[House Hearing, 112 Congress]
[From the U.S. Government Publishing Office]
PDUFA V: MEDICAL INNOVATION, JOBS, AND PATIENTS
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED TWELFTH CONGRESS
FIRST SESSION
__________
JULY 7, 2011
__________
Serial No. 112-70
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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 Chair 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 JAY INSLEE, Washington
CHARLES F. BASS, New Hampshire TAMMY BALDWIN, Wisconsin
PHIL GINGREY, Georgia MIKE ROSS, Arkansas
STEVE SCALISE, Louisiana ANTHONY D. WEINER, New York
ROBERT E. LATTA, Ohio JIM MATHESON, Utah
CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina
GREGG HARPER, Mississippi JOHN BARROW, Georgia
LEONARD LANCE, New Jersey DORIS O. MATSUI, California
BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin
BRETT GUTHRIE, Kentucky Islands
PETE OLSON, Texas
DAVID B. McKINLEY, West Virginia
CORY GARDNER, Colorado
MIKE POMPEO, Kansas
ADAM KINZINGER, Illinois
H. MORGAN GRIFFITH, Virginia
7_____
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan
JOHN SHIMKUS, Illinois 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)
(ii)
C O N T E N T S
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Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 3
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 4
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 4
Hon. John D. Dingell, a Representative in Congress from the State
of Illinois, opening statement................................. 5
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, opening statement.................................... 6
Prepared statement........................................... 8
Hon. Phil Gingrey, a Representative in Congress from the State of
Georgia, opening statement..................................... 10
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, opening statement............................... 10
Prepared statement........................................... 13
Witnesses
Janet Woodcock, Director, Center for Drug Evaluation and
Research, Food and Drug Administration......................... 16
Prepared statement........................................... 18
Answers to submitted questions............................... 154
Paul J. Hastings, President and Chief Executive Officer, OncoMed
Pharmaceuticals, Inc........................................... 77
Prepared statement........................................... 80
Jonathan S. Leff, Managing Director, Warburg, Pincus LLC......... 93
Prepared statement........................................... 95
Marc Boutin, Executive Vice President and Chief Operating
Officer, National Health Council............................... 110
Prepared statement........................................... 112
Ellen V. Sigal, Chair and Founder, Friends of Cancer Research.... 122
Prepared statement........................................... 124
Allan Coukell, Director of Medical Programs, Pew Health Group,
The Pew Charitable Trusts...................................... 129
Prepared statement........................................... 131
Submitted Material
Statement, dated July 7, 2011, of the American Hospital
Association, submitted by Mr. Engel............................ 58
Letter, dated February 8, 2012, from Jeanne Ireland, Assistant
Commissioner for Legislation, Food and Drug Administration,
Department of Health and Human Services, to Mr. Dingell........ 150
PDUFA V: MEDICAL INNOVATION, JOBS, AND PATIENTS
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THURSDAY, JULY 7, 2011
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:00 a.m., in
room 2123, Rayburn House Office Building, Hon. Joseph R. Pitts
(chairman of the subcommittee) presiding.
Present: Representatives Pitts, Burgess, Shimkus, Rogers,
Myrick, Murphy, Blackburn, Gingrey, Latta, Lance, Cassidy,
Guthrie, Upton (ex officio), Pallone, Dingell, Engel, Capps,
Gonzalez, and Waxman (ex officio).
Also present: Representatives Bilbray and Christensen.
Staff present: Gary Andres, Staff Director; Clay Alspach,
Counsel, Health; Howard Cohen, Chief Health Counsel; Ryan Long,
Chief Counsel, Health; Alan Slobodin, Deputy Chief Counsel,
Oversight; Jeff Mortier, Professional Staff Member; Andy
Duberstein, Special Assistant to Chairman Upton; Debbee Keller,
Press Secretary; Chris Sarley, Policy Coordinator, Environment
and Economy; Heidi Stirrup, Health Policy Coordinator; Lyn
Walker, Coordinator, Admin/Human Resources; Carly McWilliams,
Legislative Clerk; Kirby Howard, Legislative Clerk; Rachel
Sher, Minority Senior Counsel; Stephen Cha, Minority Senior
Professional Staff Member; Alli Corr, Minority Policy Analyst;
Karen Lightfoot, Minority Communications Director and Senior
Policy Advisor; Eric Flamm, FDA Detailee; and Karen Nelson,
Minority Deputy Committee Staff Director for Health.
Mr. Pitts. The subcommittee will come to order. The Chair
recognizes himself for 5 minutes for an opening statement.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
The Prescription Drug User Fee Act, PDUFA, was first
authorized by Congress in 1992 with the goal of expediting
human drug applications through the Food and Drug
Administration's approval process. Under the Act and in
subsequent reauthorization, the drug industry pays user fees to
FDA, and FDA commits to meet performance goals such as
reviewing applications within a certain period of time. This
construct was designed to give industry certainty and
predictability, but also to speed new drugs and treatments to
the public. Details of the agreement between FDA and industry
will be published on September 1st of this year, and by January
15, 2012, FDA will send its final recommendations to Congress.
The current PDUFA authorization expires September 30, 2012,
and it is my intention to have the reauthorization legislation
signed into law by June 30 of next year. PDUFA is too important
to leave to the last minute. The drug industry employs
thousands of people here in the United States, providing good
jobs that we cannot afford to lose.
The forthcoming study from Patel Memorial Institute has
found that every job in the biopharmaceutical sector supports
nearly six additional jobs in the greater economy. If PDUFA is
not reauthorized, this study estimates that 130,000 to 260,000
jobs would be lost. Americans are the most innovative people on
Earth.
Given certainty, predictability and transparency in the
approval process, venture capitalists will continue to fund new
research and companies will continue to develop new and
innovative drugs. What we have heard, however, is that
certainty, predictability and transparency oftentimes do not
characterize the FDA's approval process. Frustrating both the
drug sponsors and the public who are waiting for treatments and
cures to everyday maladies, chronic illnesses and terminal
diseases.
The American people expect and have a right to expect that
the Federal Government is doing everything possible to ensure
that drugs on the market are safe and effective. They also have
a right to expect that applications for life-enhancing and
lifesaving drugs are not languishing on a reviewer's desk at
the FDA. It is my hope that the new agreement balances both of
these considerations, and I look forward to hearing from FDA,
the drug industry, patient advocates and researchers today on
our panels.
I yield the remainder of my time to Dr. Burgess.
[The prepared statement of Mr. Pitts follows:]
[GRAPHIC] [TIFF OMITTED] T2917.001
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 am mindful of the fact that the last reauthorization was
June of 2007, so it is a little over 4 years ago. At that time,
I was concerned about some of the restrictions that this
committee placed on the advisory panels that advise the FDA
about the approval or non-approval of drugs and devices. One of
my concerns was we didn't follow the Institute of Medicine
guidelines that no more than 40 percent of the people who are
on the advisory committees have an interest in the product
under consideration, and it was the will of the committee over
my objections that no one on these advisory panels should have
any interest or perhaps even any knowledge of the drug or
device being considered.
I thought that was a serious and glaring oversight on the
part of this committee, and I discussed it with then-Chairman
Dingell extensively and offered amendments that were repeatedly
voted down on party lines. But that is an oversight that I hope
that this committee can now correct in this reauthorization
period.
It appears we saw it unfortunately on display with the
Avastin advisory panel last week in that there, to the best of
my reading of the makeup of that group, there was not a
specialist who dealt with breast cancer patients on that
advisory panel so that there was no one on that advisory panel
who actually followed a patient who was on Avastin for their
breast cancer. Now we are left to defend the decision from the
advisory panel to the FDA about the removal of that drug. And
we are in a difficult position with Avastin because some people
are apparently dramatically helped. Other people, the help is
not so great. But it is, I think, incumbent upon us to get that
right.
Other things that I think we need to do, we need to discuss
the possibility of surrogate endpoints for studies within the
FDA. Certainly that was useful in the early days of the AIDS
research back in the 1980s. And the fact that we base
everything upon survival statistics now and we are not looking
at things like tumor burden or some other surrogate endpoint I
think is a mistake on the part of our advisory panels.
I thank the chairman for yielding the time and I yield back
the balance of my time.
Mr. Pitts. I thank the gentleman and recognize the ranking
member of the subcommittee, Mr. Pallone, for 5 minutes for an
opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairman Pitts, and I welcome
today's hearing on this very important subject.
Five years ago, this committee led the way in making grade
strides in FDA policy and safety measures. In fact, some have
said it was the most extensive overhaul of FDA policy and
procedure in decades. What is important to note, however, is
that this committee worked through the issues in a bipartisan
manner, and I am proud of the consensus that we reached.
That legislation was supported by members, consumer groups
and industry stakeholders. Together we recognized the need for
a strong and well-resourced FDA to complete its mission. In
addition, we accepted the reality that FDA must have the
ability to be well-versed on the best science in order to get
the safest and most effective drugs to the marketplace.
Now, in doing so I recognize that FDA must minimize the
inappropriate burden it placing on the drug companies so that
they do not stifle innovation. America's competitiveness
depends on our ability to innovate and keep America number one,
and as such I continue to believe that the government must be
responsible for facilitating an environment where Americans can
continue to innovate. This is the key to creating new thriving
industries that will produce millions of good jobs here at home
and a better future for the next generation. That said, we must
not sacrifice safety and efficacy in exchange for innovation.
PDUFA has been a true success and we must build on that
success. We can't move backwards under the auspices of economic
benefits.
So, Mr. Chairman, I hope we can move in the same bipartisan
spirit as we did in 2007. Even more so, I hope that we can
produce consensus legislation free of conflict and contentious
issues. I look forward to working with you and my colleagues on
this committee as this process moves forward and I welcome
today's hearing as a first step towards that goal.
I wanted to yield 2 minutes to my good friend from
Michigan, Chairman Dingell, but I still have another minute
left, so let me say that I would like to close by commenting on
the importance of the Drug Safety Enhancement Act. That is a
bill that I coauthored with Mr. Dingell and Representatives
Waxman and DeGette.
High-profile risks associated with the globalized drug
supply like the Heparin crisis of 2007 have put Americans'
lives at risk and our bill would equip FDA with the authorities
and resources this it needs to keep peace with an increasing
international marketplace of products so that Americans can
have confidence that drugs they rely on will help them get
better and not make them more sick.
So as we move forward, I will continue, Mr. Chairman, to
make reference to the Drug Safety Enforcement Act and that bill
because I do think it is important and also has a place during
this PDUFA debate.
I see the gentleman is here. I yield to Chairman Dingell.
OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Dingell. Mr. Chairman, I thank the gentleman and I
thank you for holding today's hearings. I ask unanimous consent
to revise and extend my remarks because of the shortness of
time here.
I commend you for the hearing today with regard to the FDA
amendments that we are discussing with regard to PDUFA. This is
important. If everyone will recall, it has been accepted, it
has been a tremendous success because of the cooperation
between government and industry.
However, we need to address more problems. Commonsense
authorities, like mandatory recalls, subpoena power, ability to
seize and destroy imported drugs and raw materials at the
border, making delay or refusal for inspection a prohibited
act, are now needed to ensure that Food and Drug has the
capabilities to properly oversee safety of our drug supply.
These are authorities that would be given FDA under H.R.
1483, the drug safety bill I introduced with my colleagues Mr.
Waxman, Mr. Pallone and Mrs. DeGette. These are authorities
that are desperately needed in order to address the safety of
our American public. I would note that without them, imports of
dangerous components and raw materials of pharmaceuticals, as
in the case of Heparin, continue to threaten the well-being of
our people.
My colleagues will remember that in the last Congress, we
passed a food safety bill, which gave many of these authorities
to Food and Drug, and which was, in fact, supported by the
industry. It passed out of this committee by a heavy majority.
It also passed the House and the Senate by a very large
majority, and it is now standing to help and protect the
American people.
I would hope that we would follow the example that we set
last Congress when we worked together in a remarkably
bipartisan fashion to see to it that we went well beyond just
scratching the surface with regard to food safety and do a
similar thing with regard to prescription pharmaceuticals and
so move to protect the health, safety, life expectancy and to
ensure that pharmaceuticals will not cause harm or death,
particularly where it is from imported raw materials for the
manufacture of finished products.
I thank you, Mr. Chairman. I thank the gentleman from New
Jersey. I yield back the balance of my time.
Mr. Pitts. The chair thanks the gentleman and recognizes
the full committee chairman, Mr. Upton, for 5 minutes.
OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Upton. Thank you, Mr. Chairman.
This is the first hearing of the 112th Congress on the
reauthorization of Prescription Drug User Fee Act in the
current state of medical innovation in America. I look forward
to discussing FDA regs and how they effect innovation, job
creation and the American patient's accession to life-improving
drugs.
Congress last reauthorized PDUFA in 2007 with the Food and
Drug Administration Amendments Act. That law as we know expires
in September of 12, 2012, which is why our work to reauthorize
this law begins today.
One area that the committee will examine is the lack of
predictability and certainty at the FDA. These problems at FDA
appear to be stifling American innovation, costing Americans
jobs and obviously hurting American patients. Another area we
will examine is the risk-benefit analysis used by FDA when
approving drugs and whether the agency is striking the right
balance on delicate issues. These are concerns that the FDA is
failing to consider the views of patients who need access to
lifesaving drugs, including those drugs that carry some risk.
The committee will evaluate provisions of the Food and Drug
Administration Act amendments, including those affecting
advisory committees in the risk evaluation and mitigation
strategies. The rigid unrealistic conflict of interest
provision has prevented in my view the FDA and its advisory
committees from utilizing some of science's best minds and left
advisory committee slots unfilled. We have to look at the
implementation of this provision as to whether it really has
caused delays in the approval process.
Our goal has to ensure America remains the leader in
medical innovation. When the law works properly, the field
creates new jobs and ensures American patients do have access
to the best therapies available.
I thank the chairman, and I yield the balance of my time to
Dr. Gingrey.
[The prepared statement of Mr. Upton follows:]
[GRAPHIC] [TIFF OMITTED] T2917.002
[GRAPHIC] [TIFF OMITTED] T2917.003
OPENING STATEMENT OF HON. PHIL GINGREY, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF GEORGIA
Mr. Gingrey. I thank the overall chairman for yielding to
me.
I believe the Prescription Drug User Fee Act
reauthorization gives an opportunity to review the ways in
which we can help improve the FDA approval process. In an age
where our economy is fighting an international battle to remain
the leader in medical innovation and the jobs that goes with
those industries and patients in other countries have access to
medical treatments that American patients do not, we need all
hands on deck. No longer can we afford to sideline experts
simply because of their ties to industry.
One idea I believe that deserves consideration, Mr.
Chairman, is drawing from the joint NIH-FDA Leadership Council.
This council was created in 2010 to spearhead collaborative
efforts to improve the FDA regulatory review process. This
initiative is a good, proactive first step toward improving and
modernizing the FDA.
However, I believe if we are going to be truly successful
in improving both the efficiency of the FDA as well as our
understanding of how emerging technology can be used to improve
regulatory review, other parties need to be at the table.
Agencies like the CDC and Homeland Security, experts from the
drug industry and academia, as well as patient advocates all
need to be involved. A stakeholder group made up of various
agencies, scientific leaders and business and academia and
patient advocates can help support the FDA in its mission to
advance regulatory science as well as other meaningful reforms
and emerging public health issues. I look forward to working
with Dr. Hamburg, the chairman and this committee on the issue.
In addition, this committee has spent years studying the
oncoming public health threat posed by antibiotic resistance.
It is a threat to our patients, it is a threat to our troops,
and in the hands of terrorists, our national security. My
colleagues and I on this committee, four Republicans, three
Democrats, have introduced H.R. 2182, the GAIN Act. If we are
to have the drugs needed to fight the looming threat of drug
resistant bacteria, our legislation is an important first step
in that fight. I hope to see it considered by this committee,
this Congress, the 112th.
With that, Mr. Chairman, I thank the overall chairman for
yielding to me and I yield back the remaining time.
Mr. Pitts. The chair thanks the gentleman and at this time
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. Thank you, Chairman Pitts, for holding this
hearing today.
I think we can all agree that it is critically important
that there be a vibrant and flourishing innovation in the
pharmaceutical industry. The medicines this industry has
brought us have saved countless lives and improved the quality
of life for people the world over. Unfortunately, by most
accounts we are in the midst of a dramatic slowdown in drug
development in the U.S. The reasons for the slowdown are
complex and multifaceted. At a time when you would expect there
to be a surge of innovation, for example, because there is an
unprecedented number of drugs coming off patent, the opposite
appears to be true. I hope our witnesses will help us
understand what is causing this innovation deficit and what we
can do to help our drug companies succeed.
A rising chorus of voices have begun to assert the view
that it is the FDA that is responsible for this downward trend.
These critics claim that the FDA takes far longer to approve
drugs than its counterparts in Europe. Some claim it takes the
U.S. twice as long as Europe. Others claim it takes three times
as long. These claims may sound convincing, but we have yet to
see the data to support them.
I am aware of only one peer review study comparing drug
approval times in the United States and Europe, and it found
the exact opposite. This study, which examined the approval of
35 new cancer drugs, was conducted by one of our witnesses
today, the Friends of Cancer Research. It found that the FDA is
actually approving these lifesaving therapies much faster than
its European counterparts.
Some view every decision FDA makes through the prism of
whether it is good for the pharmaceutical industry. But that is
not the right perspective. The question we should be asking is,
what is the right decision for patients? It is in no one's
interests to have a weak FDA. American consumers depend on FDA
to verify the drugs we are taking are truly safe and effective.
If Americans lose confidence in the FDA, they will lose
confidence in the pharmaceutical industry as well.
We should all be united in the goal of ensuring that we
have a strong, well-resourced FDA that is armed with a full
compliment of authorities to protect us from unsafe drugs and
to assure that these drugs work. That is FDA's fundamental
mission, and that is why I strongly oppose any legislative
proposal that would prevent FDA from insisting on adequate data
from clinical trials and force it to approve drugs on an
incomplete record. These proposals would prove disastrous for
the safety and efficacy of our drugs supplied.
The title of this hearing suggests that our colleagues
across the aisle believe that FDA's mission should encompass
job creation. Democrats have been leading the charge for
legislation to promote jobs and we have been bitterly
disappointed by the failure of the House to pass pro-jobs
legislation. But we should not be misled. I hope we would all
agree that FDA should not take jobs into consideration when it
is reviewing the safety and effectiveness of a new medicine. We
want FDA to ensure that the drugs we take are safe and
effective. Whether jobs will be created is simply not a part of
that scientific public health equation.
I do believe there are areas in which the agency's
regulation of drugs could improve. For example, improvements in
FDA's scientific capacities will enable FDA to identify early
end-points that can predict whether a drug will be effective
which can result in better design of clinical trials and faster
approval of new drugs. Making these kinds of strides require we
work from real data, not self-serving urban myths.
