Molecular Entity review model, or
NME review model, will improve the review process for new
molecular entity drug and biologic applications. This will be
particularly significant for patients because NMEs are novel
compounds that have the potential to address unmet medical
needs and advance patient care. Specifically, it is anticipated
that earlier and more comprehensive communication between the
agency and drug sponsors as required in this enhanced review
model will improve the rate of on-time first-cycle successes.
The success of the new review program and of the agency's
ability to achieve its drug review goals will be independently
assessed in 2015 and 2017.
PDUFA V will continue to provide FDA with the necessary
tools and resources that are essential to support patient
safety and promote medical innovation through enhanced
timeliness, completeness and efficiency of the drug review
process. PhRMA encourages Congress to reauthorize PDUFA in a
timely manner based on the negotiated PDUFA V performance goals
and to minimize the inclusion of additional provisions that may
have the unintended consequences of distracting from the Act's
original intent.
The Best Pharmaceuticals for Children Act and the Pediatric
Research Equity Act have been extraordinarily successful in
improving medical care for children by driving research to
create innovative medicines for use in pediatric patients.
According to the FDA, the current pediatric exclusivity program
has done more to spur research and create critical information
about the use of medicines in pediatric patients than any other
government initiative. Ensuring that the pediatric exclusivity
incentive is preserved is key to continued innovation and
improved pediatric medical care in the face of rising research
costs.
Since its initial enactment and subsequent
reauthorizations, BPCA and PREA have been subject to a sunset
clause under which their provisions expire after 5 years unless
reauthorized by Congress. To build upon the tremendous success
of BPCA and PREA in improving medical care for children,
Congress should permanently reauthorize BPCA and PREA.
We would particularly like to thank Representatives Eshoo,
Rogers and Markey for their work towards a bipartisan effort
for a permanent reauthorization of these important pieces of
legislation.
In summary, PhRMA and its member companies are committed to
working closely with FDA, Congress and all stakeholders to
ensure the continued success of PDUFA in bringing safe,
effective and innovative medicines forward to address unmet
medical needs for all patients including children. PhRMA
therefore urges Congress to reauthorize PDUFA V and to
permanently reauthorize BPCA and PREA in the most expeditious
manner possible.
Thank you, and I would be happy to entertain any questions.
[The prepared statement of Dr. Wheadon follows:]

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Mr. Pitts. The chair thanks the gentleman.
Ms. Radcliffe, you are recognized for 5 minutes.

STATEMENT OF SARA RADCLIFFE

Ms. Radcliffe. Thank you. Chairman Pitts and Ranking Member
Pallone, I appreciate the opportunity to be here today. I am
Sara Radcliffe, Executive Vice President for Health for the
Biotechnology Industry Organization, BIO. I led BIO's
engagement in the Prescription Drug User Fee Act technical
discussions with the Food and Drug Administration and managed
BIO's involvement in the biosimilars user fee technical
discussions as well.
BIO supports quick enactment of the PDUFA V recommendations
and we are supportive of the draft user fee package that the
committee has released. This committee has reached strong
bipartisan compromises on many issues that of critical
importance to our industry. We believe that enhancements under
PDUFA V will improve the drug development and review process
through increased transparency and scientific dialog, advance
regulatory science and strength postmarket surveillance. Most
importantly, from the standpoint of young, innovative
companies, our hope is that PDUFA V will provide patients and
doctors with earlier access to the cures and treatments of
tomorrow.
The PDUFA V legislation will reinforce FDA's review
performance and get back to basics for patients. These
enhancements include a New Molecular Entity review program that
will lead to fewer review cycles and earlier patient to needed
treatment, enhanced communication during drug development,
regulatory science modernization and robust drug safety and
postmarket surveillance capacities.
BIO supports FDA's ongoing implementation of a well-
constructed, science-based pathway for the approval of
biosimilar products. Establishing a sound BSUFA was also a
priority for us. A transparent, predictable and balanced
regulatory framework for the review and approval of biosimilars
accompanied by reasonable performance goals and a dedicated
independent funding stream will ensure that FDA can facilitate
the development and evaluation of biosimilar products.
There are a number of other important provisions included
in the draft that are of critical importance to BIO.
Modernizing the Accelerated Approval pathway has been a top
priority, and we are extremely pleased that the draft included
H.R. 4132, the Faster Access to Specialized Treatments, or FAST
Act, introduced by Congressmen Cliff Stearns and Ed Towns. FAST
will ensure that FDA can utilize the Accelerated Approval
pathway as fully and frequently as possible while maintaining
FDA's safety and effectiveness standards.
The Accelerated Approval pathway has been a great success
story. In certain disease areas such as cancer and HIV, the
pathway has stimulated an explosion of investment in innovation
and has brought immense benefit to patients. We appreciate
Congress working to expand the pathway so that patients
suffering from other life-threatening and rare diseases can
benefit as well.
The Best Pharmaceuticals for Children Act and Pediatric
Research Equity Act have greatly improved health outcomes for
children. However, the 5-year sunset periods have resulted in
an uncertain regulatory environment for pediatric drug
development that makes it difficult for our company and
practically impossible for the FDA to issuance guidance to
promote understanding of the current regulatory framework. BIO
thanks Congressman Mike Rogers, Congresswoman Anna Eshoo and
Congressman Ed Markey on their championship of this important
issue and we support the inclusion of their legislation in the
committee draft.
It is also important that FDA has access to the most
knowledgeable and most qualified scientific minds to help
inform key public health decisions and evaluate the safety and
effectiveness of innovative new cures and treatments for
patients. BIO thanks Representative Burgess and Ranking Member
Pallone for their work to enhance FDA's ability to impanel
highly qualified external scientific advisors while maintaining
the highest levels of integrity for these proceedings.
Additionally, BIO looks forward to continuing to work with
the committee to enhance oversight over the upstream supply
chain for pharmaceutical ingredients and modernizing the
downstream domestic supply chain for finished pharmaceutical
products. BIO supports the establishment of strong, uniform
national standards for serialization and tracing systems rather
than relying on the emerging patchwork of individual State
mandates. In this case, BIO believes that Congress should enact
laws governing drug product serialization and traceability
systems that regulators can leverage to hold supply chain
member accountable for ensuring that legitimate product reaches
the patient. A national system using existing and proven
technologies would best protect supply chain integrity and
patient safety.