We should require a significant influx of resources. It is
ironic that at the same time they are complaining that FDA
should do a better job, the Republicans in the House passed a
budget and an appropriations bill that would gut FDA funding by
over $500 million.
I want to turn briefly to the fact that we have an
increasing globalization of our drug supply. The world has
changed from the time of the original Food, Drug and Cosmetic
Act. Today, more than 80 percent of active pharmaceutical
ingredients are manufactured abroad, with China and India
comprising the largest sources. Just yesterday, The Wall Street
Journal talked about poor regulatory oversight of Chinese
pharmaceuticals. That is why it is important to look at the
Drug Safety Enhancement Act, which will go a long way toward
providing FDA with these much-needed resources.
Mr. Chairman, our staff has reached out to your staff and
Mr. Upton's as well requesting we engage in a bipartisan
process to look at this bill and work toward incorporating
whatever we can ultimately agree upon into the PDUFA package
next year. I hope we can count on this opportunity to work
together because it is in the public interest.
Thank you very much, Mr. Chairman.
[The prepared statement of Mr. Waxman follows:]
[GRAPHIC] [TIFF OMITTED] T2917.004
[GRAPHIC] [TIFF OMITTED] T2917.005
[GRAPHIC] [TIFF OMITTED] T2917.006
Mr. Pitts. The chair thanks the gentleman. The chair thanks
the members for their opening statements. Any other opening
statements will be entered into the record.
The chair thanks the witnesses for agreeing to appear
before the committee today. Your written testimony will be made
a part of the official record. We ask you summarize your
opening statements in 5 minutes.
We have two panels today. The first panel contains a single
witness. Dr. Woodcock is the Director of the Center For Drug
Evaluation and Research at the Food and Drug Administration.
Welcome, Doctor. You may begin your testimony.
STATEMENT OF JANET WOODCOCK, DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION
Ms. Woodcock. Thank you, Mr. Chairman and members of the
subcommittee. I am Janet Woodcock, Director of the Center For
Drug Evaluation and Research at FDA, and I would like to thank
you for this opportunity to testify about the prescription drug
user fee program, or PDUFA, as I am going to refer to it.
Congress instituted this program because patients in the
United States were not getting access to new medicines as
quickly as people in other parts of the world. This problem is
called the drug lag, and it became particularly severe in the
1980s.
The chart we have brought, which you can see over there,
shows that PDUFA really had an impact on this drug lag. In the
1980s, as you see, fewer than 10 percent of new medicines
reached American patients first. They were available first in
other parts of the world. PDUFA was started in 1992 and, as the
data show, it quickly improved the availability of new
medicines to the point now where we lead the world in
introduction of new medicines.
I am a rheumatologist. I am a doctor who treats autoimmune
diseases and arthritis, and I can attest to the revolution of
therapies that has occurred since the start of PDUFA. Diseases
that were crippling now have effective treatments that allow
patients to lead full lives.
Recently, my seat mate on a plane showed me pictures of her
wonderful gardens that she cared for herself. She told me that
10 years ago she was confined to a nursing home and it was only
when she was started on a treatment, a new treatment for her
autoimmune disease, that she was able to improve and is now
active and well. This is the kind of treatments that we have
seen coming out during the PDUFA period.
So since the start of PDUFA, increasing numbers of new
medicines were available first in the United States. Currently
we lead all other countries in the introduction of new
therapies. Every 5 years, PDUFA must be reauthorized, and each
cycle of reauthorization has brought new enhancements to the
program. Most recently, there has been a focus on improving
drug safety monitoring and that was the focus of the last
cycle. Successful innovations, such as our sentinel initiative,
resulted from that safety focus.
For this cycle of PDUFA renegotiation, Congress directed
FDA to conduct a very open and inclusive process with
significant stakeholder participation. We have done so, as
detailed in my written testimony, and I believe the outcomes of
the negotiation have really been improved as a result of this
new process.
Now, the drug development enterprise is in a very different
place than previous PDUFA negotiation cycles. Drug development
faces many of the problems other industries do right now due to
the economic turn-down. But more significantly, there is a
severe productivity problem worldwide in drug development in
which an ever-increasing R&D investment is producing ever-fewer
new drugs. This isn't just true in the U.S. It is true
everywhere. It is no exaggeration to say that the industry is
in crisis.
At the same time, the scientific opportunities have never
been greater. It is incredibly frustrating to see the explosion
in biomedical knowledge and at the same time to watch the
struggles and repeated failures of drug development programs
that try to utilize this knowledge. Despite these serious
problems, things may be looking up. This year to date, FDA has
approved 20 new medicines, just one short of the total approved
last year, and many of these medicines are game-changers for
patients. We do see a rise in new development programs coming
into the FDA as well.
We have been moving through the process set down by
Congress for this cycle of PDUFA negotiations and we have
developed a set of recommendations that are laid out in my
written testimony. These include new steps to incorporate
scientific advances into regulation so we can do what we can
for the problems that industry is facing; also providing for
meaningful patient input into the standards of benefit and risk
that FDA applies to these new products; to provide a more
transparent and predictability review process for sponsors, and
there is quite a bit in there for that; and to further enhance
drug safety.
In closing, I would say that in addition to these
challenges, the pharmaceutical industry and FDA does face the
challenges of globalization, which are ever-increasing and are
well covered, and I am sure you are aware of, both in clinical
trials being done all around the world and medicines being made
all around the world. We still have to ensure the safety and
effectiveness for our patients.
We look forward to working with Congress on all these
challenges. We feel that the success that is demonstrated of
PDUFA can be extended and we can do the right things, both for
the patients in this country and for the industry that brings
them new medicines.
[The prepared statement of Ms. Woodcock follows:]
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Mr. Pitts. Thank you. I will now begin the questioning and
recognize myself for 5 minutes.
Mr. Gingrey. Mr. Chairman, we cannot hear you. Your mic may
not be working.
Mr. Pitts. All right. I will hold it closer.
According to reports from the California Health Care
Institute, and Ernst & Young and testimony here today, FDA's
regulatory uncertainty is stifling American job creation. To
compound the problem, foreign countries like those of the EU,
China and India, are proactively trying too take American jobs
by making their regulatory systems more predictable and
efficient and creating an ideal innovation climate for
companies. Given the importance of these innovator companies to
our country and our Nation's patients, these developments are
disconcerting, to say the least.
While foreign regulatory bodies are becoming more
efficient, FDA appears to be going in the opposite direction.
Is FDA, first of all, aware that these foreign countries are
proactively trying to take American jobs?
Ms. Woodcock. We are aware that both Europe, which has the
Innovative Medicines Initiative, Singapore, China, many
countries are looking to build a very strong R&D biomedical
development industry in their countries. Absolutely.
Mr. Pitts. The second question: What is FDA's role in
creating a hospitable climate for American innovator companies
so that they can create jobs and create new lifesaving
therapies for patients here?
Ms. Woodcock. Well, first of all, I would like to start
with the facts, all right? That chart shows when the U.S. is
the country that first launches a drug in our country, and you
can see that is continuing to go up. So that is compared to all
other countries worldwide.
You will also hear testimony about a comparison to Europe.
And we are not in competition with Europe, but you can see in
the U.S., the drug approval process is faster and drugs reach
patients more quickly than in Europe. That is simply one
comparison. However, we, since 2004 when we put out what was
called the Critical Path Report, have been working with
industry to try to solve a lot of both the scientific and
regulatory problems that impede innovation and keep drug
development from proceeding smoothly.
So we are very aware of this. It is a problem for us as
well as for the industry. The people who work at the Center for
Drugs and regulate new drugs are doctors, and they are
rheumatologists and they are pulmonologists and they are cancer
doctors and infectious disease doctors. They know their
patients need additional therapies and they want to see them
out there for the patients. So this drug development enterprise
is important for everyone and it is important to get it right.
Mr. Pitts. And what has the FDA done to forestall the
attempts by the EU, China and India to take our jobs?
Ms. Woodcock. FDA has a very predictable drug review
process. In fact, our review process is the most predictable
part of drug development. If you can get through all the
clinical phases of drug development where you test it on
people, the process that FDA uses is extremely predictable. And
that is a result of the user fee program.
Right now we have the highest rate ever of what we call
first cycle approvals, which is if companies send in their
application, they get it approved on the first try. And we have
timelines for that and we meet our timelines of review. So we
have a very predictable and open process, and companies usually
come first to the United States with applications for their new
drugs.
Mr. Pitts. OK, another question. I have heard from many
patients that they believe their interests are not taken into
account during the FDA approval process. Patients, including
those with life-threatening diseases, are willing to tolerate
additional risk in order to try these new drugs that will
hopefully save their lives. How does FDA take patients into
account when reviewing new drugs and how does it account for
patients and their willingness to tolerate additional risk?
Ms. Woodcock. The patients are the most important part of
this. It is really for patients that medicines are developed
and that the FDA does the review process, and we fully
understand that people facing more serious diseases are willing
to take higher risks.
For example, we have a drug for multiple sclerosis that
causes sometimes a rare, very serious and often fatal brain
disease, and that drug was briefly withdrawn from the market
because of doing this. When we talked to the patients, they
said we are willing to take this risk, because this drug really
helps prevent the progression of multiple sclerosis. That drug
is available now to patients because we understand that when
you face such terrible diseases, you are willing to take risks.
Mr. Pitts. My time has expired. I recognize the ranking
member for 5 minutes for questions.
Mr. Pallone. Thank you, Mr. Chairman. And Dr. Woodcock,
some of my questions are along the same topic, if you will, as
the chairman. I guess this really shows that we are being
bipartisan today.
Most of my colleagues have been told that FDA is
responsible for what is claimed to be a significant slowdown in
development and marketing of new and innovative
pharmaceuticals. Whether that is true or not, that is what we
are told.
There is a statement in Mr. Leff's testimony, he is on the
next panel, which sums up what I hear. He states, ``While many
factors have contributed to the escalating cost, time, and risk
of new drug development, a changing regulatory environment at
the FDA is the most significant.''
He attributes this, in large part, to increasing public
pressure on FDA to focus more on safety and lesson benefit in
the wake of the emergence of safety problems associated with
Vioxx in 2004. He further points to numbers showing that FDA
approved an average of 36 new drugs and biologics per year from
1996 to 2004, but an average of only 21 per year from 2005 to
2010.
My question is, how do you respond to these claims? Is it
really true that there was a sudden dropoff in approvals right
after 2004 and that approvals in the years immediately
preceding 2004 were well over one and a half times as frequent
as in the years immediately after 2004, and has FDA really
become too risk averse and not focused enough on benefits such
that maybe innovation is being blocked.
Ms. Woodcock. Well, I appreciate these questions. As a
physician, I will tell you, I think it is important, though, to
establish the diagnosis before we move to treatment. So it is
really important to understand the facts.
The facts are, first of all, as we have already discussed,
the FDA approves drugs and gets them on the market more
regularly first than any other country in the world, all right?
We are meeting all of our PDUFA goals for review times, so our
review time is very prompt. We are approving more than two-
thirds of critical new drugs, those important new drugs that
will make a difference for patients, on the first round. After
they are approved, we review them and then they get on to the
market. And we have the highest rate historically in 20 years
right now of these first round approvals.
So FDA is moving promptly and is approving a high
percentage of the drugs that are submitted to us. However, we
can't approve drugs that don't come in the door. And this
slowdown is worldwide. This is not a FDA phenomenon. The
pharmaceutical industry is suffering a crisis and we are not
seeing as many submissions to us, nor is the EU, nor are the
other regulatory authorities around the world, and this
scientific challenge I think is the major problem that we face.
Mr. Pallone. You have already, in response to the
chairman's question, mentioned Europe. I read a study published
in the July issue of Health Affairs by Friends of Cancer
Research, which found that FDA actually approves cancer drugs
significantly more quickly than its counterpart in Europe. Now,
that was just for cancer drugs. But how does FDA compare with
Europe in approval times of other classes of drugs besides
cancer drugs?
Ms. Woodcock. This is true for all of the high priority
drugs that are going to make a difference for patients. We
don't have all the data in a tabular form that we can give you,
but we have looked into this.
For example, we just approved two drugs for hepatitis C--
treatment of hepatitis C. Hepatitis C has been poorly treated.
The treatment has difficult side effects and it often leads to
liver failure and need for liver transplant and even death. We
have just approved two new drugs that have a high rate of what
is called virological response or cure, so we expect that many
more people will be able to be cured for hepatitis C. Those two
drugs are not approved anywhere else in the world right now.
Mr. Pallone. Let me just ask you, would you say FDA could
make some improvements in terms of helping industry proceed
through the regulator process, and more specifically, where do
you think the major roadblocks are going from earliest research
to drug approval? Where can more effective improvements be made
to shorten the time between discovery and marketing?
Ms. Woodcock. The scientific breakthroughs we are currently
experiencing with targeted therapy or personalized medicine or
whatever, and I don't have time to go into it here, are giving
us new opportunities to have new development pathways. We have
been giving very significant thought to that, and I think we
will be coming forth with some new development pathways that
can help speed these medicines along and get them to patients
sooner.
This doesn't involve FDA review, because if we get a really
good product into FDA, we can review it and get it on the
market really quickly. What people are alluding to is the
development time takes a long time. So we have some ideas about
how to improve drug development for these highly effective
therapies and we will be starting some efforts on that.
Mr. Pallone. Mr. Chairman, could I just ask, I don't know
if she does have something that she could follow up with on
that, but if I could ask through you if there is more
information, you could send us in writing about those new
trends, I would appreciate it.
Ms. Woodcock. I would be happy to do so.
Mr. Pitts. If you would provide that to the committee.
The chair recognizes the vice chairman, Dr. Burgess, for 5
minutes of questions.
Mr. Burgess. I thank the chairman for the recognition. Dr.
Woodcock, thank you for being here again.
Reference was made to the European Medicines Agency, that
is, the FDA is actually more rapid. Now, would it be fair to
say that the timeline is more predictable at the European
medicines agency and the FDA?
Ms. Woodcock. Our timelines are very predictable.
Mr. Burgess. Does that include a timeline start to finish,
or a timeline where you reset the clock because you have asked
for new information or a different study to be done? Because
this is the question that people come in with. I see people in
my office literally every week with a drug or device who say
that the FDA changes the rules of the game when we are deep
into the process. I can't get any of them to come here and
testify before this committee because they are frightened,
quite frankly, of you and your agency. They are scared to speak
up because they know that that could reset the clock once
again.
Is this a fair criticism that I am getting from people who
have drugs and devices before your agency?
Ms. Woodcock. As I said, we ought to start with the facts.
The facts show that we are approving a very high percentage of
priority drugs, an extremely high percentage on the first
cycle. So that is a 6-month review, all right, generally
speaking. And so that is a very predictable review.
The second issue you are raising is do we change the
standards? Sometimes as we learn about side effects of drugs as
they are on the market and we gain more information, then we do
need to ask companies that have additional drugs in that class
or whatever to look for those side effects and study them
before marketing. So that does happen sometimes.
Mr. Burgess. It is not just sometimes. It seems like it
happens all the time. Now, I have to be careful not to confuse
drugs and devices, but let me talk about devices for just a
moment.
I met a physician out in West Texas who developed a method
for conscious sedation that was much more safe than anything
that he had used in his practice as an anesthesiologist. It
came to him while he was watching his newborn son being
circumcised. And while it turns out that this device would not
help in newborn circumcision, there are many other clinical
applications where it would be very efficacious. As he told me
this story, he said, just to put it in context for you, I
developed this as a consequence of my son being a newborn and
undergoing this procedure. And he is going to college this
weekend, we are packing the car up to take him to wherever, and
the device is no closer to being approved than it was 17 years
before.
Now, this individual no longer had a financial interest. It
was simply because it was his baby literally, his idea that he
wanted to see come to fruition and help patients. He sold it to
a large medical manufacturing entity. But this thing was still
bogged down in the process, and it was months and years of FDA
advisory panels and this sort of thing. Even when they got
clean bills by the advisory panel, then for some reason, the
FDA would overrule and send them back to the starting point.
He is not alone. There are other device manufacturers in my
office, again, literally every week, and probably because this
hearing is being televised, I will hear from a lot more of them
now. But can you address that? We talked about the devices that
are being off-shored because the environment is more friendly
in other locations. You admit that other countries are actively
recruiting our innovators. Are you working on that?
Ms. Woodcock. Certainly. The reason that drug companies are
going offshore has to do with the cost of either manufacturing
or the cost of doing clinical trials. They are still submitting
drugs to the U.S., because we are a large market. And as you
see, we get drugs on the market before any other country in the
world most frequently.
As far as----
Mr. Burgess. I am going to run out of time, so let me go
back to what you were talking about initially where you said
your time line, that you are good, you are meeting your
performance goals. There is a study from the California Health
Care Institute where they talk about the FDA not meeting its
goals and that your times have slipped since the last PDUFA
reauthorization in 2007. Can you address that for us?
Ms. Woodcock. Certainly. In the year or so after the
passage of the Amendments Act, we were given a very large
assignment of work by Congress in the Amendments Act which had
many, many activities that we had to do. We made that our
priority and accomplished those activities that we were
directed to do by Congress.
During that time, our goals did slip slightly and we failed
to meet some of our goals, although we still had a very high
performance. That situation has been rectified and we are now
meeting and exceeding our user fee goals again.
Mr. Burgess. According to this study, you have slipped 28
percent. It is fair to say the Democrats' last reauthorization
slowed you down. Let's hope this reauthorization doesn't
perform similarly.
Thank you, Mr. Chairman. I will yield back.
Mr. Pitts. The chair thanks the question and recognizes the
gentleman Mr. Gonzales for 5 minutes for questions.
Mr. Gonzalez. Thank you very much, Mr. Chairman, and
welcome, Doctor. Quickly following up on Dr. Burgess' question,
it is very interesting, because I think there has been some
comments that we are losing jobs and such and investment in the
United States because pharmaceutical companies want to do
things outside of the United States, and the reason for that is
the slow, cumbersome regulatory system that the FDA presents.
Your response was that is not necessarily true. If cost is
cheaper in another country, whether it is manufacturing or
research and development, that is where the investment may be
made, and it is strictly more on finances than anything else,
eventually that particular company, whatever it manufactures,
whatever it presents for consideration, is still going to come
through FDA, that is right, and the reason, and you cited it,
is that this is an incredibly lucrative market for
pharmaceuticals, the United States of America.
Would you say that in the United States of America, maybe
there is a greater profit margin for pharmaceuticals than in
other countries?
Ms. Woodcock. I am not really qualified to comment on that.
I am a doctor, not an economist. Sorry.
Mr. Gonzalez. Do you know of any literature that might
support the proposition that because of the system that we have
in the United States, we may well be paying more for a certain
drug, the same drug that is available here in the United States
as well as in other countries?
Ms. Woodcock. Yes, I am certainly aware of that.
Mr. Gonzalez. How is FDA approval viewed? And I guess you
can congratulate yourself because I assume it is very
favorable, how is FDA approval viewed worldwide in other
markets in other countries?
Ms. Woodcock. Well, FDA has generally been viewed as say
one of the gold standards. We provide a scientific and
technical and highly unbiased review, and we base it on the
evidence. We are really the only place in the world that goes
down to the patient level data, and we get that data in and
review it. So we are confident when we make a decision that is
based on the actual evidence that has been generated. Many
countries in the world look to FDA, all of our standards, our
standards for manufacturing, our standards for clinical trials
and so forth. But we have made a lot of efforts to harmonize
those internationally through various arrangements that have
been made.
Mr. Gonzalez. Let's just say that there was just total
reciprocity and you could sell a drug that was manufactured and
approved by another country, this is a make-believe world. In
your position, of all the countries, which regulatory agency
regarding drug approval would you depend on before you would
prescribe that drug for a patient? I know you are from the FDA
and this may be quite an obvious answer. But seriously, if you
were a physician in another country, wouldn't it be FDA, the
United States of America?
Ms. Woodcock. Well, I certainly have spoken to many
physicians and many regulators around the world, and our
process is viewed as a very robust and excellent process that
people look up to as a gold standard.
Mr. Gonzalez. We want you to do things timely, we want you
to do it efficiently for all the right reasons, but not at the
cost of quality and safety. That is the only point I think all
of us would agree on.
How do other countries finance their regulatory--let's say
their FDA, their equivalent of FDA?
Ms. Woodcock. In Europe, there are user fees. It is not the
same arrangement because the countries give scientific experts
to the process and there are multiple countries involved in the
EU. There are different arrangements around the world. Many of
them involve user fees of one type or another. Many countries
do not have the personnel, scientific personnel and resources,
to mount a kind of review that we do, so they rely upon
conclusions from the World Health Organization, from the FDA,
and from others.
Mr. Gonzalez. I guess my final question, I have 30 seconds,
and that is, we have been referencing what FDA means in the
United States and such. We do not defer to other governmental
regulatory agencies in other countries for the safety of our
pharmaceuticals, is that correct?
Ms. Woodcock. That is correct.
Mr. Gonzalez. Thank you. I yield back.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman Mr. Shimkus for 5 minutes for questions.
Mr. Shimkus. Thank you, Mr. Chairman.
Dr. Woodcock, thank you. You are not an economist, and
although we have a lot of physicians on the committee, most of
us are not, so you are in good company here.
From your opening testimony, the words I caught on to was
the drug lag, R&D, investment, fewer drugs because of that. We
are going to have a venture capitalist, I think, on the second
panel, an investor, talking about, and that is where we are
trying to marry how do we keep capital going into this.
I don't mind talking about the great job creating aspects
of a thriving pharmaceutical industry that is putting safe and
efficacious drugs out on the market. At a time when we are
looking for job growth, that sector can do that, the
telecommunications sector can do that, the energy sector can do
that. But as my friend Charlie Gonzales was talking about, we
still want it safe, and that is a big criteria. Globalization
does play a big role, another word in your opening testimony.
So it is in these concerns that we--the issue of our
European competitors, who have some quality standards, may be
starting to close that gap, plus Asian producers who may be
closing that gap. But we have had concerns about what we
receive there. This committee has had numerous testimony on
stuff, not just on pharmaceuticals, but also, just food
products and stuff that has been of great concern.
Some of us have been focused on the antibiotics issue,
which I would like to turn to a little bit, bacterial
resistance to antibiotics, which I know is a concern to you
all. Part of your guidance there was some concern that your
agency was not giving adequate guidance for clinical trial
design for new antibiotics, especially in the case where no
treatment existed for a given infection.
Can you discuss what progress the FDA has made in this area
since you last testified?
Ms. Woodcock. Certainly. We have been working with the
foundation for NIH that convened a group that is working on
endpoints for clinical trials for different classes of
antibiotics. I think this is very promising. We also have been
having discussions about basically untreatable infectious
diseases, multiple drug-resistant infections and how one would
do trials, and we do hope to get out some guidance on that.
We don't know either, all right? This is unchartered
territory. So we can put our best ideas forth, but we don't
have all the answers about how to study these. I think we will
show considerable flexibility in the standards that we apply
when we are talking about diseases, infectious diseases that
really lack any alternative treatment.
Mr. Shimkus. Can you give me any thoughts on the need for
new antibiotics to treat resistant infections?
Ms. Woodcock. The bugs are always ahead of us, all right,
and that is something we just have to live with, that the
infectious organisms can mutate very rapidly. We give
antibiotics out to a lot of people. We put the bugs under
selective pressure, and bingo, we have resistant organisms that
we can't treat very well.
So this is an ongoing problem where we need a robust
pipeline of new antibiotics, and to some extent, we need some
effective antibiotics that we don't use very much, all right,
that we hold in reserve for those types of situations, because
if we use them broadly, then the bacteria become resistant.
Mr. Shimkus. On a separate issue now, talking about the FDA
advisory committee and situations in which an individual may be
disqualified because they have worked on a clinical trial for
an unrelated product, not a related product, and that is, I
think, an issue--is that true? Do you know of cases where
someone has been disqualified because they worked in a clinical
trial for an unrelated product, and does that hurt in this
clinical time lag that we are kind of debating today?
Ms. Woodcock. Yes, it is true. It is also true we have
difficulty recruiting qualified people and having highly
qualified panels. In some cases, we have had to delay advisory
committees because of the difficulty, because once we go
through in great detail, all the financials of the individuals
we have nominated, we find that they have to be excused from
participating.
Mr. Shimkus. Thank you, Mr. Chairman. Thank you, Dr.
Woodcock.
Mr. Pitts. I thank the gentleman and recognize the
gentlelady from California, Ms. Capps, for 5 minutes for
questions.
Mrs. Capps. Thank you, Mr. Chairman.
And thank you for your testimony, Dr. Woodcock.
I would like to reiterate for a minute what others on the
panel have been saying.
The PDUFA program has largely been a successful and
creative partnership, in my opinion. And I look forward to
working with my colleagues on both sides of the aisle to
strengthen the program during this reauthorization process.
Moreover, I think a lot of what we have heard today reinforces
the importance of giving the FDA the resources it needs to
ensure that the agency can do its work independently and in a
timely manner while ensuring patient safety.
While the FDA's drug review process has a great number of
strengths, I am concerned about reports that clinical trials
data submitted to the FDA do not routinely include reporting
based on sex or other important demographics. For example, one
study found that, despite FDA regulatory requirements that
require the reporting of a broad range of demographic data,
more than one-third of the time this information is not being
provided. In addition, a 2007 study specifically looking at
heart disease clinical trials--and, of course, heart disease
being the number-one killer of women--found that only 25
percent of trials report sex-specific results in scientific
journals.
These issues were highlighted in a 2010 Institute of
Medicine report entitled, ``Women's Health Research: Progress,
Pitfalls, and Promise,'' which found that--and this is a quote
from the report--``inadequate enforcement of recruitment of
women and of reporting data by sex has fostered suboptimal
analysis and reporting of data on women from clinical trials
and other research.''
Its recommendations included specific strategies for the
agency. And another quote from them, which I am sure you know
about: ``For medical products, drugs, devices, and biologics
that are coming to the market, the FDA should enforce
compliance with the requirement for sex-stratified analysis of
the efficacy and safety and should take those analyses into
account in regulatory decisions.''
Unfortunately, as you know, there is a limited transparency
with these applications, making it difficult for the public or
prescribing physicians to know if any improvements on this data
collection are being made. So my question is, can you discuss
this work with us, please? What has FDA done to address the
gaps in these data?
Ms. Woodcock. Well, interestingly, when I started at the
Center for Drugs in 1994 for the first time, I was instrumental
in getting this regulation done that required reporting by sex,
of how many women were in trials, you know, what the results
were by sex and so forth.
I don't know the answer to your question. I am going to
have to get back to you. My impression was that we have
standard tables on reporting by sex, both for outcomes as well
as how many people were recruited in the trial and all the
other variables. So I am very surprised to hear what you have
to say, and we can get back to you on this.
Mrs. Capps. Well, I do--I think this is really important. I
want to make sure that--there are a number of diseases, not
just heart disease, that have different symptoms for the
different genders. And I am under the impression and this
article would give--the Institute of Medicine report in 2010
would indicate that there is limited transparency within that
application process. So that it would be very difficult for the
public, it would be difficult for FDA, and it would certainly
be difficult and challenging for the medical provider to know
if any improvements on the data collection are being made.
And I look at the legislation I have introduced in this--
that passed out of the House in the past, the HEART for Women
bill, which specifically addresses this issue to ensure that
these important data are being used to keep all Americans
healthy.
So if you have any final thoughts--this is a topic I want
to see thoroughly explored by the Food and Drug Administration
and a report submitted back to us on whatever findings that you
have.
Ms. Woodcock. I think part of the problem that we have in
getting timely data on this and providing it is that we don't
get all the information in a standardized electronic format. If
we did that, we could easily run reports on these standard
tables and we could tell everything there is to know about
reporting by sex.
In the new PDUFA recommendations that we are putting forth,
there is a requirement that we get standardized all-electronic
data. And this would extremely help transparency of this issue
and many others.
Mrs. Capps. Mr. Chairman, I think this is a really
important topic.
And I would like to request that we have follow-up data
that you provide, FDA provides, to us on the progress that has
been made and/or any other changes that should occur so that we
can get this information.
Ms. Woodcock. I would be happy to do so.
Mrs. Capps. Thank you very much.
And I yield back.
Mr. Pitts. The chair thanks the gentlelady and recognizes
the gentlelady, Ms. Myrick, for 5 minutes for questions.
Mrs. Myrick. Thank you, Mr. Chairman.
And thanks for being here and for your thoughtful comments
today.
My concern is about the FDA's ability to approve potential
drugs to treat deadly diseases. For example, we know a drug
like Avastin has toxicities that aren't well-tolerated by some
patients, but for some patients, especially metastatic breast
cancer patients, it does not extend their survival, but for
others it does extend their survival. And metastatic breast
cancer patients are facing a deadly disease, as we all know,
and many are willing to take that toxicity risk if the drug
helps keep them alive. I believe you said that in your
testimony today.
And so I applaud your efforts, you know, to promote the
need for biomarkers and screening tests so that scientists and
physicians have more certainty about which patients respond to
certain particular treatments. But if we don't have the
screening tests now, I don't think we should restrict access or
pull approval for a drug simply because we are not sure how to
define the category of patients who will respond.
So why can't the FDA approve the drug with appropriate
warnings for doctors and patients by informing the doctors that
many of their patients might not respond and that there are
risks involved, I mean, as an example?
Ms. Woodcock. Well, I cannot comment on the Avastin
situation very specifically. The Center for Drugs has made a
recommendation, and now it is before the FDA commissioner. And
we have had a hearing and so forth.
Generally speaking, if we have found that a drug saves
lives, then we will approve it, regardless of many serious side
effects, as long as the survival advantage is not outweighed by
mortality caused by drug side effects, OK?
Mrs. Myrick. Yes.
Ms. Woodcock. So we have many, many drugs--we have recently
approved several cancer drugs----
Mrs. Myrick. Right.
Ms. Woodcock [continuing]. That are very toxic----
Mrs. Myrick. Right.
Ms. Woodcock [continuing]. All right? And people know, if
they are going to take those drugs, they may be facing--they
may die from the side effects. That is true of cancer
treatment. But they are trying to extend their lives.
Mrs. Myrick. Well, I know there are women who have taken
this particular drug, Avastin, you know, for 3 or more years,
and they are still doing well, so. I understand, it is just a
little frustrating, because I know if you are in a position
where you really have this disease and you want to do
everything you can to extend your life.
One more question on this same line. The FDA and the
European Union's drug-approval body reviewed the same data on
Avastin as a metastatic breast cancer treatment. And I
understand it is approved there for HER2-negative metastatic
breast cancer, and it is widely used in Europe for those
patients.
So what is the difference? How do you explain the
difference between what they are doing and what we do? Because
I know it is all global, and we look at all of it together.
Ms. Woodcock. We do look at all the same data. We have
certainly talked to the EU about their decisions. Sometimes we
reach different decisions. We approved Avastin for a deadly
brain cancer----
Mrs. Myrick. Right.
Ms. Woodcock [continuing]. Called ``glioblastoma'' that
they did not approve Avastin for. So sometimes various experts
come to different opinions.
But I can assure you that we have--our breast cancer
oncologists at FDA are dedicated to the treatment and,
hopefully, eventual cure of breast cancer and getting the best
possible agents out there for women.
Mrs. Myrick. Oh, no, I don't have any question about that.
I guess my question is more about the fact of how we restrict
some of these when they do work for a large share of women,
even though there is a mortality rate in allowing the usage for
those women for those drugs.
Ms. Woodcock. The trials that we looked at--and this is
from the Center for Drugs, again, because it is up on appeal
right now--but in the trials that were done of Avastin in
breast cancer, there was no survival advantage at all. And
there was also no----
Mrs. Myrick. But--and I understand. But the point is, if it
is helping some people and they are willing to take the risk, I
guess I go back to the same thing, should we not allow them to
have that opportunity? And that is really where I am coming
from.
Ms. Woodcock. I understand.
Mrs. Myrick. I yield back, Mr. Chairman.
Mr. Burgess. Would the gentlelady yield to me for a moment?
Mrs. Myrick. Yes.
Mr. Burgess. Just on that question on Avastin, just looking
at the list of people who were on the advisory panel last week
who rendered this opinion, I don't see anyone--maybe you can
educate me differently--I don't see anyone that would have had
the ongoing daily treatment of breast cancer patients under his
or her control. You had a lot of experts and a lot of
oncologists, but I didn't see a specific specialist in the
specialty of metastatic breast cancer.
Wouldn't you want someone like that on a panel rendering
that type of opinion?
Ms. Woodcock. Well, this was not run by the Center for
Drugs, and so I can't comment. I agree, there was no breast
cancer expert, to my knowledge, on that panel.
Mr. Burgess. Thanks, Mr. Chairman.
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.
Ms. Woodcock, good to see you again.
I mentioned in my opening statement that we want to ensure
that innovation in the pharmaceutical industry is vibrant. This
is an important national priority. I also think it is important
to assure that the drugs that reach patients are both safe and
effective. That is the mandate to FDA.
When critics assert that FDA is somehow stifling
innovation, we need to look very carefully behind those claims
and insist that we have reliable and accurate data to
substantiate them. Without this kind of data, we can very
quickly get to a place where the so-called solutions are being
proposed to a problem that may or may not exist in the first
place.
The same critics allege FDA's slowness is because of
regulatory changes that I fear could prove--they are suggesting
some of these regulatory changes--for instance, some have
suggested that Congress pass legislation preventing FDA from
having the ability to insist on critical trial data that FDA
feels is necessary and force it to approve drugs on the basis
of less information.
Specifically, some have also suggested that the FDA be
required to approve drugs for certain conditions on the basis
of a single study instead of two randomized, placebo-controlled
trials. In 1997, we did adopt a law that gave the FDA
discretion to do less than two randomized trials, and then we
hear critics claiming that FDA has not used this discretion,
always insisting on two trials.
Now, we are not scientists; we rely on you to make
scientific decisions at the FDA. But we hear all the time about
how FDA is taking too long and asking for information that is
not necessary.
Can you comment on this? Is it true that FDA has failed to
use the discretion we gave you in PDMA and that the agency
always insists on two trials? Would FDA be concerned about
legislation that spelled out the number or type of clinical
trials that the agency could look at in assessing a drug
application?
Ms. Woodcock. Well, first, let me say, I would be concerned
about trying to legislate at a more detailed level what type of
evidence is required. We try to match the evidence to the
situation, the requirement of evidence to the situation. So for
rare diseases or mortal diseases, less evidence usually is
required.
For example, we did a study of orphan data, and half of
orphan approvals were based on a single trial, one trial.
Recently, this year, we have approved seven orphan or rare
disease indication, all right? Some new products, some efficacy
supplements. For one of those, there was no human trial--it was
done on animal data--to show efficacy, right? In one of them,
there were 17 patients. And this was a rare disease. But there
wasn't a randomized trial. We compared how the patients were
doing before they took the drug compared to how they did after
they took the drug.
Mr. Waxman. So you use that discretion like you have under
the law to set up priorities, how serious the disease is, how
small the population may be that is being affected by a
particular disease or would be helped by a particular drug. And
you feel that if we micromanaged your activities by specifying
that this trial is all that is needed or that trial is
sufficient, that we would end up with, what, stultifying FDA or
not letting you do your job?
Ms. Woodcock. We might slow things down.
Mr. Waxman. Slow them down even further?
Ms. Woodcock. That is what I think, because we would be
involving a lot of lawyers and whether we were obeying the law
in medical decisions that we were making. Nothing against you
lawyers, but sometimes that slows things down a little bit.
I would say that we have considerable flexibility. And,
say, a drug for headache pain that is going to be used by
millions of people, all right, you want to know more about
that--you want to know it is not going to cause a stroke, for
example--than a drug here for the orphan indication or for a
disease where people are dying and they don't have any other
alternatives. We have great flexibility in the standards that
we apply.
Mr. Waxman. Has there been a change in FDA's protocols for
reviewing drugs? In other words, has there been something
where, according to Mr. Leff, who is going to testify in a
while, that FDA has shifted to a more cautious decision-making
posture, begun to require more and more data to provide a
higher degree of statistical proof of both efficacy and safety?
And it sounds like FDA has somehow formally changed the drug
review process. Is that an accurate statement? How do you
respond to that?
Ms. Woodcock. No. I believe that we still have the
standards of safety and effectiveness that we have always had,
and we continue to apply them.
We have learned, though--we have learned some things. For
example, we have learned that drugs that raise blood pressure
will cause a certain incidence of strokes. And so, for example,
in obesity, if you are going to have a drug to treat obesity,
maybe it causes weight loss, but if it raises the blood
pressure--I mean, you are treating the obesity, in part, to
decrease cardiovascular complications, OK?
Mr. Waxman. Right.
Ms. Woodcock. What if, in fact, you are actually going to
increase them?
So we have to know, because the standard is that it works,
right? And patients take these drugs because they believe they
are going to better their lives and better their health. And
so, when we learn new medical facts, new scientific facts, we
have to make sure that they are taken into account in the drug
development program. But that is part of the standard of safety
and effectiveness.
Mr. Waxman. Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentlelady, Ms. Blackburn, for 5 minutes for questions.
Mrs. Blackburn. Thank you so much, Mr. Chairman.
And we appreciate that you are here, Dr. Woodcock.