Thank you again for the opportunity to testify. We look
forward to working with all of you to ensure that the user fee
package is quickly enacted.
[The prepared statement of Ms. Radcliffe follows:]

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Mr. Pitts. The chair thanks the gentlelady.
Mr. Gaugh, you are recognized for 5 minutes for an opening
statement.

STATEMENT OF DAVID GAUGH

Mr. Gaugh. Good afternoon, Chairman Pitts, Ranking Member
Pallone and members of the subcommittee. I am David Gaugh, Vice
President of Regulatory Science for the Generic Pharmaceutical
Association and a Licensed Pharmacist. GPhA represents the
manufacturers and distributors of finished dose pharmaceuticals
and bulk pharmaceutical chemicals.
Generic pharmaceuticals account for 80 percent of all
prescription drugs dispensed in the United States but consume
just 27 percent of the total drug spending for prescription
medicines. Today's generic industry is one marked by diverse,
innovative companies who have grown to become global leaders in
providing equivalent medicines. At the same time, generic
competition continues to play a vital role in driving
pharmaceutical innovation. This growth in the generic industry
has led to the creation of tens of thousands of new American
jobs and dozens of States across the country. It has also
served to underscore the critically important role of the Food
and Drug Administration. However, the administration remains
underfunded and responsibility of ensuring access to safe and
affordable medicines is one that is shared with the rest of the
entire pharmaceutical industry, not just the FDA. That is why
the generic industry has stepped up to help provide the FDA
with additional resources to address the ongoing challenges
caused by an increasing global drug supply chain, the increase
in the agency's workload and the regulation of complex
technologies.
Currently, more than 2,700 generic drug applications are
awaiting approval from the FDA's Office of Generic Drugs, and
the average approval time for an application is now stretching
beyond 30 months, more than five times longer than the
statutory six-month review time that was called for in Hatch-
Waxman. Unfortunately, this backlog keeps safe, low-cost
generic drugs off the market and reduces competition that may
drive prices down even further.
The proposed Generic Drug User Fee Act, or GDUFA, that we
are discussing today will help alleviate this backlog and
expedite consumer access to these generic drugs. GPhA also
recognizes, however, that while providing early access to
effective medicines is critical and is a key aim of the other
user fee programs, an equally important pillar of FDA and
industry is to ensure drug safety. That is why GDUFA takes the
unprecedented step of holding all players contributing to the
U.S. generic drug system both foreign and domestic to the same
inspection standards and enhances FDA's ability to identify and
require the registration of active pharmaceutical ingredients
and finished fill dosage for manufacturers involved in each
generic drug product that is sold in the United States. It is
paramount that we work to shape the future of our country's
generic drug industry. We also work to bring the FDA into the
21st century and ensure that the agency's authorities to
achieve its mission in this global age are up to date.
This is further exemplified by the other fee program we
will discuss today, which is for generic biologic drugs or
biosimilars. Biologic medicines are often the only lifesaving
treatment for many of the more severe diseases encountered in
patients today. In many respects, they represent the future of
medicine. However, their price tag can keep these products out
of the reach of many patients.
During the biosimilar user fee negotiations, GPhA expressed
its support for the user fee funding to provide FDA with the
adequate resources to apply consistent regulatory standards to
all biologics and review new applications as they are filed.
Both industry and patients will benefit from this user fee
program by gaining a higher degree of certainty in the
timeliness of applications and their reviews. We applaud the
FDA for recognizing the importance of the biosimilars and the
need to apply state-of-the-art science in an agency activity
governing the review and approval of these very important
drugs.
Now let me turn to drug shortages. The generic
pharmaceutical industry has spearheaded the development of an
unprecedented multi-stakeholder private sector collaboration
which we believe will accelerate the recovery of certain
critical drugs in short supply to the patients in need. This
solution, which has been labeled the Accelerated Recovery
Initiative, will play a crucial role in assisting the FDA with
a more accurate, timely and comprehensive review of current
potential drug shortages and in establishing practices to
lessen or even eliminate in some cases current shortages.
Finally, we urge the inclusion in the user fee legislation
of a proposal introduced by Ranking Member Pallone and
Representative Guthrie, H.R. 4332, the Generic Drug Application
Review Fairness Act, which will ensure that generic drug
manufacturers are not unfairly penalized for delays in the drug
application approval process.
In conclusion, Mr. Chairman, this is truly an historic time
for GPhA. Nothing is more important to our industry than
ensuring patients have access to lifesaving generic medications
they require and these historic agreements will provide the
critical step towards accomplishing that goal. Thank you.
[The prepared statement of Mr. Gaugh follows:]

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Mr. Pitts. The chair thanks the gentleman.
Mr. Levitt, you are recognized for 5 minutes.

STATEMENT OF JOSEPH A. LEVITT

Mr. Levitt. Thank you. Chairman Pitts, Ranking Member
Pallone and members of the committee, my name is Joe Levitt. I
am a partner in the law firm of Hogan Lovells, and I am here
today on behalf of AdvaMed, MDMA and MITA, the three trade
associations who participated in the MDUFA negotiations with
the FDA. I was on that negotiating team throughout that
process, and I am pleased to be testifying with you here today.
I also spent 25 year at the FDA and for 6\1/2\ of those years
during the 1990s I held the senior position in FDA's Medical
Device Center.
As many of you know, the medical technology industry has
been a true success story for patients and for the U.S.
economy. Our industry truly leads the world but our leadership
is slipping. One key reason, perhaps the most important reason,
is the decline we have seen in FDA efficiency, consistency and
predictability in recent years. To their credit, the FDA
leadership has recognized the need to vigorously address the
issues affecting the device center. The new user fee agreement
has the potential to be a significant additional step in the
right direction. It is good for industry, it is good for FDA,
and most of all, it is good for American patients.
The user fee agreement builds the conditions for success in
a number of major ways. First, for the first time ever, this
user fee agreement establishes average total time goals for FDA
review. Our previous agreements had set goals only for terms of
the FDA clock but what matters most to industry and to patients
is the actual calendar, the time from beginning of submission
to final FDA decision. By setting in place this new goal,
efforts will be focused on the metric that truly matters.
Second, the agreement also establishes improved goals for
time on the FDA clock. These goals are a key management tool
for the agency and they work in concert with the total time
goal to produce better performance than either could achieve
alone.
Third, the agreement includes new procedures that we
anticipate will improve the review process. These include
before the review actually begins meaningful presubmission
interactions between FDA and companies to be sure everybody is
on the same wavelength going in, during the review process a
mandatory mid-course substantive interaction between FDA and
the company midway through the process to check in and be sure
we are all on the right wavelength there, and finally at the
tail end, a new procedure that we call ``no submission left
behind'' so that if FDA time target is missed, that submission
does not fall off the radar screen.
Fourth, the agreement provides for greater accountability.
Under the agreement, there will be quarterly and annual
reporting on a variety of key metrics that both industry and
FDA agree are important. In addition, the agreement provides an
analysis of FDA's management of the review process by an
independent consulting organization coupled with FDA corrective
action plan to address opportunities for improvements. We see
this as being critical. It is a way to bring fresh eyes to the
issues and work constructively towards meaningful process
improvements.
Finally, to give FDA the additional tools to meet the new
goals, the agreement provides for $595 million in user fees
over the life of the agreement. Additional reviewers, lower
management-to-reviewer ratios, enhanced training and other
resources totaling about 200 additional FTEs for the agency are
provided by the agreement and will give FDA what it needs to
improve performance.
Of course, no agreement, no matter how good on paper, is
self-executing. Making it work as intended will require the
full efforts of all concerned. Continued oversight and interest
from the Congress will also be important. Patients are
depending on all of us.
In conclusion, I should note that a number of legislation
proposals have been introduced with the goal of improving FDA's
operations also. We are appreciative of efforts by all members
who seek to give FDA the tools and structure it needs to
succeed. At the same time, I want to emphasize that we are
strongly committed to the user fee agreement as negotiated and
do not support any proposals that would change the terms of the
agreement or undermine its goals. Just as the user fee
agreement has the potential to help FDA move in a positive
direction, failure to reauthorize the program in a timely way
would be nothing short of catastrophic, as my colleagues on the
panel have also echoed.
So I thank the committee for the opportunity to testify and
urge it act promptly to reauthorize the program which is so
critical to patients, to FDA and to our industry.
[The prepared statement of Mr. Levitt follows:]

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Mr. Pitts. The chair thanks the gentleman.
We are in the middle of a vote on the floor. We have about
10 minutes. We will take one more witness and then we will
break for the vote.
Mr. Coukell, you are recognized for 5 minutes.

STATEMENT OF ALLAN COUKELL

Mr. Coukell. Thank you, Mr. Chairman, Ranking Member
Pallone and committee members. I appreciate the opportunity to
testify.
My name is Allan Coukell, and I am the Director of Medical
Programs for the Pew Health Group. Our research and analysis
aim to improve the safety and well-being of American consumers
with the major focus on drugs, medical devices and the FDA. I
will focus today on the importance of the FDA user fee
agreements to patients and public health and about three key
policy areas that the committee is considering.
Since 1992, PDUFA agreements have given FDA significant and
sustained resources, allowing for faster reviews of new
products. Indeed, preliminary results of a study that Pew has
funded show that FDA reviews drugs faster than its counterparts
in the E.U. and Canada. The development of new antibiotics is a
particular focus for Pew's Antibiotics and Innovation Project,
and we thank this committee for consideration of the GAIN Act,
the bipartisan bill introduced by Mr. Gingrey that would grant
extra market protection to certain antibiotics.
Unlike other drugs, antibacterials lose their effectiveness
over time as the bugs become resistant. That is why experts are
so alarmed about the years-long decline in new antibiotics and
the dearth of products in late-stage development. We look
forward to working with this committee to see that this
provision targets and incentivizes the drugs we most need,
those that treat serious or life-threatening infections.
Turning now to medical devices, we ask Congress to swiftly
reauthorize MDUFA. Under this new agreement, FDA would add 200
device staff and nearly $600 million for the review of device
applications. Let me illustrate the importance of this funding
with an analysis recently commissioned by Pew showing that
FDA's Device Center has a higher attrition rate than the
Centers for Drugs and Biologics or the Office of Regulatory
Affairs. In fact, nearly 10 percent of FDA's device staff left
in fiscal year 2010, and the majority reported not having
sufficient resources to get their job done. To function
effectively, the center must have adequate funding.
But let us never forget that true innovation is not just
about speed to market but about developing products that are
safer or more effective than existing drugs and devices, and
because medical devices often enter the market with little or
no clinical data, it is especially important that we have a
robust system for postmarket surveillance, and we urge this
committee to include legislation that will medical devices to
FDA's Sentinel Surveillance System which is currently on for
drugs, require that FDA issue and implement rules that assign a
unique identifier like a barcode to each new device as we have
on most other things that we buy, and clarify the agency's
authority to order safety studies when necessary for high-risk
devices. We must also ensure that these studies are completed
in a timely way. Such a system would detect safety problems
faster and would facilitate innovation by increasing the
confidence of the public and the FDA on marketed devices.
On safety, I am pleased to note that the landmark new
generic drug user fee agreement while speeding the review of
these products will also enhance safety by ensuring that FDA
performs more inspections of overseas generic drug plants. As
Pew's drug safety project has noted, 80 percent of the
ingredients in our drug supply now come from overseas yet we
inspect U.S.-based drug makers every 2 years, as the law
requires. Meanwhile, the FDA inspections in China, for example,
average out about every 17 years. Addressing this disparity
will level the playing field for U.S.-based manufacturers and
help to protect patients. Congress should hold FDA accountable
by ensuring that no facility goes indefinitely without an
inspection. But inspections are only part of the story. Several
additional key measures would improve confidence in the supply
chain.
For example, we should ensure that every company takes
responsibility for its own upstream suppliers, verifying that
appropriate quality systems are in place. We should reward
manufacturers who have strong systems. We support a national
track-and-trace system for drugs but such a system must include
standards that will detect counterfeits before they get to
patients and, for example, provide law enforcement with the
tools needed to address illegal-drug diversion.
We thank the committee for its bipartisan work on the
prescription drug supply chain. A poll we commissioned showed
that Americans of all political persuasions recognize the risks
and support Congressional action.