I want to stay with the line of questioning that Ms. Myrick
had started with you, looking at this approval process. I had
gone through the forensic cancer research report on FDA and the
EMA, European Medicines Agency, looking at those approvals from
2003 to 2010. And, you know, that said, well, FDA was faster
than EMA. But when you look at the year by year on that--and I
am sure you have done that--and you go back to 2007 or 2008,
there is a significant narrowing of the lag in cancer medicine
approval times between the FDA and the EMA. And that was
repeated--the noting of that lag was repeated in the California
Healthcare Institute--and I know you are familiar with that
report--and also the Boston Consulting Group report.
So I want to ask you four questions relative to that,
because I think this should be of great concern with us. And it
ties into what we hear from our constituents, who are concerned
about the process that you are having individuals go through,
as they try to file and go through the approval process.
So here are the four questions for you on that: Number one,
what accounts for these trends? Number two, is the FDA getting
slower and more inefficient? Number three, is the EMA getting
better and more efficient? And, number four, is it a
combination of things?
Because if we are getting slower, we need to nip this in
the bud and we need to know what the precise problem is. Can
you define that?
Ms. Woodcock. Well, I can't remember each one of your four
questions----
Mrs. Blackburn. I will be happy to submit for writing.
Ms. Woodcock. Right.
The FDA most recently--our most recent data for 2011 show
that we have the highest first-action approval rate we have
ever had, which means the applications are coming in and they
are getting out the door on the first cycle. And that, for
priority applications, is 6 months usually. All right? So you
can't get too much faster than that, all right?
The Europeans may be getting faster. Another hypothesis or
thought is that the applications are getting better, all right?
If the industry fully understands what the regulators want and
they have a very important drug that is needed by the
population, then it usually will move through the regulatory
process in any country very rapidly.
So we don't feel we are in competition with the European
Union or whatever. We were simply responding to criticism that
it was taking us twice as long or three times as long as they.
If the drug were approved simultaneously around the world and
available to all patients with whatever disease, say, hepatitis
C, that would probably be the best outcome.
Mrs. Blackburn. Well, and I agree with you on that. And I
think that the two things that we hear you could kind of
distill down to companies that are spending billions of
dollars, want to make certain that they are provided with both
transparency and consistency in that FDA review process. And
they want to make certain that you all are conducting these
with certainty and predictability. And as you well know, that
has been a problem.
One other question I wanted to ask you about, because I
have written you about the PGAs and the issue that is there.
And I was due a response--I am trying to find it--by the end of
June, and I still have not had a response from you all about
the products that are there, with the PGAs and what you are
doing with those over-the-counter, unapproved, PGA-containing
eyelash growth products.
What are you doing to investigate the marketing of those
products and to restrict those in the marketplace? And do you
plan to take enforcement action against all companies marketing
these companies without FDA approval?
I think that all of us who look at the market for young
women, we are very concerned about these products in the
marketplace.
Ms. Woodcock. Yes, we are looking into this issue. As you
know, there are numerous products in the marketplace, dietary
supplements, that have been contaminated with many dangerous
drugs. And so we have been taking action on products that are
contaminated with these drugs. And we are looking into this
issue, and we will be happy to get back to you on our progress.
Mrs. Blackburn. OK. I am speaking specifically of the
eyelash----
Ms. Woodcock. I know.
Mrs. Blackburn [continuing]. Growth.
Ms. Woodcock. I know.
Mrs. Blackburn. OK. Well, we were due a response by the end
of June.
Ms. Woodcock. Yes, I am sorry that you have not received
that in a timely manner.
Mrs. Blackburn. OK. And I think that we want to know that
there is action taken against these unapproved----
Ms. Woodcock. Yes.
Mrs. Blackburn [continuing]. Products. Thank you.
I yield back.
Mr. Pitts. The chair thanks the gentlelady, recognizes the
gentleman, Mr. Engel, for 5 minutes for questions.
Mr. Engel. Thank you, Mr. Chairman. I want to thank you for
holding this important hearing today. As we all know, the
reauthorization of PDUFA is vitally important to both patients
and industry alike.
As many of us remember, PDUFA was originally enacted in
1992 to address the unusually long and unpredictable wait
period that it used to take for new drugs to be approved for
market consumption. At that time, it would take an average of
more than 2 years for a new drug to be approved, which meant
that patients would not have access to new medicines when they
needed them, and innovation suffered.
I am proud to say that, since then, we have come a long way
in making more drugs available to patients while maintaining
safety. I recognize that the system is not perfect, but we have
come a long way.
Mr. Chairman, as we move along in the reauthorization
process, I look forward to working with the various
stakeholders and my colleagues on the other side of the aisle
to address ways in which Congress can strengthen the FDA and
achieve our common goals. I mention working with my colleagues
on the other side of the aisle because I think it is very
important that we remember that this is not a partisan issue.
However, the appropriations bill that was passed last month
cut the FDA's funding drastically, and I think that was a
mistake. How can we expect the FDA to do their job effectively
and efficiently while at the same time take away the valuable
resources they need to do it? This only hurts patient safety,
and it also hurts one of our strongest and most innovative
industries.
So, Dr. Woodcock, let me ask you this. Today we are
discussing legislation that authorizes prescription-drug user
fees, which are critical to the FDA's ability to approve drugs
more quickly while at the same time the House is cutting the
funding. Can you tell me how you plan to reconcile these cuts
and see that new, innovative drugs continue to come into the
market in a timely manner?
Ms. Woodcock. Well, I mean, any cuts would make various
programs at FDA more difficult. We also approve generic drugs,
and the flow of those is important to keeping health-care costs
under control in the United States. And we would become more
challenged, I think, in our review of generic drugs if we had
substantial cuts. We also manage post-market drug safety
problems, and that requires a considerable amount of resources
and effort.
We also keep guard over quality of all the drugs in the
United States. And, as has already been mentioned, the import
of drugs from all around the world and manufacture around the
world have challenged us to make sure that we are able to
ensure high quality of the U.S. drug supply. So that would be a
challenge. Also, clinical trials are conducted all around the
world, and so we are having to inspect those clinical trials
wherever they might be held.
In addition, as you alluded to, this would have an impact
on our ability to promote innovation in new drug regulation and
in drug development, which is something that is very dear to my
heart.
Mr. Engel. Let me ask you--as you know, many doctors and
hospitals are struggling to cope with unprecedented drug
shortages in the United States. Drug shortages obviously lead
to delays in treatment and force the use of alternative drugs,
which can result in unintended consequences. This shortage is
endangering cancer patients, heart-attack victims, accident
survivors, and many other ill people.
So let me ask you this. Before I ask you this, I want to
ask the chairman for unanimous consent to put into the record a
statement from the American Hospital Association on behalf of
our hearing today.
Mr. Pitts. Without objection, so ordered.
Mr. Engel. OK, thank you. Thank you, Mr. Chairman.
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Mr. Engel. So let me ask you this, Doctor. From the FDA's
perspective, what is the problem with drug shortages, and how
can we address it?
Ms. Woodcock. Drug shortages have multifactorial problems,
all right? They are related, often, to drugs that are off-
patent, that only have one manufacturer that is approved in the
United States, and that eventually have aging facilities.
We work tirelessly to try and ameliorate drug shortages in
the United States. And, from our point of view, although there
are these structural problems, what would help us the most
would be to have early notification if a company is planning to
stop making an essential drug or temporarily go out of
production, so that we could make arrangements to substitute
something else, to get another drug available for doctors and
patients. And we have been able to do that many times when we
have actually had advanced notice.
Mr. Engel. Let me ask you--the final question is, you
mentioned in your testimony that the FDA allows access to
investigational products through clinical trials. And this
allows patients who may need a treatment that is not currently
on the market to access innovative treatments. You mentioned
also in your testimony that are times when patients cannot
enroll in critical trials.
Could you explain why and what some of the challenges are
that these patients face when considering the clinical trial?
Ms. Woodcock. Well, there is difficulty in the U.S. in
accessing clinical trials. But there is a broader issue of
treatment access, which is a person who lacks alternative
therapy and there is no other approved drug that might work for
them, so they would like to access an investigational product--
drug.
We recently passed regulations about a year ago that
broadened and liberalized and rationalized access protocols for
investigational drugs. The FDA believes that people with
serious illnesses who lack alternative therapy should be able
to get investigational drugs on a treatment basis.
Mr. Engel. Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Georgia, Dr. Gingrey, for 5 minutes.
Mr. Gingrey. Mr. Chairman, thank you.
And, Dr. Woodcock, thank you very much for your testimony.
Let me ask you a couple of quickies. Did you tell the
committee that your specialty is rheumatology?
Ms. Woodcock. Yes.
Mr. Gingrey. OK, thank you.
In regard to my colleague from North Carolina, in regard to
the question on Avastin, can you assure the committee the
decision on Avastin--and I guess that final decision is in the
hands of the commissioner at this point; it looks like it
probably will not be approved for advanced breast cancer,
although it will continue to be approved for colon, and you
mentioned a type of brain cancer that it is still approved
for--this decision, can you assure us, is not based on the cost
of that drug?
Ms. Woodcock. We never look at the cost of drugs when we
are doing our decisions. It is not within our mandate, and it
is not something that we look at.
Mr. Gingrey. You never look at the cost of the drug?
Ms. Woodcock. No.
Mr. Gingrey. OK.
Mr. Shimkus brought up a question about the need for new
antibiotics, and I think that your response to his questions
was reassuring to me. And I think you probably know that Mr.
Shimkus and myself and others on this committee, in a very
bipartisan way, have introduced H.R. 2182, the GAIN Act, to try
to get more antibiotics to the market and the problems that we
have in regard to that, because if they are used properly, then
the market for the sales of those drugs is very limited----
Ms. Woodcock. Right.
Mr. Gingrey [continuing]. As it should be, if they are used
properly.
Can you also give me your thoughts on the need for new
diagnostics to properly identify infectious diseases? For
example, would new diagnostics have helped in the recent E.
coli outbreak in Germany?
Ms. Woodcock. Certainly. We feel that, particularly, point-
of-care diagnostics that could be used at the bedside by
clinicians to rapidly identify the bacteria and also
potentially resistance profiles would be just an outstanding
advance in infectious disease. And we have certainly talked to
the Infectious Disease Society about this and others.
So if we could target our antibiotics better--as you well
know as a clinician, we do a--whatever you call it--a shotgun
approach to treatment until we have the cultures and we know
what the patient has. And so, for many days or maybe total
course of treatment, it may be empirical, and so we don't know
what we are treating. And this leads to a more widespread
resistance, I believe.
Mr. Gingrey. And that, of course, is part of our bill, as
well. And I thank you for that response.
Very quickly, my last point, I wanted to address the
Sentinel Initiative, the post-market risk identification/
analysis system.
And the reason I wanted to be sure of your specialty of
rheumatology, there is a drug--I think it is pronounced
``Remicade.'' Am I correct?
Ms. Woodcock. Yes, uh-huh.
Mr. Gingrey. --Remicade, that was approved. And I wanted to
ask you, if you know, was that approved under orphan drug
status? I know it has been on the market maybe for as much as
20 years--well, maybe not quite that long. But the drug being
used for Crohn's disease and with pretty good results. But my
understanding is that up to 5 percent of individuals will
eventually, if they have taken that drug for Crohn's disease,
they will eventually come down with leukemia. And, you know, to
me, that seems awfully high. And maybe I am being affected
because it happened to a family member just recently, who ended
up dying of her leukemia. She was helped tremendously several
years ago by use of this drug.
What is the threshold? A 5 percent, to me, risk from taking
a drug and then ultimately developing leukemia, which is pretty
life-threatening--in her case, it was definitely life-
threatening and life-ending--where is the threshold in regard
to what we are looking at in the Sentinel Initiative, the post-
market analysis of these drugs?
Ms. Woodcock. Well, generally what we are doing with all
the immunosuppressant drugs is having registries and long-term
follow-up. So we can also use Sentinel for evaluating these
longer-term outcomes. But we are also watching patients
observationally over time.
And we can get back to you on what we know right now about
the occurrence of malignancies as well as infections,
opportunistic infections, as a result of all the classes of
immunosuppressive drugs that are used.
Mr. Gingrey. Dr. Woodcock, I would really appreciate that,
both as a Member of Congress and personally. I would really
appreciate you getting back to me with a report on that. And I
thank you very much.
Ms. Woodcock. I would be happy to do that.
Mr. Gingrey. I yield back.
Ms. Woodcock. And if I may say one thing about this, this
really illustrates the balance of benefit and risk, because
malignancies are not apparent immediately, all right? And so,
you could say, well, this is a wonderful drug, we should just
get it out there, and everyone should take it. But what we find
out is, yes, there are breakthrough--tuberculosis, whatever,
and there are also cancers that occur late. And this is where
we have an obligation to patients to find out as much as we
possibly can, so they can make their decision.
Mr. Gingrey. Thank you.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman, Mr. Latta, for 5 minutes for questions.
Mr. Latta. Well, Doctor and Director, thanks very much for
being with us today. I really appreciate your testimony today.
And just to kind of maybe follow up a little bit of the
questioning that has already been asked, but one of the areas
that I would like to go into is about especially on the obesity
and diabetes side, with the drugs out there and the therapies
that are being brought forth, and especially with the FDA
approval process. Because, as we all know, especially young and
old alike, both these, diabetes and obesity, are affecting a
huge portion of our population and increasing our costs.
Especially, it is a huge driver on the Medicare side.
And the question is, what are you doing to encourage the
development of new therapies to treat these diseases,
especially using your authority under REMS----
Ms. Woodcock. Pardon me. I am having trouble hearing you.
Mr. Latta. OK. You know, this is sometimes also the room
that we use for our telecommunications subcommittee. And I am
sorry--is that better?
Ms. Woodcock. Yes.
Mr. Latta. OK. The way some of our mikes pick up.
But the question I have then is, what are you doing
encourage the development of new therapies to treat these
diseases, especially using your authority under REMS to follow
the drugs closely after their approval?
Ms. Woodcock. We share the understanding of the need for
new treatments for diabetes and for obesity. And I would point
out that for diabetes, in early 1990s, there were only two
types of therapies available for the treatment of Type 2
diabetes, and now we have 11 new classes of drugs that are out
there. So there has been a tremendous blossoming of attempts to
get new therapies for diabetes out there.
And, in fact, we are seeing the pipeline continue. And we
have put out guidance about cardiovascular risk in diabetes
drugs that companies have been able to deal with and follow,
and we have approved new diabetes drugs recently. So we see a
robust pipeline there.
In obesity, the problem is different. We have had to take
three obesity drugs off the market because they cause stroke.
We have had to take another class of obesity drugs off the
market because of heart-valve disease. And you can see with
young people, if we expose them to an agent widespread that
causes heart-valve disease, we would have another epidemic on
our hands. So we must make sure that these products have
adequate safety.
But we recognize the obesity epidemic. And what we are
doing is we are going to have a scientific meeting about
obesity and cardiovascular safety. And we are also planning to
have a series of stakeholder meetings, where we bring in the
very attritions and the patient groups and the FDA and other
experts to talk about how diabetes drugs should be developed.
And I think this will be very helpful to the industry.
Mr. Latta. Let me ask this. I think you said that you took
several off the market last year. I believe also, if my
information is correct, that the FDA also denied three
consecutive applications for approval of new obesity drugs last
year.
Ms. Woodcock. That is correct.
Mr. Latta. Now, was that for the same reasons, or what was
the cause of that?
Ms. Woodcock. Different--well, one drug had a blood-
pressure problem, which was the reason we had to remove other
diabetes drugs off of the market. They were causing strokes.
Last year, we removed a drug, Meridia, from the market because
of stroke. A trial was done that showed that even though people
lost weight, they still got an increased number of strokes when
they took this weight-loss drug. So it was removed from the
market.
So one of the problems that we are identifying is many of
the weight-loss drugs increase blood pressure, and we have to
make sure they are not causing an excess of strokes, OK? But
some of the other weight-loss drugs have other types of
problems that we are looking at.
Mr. Latta. Thank you very much.
And, Mr. Chairman, I yield back.
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.
Thank you, Dr. Woodcock.
I know you all have a difficult job anytime you approve a
drug as you go forward. And just think about the long term as
you move forward, of course there is a--so it is a quandary.
But there are a lot of people waiting on the approvals as you
move forward.
And my friend, Ms. Myrick, Representative Myrick, covered
some of it, but I just got a text this morning from my brother,
and I am going to share this a little bit. Well, first, my
brother called me yesterday. He has a best friend in the Navy,
was in the Navy, whose wife had breast cancer. And they were
one of the ones who flew from Seattle, Washington, to, I guess,
Baltimore a couple of weeks ago. And the text says, ``Thanks
for talking to Nancy yesterday. She knew we were having this
meeting. They are great people, and thanks for the quick
response. The bottom line is, they have been through a lot, and
she has lived much longer than she was supposed to.'' And I
really read that to give you that line.
And it seemed like with Avastin that--I talked with her
quite a while on the phone yesterday, and she said her mother
has breast cancer but very localized. And she realizes Avastin
wouldn't be something that her mother should be taking. But she
did say, when she discovered she had breast cancer, when they
found the breast cancer, she had four tumors on her liver. I
think that is what she said. And so, therefore, it looked like
she had made the decision. She realizes the toxicity, but she
really believes that Avastin is--and she is distraught--has
really increased her life expectancy.
So the question--and maybe this wasn't your area, as you
said--was Avastin not approved for breast cancer because of the
side effects or because there is no clinical proof that it
actually works?
Ms. Woodcock. Avastin was approved under accelerated
approval for breast cancer. It was already on the market for
other cancers, all right?
Mr. Guthrie. Right, right.
Ms. Woodcock. And then, subsequently, it was approved under
accelerated approval.
What that means is, then the drug developers have to prove
that the promise, OK, that was approved under accelerated
approval is real, all right? And so the company did additional
trials, and they did not show any survival advantage.
The original trial it got approved on showed something
called progression-free survival. What that means is you live
longer with your tumors not growing on scans.
Mr. Guthrie. OK.
Ms. Woodcock. All right? It doesn't mean you live longer.
It means that your tumors are stable longer. And so the
original trial showed, in women getting Avastin, their tumors
stayed stable longer, all right?
Mr. Guthrie. OK.
Ms. Woodcock. What we asked the company to say--well, show
that means something, show that translates to either quality of
life, better quality of life of the people or longer life of
people, all right? And they were not able to show either of
those in the subsequent trials that were done.
That does not mean that Avastin is not an active drug,
perhaps, for some women, but we do not know what women. And it
does have very serious, potentially fatal side effects.
Mr. Guthrie. Right. She recognized that. We had talked on
the phone--and so the issue really wasn't just the side effects
and it could be fatal. But you are saying it really didn't show
that it extended the life as you move forward.
Ms. Woodcock. It did not. In that population. And that is
not a population that is selected by some marker to respond
well to Avastin. It may well be if they could come up with a
biomarker and say, ``These women are the women who should take
this drug,'' then it might be possible to figure out who the
drug is good for.