I will conclude with a reference to FDA's mission
statement, which acknowledges the agency's dual role:
protecting patients and ensuring innovation. The user fee
agreements support both aims, and we urge Congress to pass them
quickly along with the three essential additions: drug supply
chain safety, antibiotic development and medical device safety.
Thank you, and I welcome your questions.
[The prepared statement of Mr. Coukell follows:]

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Mr. Pitts. The chair thanks the gentleman.
That concludes the opening statements. We are in the middle
of a vote. I think we have about 5 minutes left, so at this
point the subcommittee will break until the third vote. Five
minutes after the third vote, we will reconvene. The
subcommittee stands in recess.
[Recess.]
Mr. Pitts. The recess having expired, we will reconvene the
Subcommittee and go to the questioning. I will now begin the
questioning and recognize myself for 5 minutes for that
purpose.
First of all, Dr. Wheadon, how does the PDUFA agreement
help mitigate the issue of delayed reviews of drug applications
at FDA and help America maintain their role as the leading
innovator in the pharmaceutical space? If you would please
elaborate on that.
Dr. Wheadon. I will answer that, Chairman Pitts, on two
fronts, focusing initially on the New Molecular Entity----
Mr. Pitts. Is your microphone on? Just pull it down. Yes.
Dr. Wheadon. Focusing initially on the New Molecular Entity
Review Program, that was really set up to enhance ongoing
communication between drug sponsors and FDA such that sponsors
would understand up front what FDA expectations may be as they
enter into the review. As the review progresses, there would be
feedback to the sponsor. There are questions that come out of
the review that could be answered contemporaneously rather than
waiting until the end of the review. The intention is that by
the time you get to the end of the review, most of the issues
could have been discussed and hopefully rectified, allowing for
FDA to make a final action, hopefully an approval, thus
allowing the drug to be approved in the first cycle and
available to patients.
Beyond that, the other aspects of the agreement, the
availability of innovative medicines to patients, really looks
at the regulatory science initiatives, things like benefit-
risk, biomarker development, pharmacogenomic processes,
enhancing the utilization of REMS in terms of standardizing
that process rather than starting from square one with each
necessity for utilizing of REMS for approval.
So taken as a whole, the intention is to make the review
process more efficient and more effective use of FDA resources,
allowing for a thorough review but hopefully a one-cycle review
and ultimately really addressing the issue that we started out
looking at, and that is for roughly 50 percent of applications,
they don't get approved in the first cycle. They ultimately do
get approved with following cycles of review. That is an
inefficient use of FDA resources and that is really what we are
trying to tackle with the agreement.
Mr. Pitts. Ms. Radcliffe, would you like to add to that as
far as bio is concerned?
Ms. Radcliffe. Yes, I would. Thank you. I would like to
support everything that Dr. Wheadon said about the weight of
the PDUFA Technical Agreement will enhance the availability of
products for patients but mention also one other thing. It was
particularly important for our small companies and that was a
provision to enhance timely interactive communication during
the drug development phase. Our small companies tell us that
very often they have simple, informal questions where they need
timely answers in order to proceed. We were very pleased that
the Agency agreed to state explicitly that they have a
philosophy of timely, interactive communication with sponsors
and also that we were able to agree to establish a liaison
staff that would work to ensure that that communication occurs.
Mr. Pitts. Thank you.
Mr. Gaugh, the discussion draft includes a section on
expediting manufacturing changes to alleviate a drug shortage.
Would you comment on this provision, tell us how it would help?
Mr. Gaugh. I am sorry. Could you repeat that?
Mr. Pitts. Yes. The draft includes a section on expediting
manufacturing changes to alleviate drug shortages. Comment on
that provision.
Mr. Gaugh. Yes, in today's environment it takes anywhere
from 18 to 24 months for those review cycles to occur, so if
you have a product that is in drug shortage, that is an
additional time point with everything else that you are adding
to it. The provisions in here are going to be for expedited
review, which could be as quickly they say as 3 to 6 months,
which would help tremendously.
Mr. Pitts. Mr. Levitt, can you explain IDEs--what are they,
what companies get IDEs traditionally, how does FDA evaluate
IDEs? I understand FDA has a new policy on IDEs. How does that
differ from previous policy and what is your opinion of the new
policy?
Mr. Levitt. OK. An IDE stands for Investigational Device
Exemption. What it basically means is that FDA reviews
applications for new clinical studies. New clinical studies are
needed generally for all Class 3 devices going through the
premarket approval process and for a small minority of 510(k)
products. But if a company wants to test their device in humans
and it doesn't fit into one of the minor categories that they
are exempt from submitting, then they submit an application to
the FDA that includes the data to show that the device is safe
enough to test in humans. So the first question is safety. And
the second question is, what is the protocol that they are
going to use during the study? They will submit those to FDA.
FDA has 30 days only to review that, reflecting that FDA's
review is really just to focus on is it safe and is this
essentially a bona fide study where the potential benefits
outweigh the potential risks. So that is the historical
process.
What has happened recently is that FDA has brought greater
scrutiny to the clinical protocol part and they are trying to
say that you can only do this clinical study if it is good
enough to get final approval. And there is a lot of concern
within the industry that that is much more than has ever been
done in the past and is certainly much more than the
regulations their statute require, that the process should be
able to go forward at the pace that the company is prepared to
undertake. It might be a preliminary study, it might be a study
that will depend on how strong the results are, how big you
need.
And so I think the concern that you are hearing is that
that study should not be the most robust possible, but instead,
the FDA should allow the study to go forward if it is safe and
if it is bona fide research where the potential benefits
outweigh the potential risks and there is valid information to
be learned from the study. That essentially is the company's
call on how they want to investigate the device and develop the
program.
Mr. Pitts. The chair thanks the gentleman. My time is
expired.
The ranking member is recognized for 5 minutes for
questions.
Mr. Pallone. Thank you, Mr. Chairman.
I wanted to start with Mr. Gaugh. I appreciated GPhA's
support for the bill that Representative Guthrie and I recently
introduced, the Generic Drug Application Review Fairness Act.
We heard earlier from Dr. Woodcock about the long review times
for generic drug applications that currently exist. If the
median review time for generic drug applications currently
exceeds 30 months, how does that impact the generic
manufacturers and what are the consequences if you will?