Mr. Guthrie. Uh-huh. So it could be a--and she could be
one----
Ms. Woodcock. That is right.
Mr. Guthrie [continuing]. A select group of circumstances
that it affects--because drugs interact with all of us
differently--that would actually--and I know from our
conversations she is convinced that she is still here because
she was on Avastin.
And one other thing a lot of people have said--I only have
about a minute, so I will just ask it really quick. You know, I
do hear from a lot of our people in the drug field,
pharmaceutical field, saying that they are having difficulty
getting things approved. You have heard that from several of us
here. You all must be hearing the same thing. And maybe what
you are saying is 2011 has been better than 2010 and 2009 and
2007.
So are you already acting to the fact that people said they
are getting things difficult--like you said, 2011 has been
pretty successful, but I am really not hearing people saying
that, ``We have had difficulty in the past, but it seems to be
getting better.'' So I don't know if you are hearing the same
thing. And just comment on that. I have about 40 seconds left.
Ms. Woodcock. Well, I would propose to you that the people
who come into your office are not the people who have had a
successful experience. And so you have what we call a biased
sample, all right? And even if, like, 90 percent of the people
are getting through and we are having a tremendous--I am not
saying all this will continue, but this year we are having an
extremely high approval rate because the drugs that are coming
in are--many of them are very significant advances, all right?
But the people I think who come to talk to you continue to
be the people who are having a difficult time. And so I don't
know that you would see any change in your experience.
Mr. Guthrie. So they are not coming by to see us just to
say, ``Thanks, it really went well''? We hear that sometimes
too.
Thanks a lot.
Ms. Woodcock. Thank you.
Mr. Pitts. The chair thanks the gentleman, recognizes the
ranking member emeritus of the committee, Mr. Dingell, for 5
minutes.
Mr. Dingell. Mr. Chairman, I thank you for the hearing.
And I thank you for your courage.
Ms. Woodcock. Thank you.
Mr. Dingell. I wanted to ask a ``yes'' or ``no'' question.
I hope you will respond.
Do you have the ability to fully control the safety of
imported pharmaceuticals, yes or no?
Ms. Woodcock. No.
Mr. Dingell. Do you have the authority to control the
safety of raw materials or imported pharmaceuticals?
Ms. Woodcock. No.
Mr. Dingell. Do you have the authority and the resources
you need to address the safety of components now being imported
into this country, yes or no?
Ms. Woodcock. No.
Mr. Dingell. Do you have the necessary authorities and
resources to see to it that drugs are only imported from
facilities overseas that are properly observing good
manufacturing practices--that is a word of art--yes or no?
Ms. Woodcock. No.
Mr. Dingell. Do you have the ability to see to it that raw-
materials suppliers also engage in good manufacturing practices
abroad?
Ms. Woodcock. No.
Mr. Dingell. Do you have the resources needed to conduct
foreign drug-facility inspections with the same frequency as
domestic drug-facility inspections?
Ms. Woodcock. No.
Mr. Dingell. How often can you get by to see a foreign drug
manufacturer?
Ms. Woodcock. Every 9 years or so.
Mr. Dingell. Every 9 years?
Ms. Woodcock. Yes.
Mr. Dingell. You get by to see dog-food manufacturers every
year or so.
Ms. Woodcock. Yes, probably a little more--a little over a
year.
Mr. Dingell. Do you need additional resources to increase
inspections of foreign drug facilities?
Ms. Woodcock. Yes.
Mr. Dingell. Do you need additional authorities to be
effective in that?
Ms. Woodcock. Absolutely.
Mr. Dingell. Do you have the ability to freely share
information about a drug with your trusted domestic and foreign
counterparts in the instance of something like another heparin
crisis, yes or no?
Ms. Woodcock. No.
Mr. Dingell. Do you need this ability?
Ms. Woodcock. Yes.
Mr. Dingell. Do you have a clear authority to require
manufacturers to assure the safety of their food chain, yes or
no?
Ms. Woodcock. Their food chain?
Mr. Dingell. Yes--I am sorry, the supply chain. I
apologize.
Ms. Woodcock. Thank you. No, we do not.
Mr. Dingell. Do you need this authority?
Ms. Woodcock. Yes.
Mr. Dingell. Do you have the authority to require
manufacturers to notify you if they suspect their drug may have
been counterfeited, misbranded, or adulterated?
Ms. Woodcock. No.
Mr. Dingell. Do you have the ability to properly assure the
safety of both raw materials for the manufacture of
pharmaceuticals and pharmaceuticals as they are imported into
this country?
Ms. Woodcock. No. And I think we are one of the few
countries that does not have that authority.
Mr. Dingell. Do you need this authority?
Ms. Woodcock. Yes.
Mr. Dingell. Do you have the authority to require companies
to recall a drug, yes or no?
Ms. Woodcock. No.
Mr. Dingell. Do you have that authority with regard to
imports?
Ms. Woodcock. No.
Mr. Dingell. Do you have that authority with regard to raw
materials and things like that?
Ms. Woodcock. No.
Mr. Dingell. And components?
Ms. Woodcock. No.
Mr. Dingell. Now, let's go to the question of heparin. A
lot of bad heparin got out because, currently, you couldn't get
over to China to see what the raw material was like and what
was safe or unsafe with it. Is that right?
Ms. Woodcock. That was part of the problem.
Mr. Dingell. What was the other part?
Ms. Woodcock. I think the tests were out of date for
heparin.
Mr. Dingell. The what?
Ms. Woodcock. The testing standards, the U.S. standards,
international standards.
Mr. Dingell. Were they adequate or inadequate?
Ms. Woodcock. They were inadequate.
Mr. Dingell. OK. Do you have authority to address that
problem?
Ms. Woodcock. No, not fully.
Mr. Dingell. Not fully or just not at all? If you can't do
it fully, you can't do it at all, can you?
Ms. Woodcock. Can you repeat the question?
Mr. Dingell. Would you submit a brief monograph to this
committee for the purposes of the record----
Ms. Woodcock. Certainly.
Mr. Dingell [continuing]. Explaining what happened in the
heparin case and what abilities you need to address imports not
just of finished products, pharmaceuticals, but also raw
materials and components, please?
Ms. Woodcock. We would be happy to do that.
Mr. Dingell. Thank you.
I ask unanimous consent that the additional matters
requested be inserted in the record at the appropriate point,
Mr. Chairman.
Mr. Pitts. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Dingell. Mr. Chairman, I thank you for your courtesy.
And I thank our witnesses.
Mr. Pitts. The chair thanks the gentleman, recognizes the
gentleman from New Jersey, Mr. Lance, for 5 minutes for
questions.
Mr. Lance. Thank you, Mr. Chairman.
Good morning, Doctor.
I have the honor of being the Republican co-chair of the
Rare Disease Caucus. And I want to thank the progress that the
FDA has made regarding the advancement of orphan product
development. And given the fact that a large number of products
approved by the agency are for orphan indications, it is clear
to me that the FDA's increased focus on development and
approval of orphan products is important to all stakeholders in
the rare-disease community.
I am particularly interested in learning more about the
Office for Rare Diseases, created last year. As I understand
it, the goal of that office is to facilitate and support
research, product development, regulations and approval of
biopharmaceuticals for the treatment of rare disorders and to
serve as a focal point for stakeholders and developers of drug
and biological products.
If one of the primary objectives of the Office for Rare
Diseases is to ensure collaboration among scientists and
clinicians throughout CDER, what steps are being taken and what
are the plans for the future to ensure adequate resources that
are allocated to this office?
Ms. Woodcock. Thank you.
Yes, as part of enhancing regulatory science and expediting
drug development within the proposals we have for the new user-
fee program, we have a portion on rare diseases, which would
improve resources, add additional resources to our attention to
rare diseases, including to that office.
Mr. Lance. And will you be engaged in that activity? And
what time frame, Doctor?
Ms. Woodcock. The new user-fee program hopefully will be
passed and be able to be implemented in 2013. And, at that
point, we would have additional resources to put----
Mr. Lance. So this would be an action probably we would
take next year regarding PDUFA, next year?
Ms. Woodcock. Yes.
Mr. Lance. Thank you. Well, I look forward to working with
you and other interested stakeholders in this issue. It is
important, I think, to the entire Nation and certainly
important to the district and State I serve, which we believe
is one of the medicine chests of the world.
On a different topic, on biomarkers, innovative drug
development is increasingly dependent on the use of new
biomarkers of disease to target the right patients. Could you
tell us what you are doing to encourage the use of biomarkers
in drug development?
Ms. Woodcock. Thank you.
I think since 2004 FDA has really been in the forefront of
this; we have been encouraging the use of biomarkers. And we
have published numerous guidances. We have done a lot on
something called pharmacogenomics, because a lot of these would
be genetic markers.
And we also now have a proposal in the new user-fee
enhancements where we would like to enhance our activities on
biomarkers and pharmacogenomics, because we feel this does have
tremendous promise for patients and for drug development.
Mr. Lance. Well, thank you, Doctor. This is my first
opportunity to meet you. I am new to the committee, and I look
forward to working with you.
And I yield back the balance of my time.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Louisiana, Dr. Cassidy, for 5 minutes for
questions.
Mr. Cassidy. Thank you, Dr. Woodcock, for testifying.
Newly active substances, just so I am clear on the
definition, if somebody has a drug and they make it a single-
day therapy, a prolonged release if you will, as opposed to a
QD, does that qualify the new--so it is just a truly new drug?
Ms. Woodcock. Yes, it has to be first, you know, time and
first exposure to humans of this molecule, basically.
Mr. Cassidy. Got you.
Secondly, just to follow up on what Mr. Dingell asked
about, man, if you are inspecting dog-food factories a little
bit over a year but only going abroad every 9, couldn't you
redirect resources from the dog-food factory--I am saying that
as a pet owner--to--and, of course, it sounds tongue-in-cheek,
but, actually, it is a very serious question.
Ms. Woodcock. Well, Congress directs resources to drug
programs separately from foods or veterinary medicine. So they
are all separated out, and we have to expend those based on the
appropriation, OK?
Mr. Cassidy. So, would it be--not to put you in a box, but
if Congress redirected some of the funds currently used for dog
food, as an example, metaphorically if you will, to inspecting
companies abroad to make sure they have good clinical or good
manufacturing practices, would that be a reasonable thing?
Ms. Woodcock. Well, I think, then, that is a tradeoff. The
Congress has recently asked FDA to accomplish a great deal more
tasks under food safety, with their new food-safety bill. And
those inspectors are all busy trying to accomplish those
activities.
So we have tried--we are trying to redirect domestic
inspection resources to do overseas inspections. And that has
been the main effort that we are working on.
Mr. Cassidy. So, then, to follow up that, one thing you
could do within this silo, almost, of funding is--because I
have had domestic drug manufacturers complain, ``Listen, I am
checked every 6 months, and yet my competition is checked every
9 years.'' It isn't a competitive issue for them; it is a drug-
safety issue.
So could you elaborate a little bit more on that occurring?
Because it seems a very reasonable approach.
Ms. Woodcock. Yes, I think that we are moving--we have been
trying to move in that direction. That is a desirable thing to
do, to have a uniform level of inspection around the world that
is also risk-based, OK? So the riskiest plants should receive
the most frequent inspections, whether they are in the U.S. or
whether they are in China or elsewhere. It has just been
logistically very difficult to accomplish this.
Mr. Cassidy. Now, again, just to, again, pursue--it just
seems so logical. I mean, you are going to go buy a ticket to
go to Bangalore and inspect the plant there. Why would that be
logistically complicated instead of going to New Jersey?
Granted, New Jersey is a train ride and Bangalore is a trip.
But, nonetheless, it does seem as if maybe it is a prejudice,
that probably the people in New Jersey have better practices or
one that we trust more than maybe just a startup in Bangalore?
Ms. Woodcock. Yes, the inspections are done by our field
organization. It is not a part of the Center for Drugs. And
they have a union, and they have agreements about foreign
travel and how much you can get people to go and do things
overseas.
Mr. Cassidy. You mean there is a union agreement which is
keeping us from being able to inspect foreign manufacturers?
Ms. Woodcock. Partly. That is my understanding.
Mr. Cassidy. You mean the union agreement is keeping us
from inspecting these more frequently than every 9 years?
Ms. Woodcock. Well, the work conditions. It is just very
difficult--my understanding; I don't supervise that
organization--to shift resources to have a larger number of
foreign inspections done.
Mr. Cassidy. I have to admit, as a physician practicing, it
gives me great concern for the safety of my patients that that
is what is limiting our ability.
Ms. Woodcock. We would be happy to get back to you with a
more complete explanation.
Mr. Cassidy. Please. Because that is so incredibly
troubling. Which union is that?
Ms. Woodcock. Pardon me?
Mr. Cassidy. Which union is that?
Ms. Woodcock. NTEU.
Mr. Cassidy. I only have 50 seconds left. Let me gather my
thoughts after that.
If we had not had that union agreement, would the heparin
tragedy have been avoided?
Ms. Woodcock. I think it would still be difficult to move
people from their established inspection routine and get them
to travel repeatedly overseas.
Mr. Cassidy. Why don't we just----
Ms. Woodcock. But we are moving in that direction.
Mr. Cassidy. It may be difficult with the current
employees, but it sounds like, if that is where the problem is,
then we just need to find employees that will go, correct?
Ms. Woodcock. Well, there is also a problem with resources.
I don't want to understate that, OK? That it is going to take
more people to do all of these inspections overseas, and it
would--it is not as efficient as inspecting a certain number of
plants in a certain geographic area.
Mr. Cassidy. I accept that. But, on the other hand, if you
are going to find out where the problems are, and if we can
trace them--the bulk of them to these companies overseas,
manufacturing plants overseas, it just seems that is where you
should be looking.
Ms. Woodcock. Well, we definitely should go where the money
is. But I would say that we have certainly found manufacturing
problems domestically recently. Some of them have been high-
publicity problems. And we have to maintain good coverage of
those firms, as well.
Mr. Cassidy. I accept that. On the balance, what would be
the percent of the domestic versus foreign that have resulted
in deaths?
Ms. Woodcock. I don't think we have that kind of data.
Mr. Cassidy. OK.
I yield back. Thank you.
Mr. Pitts. The chair thanks the gentleman, recognizes the
gentleman from Pennsylvania, Dr.----
Mr. Dingell. I forgot to ask one question. Could I ask just
one question?
Mr. Pitts. Go ahead. Please.
Mr. Dingell. To the witness, if you please, H.R. 1438, the
Drug Safety Enhancement Act of 2011, would this afford you the
authorities you need to deal with the heparin problem?
Ms. Woodcock. Yes.
Mr. Dingell. It would.
Ms. Woodcock. Yes.
Mr. Dingell. Would you give us a little memo on why that
is, for inclusion in the record?
Ms. Woodcock. We would certainly be happy to.
[The information appears at the conclusion of the hearing.]
Mr. Dingell. Mr. Chairman, you have been enormously
courteous, and I thank you.
And I apologize to my colleague for having interfered with
his time.
Mr. Pitts. That is all right.
The chair thanks the gentleman and recognizes Dr. Murphy of
Pennsylvania for 5 minutes.
Mr. Murphy. Welcome, Doctor. It is good to have you here.
Ms. Woodcock. Thank you.
Mr. Murphy. There was an article in yesterday's Wall Street
Journal written by Roger Bate. I don't know if you had a chance
to see that. But in that, he pointed out a number of things
about the risks that come to western firms from these small,
hard-to-detect flaws, with the trace impurities from unhygienic
practices, which seems to summarize what we are dealing with
here.
The FDA--excuse me--the Federal Food, Drug, and Cosmetic
Act provides a drug is adulterated unless the methods used for
the manufacturing of a drug product conform to current good
manufacturing practices. Can you explain the role and
importance of the good manufacturing practices that FDA looks
at in their approved products?
Ms. Woodcock. Good manufacturing practices are a quality
system, and you are probably familiar with quality systems from
other areas of manufacturing. These really apply to mass
production. So it is one thing to make a drug in a laboratory
and have a lot of scientists looking over it. It is another
thing to make it in a factory and make millions of doses and
make them repeatedly sterile, potent and uncontaminated, and
that requires adherence to a quality management system.
The good manufacturing practices is a set of codified
regulations that FDA has that establishes kind of the minimum
standards for doing that.
Mr. Murphy. Now, you have talked about the supply chain. I
know Mr. Dingell brought that up, too. So what is preventing
the FDA from updating its GMPs, requiring drug companies to
verify their suppliers are complying with the law on providing
quality ingredients? Can you tell me a couple of items there
that are preventing you from doing that?
Ms. Woodcock. Well, it is possible with a very long
process, we could modify some of the good manufacturing
practices regulation, but others--I think of the things that
Mr. Dingell--other authorities that he was referring to would
require legislative authorization.
Mr. Murphy. In part of looking at that, you understand that
this entire Nation is looking upon Congress to find ways to
save money and also to look at health care costs, particularly
Medicare and Medicaid which is spinning out of control.
Is the FDA involved in or do you know of any other Federal
agencies looking at a number of aspects? For example, when we
look at some of these medications, and the estimates are, as an
example, as much as 5 percent of ingredients may be impure, may
have impure drug content, and we are looking at $1.74 billion
and rising of imports here.
Does anybody have any information on the impact on health
care, such as drug shortages, and what that means to health
care costs, tainted drugs that then effect extended stays in
hospitals, return visits to physicians office and emergency
rooms? Is that something that you or anybody else is studying
the impact on health care costs?
Ms. Woodcock. I wish we had that kind of data, but we do
not. It is very difficult to link drug quality health problems
with health outcomes, and Heparin was a dramatic example where
we saw that. But we don't have overall data like that, and I
don't know that anybody else does.
Mr. Murphy. Well, that is certainly troubling. While we are
looking at this, I know that studies have said just when
patients--when patients, we have looked at something like 75
percent of people don't take their medication properly and a
study recently said that is a $250 billion drain on the system.
But then when they do take medications according to doctors
orders, and we find out there are flaws with some of the
content of generic drugs, I don't want to malign generics
because we are also encouraging physicians to write
prescriptions for generics, and yet at the same time if we are
not inspecting these plants properly we end up with causing
more problems.
So, does FDA have any positions they recommend then in
terms of what other branches of government, Medicare and
Medicaid should be doing? Are they requiring doctors to write
prescriptions for generics while at the same time we can't
assure that those are pure?
Ms. Woodcock. Well, I would point out that Heparin was not
a generic drug. There were various versions of Heparin on the
market, but that was not a generic drug. This is not
necessarily a generic drug problem. This is pervasive drug
quality problem, and we don't have evidence that generics
particularly have additional quality problems over innovator
drugs.
So I think physicians should write for generic drugs with
confidence. But we do need to make sure we manage the supply
chains, that we and mainly the companies have the systems in
place to make sure that they maintain the quality of their
drugs that are sold in the United States.
Mr. Murphy. I appreciate you pointing that out about
generics. That is a very important fact. We don't want people
to be worried about that. It has to do with the content that
comes over.
You had mentioned that plants can be inspected about once
every 9 years. The GAO says it is more like every 13 years or
so. Plus isn't it true that when you are inspecting a plant in
the United States, you can just show up on a surprise visit if
you wish?
Ms. Woodcock. Correct.
Mr. Murphy. And the chances of surprising someone in China
is slim and none?
Ms. Woodcock. Right.
Mr. Murphy. So they have a chance to change that. And so on
this globalization of drug manufacturing and supplies, are
there caveats that the FDA is saying then to manufacturers in
the U.S. that even though you cannot inspect this, other
standards you are asking them to handle on their own with this
as well?
Ms. Woodcock. Yes. Basically we feel that the ultimate
responsibility lies with the manufacturer. We are not their
quality assurance group. We are auditors to make sure that they
are obeying the rules and that they are maintaining quality,
and we audit all around to make sure they do that.
There is also testing, which isn't everything, but having
good analytical tests for potency, sterility and making sure
the manufacturers conduct those tests, and for impurities, can
go a long way to help ensure the safety of the drug supply.
Mr. Murphy. Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman and recognizes
the gentleman from Michigan, Mr. Rogers, for 5 minutes.
Mr. Rogers. Thank you, Mr. Chairman. Thank you, Doctor, for
being here.
Is venture capital important in the development of the next
generation of pharmaceuticals, do you believe?
Ms. Woodcock. Yes, venture capital is very important to a
segment of the drug development industry, the smaller and
arguably more innovative side of the industry.
Mr. Rogers. They are targeting special treatments for
cancer or for sepsis or all of those things, right? That is
where the venture capital kind of flows to those innovative--so
you are arguing it an important part hopefully of the next
cure, we would hope?
Ms. Woodcock. Certainly for innovation. The biotech sector
depends on venture capital.
Mr. Rogers. I happened to be reviewing the testimony of
someone on the panel, Jonathan Leff. I am just going to read
some things from here just to get your perspective on this.
``During 2010 and 2011 to date, first time fundings of life
sciences ventures, a key leading indicator of the health of the
innovation ecosystem, has decreased by more than 50 percent due
to prior years.''
That is a problem, isn't it?
Ms. Woodcock. Yes.
Mr. Rogers. What would you attribute that problem to?
Ms. Woodcock. The problem is due to the failure rate and
the fact that--again, I am not an economist, but what I have
been told is that these firms are not successful enough to
merit the return on investment, and also there is a longer term
development cycle, that venture capital prefers a shorter
return, and so biotech has become less attractive.
Mr. Rogers. So it is all the investors that are pulling out
of the market. It wouldn't have anything to do--here is his
assessment. ``The FDA's shift in recent years to an
increasingly cautious risk-averse posture towards new drug
approvals has the unintended consequence of reducing investment
in life sciences innovation due to the significant additional
time,'' which you mentioned, ``cost and uncertainty it has
added to the drug development process.'' True?
Ms. Woodcock. Well, there is uncertainty in the drug
development process, and that is the main problem. To lay it
all at the feet of the FDA I don't think is correct. McKenzie
has recently done a study where they looked at failures in
Phase III development, which is clinical--the last stage of
clinical trials, and of products that failed there, fifty
percent failed because they had no benefit compared to placebo.
It is really hard to attribute that to the FDA.
Mr. Rogers. I certainly understand. But if the FDA doesn't
recognize it has a problem, we will never get any segment of
that fixed?
Ms. Woodcock. I recognize it. As I said in my oral
testimony, I think there is a crisis in the industry, and it is
pervasive and it is very concerning.
Mr. Rogers. What would be your recommendation for Congress
to try to help us through that particular process? Can you
clearly say that the added time and bureaucracy and investment
is gaining--it is worth the sacrifice of losing innovation and
attracting capital? Is it worth it?
Ms. Woodcock. We feel that the scientific challenges are
the problem, not the regulatory challenges. So I would disagree
with Mr. Leff on this. And our data shows that we have a very
high rate of first cycle approval. So it is hard to lay this at
FDA's feet.
I was hesitating in responding to you because I have a
whole list of prescriptions for this problem that I have been
promulgating for some time, and I would be happy to share those
with you outside of this venue, because they are fairly
extensive.
Mr. Rogers. I would be delighted. With your permission, I
would receive that at your earliest convenience. I think that
would be helpful.
The lines in the sand are hard things, and when you look at
the real decrease in investment, to say that the FDA isn't a
part of that problem is a little concerning. Let me give you
some other statistics here I find shocking.
The venture capital funds raised have decreased 25 percent
in 2010 just over 2009, and that is the third consecutive year
of decline. The share of venture capital invested in
biotechnology declined from 18 percent in 2009 to 12 percent in
2010. From 2008 to 2010, investment in U.S. Life sciences
companies declined by $2 billion.
That is significant. And I agree with you, it is a crisis
that we are going to have to deal with. As a cancer survivor
myself, I hope somebody is willing to put up the capital to go
through the process, and I want the FDA to understand that
there are risks involved and they should be part of the process
to help quickly determine the efficacy of that particular drug.
I am concerned that the risk aversion has crept into the
FDA to a point that it is costing us innovation in the United
States, and to me that is an unacceptable outcome.
Do you think there would be any value in having a category
of drug, and I heard the discussion earlier, you know, if I am
sitting with my oncologist and my oncologist tells me that this
is the particular drug that I have seen work, it has saved
someone's life, it has added years to their life, but the FDA
says I can't give it to you even if I explain all the risks
involved, is there a better way to do that?
Ms. Woodcock. Well, I don't think the FDA--that is the
FDA's posture, that people can't give drugs to patients. As I
said earlier----
Mr. Rogers. Well, if you take it off the market, it clearly
is.
Ms. Woodcock. Are you talking about Avastin?
Mr. Rogers. Yes. As an example. I just used that as an
example.
Ms. Woodcock. Avastin is on the market for other
indications and will remain on the market.
Mr. Rogers. I don't want to debate if you feel that is the
right decision. But shouldn't there be the opportunity--I tell
you that, because many a Member will run into a constituent who
will fly out of the country to get access to a drug because
they have made the conclusion that their life is at a point
where they are willing to take that risk.
Ms. Woodcock. Right.
Mr. Rogers. Is there some value in that in the United
States? Do we have to force people to go to Mexico to do this?
Ms. Woodcock. We don't stand between people getting
investigational drugs if they have no other options, and we
passed regulations about 18 months ago that provide a broad
range of ways to access totally investigational drugs,
especially for people who have exhausted other types of
therapies. So we agree that people have a right to take
substantial risk.
Mr. Rogers. At their own risk.
Ms. Woodcock. Yes.
Mr. Rogers. I would love to work with you on the expansion
of that. I think there have been some problems in the past and
currently that I think we can, working together, solve this
problem for literally thousands and thousands of people who are
at a pretty emotional place in their life and are willing to
take some risks.
With that, I yield back.
Mr. Pitts. The chair thanks the gentleman.
That concludes our first panel. Dr. Woodcock, thank you
very much for your testimony, for your answers to our
questions.
At this point, we will call the second panel. I think we
will take 5 minutes here just to check the mikes and then we
will reconvene.
[Recess.]
Mr. Pitts. I think we are ready to reconvene. Our second
panel has a number of witnesses, and I will introduce them and
ask them to testify in this order.
Paul Hastings is the President and Chief Executive Officer
of OncoMed Pharmaceuticals. Jonathan Leff is the Managing
Director of Warburg Pincus. Mark Boutin is the Executive Vice
President and Chief Operating Officer of the National Health
Council. Dr. Ellen Sigal is the Chair and Founder of Friends of
Cancer Research. Lastly, Allan Coukell is the Director of
Medical Programs of the Pew Health Group of the Pew Charitable
Trust.
Your written testimony will be made a part of the official
record. We ask that you summarize your opening statements in 5
minutes.
Mr. Hastings, you may begin.
STATEMENTS OF PAUL J. HASTINGS, PRESIDENT AND CHIEF EXECUTIVE
OFFICER, ONCOMED PHARMACEUTICALS, INC., ON BEHALF OF
BIOTECHNOLOGY INDUSTRY ORGANIZATION; JONATHAN S. LEFF, MANAGING
DIRECTOR, WARBURG PINCUS, LLC; MARC BOUTIN, EXECUTIVE VICE
PRESIDENT AND CHIEF OPERATING OFFICER, NATIONAL HEALTH COUNCIL;
ELLEN V. SIGAL, CHAIRPERSON AND FOUNDER, FRIENDS OF CANCER
RESEARCH; AND ALLAN COUKELL, DIRECTOR OF MEDICAL PROGRAMS, PEW
HEALTH GROUP, THE PEW CHARITABLE TRUSTS
STATEMENT OF PAUL J. HASTINGS
Mr. Hastings. Thank you. Chairman Pitts, Ranking Member
Pallone, members of the committee, my name is Paul Hastings. I
am the President and Chief Executive Officer of OncoMed
Pharmaceuticals. I am here testifying on behalf of the Biotech
Industry Organization's 1,100 members, where I serve as Vice
Chairman of the Emerging Company Section; that would be small
companies. I also chair the Bay Area Life Sciences Association,
and I am a member of the board of the California Health Care
Institute. All of these organizations represent innovative life
science companies.
I have over 25 years of experience in the biotechnology and
pharmaceutical industry. My current company, OncoMed
Pharmaceuticals, is developing molecules based on new
understandings of how tumors grow and spread. Specifically, we
are trying to block biological pathways critical for the
survival of tumor initiating cells. These cells are more
resistant to current therapies and promote the growth of
cancerous tumors. Thus, our products offer real advancement in
the treatment of cancer. We presently have three products in
Phase I and Phase I-A clinical trials after being in existence
for 6 years.
Companies like mine are generating many new therapies to
treat patients suffering from a myriad of unmet medical needs.
Of the 172 scientifically novel and orphan drugs approved from
1998 to 2007, 52 percent of them were discovered or developed
by biotechnology companies. We offer tremendous hope to
patients, with over 3,700 new biotherapeutics in development.
Biotechnology is an American success story. Our life
science sector accounts for over 7 million in direct and
related jobs. We create high-paying jobs in our companies and
support employment and provide vital revenue for our
universities and medical centers through the clinical trials we
conduct, thus employing people in those important State and
local universities and medical centers. We have a national
imperative to foster the development of innovative treatments
and therapies.
By 2030, almost one out of every five Americans will be 65
years or older, which means dramatically increased costs
associated with treating chronic disease. Innovative medicines
can help offset these costs by preventing or delaying the need
for other costly services such as emergency room visits and
hospitalizations. If you just simply reduce cancer deaths by 10
percent, that is equal to $4 trillion in economic value.
Our position as global leadership is a position we can no
longer presume to keep. We face international threats, such as
India and China and the European Union increasing funding and
incentives for biotech companies, while at the same time
investment in the U.S. has decreased markedly.
To encourage innovation and maintain U.S. leadership, we
must have an FDA that is empowered and able to effectively and
consistently review breakthrough treatments and therapies.
There are several troubling trends that threaten to severely
hamper our ability to innovate. For example, only half of the
products submitted to the FDA are approved on the first
submission. From the average of the previous PDUFA rounds of
2003 to 2007 to today, drug and biologic approval times have
increased 28 percent, and between 1999 and 2005 the average
length of clinical trials grew by 70 percent.
Regulatory uncertainty deters future venture investment in
biotechnology companies. This results in longer time for
development, not time for approval once drugs are submitted,
longer time for development when you start the development
process in Phase I; lower investment, fewer cures for patients,
and not as many life science jobs.
It is important to maintain a balanced and consistent
regulatory system. To that end, among BIO's top priorities
throughout the PDUFA technical discussions was to promote
innovation by fostering scientist-to-scientist dialogue between
FDA and sponsors concerning high priority rate limiting
scientific issues that arise during drug development. We are
pleased that FDA agreed to adopt a new policy that timely
interactive communication with sponsors during the drug
development is a core activity to help achieve the agency's
mission.
BIO believes that PDUFA should be reauthorized in a timely
and expeditious manner. However, additionally, last week during
the BIO international convention, we unveiled a package of
policy proposals entitled Unleashing the Promise of
Biotechnology: Advancing American Innovation to Cure Disease
and Save Lives. This is a BIO initiative, with the thought in
mind to come with you with not complaints but solutions. The
FDA policy recommendations described in my written testimony
are designed to ensure a clear and effective pathway for
turning ideas into realities that will benefit patients and
improve public health. The proposals are focused on creating a
modern, forward looking FDA and creating more effective
clinical research and development processes.
Some of the highlights of our proposals include updating
the FDA mission statement to reflect its role in advancing
medical innovation; providing FDA with the management,
budgetary and advisory authorities reflective of its role in
regulating a quarter of our country's GDP; providing FDA with
authorities, expertise, implementation mechanisms to ensure the
development of forward-thinking strategies and implementation
of modern regulatory science into their review practice;
expanding and improving the accelerated approval pathway into a
progressive approval mechanism for innovative products for
unmet medical needs that would also serve to ensure a risk-
benefit analysis that incorporates the safety and needs of
patients in the real world.
Lastly, proposals to further empower the FDA to utilize a
weight of the evidence approach and ensure that the FDA
communicates to sponsors in clear terms why risk was determined
to outweigh benefits and why other agency authorities, such as
REMS, are insufficient.
Thank you for the opportunity to share with you our
thoughts today.
[The prepared statement of Mr. Hastings follows:]
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Mr. Pitts. The chair thanks the gentleman.
Mr. Leff, you are recognized for 5 minutes.
STATEMENT OF JONATHAN S. LEFF
Mr. Leff. Thank you. Chairman Pitts, Ranking Member
Pallone, and members of the committee, my name is Jonathan
Leff. I am a managing director at Warburg Pincus, where I lead
the firm's investment efforts in biotechnology and
pharmaceuticals. I have more than 15 years of experience as a
life sciences venture investor and have served on the boards of
and helped build more than 15 small entrepreneurial companies
involved in developing novel therapies for a range of diseases,
companies not unlike the one that Mr. Hastings described. It is
my privilege to be here today.
Venture capital provides the essential fuel for medical
innovation by funding the development of novel therapies, an
endeavor that requires hundreds of millions of dollars over
many years or even decades. Venture capital has been a primary
source of this vital risk capital, has funded the development
of an entire generation of important new medicines, and has
financed and helped build almost every successful biotechnology
company in the U.S., creating well over 1 million high quality
jobs.
Today, however, the U.S. medical innovation ecosystem is in
jeopardy. Life sciences venture capital is experiencing an
alarming decline. The primary reason is that the cost, time and
risk involved in developing new drugs and biologics have
increased to unsustainable levels. As a result, vital risk
capital is being diverted to other industries and to other
countries. At a time when medical research is exploding with
potential, many scientific discoveries are not being developed
into new medicines due to lack of investment capital.
While many factors have contributed to the escalating cost,
time and risk of drug development, a changing regulatory
environment at the FDA is the most significant. In the early
1990s, Congress and the FDA worked together to shape a new drug
approval system designed to balance the goal of ensuring drug
safety with the desire to speed new therapies to seriously ill
patients. As a result of this balanced regulatory environment,
for example, HIV is no longer a death sentence, cancer patients
have access to many dozens of important new medicines, and the
U.S. has established itself as the world's leader in life
sciences innovation.
By the middle of the last decade, however, the political
backdrop and public consensus that made all of this possible
had changed. Following the safety issues with Vioxx, the public
discourse began to heavily emphasize drug safety. Far from
being congratulated for speeding new treatments to sick
patients or for advancing medical innovation, FDA has instead
come under heavy criticism for failing to do enough to ensure
patient safety.
Naturally, FDA officials have responded to this changing
environment, including congressional hearings and media
attention, and have shifted to a more cautious, risk averse
posture in the new drug approval process, emphasizing the
potential risks of new treatments more than their benefits to
patients. My written testimony provides examples of how this
shift has become evident.
Without question, protecting patients from harm is an
essential element of what the public expects from the FDA. But
so too is enabling the timely development and availability of
new therapies. Finding the right balance is the central
challenge of the new drug approval process. However, I want to
emphasize that the way this balance is struck by regulators and
by policymakers has tremendously important implications for
U.S. leadership in medical innovation.
FDA's shift in recent years to an increasingly cautious
posture toward drug approvals has had the unintended
consequence of reducing investments to life sciences innovation
due to the significant additional time, cost and uncertainty it
has added to the drug development process.
In the face of new hurdles to FDA approval, investors are
moving away from critical areas, including cancer, diabetes,
rare diseases and many others. I believe these problems are
fixable if we act now. Twenty years ago, U.S. policymakers and
the FDA rose to the challenge. We have the opportunity to do
the same today.
My recommendations are as follows: Strengthen FDA's mission
statement to reflect the importance of innovation; expand the
accelerated approval pathway into a progressive approval system
for new drugs that offer a significant advance; empower FDA to
weigh all evidence in the context of the disease being treated
in assessing benefit versus risk in new drug approvals; fully
detail the FDA's benefit-risk calculus when denying or delaying
approval in favor of collecting more data; and, finally, ensure
that FDA is provided with the resources that it needs to
accomplish its mission.
I look forward to working with the committee to
reinvigorate and strengthen U.S. leadership in medical
innovation. Thank you.
[The prepared statement of Mr. Leff follows:]
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Mr. Pitts. The chair thanks the gentleman, and recognizes
Mr. Boutin for 5 minutes for an opening statement.
STATEMENT OF MARC BOUTIN
Mr. Boutin. Thank you, Mr. Chairman, Ranking Member
Pallone, and distinguished members of the committee. My name is
Mark Boutin, and I am the Executive Vice President and Chief
Operating Officer at the National Health Council, which
represents approximately 133 million people with chronic
diseases and disabilities.
Our membership includes large patient advocacy
organizations like the American Cancer Society, the American
Heart Association, as well as smaller organizations like the
Alpha One Foundation and the Children's Foundation. We provide
a united voice for people with chronic diseases and
disabilities.
Our membership also includes organizations such as the
American Academy of Cardiology, nonprofits with interests in
health, including family care giving organizations, and
business and industry. Our governance is controlled by the
patient advocacy organizations, and we represent patients, not
consumers.
I make that point because often patients and consumers are
confused. While we have a lot in common, we are at opposite
ends of the same spectrum. We define patients as people with
chronic diseases and disabilities. They are people who will use
the health care system to manage their daily lives. They will
use the health care system until they die.