Mr. Gaugh. Well, you heard in earlier testimonies if you go
back to the statute that it is 6-month review time, which we
are well, well past that, 30 months, so almost 2 years past the
statute. So in that 2-year time point, once you have put your
drug application in, market dynamics can change significantly
in that additional 2 years. So it may be a situation where by
the time the 30 months has expired, the market is not still
effective for the company to get into. That is one issue.
Mr. Pallone. And what about the significance of the 180-day
exclusivity period for generic firms?
Mr. Gaugh. The 180-day exclusivity has become a real factor
because in that approval process, it affects first-filers in
paragraph 4 certifications, and if you don't have the product
approved or tentatively approved by the FDA within that 30-day
time point, you lose your 180-day exclusivity.
Mr. Pallone. Do you know how many applications since maybe
2003 have unfairly lost the 180-day exclusivity because of the
FDA review delay?
Mr. Gaugh. Somewhere in the range of 8 to 10.
Mr. Pallone. OK. I mean, it seems to me that the increasing
meeting of approval time of generic drug applications is
unintentionally placed into jeopardy the 180 days of
exclusivity rewarded to the generic applicants, and I am
hopeful that my colleagues will support inclusion of the
Generic Drug Application Fairness Act into the User Fee
package, which is being considered, because this would at least
temporarily fix the consequences that you discussed.
Let me ask Mr. Wheadon, if you would, we heard from Dr.
Woodcock a little bit ago that there is added language to the
discussion draft that was not part of the negotiated PDUFA
agreement, and in FDA's view, these extensive reporting
requirements would place a burden on the Agency and could
result in an unwarranted reshuffling of resources in other
areas. What is PhRMA's view on this added provision?
Dr. Wheadon. Well, there are two aspects to consider. In
many meetings with the FDA we have asked for data going down to
the division level so that we can see whether or not there were
some learnings to be garnered in terms of divisions that
actually are more efficient versus those that may not be as
efficient. Having said that, we also recognize that we don't
want to burden the Agency with a panoply of measurements coming
out of the PDUFA agreement. As Dr. Woodcock described, that may
have the unintended effect of diverting resources from the
needed activities of reviewing applications and getting those
applications acted upon. So it is a very nuanced position if
you will that in terms of getting data down to the review
division can be useful and we certainly have asked for such
data, but we don't want to have so many measurements loaded
onto the Agency such that they aren't able to do the basic work
that they are there to do.
Mr. Pallone. But I mean you said--and I think she said--
that this wasn't part of your original agreement, correct?
Dr. Wheadon. The review division data was not part of the
original, no.
Mr. Pallone. OK. You are kind of answering it but, you
know, I know you are trying to kind of--you are expressing your
concern that we have to be careful but I guess my concern would
be even if we knew that FDA could fail to accomplish other
activities because of the need to shift their times and
resources, you know, do you think that adding that would make
sense if that were the consequence?
Dr. Wheadon. Certainly if it was resource-neutral, if we
could, for example, substitute review division data for other
measurements that are currently being collected such that the
resources are not diverted from needed activities along drug
approval----
Mr. Pallone. Yes, but she said that is not likely.
Dr. Wheadon. But if there are ways that you can do it and
not be overly burdensome, we would be supportive of getting
review division data.
Mr. Pallone. I think that we all agree that we have to be
careful. If we were to tinker with the negotiated language that
PhRMA signed off on we could very well hinder FDA's ability to
accomplish their other performance goals. So I think you are
basically expressing the view that you wish there were some way
to accomplish this without jeopardizing the other.
Dr. Wheadon. Exactly.
Mr. Pallone. All right. Thanks. My time is completed. Thank
you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman. I recognize the
vice chairman of the subcommittee for 5 minutes for questions.
Mr. Burgess. I thank the chairman for the recognition.
Mr. Levitt, let me ask you a question just so I have my
facts correct. Your previous experience was as a deputy
director at the Center for Devices and Radiological Health?
Mr. Levitt. That is correct. I was deputy director for
regulations and policy.
Mr. Burgess. And currently, you are with the Medical Device
Manufacturers, is that correct?
Mr. Levitt. Currently, I am a lawyer at the law firm Hogan
Lovells, and I am representing AdvaMed and the other trade
associations here today.
Mr. Burgess. In either role, can you imagine a scenario
where it would be a company's business plan to go to market
with something that they knew was flawed and going to cause
harm or damage to patients? Would that be a viable business
strategy?
Mr. Levitt. It is hard for me to imagine anybody having
that business strategy.
Mr. Burgess. But you have heard the exchanges this morning
between Mr. Markey and Dr. Shuren, myself and Dr. Shuren. Do
you have any thoughts on what you have heard this morning? Do
you think there is a risk out there that rogue companies are
going to be putting damaging products out there on the market
that the FDA's hands are essentially tied and they can't do
anything?
Mr. Levitt. I think it is hard for me to believe that there
is a significant issue, problem there that needs legislation.
The reviewers have enormous latitude to ask questions on
devices. There almost always are incremental differences
between new devices and old ones, and as has been pointed out,
even after a final 510(k) decision is made, the Agency has
additional authorities to prevent adulterated or misbranded
devices from going onto the market. It is hard for me to
believe--and Dr. Shuren, I thought, said as much--that the
Agency doesn't believe it has let out onto the market unsafe
devices.
Mr. Burgess. And just from where I sit here, that was
pretty troubling. Even if there is only a handful, we really
need to know those devices and where the system failed us if
that is happening. And I am with you. I cannot believe that it
actually is happening. In today's medical legal climate, I
don't think a company could exist if it pursued such a
strategy.
Mr. Levitt. Right. I think we would have to see the
examples, but I can't imagine any company going in with a
business plan to say I am going to sell a flawed device.
Mr. Burgess. Additionally--and of course your testimony
and, Mr. Coukell, I think your testimony as well--the
indication was that specifically the Center for Devices and
Radiological Health required an additional 200 employees. Did I
pick up that information correctly?
Mr. Coukell. Yes, sir, that is a consequence of the User
Fee Agreement that has been negotiated between the industry and
FDA.
Mr. Burgess. And will these 200 new employees, will they be
housed at White Oak or will they be reviewers out somewhere
else in the country or will they be put on the job inspecting
manufacturing plants? Where do they go? I visited Dr. Shuren.