Consumers use the health care system on an ad hoc basis,
often for acute instances. An easy way to put your arms around
it is imagine that you have mild hay fever. It acts up in
spring. There are many options to address hay fever, over-the-
counter prescriptions. But I can tell you if a new product
comes to market and it has serious side effects, perhaps it
causes severe headaches, rashes, diarrhea, vomiting, you are
not going to be willing to take a risk on that new medicine.
But if you discover that you are having intestinal
problems, you go to your doctor after putting it off for some
time and you are diagnosed with pancreatic cancer and you are
told you have 11 months to live, your willingness to take a
product that might extend your life by 6 months will
dramatically increase. You might be quite happy to take that
same product that causes the rash, severe headaches, diarrhea,
vomiting. It doesn't change your tolerance for risk for the hay
fever medicine. Benefit-risk is an incredibly complex issue and
one of the things I would like to address today.
As has already been referred to earlier, the patient
advocacy community actually chained themselves to the fence at
FDA and NIH nearly 20 years ago asking for significant change,
and as a result of that, they went to the FDA and said, let's
be allowed to have early access to treatments. And the FDA
appropriately said, no, we are not going to allow you to have
access to those treatments. We don't know what the risks of
them are.
The patient community said, you know what? I am going to be
dead in 2 years, I am willing to accept that risk. And the FDA
responded and Congress responded with the first iteration of
PDUFA. As a result, we have seen dramatic improvements in terms
of early access to new treatments and the development of new
treatments, and we in the patient community have been very
pleased with the success of these products.
Unfortunately, the patient communities, somewhat naively,
thought we were done. We are relatively new to advocacy. We
really only started about 25 years ago. We actually stepped
back to a large extent from the FDA and the environment
shifted, and what we have seen is significant change. We are
back at the table now saying that we need to look at these
issues in different ways.
What I would like to do is address two interrelated issues,
the first being benefit-risk, the second being conflict of
interest.
As I said, benefit-risk is a complex issue. The FDA is
charged with looking at benefit-risk from a population-based
model. But as we know, benefit-risk is very much an individual
decision. It is very personalized to the individual person and
their family caregivers.
Take for example Mark Stecker, who is somebody that about 7
years ago was walking in Manhattan and realized he had a limp.
Shortly thereafter he was diagnosed with MS. He is now confined
to a wheelchair, and he runs a blog, and he is very articulate
about saying that he is very interested in assuming far greater
risk than he is currently allowed.
I would say to you, many people in the disability and
disease community feel the same way. While we had great success
for HIV and AIDS, to some extent cancer and to a lesser extent
heart disease, there are many conditions, from rare diseases to
larger conditions like Alzheimer's, MS and other neurologic
conditions without effective treatments, with many people
willing to accept risk that they are often not allowed to.
As I said, this is complex, and risk determinations can
vary from condition to condition. Somebody with Alzheimer's is
probably more likely to take a risk than somebody with heart
disease. It can change even within an individual. If you think
about somebody with breast cancer that is in their late
twenties and they have two children, their willingness to take
a risk that might extend their life long enough to see their
children grow up and get married, because it is very
pronounced. But you could have another woman in her eighties
with the same diagnosis who might choose a different product
that is going to allow her to have better quality and perhaps
less longevity.
At this point in time, it is important to recognize that
there is no Federal regulatory body anywhere in the world that
has identified benefit-risk or crafted a clear framework for
benefit-risk. As part of the PDUFA negotiation, the stakeholder
community was involved, and this was a huge priority for the
patient community, and we were able to work with the FDA and
industry to insert a benefit-risk analysis into the agreement.
This will allow for a great deal of consistency, transparency
and effective communication. It will allow for the benefits to
be more clearly defined and it will allow for contacts and
credibility.
I apologize for running over my time. Thank you.
[The prepared statement of Mr. Boutin follows:]
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Mr. Pitts. The chair thanks the gentleman, and recognizes
Dr. Sigal for 5 minutes.
STATEMENT OF ELLEN V. SIGAL
Ms. Sigal. Good afternoon, Chairman Pitts, Ranking Member
Pallone, and all members. It is a great honor for me to testify
today.
My name is Ellen Sigal. I am chair of Friends of Cancer
Research. Friends of Cancer Research is a Washington-based
think tank. We publish. We are involved with the American
Cancer Society, professional societies, patient groups,
advocates. Our sole mission is really the integration of
science for better treatment for patients.
This is very personal for me, as it is for all of you.
Friends started 15 years ago when I lost my 40-year-old sister,
leaving a 4-year-old child. Since then, my mother died of
pancreatic cancer, my father died of prostate cancer, my
husband has cancer, and there is no one that we all don't know
that isn't impacted. So this mission is quite personal for me
and for all of you.
My testimony today is intended to give a perspective on
what can be done. First of all, the urgency of getting new
life-saving treatments to patients in the safest and quickest
possible way; the importance of maintaining our global
competitiveness; and finally to realize the full potential of
biomedical research and the role that all sectors play. None of
these things can be accomplished without a fully resourced and
scientifically vigorous FDA.
For many years we have been hearing about the slowness of
FDA and particularly in oncology, so the agency has been
portrayed by many critics as slow and inefficient compared to
other countries. The criticism is particularly concerning in
the field of cancer, where severely ill patients have few
effective options. A new Friends of Cancer Research study
published in Health Affairs revealed that FDA is approving
anti-cancer drugs much faster than its overseas counterpart,
the European Medicines Agency. What is important is the
standard is high. It is the gold standard on both.
Of its findings, our study revealed that FDA not only
approved more cancer drugs than Europe, but they did so at a
significantly faster rate. FDA approved average drugs in 182
days, while EMA averaged 350 days. Access to new medications 5
\1/2\ months sooner has undoubtedly improved the lives of 1.5
million Americans diagnosed with cancer every year.
While we praise this and we think this is very important,
this cannot be accomplished nor sustained without
appropriations needed to continue this effort. I have very
specific recommendations that are in my testimony, and I would
like to talk about a few of them.
First and foremost, FDA has to have the scientific tools,
the regulatory science programs better to enable them to make
these very complicated decisions. Whether it is adaptive trial
design, validation of biomarkers, it is urgent that they have
the resources to really have this. We believe very strongly and
support the continuance of accelerated approval process. Ten of
the 32 new oncology products in our study utilized this
mechanism.
We also are recommending expedited development programs to
address challenges to the current multi-phase sequential
development process. This could be particularly important to
ensure scientific rigor for targeted therapies. We want to
ensure that FDA has the highest quality access to the best
expertise possible in making informed decisions, and we believe
patients have a very important role at that table and that role
has to be accelerated.
A weakened, underfunded FDA will cause companies to take
research overseas, creating a loss of jobs and billions of
dollars in investment, it will threaten our standing as global
leader, and, most importantly, it will delay getting
potentially lifesaving treatment to patients battling disease
and illness.
The role of the Food and Drug Administration as a component
of medical innovation is critical, but successful innovation
does not solely include the FDA. Our data indicates that the
end stage review is on average half the duration of the FDA
U.S. and EMA. While this indeed translates to American cancer
patients gaining access to new drugs, it does not address the
fundamental challenges to advancing health innovation that are
currently facing our society.
In order to resolve the larger problem, all of the sectors
represented at this hearing today and several of those that are
not must at all times set aside the individual interests and
work towards the common goal of improving the health of the
country, both economic and personal, through innovation. As
patients, we all have been and we all should demand it. The
people will all work on behalf of the deserved. We are asking
that everyone work together towards these goals.
Thank you.
[The prepared statement of Ms. Sigal follows:]
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Mr. Pitts. The chair thanks the gentlelady, and now
recognizes Mr. Coukell for 5 minutes for an opening statement.
STATEMENT OF ALLAN COUKELL
Mr. Coukell. Mr. Chairman, Ranking Member Pallone, members
of the subcommittee, thank you for the opportunity to present
testimony.
My name is Allan Coukell. I am a pharmacist by training and
Director of Medical Programs in the Pew Health Group, whose
mission is to improve the health of all Americans through
research and critical analysis.
Pew's work addresses a range of FDA-related issues, but my
focus today is the safety and security of the pharmaceutical
supply chain. Next week we will release a report entitled
``After Heparin: Protecting Consumers from the Risks of
Substandard and Counterfeit Drugs.'' Our research for that
report included dozens of interviews with industry and
regulatory experts and was informed by a recent public meeting
that brought together pharmaceutical manufacturers,
distributors, pharmacies, the FDA, State regulators and other
analysts and stakeholders.
The meeting heard that while the vast majority of drugs in
our pharmacies and medicine cabinets are not counterfeit or
adulterated, drug manufacturing has changed dramatically in
recent years. It has become globalized and increasingly
outsourced, and this creates new risks, risks dramatically
illustrated not long ago with the intentional adulteration of
the blood thinning drug Heparin.
In 2007, health officials began to receive the first of
what would ultimately be more than 500 reports of patients who
experienced unusual adverse events, some of them fatal, after
receiving this drug. The problem was traced to a contaminant, a
substance introduced in place of the pure drug, and this
occurred not in the premises of the U.S. manufacturer, but in
China where the drug's raw ingredient was sourced from a
complex network of suppliers.
The evidence suggests that the adulterant was introduced
deliberately on a large scale and for economic gain. Whoever
made it must have known that the substance wouldn't be detected
by the standard tests. By one estimate, the crime netted more
than $1 million in profit.
Later investigations pointed to other failures that
underlined the need for systemic improvement. In particular,
the manufacture did not audit its supplier over several years.
The FDA approved the Chinese plant without an inspection,
partly because agency databases confused two different
facilities. Inspectors later found manufacturing quality
issues, including poor control of incoming materials. And
neither the FDA nor the manufacturer was ever able to gain
complete access to that upstream supply chain.
The incident represents a clear breach of the U.S. drug
supply, and to this date no one in any country has been held
accountable nor has Congress acted to update the statutes that
govern drug manufacturing.
What we heard at our meeting from a variety of experts was
that without changes to the system, another such event is
inevitable, not if, but when.
The number of drugs and ingredients made at non-U.S. sites
doubled over the past decade. About 40 percent of our finished
drugs and 80 percent of their active ingredients now come from
overseas, often from developing countries. Current law requires
FDA to inspect every 2 years here in the U.S., but is silent on
the frequency of foreign inspections and the FDA lacks the
resources to do regular foreign inspections.
When manufacturing shifts to low cost environments with
reduced oversight, consumers are at risk, from the deliberate
acts and also from failures to meet quality standards.
Our report reviews some other recent examples, including
the problem of so-called show shadow factories, where drugs are
coming from a hidden source instead of the official factory. We
discussed cases in which manufacturers falsified or concealed
records, and we note the risk of U.S. patients receiving
counterfeit or stolen drugs that penetrate our domestic
distribution system.
Let me give you one more example, a substance called DEG
that has been linked to numerous mass poisonings around the
world. Five years ago, this sweet-tasting liquid was mistakenly
used to make cough syrup, killing dozens. The syrup had been
labeled as something else. It had passed through a series of
brokers in China and in Europe, each relabling it presumably
without testing. Many of those who died were children. This
occurred outside the U.S., but 70 years ago this same substance
killed more than 100 Americans and led Congress to pass the
Food, Drug and Cosmetic Act.
So recently there have been important steps by the FDA and
by individual companies to tighten the supply chain.
Nevertheless, we must update the act for the 21st century. Pew
advocates a number of key reforms, including measures to ensure
that manufacturers themselves better assess risk and ensure
safety and steps to ensure they are held accountable; increased
inspections overseas and new enforcement tools for the FDA,
including the ability to order drug recalls; and improved
oversight of drug distribution, including national standards
for wholesalers and assistance to track and verify the
authenticity of drugs.
I will conclude just briefly with a recent poll, a poll we
commissioned last year among likely voters, that showed
Americans are concerned about this issue, and across the
political spectrum they overwhelmingly, upwards of 80 and 90
percent, favor many of the provisions I have outlined.
This committee has long taken a bipartisan interest in the
safety of the drug supply. The American public supports those
efforts, and we should not await another tragedy.
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 and thanks the
panel for the testimony. We will now begin questioning, and I
will recognize myself for 5 minutes for that purpose.
First of all, Mr. Hastings, I have had the opportunity to
talk to many small and mid-sized American biotech companies,
and they are struggling right now partly because of increasing
review times at FDA and the lack of predictability at FDA.
Have you experienced these problems or do you know a
company who has, and what issues are biotech companies facing
today related to FDA?
Mr. Hastings. We work very--is this on? No. There we go.
Sorry about that.
Whenever there are regulatory uncertainties, there are
delays. A big piece of data that is missing today is not the
speed of approval once an NDA is filed, but the speed to which
we can enter a drug into the clinic, file an IND, get it
through Phase I, get it into Phase II. Many of us who are lucky
enough to get it into Phase III would be happy with approval
times that are faster and more expedient than other countries.
That would be great. But there is a whole process that occurs
before the drug even is filed for an NDA, and I think it is
important for us to work with the FDA, as we have.
As I mentioned, the biotech industry's focus here is on
streamlining the whole process, not just the approval process
once the NDA is filed.
Mr. Pitts. Mr. Leff, would you like to comment on that?
Mr. Leff. Sure. Thank you, Mr. Chairman, I would be happy
to.
I think the central issue, the central impact that FDA is
having on investors in medical innovation is, as I said in my
statement, the increase in the time, the cost, and the risk of
development. So it is not review times per se, although
obviously we all want fast and efficient review times. It is
the requirements that FDA is increasingly imposing for
developers of drugs to move their drugs through clinical trials
and get them in front of FDA.
So when Dr. Woodcock made the observation that FDA is
having a problem approving more drugs because they are not
seeing more drugs, they are seeing fewer drugs submitted than
in the past, I think that is absolutely right. The reason FDA
is seeing fewer drugs submitted than in the past is because
people like me and hundreds of other people like me making
investment decisions on drugs that are in development or
discoveries that are being turned into drugs are increasingly
deciding that the cost, time and risk have become too high, and
that is a function of the risk averse decisionmaking that has
increased at FDA over the past decade.
Mr. Pitts. Mr. Hastings, how many jobs does the bioscience
sector account for, both direct and indirect?
Mr. Hastings. I think I mentioned 7 million jobs indirectly
and directly.
Mr. Pitts. Seven million total. What else can we do in the
FDA space to help create jobs? How would fixing the issues at
FDA help these companies create jobs?
Mr. Hastings. Mr. Chairman, I believe that the way to
create jobs is to foster innovation, not at the expense of
safety or efficacy. One of the proposals which is to make
innovation a part of the mission statement, which, by the way,
the European Union has in their mission statement, and then
hold people accountable for innovation.
You know, innovation could be when somebody is going
through the process of--I will give a very practical example. I
am running a startup company and I file an IND and I get my
drug into Phase I. In the middle of my Phase I trial, there is
an issue. Any kind of issue could come up in Phase I. The way
the system is set up is I can pick up my phone or my regulatory
person can pick up the phone and call the FDA. And the FDA are
bound by these guidelines, by the way. The phone call takes
place. It needs to be followed up by a letter, which comes
usually 30 days later. Then you have 30 days to respond to that
letter. Then they have 30 days to respond to that letter.
Now, in that whole process, which in my mind could be
handled in a phone call, I spent as a startup biotech CEO $4
million a month on the burn of the company while the letter
writing campaign was going back and forth.
This is not the FDA's fault. These guidelines are
guidelines that have been put in place, and I think they should
be looked at as, you know, how can we streamline communication.
Again, not once the NDA is filed, but how do we help companies
innovate by making the process smoother in areas which are not
going to create more risk? I think this would be a major.
So if that occurs, I don't have to go to my venture
capitalist and say I am writing a letter now and $4 million of
burn is looking at us right down the face. He hears that $4
million and says if I could invest that $4 million in Facebook,
I could get a return in a month. You are going to burn that. I
am going to need to give you--now, for me I need $1 billion to
develop a drug, right? So that $4 million, which is huge in the
early stages of a drug company's evolution, is just a tiny
portion of what it is going to take.
So each dollar is very, very important. So for innovation
and streamlining, making processes and helping the FDA, by the
way, make processes that are less bureaucratic, providing them
with the staff they need to actually answer the phone calls,
which is something we have been working on together, would be
very helpful.
Mr. Pitts. The chair thanks the gentleman.
My time has expired, and the chair recognizes the ranking
member, Mr. Pallone, for 5 minutes.
Mr. Pallone. Thank you, Mr. Chairman. I am going to start
with Mr. Hastings also.
BIO recently released policy recommendations contained in
the document ``Unleashing the Promise of Biotechnology:
Advancing American Innovation to Cure Disease and Save Lives.''
I appreciate the need for the kinds of proposals listed under
the heading of Advancing Regulatory Science and Innovation. But
I wanted to focus on one as an example, the need to enhance
FDA's access to external scientific and medical expertise.
The FDA has repeatedly cited the need to make improvements
in the area of regulatory science, and as the BIO policy
document mentions, FDA has struggled to keep up with the rapid
pace of scientific and medical knowledge techniques and
technology. And you know FDA launched a major regulatory
science initiative designed to build on the achievements of
programs like the critical path initiative. The other proposals
in that section also seem to make a lot of sense to me.
But my problem is that each of these concepts that you
mentioned or that, I should say, the document mentions would
demand a significant infusion of resources if there is any hope
for the FDA to implement them. That is my opinion.
I just wanted to ask you if you agree with that, that we
need more resources to do these kind of things?
Mr. Hastings. I think respectfully----
Mr. Pallone. I think you lost the mike. The reason I am
asking you this is--go ahead. I am sorry.
Mr. Hastings. Somebody up there where you folks are a few
minutes ago had an overreaction to an issue with a union,
right? So I think if we can all work together to look at ways
to prioritize.
First of all, there is no question that our industry
supports the FDA being adequately staffed. We actually had an
initiative a few years ago to help them get staffed. So we
would be all for helping them get staffed. But we also
understand there are budget crises under way right now.
So I would submit, running a business, and having run many
businesses, private and public businesses, that there are
always ways to reallocate resources to do things.
External advisory boards are external people. You pay them
when they walk through the door. When they leave, you stop
paying them. That is a much more efficient use of capital than
head count. So if there are opportunities to use external
advisers to help keep regulatory science moving. In the case of
FDA, by the way, they have very few regulatory science
employees. They would like to have more. Again, we are working
on this initiative. So there are many ways to do this.
Mr. Pallone. The only problem that I have though, now we
have this FDA funding bill that the House Republicans just
passed, and that guts the FDA's funding by $570 million. It is
a cut of 21 percent from the administration's request. So
obviously I think there should be more resources. But if this
goes through, we will have 21 percent less than what the
administration is requesting.
How are we going to implement these types of things that
are in this BIO document if we make cuts? It is one thing to
add. But what about now if they cut 21 percent?
Mr. Hastings. Again, I would argue that one could look at
reallocation, and one could also look at the risk-benefit of
where one invests one's money.