It is very lovely and spacious offices out there at White Oak,
but I didn't see space for 200 more people.
Mr. Coukell. Well, there is a lot of construction out
there, sir, but I don't know the answer to that.
Mr. Burgess. OK. So we are expanding government in the
process of doing this. And I am not disputing that they are not
necessary, but at the same time, maybe, Mr. Chairman, we can,
as a written question, follow up to Dr. Shuren. We can get a
breakdown on the activities and duties of those 200 new
personnel that are going to be hired under the monies provided
by the User Fee Agreement.
Ms. Radcliffe, let me ask you a question. I have worked on
the issue of conflicts. 2007, when the reauthorization was done
that year, I thought the language on conflicts went a little
bit too far and was too restrictive. Do you think that the
concerns I had that day in June were justified about the
conflicts language being a little too restrictive?
Ms. Radcliffe. We do and we thank you very much for your
work on that issue. The conflicts of interest are extremely
important and we respect the need to ensure that conflicts of
interest don't affect the way----
Mr. Burgess. Correct.
Ms. Radcliffe [continuing]. That FDA does its very
important work. That being said, we have heard from many
stakeholders that the provisions that were put in place have
limited FDA's ability to put the right expertise on its
advisory committees, and that is also I think of great concern
to patients and certainly to industry. And so we appreciate the
effort to return FDA to being governed by the same conflict-of-
interest provisions that the rest of the U.S. Government is
governed by.
Mr. Burgess. And certainly I want to thank you for working
with committee staff to try to get that issue resolved.
Mr. Gaugh, let me just ask you a question. I mean drug
shortages come up every time we have a hearing such as this. Do
you have an opinion as to is there enough in the User Fee
Agreements, the draft that you have, is there enough in there
to deal with the issue of drug shortages from the generic
manufacturers' standpoint?
Mr. Gaugh. We believe that the draft, including to the
draft would be the private stakeholder group, the ARI,
Accelerated Recovery Initiative. Between those two, there would
be enough, yes.
Mr. Burgess. Let me ask you this. Sometimes it occurs to me
that maybe we have tightened things down too much, that the
hyper-competition that has been introduced into the marketplace
has made it unprofitable for a manufacturer to continue
manufacture of something. And then if a problem occurs with
their manufacturing floor, they just say forget it. I am out of
the business. Is that in fact happening?
Mr. Gaugh. I think part of the answer to that is, as Dr.
Woodcock said today, the majority of the drug shortages in our
environment as we see today is the sterile injectables, and
sterile injectables are a highly sophisticated process and
there is really only a handful in the United States that make
the sterile injectables. So when an issue happens with the
line, as you have said, that puts a severe crunch on the entire
pipeline.
Mr. Burgess. OK. Thank you, Mr. Chairman. I will yield
back.
Mr. Pitts. The chair thanks the gentleman and recognizes
the ranking member emeritus, Mr. Dingell, for 5 minutes for
questions.
Mr. Dingell. Thank you, Mr. Chairman.
And again, I want to thank you for this hearing but I also
want to thank my colleague, Mr. Murphy, for working with me on
the important system and issue of priority in inspections.
These questions will go first to Mr. Gaugh.
Mr. Gaugh, yes or no, under the User Fee Agreement
negotiated by the generic drug industry, your industry is
committed to paying additional fees to ensure that both foreign
and domestic manufacturers are held to the same inspection
standards? Is that correct? Yes or no?
Mr. Gaugh. Yes.
Mr. Dingell. And I believe that it is in good part because
you are concerned that our domestic industry is inspected
rather more and is policed rather more carefully than the
foreigners, is that right?
Mr. Gaugh. Yes.
Mr. Dingell. Now, again, Mr. Gaugh, yes or no, these
additional fees will ensure foreign and domestic manufacturers
are held to the same inspection frequency and standards? Is
that correct?
Mr. Gaugh. Yes.
Mr. Dingell. Now, again, if you please, the same inspection
frequency as agreed to by FDA and the generic drug industry
under the User Fee Agreement is routine inspection every 2
years, is that correct?
Mr. Gaugh. That is correct, yes.
Mr. Dingell. Now, again, do you agree routine inspections
with parity between foreign and domestic manufacturers will
help level the playing field for your industry? Yes or no?
Mr. Gaugh. Yes.
Mr. Dingell. Is it fair to say that those in your industry
are comfortable with being inspected every 2 years?
Mr. Gaugh. Yes.
Mr. Dingell. Now, thank you for your kindness.
Mr. Coukell, these questions for you, yes or no again to
the degree you can. FDA is currently required by the Federal
Food and Drug and Cosmetic Act to conduct a GMP inspection of
domestic drug manufacturers every 2 years. Is that correct?
Mr. Coukell. Yes, sir.
Mr. Dingell. Many have proposed removing the requirement
for biannual inspections and instead moving to a fully risk-
based inspection system with no minimum inspection frequency.
FDA currently uses a fully risk-based approach for inspections
of foreign drug manufacturing facilities with no minimum
inspection frequency. Is that correct?
Mr. Coukell. Yes.
Mr. Dingell. Under this approach, how is FDA currently
inspecting foreign drug manufacturing facilities?
Mr. Coukell. We look at all facilities outside the U.S. it
is about every 9 years. If we look at China, for example, it is
about every 17. Those are averages that come from the GAO.
Mr. Dingell. Now, would a fully risk-based inspection
schedule guarantee that no drug manufacturing facility went
indefinitely without an inspection?
Mr. Coukell. No.
Mr. Dingell. But it could, could it not?
Mr. Coukell. Would a fully risk-based system----
Mr. Dingell. Yes.
Mr. Coukell [continuing]. Guarantee that----
Mr. Dingell. Yes, if it just says that we are going to do
this on the basis of risk, they could say, well, we don't find
any basis for inspecting this particular facility.
Mr. Coukell. Yes, I agree with you.
Mr. Dingell. OK. Now, would a minimum inspection frequency
provide regulatory certainty to our drug manufacturers, promote
parity between our domestic and foreign drug manufacturers, and
better protect the public's health and safety?
Mr. Coukell. Yes, it would.
Mr. Dingell. Mr. Chairman, I am giving you back a minute
and 14 seconds.
Mr. Pitts. The chair thanks the gentleman.
Mr. Dingell. Thank you.
Mr. Pitts. Recognizes the gentleman from Louisiana, Dr.
Cassidy, for 5 minutes for questions.
Dr. Cassidy. I see in your testimony you are concerned
regarding the tracking of drugs in order to detect
counterfeiting. One of my concerns though, and which Dr.
Woodcock agreed, if somebody is buying from an illegitimate
online pharmacy, they are buying straight from an overseas
provider, then really the absence of an RID or something
similar, a unique identifier, would not provide any benefit.
The person is going to open up their package and they are going
to open it and they are not going to look to see, oh, my gosh,
is there something tracking it? Would you agree with that?
Mr. Coukell. I think it is important to note that there are
both legitimate and illegitimate online pharmacies and many of
our big retail chains operate online pharmacies. So if a person
is obtaining drugs from the legitimate supply, whether they are
going to a brick-and-mortar pharmacy or online----
Dr. Cassidy. Well, I agree with that totally----
Mr. Coukell [continuing]. Then it is difficult.
Dr. Cassidy [continuing]. And I don't mean to interrupt; it
is limited time.
Mr. Coukell. But----
Dr. Cassidy. In fact, that is my point. Right now, the
consumer has limited ability to tell the difference between a
legitimate and an illegitimate. And even though one of the
things we can use to track counterfeits would be this unique ID
system. Nonetheless, it still would not identify counterfeit
drugs arriving in your mailbox from an illegitimate pharmacy.
Mr. Coukell. That is correct.
Dr. Cassidy. Yes. So now, that said, Ms. Radcliffe and Dr.
Wheadon, I am very interested in these rare pediatric diseases.
Your heart tugs, they affect so few, it is hard to get an
adequate in for a clinical trial, and there is never going to
be a major investment by a pharmaceutical company if it is
based upon return, OK. I read your testimony regarding the
bills we have to promote pediatrics. What ideas do you have in
order to encourage research into cures for these terribly
tragic but rare diseases? You see where I am going with that.
Ms. Radcliffe. This is an issue of extreme interest to many
of our companies for the reason that you say. It tugs on the
heartstrings when there are these very rare pediatric
conditions and there are no cures for them. We have worked on
this issue in a number of different ways. Specific to the issue
at hand in this hearing today within the PDUFA agreement there
is a provision for helping companies to move forward with drug
development on rare conditions where FDA will have additional
resources to hire expertise and to reach out to the community
and gain input on how that may be done.
Additionally, we support--as I said in my both written and
oral testimony--the Faster Access to Specialized Treatments
Act, which seeks to expand accelerated approval in a way that
would allow the use of that pathway for more conditions by
encouraging FDA to take advantage of modern tools, whether it
is biomarkers, pharmacogenomics, predictive toxicology and so
forth, and to expand these so that pathway to----
Dr. Cassidy. Let me ask you because that seems as if those
products would be a byproduct of research focused elsewhere.
Does that make sense?
Ms. Radcliffe. In some cases, yes, but that may be a very
effective way of ensuring that those products do get developed.
Dr. Cassidy. Is there a way to encourage the pharmaceutical
companies in a market-based approach to focus resources on a
particular illness? You are more likely to get to your
destination if you go there directly theoretically than if you
just kind of as a, you know, circuitous route end up there.
Ms. Radcliffe. Right. That gets to a much broader
discussion, I think, about the incentives that are available
for research and development, whether it is R&D tax credits,
whether it is the way the products are reimbursed and so forth,
a very complicated decision that I think goes far beyond what
FDA could accomplish. FDA, however, has a huge role in ensuring
that companies have the information that they need to create
drug development programs in rare disease which encounter
challenges that are, honestly, not just related to the return
that companies get----
Dr. Cassidy. A friend of my who has such a child--so there
is kind of a personal interest in mine----
Ms. Radcliffe. Yes.
Dr. Cassidy [continuing]. He tells me that there is a bill
being considered or proposed and if the company came up with
such a drug for such a rare condition, they would get a
transferrable sort of expedited review of any other drug. Now,
would that be an effective way to do this or would that be--and
I will open that up to the panel if anybody has a thought on
this.
Ms. Radcliffe. Sure. We are aware of that legislation and
we haven't taken a position on it. That mechanism has been
tried in other settings and we certainly think that where such
a mechanism could be put in place, it is useful to do so, but
it hasn't proven so far to really be a major incentive for this
type of work.
Dr. Cassidy. Thank you. I yield back. Thank you.
Mr. Pitts. The chair thanks the gentleman and recognizes
the ranking member of the full committee, Mr. Waxman, for 5
minutes for questions.
Mr. Waxman. Thank you very much, Mr. Chairman.
Mr. Coukell, I am going to ask you about antibiotics. I
know that Pew has had a longstanding interest in making sure
that we get more antibiotics, new antibiotics, so our arsenal
is full, but I don't think we just want any antibiotics. We
don't need two versions of the same antibiotics we already
have. That would I am sure only serve to worsen the problem of
antibiotic resistance. So I want to search your views on
whether the language in the discussion draft for this hearing
will achieve this goal.
The bill, as it is currently written, would grant
exclusivity for any antibiotic to treat essentially any
resistant bacterial pathogen. Is that approach adequate to
ensure that we get only the antibiotics that we truly need? And
if not, is there another approach that you would suggest we
take so that we can better target those drugs?
Mr. Coukell. Thank you for that question, sir. I think the
goal in the discussion draft is to make it more attractive for
companies to be in the business of antibiotics. So that means
they need predictability. We need to address the serious public
health problem and we need to make sure that we are using
taxpayer resources wisely. While we are on predictability,
right now, the discussion draft has a list of bugs in it, and
the question is if you get qualified early on as you do under
the Orphan Drug Act as a qualified product, how does that carry
through to you doing your clinical studies and coming to
market? Bleach will kill resistant bugs; nobody would suggest
it is a good drug. And so the question is, is there an
established way to look at antibiotics and say here are the
ones we need and here is how it would work through to market?
And we think that looking at serious and life-threatening
infections would be a very workable way to do it. It would
address the public health need and provide great
predictability.