Mr. Pallone. All right. I know that you are part of this--
or I should say your organization is part of this alliance for
a stronger FDA whose mission is to get increased resources for
FDA. So, again, I think you can always find more efficiencies,
but I think it is going to be very difficult to do any of these
new innovations if we see a 21 percent cut, and I think that is
why the Alliance for a Stronger FDA is trying to increase
resources.
Mr. Hastings. May I respond to that? No offense, but, you
know, in our organization, when I hear an answer like that, I
say to the organization, figure it out.
Mr. Pallone. It is one thing to be able to do what they are
doing now. But to go into totally new areas with cuts in
funding, I don't see how. But whatever--let me go to Dr. Sigal,
because I only have 40 seconds left here.
I found the results of your study very interesting, the one
comparing cancer approvals in the U.S. versus Europe, and I was
surprised, given the claims about FDA's role in the innovation
downturn, to see a document like that.
What prompted you to do that study and what did you expect
to find? Were you surprised by what you found?
Ms. Sigal. I was very surprised. What prompted me was that
we were hearing consistently from academic institutions, from
developers, from biotech, from patients that the FDA is slower
and things were getting approved faster in Europe, and we know
the standards were very high in Europe. So we were very
concerned and we did the initial research in house, we did it
solely in house. And we were very shocked. As a matter of fact,
we were so surprised that we had to validate it.
I did not expect it. And I want you to know if in fact what
we were told as urban legend were true and in fact we were
slower, we would have published. So this was not a matter of
getting data that we suspected was going to--we thought we were
going to get data that showed that Europe was more innovative
and faster, so we were very surprised at it and clearly it was
very important. But there is still a lot more that needs to be
done, because the science is complex and the agency is
significantly underfunded for the innovation that they need to
go forward.
Mr. Pallone. Thank you, Doctor.
Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman and recognizes
Dr. Burgess for 5 minutes for questions.
Mr. Burgess. I thank the chairman.
Just as a follow-up to Ranking Member Pallone's
observations, last year twice Dr. Sharfstein came before this
subcommittee, once with the DeCoster egg farm hearing and once
with a hearing about are there problems with the pipeline and
restrictions in the pipeline of getting drugs and products from
NIH to the consuming public and is the FDA part of that
obstruction. And both times Dr. Sharfstein testified in
response to a direct question by me, do you need more money,
and he assured me that the FDA had all the money that it
needed.
I knew that that must be right, because for those of you
who sit up nights reading the Federal Register, you may know
that we passed, Congress passed, I voted against it, but there
was a big health care law about a year and a half ago, and it
included no new money for the Food and Drug Administration in
that big new health care law.
Mr. Hastings and Mr. Leff, let me just ask you a question.
If an innovator comes to the FDA and they have got something, a
drug or device, characterize it as a black box, if you will, it
does something good for patients, if that innovator comes to
the FDA and asks for the pathway, what are my steps to go
through getting this drug or device approved? Are they going to
get clear direction and clear instruction from the FDA as to
what procedures to follow?
Mr. Hastings. We will get guidance, some guidance or
recommendations on what to do in a situation like that.
Mr. Burgess. If it is truly innovative, maybe something
that hasn't happened before, are they likely to get an answer,
``we are not sure and you need to start and then we will
provide you guidance as go along.''
Mr. Hastings. Well, it is very difficult in the case of a
brand new innovation when there are no benchmarks to sometimes
give guidance, because everybody is looking at the same thing
and wondering what to do. I think that would therefore argue
for the ability to communicate scientist-to-scientist and work
together. This is also where some of these external advisers
could come in and be very helpful experts in the field in terms
of creating not a validated instrument that may take years to
do this, but to create a risk-reward model to move that drug
forward since it is the first in its class. That would be the
ideal thing to do.
Mr. Burgess. Forgive me for interrupting, but time is very
limited. On this risk-reward model that you just articulated,
does that exist within the FDA? If an innovator comes to the
FDA and says I have got this, help me know the stems I must
take to develop this and have it approved by the FDA, is that
model in fact in place? Does it work?
Mr. Hastings. I mean, I can't speak for the FDA. I think
that model would probably work differently division by
division, depending on who the reviewer is, depending on who
runs the division.
Mr. Burgess. That is the regulatory uncertainty. Again, I
have people come to my office all the time with these
complaints that I don't get clear direction about what I am
going to need to provide and then it all changes in the course
of development, and that obviously extends the timeline
significantly.
Mr. Hastings. Well, you made a very good point about
changing it. And, again, I don't think this is anybody's
particular fault, but I know of CEOs who are running diabetes
companies where endpoints were changed in the middle of their
Phase III clinical trials as they were ongoing and had to redo
their Phase III clinical trial. Some of those companies shut
down.
Mr. Burgess. Sure. I wish we had more time to explore that,
but Mr. Coukell, I need to ask you, you talked about the
Heparin issue which we have studied in this committee, and I
just wanted to reassure you that we do have an active and open
investigation now.
Last Congress it was a little bit difficult to get
information from the FDA. Margaret Hamburg went to China and
presumably talked to some of these individuals who were
involved with the companies that produced the product that was
contaminated with the adulterant. And you are correct, the
adulterant was a very clever molecule that could hide behind
the normal active pharmaceutical ingredient in Heparin on the
normal testing with the mass spec. It almost had to be a
criminal mind that decided to do this. I don't think it was
accidental.
But we have had significant difficulty in getting the data
from the FDA as to where they are in this investigation, why
the labs were confused and issues that you mentioned. I wanted
to reassure you that the legislative remedy really is hard to
come up with if you don't have the results of your
investigation. Unfortunately, this investigation has taken a
lot longer than I would have ever thought possible, but at the
same time you run the risk of legislating with incomplete
information.
Mr. Coukell. Yes, sir. I commend your ongoing interest in
drug safety. I think it is very important. I think it would be
highly desirable to find the culprit in that case.
Nevertheless, I think Heparin illustrates, as I outlined in
my testimony, a lot of weaknesses that we know about now, and
it was a wake-up call for a lot of folks in the industry and
for the FDA. They have all said that. The next time it happens,
it probably won't be Heparin. It will be somewhere else. I
think we do know based on that case and others some of the
things that we need to do now.
Mr. Pitts. The chair thanks the gentleman and recognizes
the ranking member emeritus, Mr. Dingell, for 5 minutes for
questioning.
Mr. Dingell. Mr. Chairman, I thank you for your courtesy
and for the recognition. I will direct my questioning to Mr.
Coukell. I would observe that I have great concern for the
tremendous amount of pharmaceutical medicines and ingredients
that are coming in from abroad. So I would like to address this
with yes or no answers here.
An increasing number of drug manufacturers are turning to
outsourcing for pharmaceutical ingredients and manufacturers.
As you mentioned in your testimony, up to 80 percent of
pharmaceutical ingredients and up to half of the finished
pharmaceuticals are purchased from clients in India and China.
FDA is currently required to inspect U.S. drug facilities every
2 years, but there is no required frequency for inspection of
foreign facilities. Food and Drug says that they investigate
foreign facilities about once every 9 years.
Is that sufficient or not?
Mr. Coukell. It is not sufficient.
Mr. Dingell. Now, until 2009 FDA did not have a dedicated
staff for foreign inspections. Rather, employees qualified to
do inspections would travel abroad. FDA now has a cadre of 15
inspectors dedicated to foreign facility inspections.
Has this current cadre been sufficient to increase
inspection of foreign facilities to a sufficient level that we
can be comfortable that our supply of these pharmaceuticals is
safe?
Mr. Coukell. They improved the local FDA's local knowledge
and have done some additional inspections, but they are not
enough.
Mr. Dingell. Thank you. Now, beyond inspections, quality
manufacturing is also critical to a safe drug supply. In 2009,
FDA issued 34 warning letters regarding adherence to good
manufacturing practices, nearly double what was issued in 2008,
ensuring manufacturing quality gets more difficult as supply
chains move overseas and are more outsourced.
Are today's GMPs sufficient to ensure manufacturing
quality, yes or no?
Mr. Coukell. No, sir.
Mr. Dingell. As you have spoken to a number of stakeholders
and experts about FDA's oversight of foreign drug
manufacturing, what if any consensus exists for increasing
foreign oversight and resources to support?
Mr. Coukell. I can't answer that with one word, sir, but
what I can tell you is we have been interested as we talked to
stakeholders across the system, I have expected to have people
say inspections aren't the answer. We didn't hear that.
Inspections are part of an overall quality system. Some major
sectors of the industry, including the generic manufacturers
and the active ingredient makers, are on record as supporting
fees to help fund additional inspections overseas, both for
safety and to provide a level playing field for American
manufacturers.
Mr. Dingell. Thank you. One approach to ensuring
manufacturing quality would be to require manufacturers to
implement quality systems that detail management
responsibilities, risk management practices, supply chain
management, record keeping amongst other components.
Do you believe requiring manufacturers to have in place a
quality system would improve the safety of our drug supply
chain? Yes or no.
Mr. Coukell. Yes, sir. Those are recommendations now, but
we need everyone to do it.
Mr. Dingell. Should such a requirement relate not only to
finished manufactured pharmaceuticals, but also to components
and raw materials?
Mr. Coukell. Yes.
Mr. Dingell. Transparency throughout the supply chain is of
particular concern and a valid one given the Heparin incident,
but Heparin is only one of the examples of our problems.
Currently, FDA recommends but does not require that companies
conduct an on-site audit of a supplier.
Do you believe requiring companies to perform on-site
audits of suppliers before a purchase agreement is made would
improve supply chain safety? Yes or no.
Mr. Coukell. Our meeting heard that every supplier and sub-
supplier should be audited by somebody.
Mr. Dingell. Now, how frequent should these audits be to
assure their effectiveness?
Mr. Coukell. I think that depends on the material and the
level of risk.
Mr. Dingell. Could you give us some kind of a horseback
guess?
Mr. Coukell. I think it is going to depend, sir. If is a
long-established relationship and a simple synthesis, it would
be quite different from a new relationship with somebody who is
making a very complex molecule.
Mr. Dingell. Now, FDA recommends but does not require
quality agreements with suppliers. Do you believe requiring
quality agreements with suppliers would improve supply chain
safety? Yes or no.
Mr. Coukell. Yes, sir, and I believe leading companies are
already doing that.
Mr. Dingell. Mr. Chairman, I apologize. I have a couple
more. May I pursue my business to its end?
Mr. Pitts. You may proceed.
Mr. Dingell. Thank you. You are most courteous.
More must also than done to ensure transparency and access
to information for products being imported into the United
States.
Do you believe requiring importers and customs brokers to
register with the FDA would help to improve FDA's general
oversight of global drug production as well as drug safety
assessments at the border? Yes or no.
Mr. Coukell. Yes.
Mr. Dingell. It is clear then that increasing foreign
inspections and improving transparency and quality throughout
the supply chain are necessary components to increasing the
safety of our drug supply, and that would also include raw
materials and components as well as finished products. I would
also add, Mr. Chairman, that H.R. 1483 would address the
vulnerabilities that we have just outlined.
I thank you for your courtesy, and I thank our panel for
their assistance to the committee.
Mr. Pitts. The chair thanks the gentleman.
Without objection, the chair recognizes Mr. Bilbray from
California for 5 minutes for questions.
Mr. Bilbray. Thank you very much, Mr. Chairman. Thank you
for a chance to ask questions. I want to thank the ranking
member for being here, because I think that this is an issue
that we can have a bipartisan effort on. From personal
experience in working with the ranking member for probably a
decade, about a decade-and-a-half I think it has been, we have
had a bipartisan effort going on water quality issues. I think
this is one of those things that the ranking member can join
with the majority in actually addressing an issue that knows no
party affiliation.
Mr. Hastings, one of the crises that I am seeing in my
district with my bio-med research people is the fact that we
have lost 50 percent of the venture capital for what we used to
say in environmental issues would be the economic soup, the
startup companies, the little guy who is the krill of the bio-
system; in other words, where the ideas and the innovation
comes from that the big guys eat up, adopt and then develop
into it. We have lost 50 percent of that capital. It looks like
we could lose 50 percent of that overseas if we don't do
something.
One of the items that has been brought up to me is how do
we infuse and get venture capital back into the field, and one
of the items is the issue that we have over $2 trillion of
American capital overseas. Do you think that it would help in
trying to backfill that loss of 50 percent if the Federal
Government looks at changing the repatriation laws here to hold
harmless if they bring the money back for research and
development?
Mr. Hastings. Resoundingly absolutely.
Mr. Bilbray. Anybody else got a comment on that or concern
with that?
Mr. Leff. Yes, I agree it would absolutely help and it
would bring capital back into this country and release
additional investment and innovation. The observation I would
make, though, is that would be a one-time benefit to the
system. It wouldn't change the trajectory necessarily that we
are on and the fundamental underlying reasons that capital is
leaving investment and innovative life sciences companies.
Mr. Bilbray. I appreciate that. I was a public safety guy.
I am just a lifeguard that triaged people and got more votes
than the next guy. But we do have a patient that is
hemorrhaging, needs an infusion, an infusion to survive, and I
think this is one thing we may be able to ask both sides to
work on.
Let me ask, Doctor, speaking of looking at systems, back in
the nineties there was a bipartisan effort made that did things
on the AIDS epidemic that we had not done for anybody else,
extraordinary efforts. We broke the rules, changed the rules,
forced the bureaucracy to respond, and I think history has
proven that was a great success.
Sadly, it looks like we did this great success and walked
away from it. In those days we had Act Up, we had Men's Gay
Health Crisis Project, we had the Treatment Action Group
putting pressure on us to change the system, and we actually
allowed patients to be at the table. We allowed, and the doctor
can go over it, whole different protocols for what was allowed
to be counted as a positive action, and we basically broke the
mold and tried innovative issues.
Is there any reason in the world why we should not go back
and look at what was successful in addressing the AIDS crisis
and apply it to the crisis we are finding right now? A good
example is why would we allow an AIDS patient on a review body
for AIDS, but would not allow a cancer patient to have the same
right to be able to participate?
Doctor, I solicit your comment about how we can address
that.
Ms. Sigal. Thank you for the opportunity. I think the HIV
model is a wonderful model. It started activism, and, most
importantly, it has had an impact. It helped patients, it
helped science, and it made a huge difference.
It is a complex scenario though, because there we had a
fire marker. We had the CD 4. We had viral load. We knew what
we were looking for. But it did start advocacy, and I would
agree with you fully that patients have not only a role but a
right to sit at the table. Ultimately these decisions impact
them. They need knowledge, they need the ability to have the
information, and they have the ability and should have the
ability to be at the table when these decisions are made.
We, along with the National Health Council and others, are
working on that and believe that we have opportunities in the
reauthorization of the User Fee Act to have a more active
patient voice. It is essential that they be at the table,
because we do impact them.
Mr. Bilbray. The one thing I saw work in the AIDS community
was the degree of urgency was brought on to the bureaucracy,
the sensitivity that they know had an impact, an adverse impact
just by denying, that at least there was opportunity there.
What I am concerned about is the study that you did showed
that if you take the long-range, there was an item. But my
question is, recently though it looks like the European
Community's review and our review are starting to close that
gap since 2008. Do you have any way of explaining why though
the trajectory looked real good on cancer drugs over the long
term, recently it looks like we are converging or going to be
crossing? In that study, did you identify why since 2008 it
looks like the numbers are changing?
Ms. Sigal. Actually we did go past, we did look at that.
And in fact, since we have concluded our study, we have had
three more approvals which they still do not have in EMA. So in
fact the trend of earlier approval, faster approval, is
continuing.
The problem is the complexity of the science. The science
is very, very, very hard. But this is not an issue of speed,
this is an issue of quality, and I can tell you as an advocate
myself we in the cancer community and other advocates of deadly
diseases, childhood cancers, other cancers, are just as anxious
as anyone to have these new drugs approved, because it will----
Mr. Bilbray. Let me tell you as a father, I am in that
category.
Mr. Chairman, I appreciate the time. I think one of the
things both sides need to talk about is the conflict of
interest regulations that historically have been with FDA and
these review bodies, because now you are getting, especially in
cancer, you are getting items coming forward that the
discipline is so limited of anybody who can make an informed
decision that you have to bring somebody in from outside and
somebody who has a connection to basically development and
certain research to be able to get the expertise to make an
informed decision. I don't think any of these conflict of
interest requirements that we put in in the past was meant to
exclude people that were essential to making informed
decisions. I hope both sides can look at modifying those rules.
Mr. Pitts. The chair thanks the gentleman. That concludes
the first round of questioning. We will go to one follow-up on
each side, if we have any. Dr. Burgess.
Mr. Burgess. Thank you, Mr. Chairman. I appreciate the
recognition.
Mr. Boutin, if I could along that line of the advisory
panels and the conflict of interest exclusions, are the
restrictions on who can serve on advisory panels hindering
activities to bring new drugs to market?
Mr. Boutin. Yes. I think there is a real challenge. Right
now, the FDA is charged with looking at multiple regulatory and
legal requirements for conflict of interest, and the standards
within each are not necessarily inconsistent, they are
different. As a result, the FDA has had to look at how do we
apply them all together.
In the previous reauthorization of the prescription drug
user fee, there was an additional requirement that compelled
FDA to limit its use of waivers, and as a result they took a
look at how they would apply the conflict of interest rules. In
their new look, they acknowledge that they are being more
strident in addressing the conflicts, and as a result what you
are seeing is it harder to fill the advisory committees, and
currently about 25 percent of the advisory committees are
vacant, and as a result there is delays in having the advisory
committees meet and the FDA has acknowledged that it has led to
delays in the approval of new treatments.
So from our perspective, we need to look at this carefully.
Conflict of interest rules are important and we recognize they
provide credibility and transparency to the process, and nobody
is suggesting they should just be done away with. However, we
have to balance the need for transparency and managing of
conflict of interest with the need to ensure that we get
treatments to people who need them.
Mr. Burgess. That was a subject of a lot of discussion when
we marked up this bill in 2007 and recognizing that for some
products. Pediatric antineoplastic plasma medications, the
universe of people that understands these is probably very
small, and it is probably very difficult to find someone who
has not worked in some way on the development of that product
at some point along the line. This was really where we painted
ourselves into a corner.
Mr. Chairman, I hope we will be serious about fixing this.
And your thoughts on things that we might do to relax or keep
the appropriate focus where it needs to be but at the same time
allow these advisory panels the ability to form and do their
work, I think that is going to be critically important when we
reauthorize.
Thank you.
Mr. Pitts. The chair thanks the gentleman.
I don't see any other questions. That concludes today's
hearing. I remind members they have 10 business days to submit
questions for the record. I ask that the witnesses all agree to
respond promptly to these questions.
With thanks to the witnesses, this subcommittee is
adjourned.
[Whereupon, at 1:20 p.m., the subcommittee was adjourned.]
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