Mr. Waxman. So target it in that way and not have it more
general----
Mr. Coukell. In some ways that is broader in the sense that
you don't have to have activity against the resistant organism
but you are tackling the public health aide, which is a
treatment for a serious or life-threatening infection.
Mr. Waxman. OK. Now, the LPAD offers an approach that I
think should be given serious consideration because it has a
potential to get important new antibiotics into market more
quickly than usually possible. However, when we are getting
products to market more quickly based on more limited clinical
data they usually require, it becomes that much more important
that we are confident that they will be used only in the small
populations for which the drug was approved.
With antibiotics, this concern is doubled. We must worry
not only about patients receiving medications that could be
dangerous to them because their safety has not been established
in broader populations, we also need to act in a way that will
preserve the efficacy of new antibiotics by using them only
when truly necessary. Do you believe that the mechanism for
limiting off-label use of antibiotics approved under LPAD will
be effective in achieving both of these goals, and if not, do
you have suggestions for additional mechanisms?
Mr. Coukell. We think it is an interesting proposal. And
let me make a couple of points about what we are thinking as we
consider it. And we are still trying to understand how it would
work. But first, it is attractive if you could have a faster
pathway and then use the drugs only in patients that you
couldn't treat with existing drugs. That would be good for
public health and it would be good for the companies assuming
there is a viable business model there. So one question is what
does it take to get these drugs to market and get that
particular designation?
And then the limited population part of the Limited
Population Provision is how do we ensure that if they are
coming with a higher risk or lower evidence that they are used
the way we intend--and there is nothing in the statutory
language that ensure that--so the question is how would
individual providers, how would payers, how would hospital
formulary committees use these drugs and ensure that they were
used only on label. And that is something that we are still
trying to understand.
And then the other thing I think you would want to know is
if you are approving drugs based on less evidence, do we have a
mechanism of post-market surveillance so we can continue to
learn as they are in clinical use?
Mr. Waxman. Well, what is your reaction to what is in the
draft?
Mr. Coukell. We are still studying. We think it is
interesting, but as I say, we are trying to understand----
Mr. Waxman. You are still thinking but it needs to be
refined in some way. You are trying to think it through?
Mr. Coukell. Trying to think it through.
Mr. Waxman. Is that it? OK. Well, we are, too, and so we
would appreciate your suggestions.
Mr. Chairman, I am going to yield back my time. Thank you.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Illinois, Mr. Shimkus, for 5 minutes for
questions.
Mr. Shimkus. Thank you, Mr. Chairman.
And it may have been noted before but I see Dr. Shuren is
still in the committee room. Thank you for being here. This is
important. Even my follow-up is going to be on the, again,
working on the IDEs and the 510(k) a little bit more. Most of
my questions will be directed to Mr. Levitt, but I do
appreciate you being here. I did like Dr. Woodcock's statement
Congress needs to define a problem that we want to address, and
we really do think there is a problem with the change in the
process in these two areas.
So with that, Mr. Levitt, you said in the explanation to
the chairman's question about--kind of explain the
Investigative Device Exemption, safety and protocol were the
two primary issues. And then the FDA's change in the
processing, that it has to be good enough for final approval.
Are there benefits to going through the Investigational Device
Exemption process even though you might not eventually get to a
final approval in the process? Are there positives going
through this process?
Mr. Levitt. Well, I think there are positives any time you
are learning new information in a structured setting under
informed consent of course about the performance of new devices
or improved devices both for safety and for effectiveness. Very
often, a company may want to try something and if it is not
working have a small trial and learn that quickly and pursue
another direction. Or they may want to proceed in a more robust
way because they have greater confidence. So I think there is
value in any clinical study that is safe and that has a bona
fide research protocol to greater learning.
Mr. Shimkus. So the FDA's change in focus--I do think there
are benefits from going through--if you meet the two criteria
of safety and bona fide protocol--and that the information you
learn may help you or may help the sector move in a more robust
path forward or to change course and start anew. That is
summarizing what you said?
Mr. Levitt. Yes.
Mr. Shimkus. I am not going to go over the issue of what is
the legal law and what is the--what was the other thing I had
here on the Administrative Procedures Act? And there are some,
I think, legal concerns with the change without it being bona
fide. You might have some experience in your legal background
and your other history with that, but I think I addressed that
enough.
On the 510(k) process, can you walk us through what
currently happens when a company makes a modification to
existing 510(k)?
Mr. Levitt. Yes. When companies often make changes to their
devices, FDA has a flowchart to help companies walk through is
this a significant change affecting safety and effectiveness?
If it is, then the company submits a new 510(k). If it isn't,
the company documents what their decision and a basis is. They
make the change and they move on. That information is available
to FDA during an FDA inspection so there is still transparency.
Mr. Shimkus. So have you heard--obviously, from the sector
now that you are representing--the concern that with the
changed rules, there may be a projected backlog of 300 to 500
percent and that this is harmful to the process, not helpful?
Mr. Levitt. Yes, I have certainly heard that. I mean what
Dr. Shuren testified this morning, if I heard him correctly,
was that FDA really was just trying to affect a little gray
zone, a small number around the margin. But as companies went
back and applied the examples, companies saying oh, no. You,
FDA, really missed the mark. This would result in just a flood
of new 510(k)s where there really is not a significant change.
But the examples that FDA gave led them to believe they would
have to submit this. So there is clearly a gap between what FDA
intended and how the industry is perceiving it. And I think Dr.
Shuren testified he recognized that and he needs to address
that.
Mr. Shimkus. I appreciate you all being here today and, Dr.
Shuren, that is why I appreciate you remaining in the committee
room because, you know, the other issue is resources, which we
can agree to disagree. But I do think we want to improve the
system. This is our one opportunity to do that.
And my time is expired, Mr. Chairman. Thank you.
Mr. Pitts. The chair thanks the gentleman.
That concludes the questioning. I would like to thank the
panel. This has been an extremely valuable hearing, very
important information.
I have a unanimous consent request to enter into the record
statements from the National Alliance on Mental Illness and the
California Healthcare Institute. That has been shared without
objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. I remind Members that they have 10 business days
to submit questions for the record, and I ask all witnesses to
respond to questions promptly. Members should submit their
questions by the close of business on Wednesday, May the 2nd.
Without objection, the subcommittee is adjourned.
[Whereupon, at 2:44 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]

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