```

[Senate Hearing 114-591]
[From the U.S. Government Publishing Office]

                                                        S. Hrg. 114-591
 
 CONTINUING AMERICA'S LEADERSHIP: THE FUTURE OF MEDICAL INNOVATION FOR 
                                PATIENTS

=======================================================================

                                HEARING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS

                          UNITED STATES SENATE

                    ONE HUNDRED FOURTEENTH CONGRESS

                             FIRST SESSION

                                   ON

        EXAMINING THE FUTURE OF MEDICAL INNOVATION FOR PATIENTS

                               __________

                             APRIL 28, 2015

                               __________

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          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

                  LAMAR ALEXANDER, Tennessee, Chairman

MICHAEL B. ENZI, Wyoming             PATTY MURRAY, Washington
RICHARD BURR, North Carolina         BARBARA A. MIKULSKI, Maryland
JOHNNY ISAKSON, Georgia              BERNARD SANDERS (I), Vermont
RAND PAUL, Kentucky                  ROBERT P. CASEY, JR., Pennsylvania
SUSAN M. COLLINS, Maine              AL FRANKEN, Minnesota
LISA MURKOWSKI, Alaska               MICHAEL F. BENNET, Colorado
MARK KIRK, Illinois                  SHELDON WHITEHOUSE, Rhode Island
TIM SCOTT, South Carolina            TAMMY BALDWIN, Wisconsin
ORRIN G. HATCH, Utah                 CHRISTOPHER S. MURPHY, Connecticut
PAT ROBERTS, Kansas                  ELIZABETH WARREN, Massachusetts
BILL CASSIDY, M.D., Louisiana

                                  
                                       

               David P. Cleary, Republican Staff Director

                  Evan Schatz, Minority Staff Director

              John Righter, Minority Deputy Staff Director

                                  (ii)

  

                            C O N T E N T S

                               __________

                               STATEMENTS

                        TUESDAY, APRIL 28, 2015

                                                                   Page

                           Committee Members

Alexander, Hon. Lamar, Chairman, Committee on Health, Education, 
  Labor, and Pensions, opening statement.........................     1
Murray, Hon. Patty, a U.S. Senator from the State of Washington, 
  opening statement..............................................     3
Roberts, Hon. Pat, a U.S. Senator from the State of Kansas.......    47
Scott, Hon. Tim, a U.S. Senator from the State of South Carolina.    51
Warren, Hon. Elizabeth, a U.S. Senator from the State of 
  Massachusetts..................................................    52
Cassidy, Hon. Bill, a U.S. Senator from the State of Louisiana...    54
Bennet, Hon. Michael F., a U.S. Senator from the State of 
  Colorado.......................................................    56
Isakson, Hon. Johnny, a U.S. Senator from the State of Georgia...    58
Casey, Hon. Robert P., Jr., a U.S. Senator from the State of 
  Pennsylvania...................................................    60

                               Witnesses

Austin, Christopher P., M.D., Director, National Center for 
  Advancing Translational Sciences, National Institutes of 
  Health, Bethesda, MD...........................................     5
    Prepared statement...........................................     7
Pettigrew, Roderic I., Ph.D., M.D., Director, National Institute 
  of Biomedical Imaging and Bioengineering, National Institutes 
  of Health, Bethesda, MD........................................     9
    Prepared statement...........................................    11
Woodcock, Janet, M.D., Director, Center for Drug Evaluation and 
  Research, Food and Drug Administration, Silver Spring, MD......    13
    Prepared statement...........................................    14
Shuren, Jeffrey E., M.D., J.D., Director, Center for Devices and 
  Radiological Health, Food and Drug Administration, Silver 
  Spring, MD.....................................................    25
    Prepared statement...........................................    27

                                 (iii)

  

 CONTINUING AMERICA'S LEADERSHIP: THE FUTURE OF MEDICAL INNOVATION FOR 
                                PATIENTS

                              ----------                              

                        TUESDAY, APRIL 28, 2015

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 10:03 a.m., in 
room SD-430, Dirksen Senate Office Building, Hon. Lamar 
Alexander, chairman of the committee, presiding.
    Present: Senators Alexander, Burr, Isakson, Collins, Scott, 
Roberts, Cassidy, Murray, Casey, Bennet, and Warren.

                 Opening Statement of Senator Alexander

    The Chairman. The Senate Committee on Health, Education, 
Labor, and Pensions will please come to order. This morning, 
we're holding a hearing on Continuing America's Leadership: The 
Future of Medical Innovation for Patients.
    Senator Murray and I will each have an opening statement. 
Then we'll introduce our panel of distinguished witnesses. 
After our witnesses' testimony, Senators will each have 5 
minutes of questions.
    This is our third hearing in the committee on examining how 
we can get safe drugs, medical devices, and treatments from the 
discovery process through the regulatory process into medicine 
cabinets and into doctors' offices for patients who need them. 
Today, we have experts from the National Institutes of Health 
and the Food and Drug Administration who can speak to specific 
challenges to that process, what NIH and FDA are working on to 
address these challenges, and barriers that remain in their 
way.
    Each of our witnesses today knows a great deal about 
innovation. Their daily work puts them up close with cutting 
edge technologies that are changing the face of modern 
medicine, from researching spinal stimulation to help paralyzed 
people regain control of their limbs to approving the next 
breakthrough medication that could cure cystic fibrosis.
    In many cases, our witnesses have overseen advancements in 
their fields that have embraced innovation and moved the 
American medical field forward for patients.
    Dr. Austin, for example, founded and directed the NIH 
Chemical Genomics Center while he was at the National Human 
Genome Research Institute to advance the translation of 
discoveries of the Human Genome Research Project into insights 
on diseases and conditions and ultimately treatments.
    Dr. Pettigrew established the Quantum Grants at the 
National Institute of Biomedical Imaging and Bioengineering to 
achieve medical moon shots by supporting high-risk, high-reward 
projects to address major healthcare problems, such as 
microchips to capture circulating tumor cells for early 
detection and to monitor treatment.
    Dr. Shuren has overseen a major advancement in heart valve 
replacement therapy and the first approval of a next-generation 
gene sequencing platform. There is not much in drug innovation 
that Dr. Woodcock has not overseen or been involved in over the 
last 10 years, including the first personalized medicines.
    What I hope to hear today is what FDA and NIH currently are 
doing and how Congress can help create the environment so the 
NIH and FDA keep pace with today's cutting edge scientific 
advancements.
    Senator Burr and I released a white paper in January that 
looked at the process of getting drugs and devices from 
discovery to medicine cabinet, and much of what the report 
covered is relevant here today. Today, medical products take 
more time and money to discover, develop, and reach the 
American patients than ever before.
    We have heard that the FDA has difficulty regulating the 
most cutting edge medical products. This disparity between the 
pace of scientific discovery and FDA's scientific knowledge is 
threatening America's position as a global leader in medical 
innovation. We read in the paper and hear stories about drugs 
and devices available to patients outside the United States 
first, such as the heart valve mentioned earlier or a drug for 
multiple sclerosis.
    Private investment is shifting away from early stage drugs 
and devices in part due to increasing regulatory burden and 
uncertainty. Countries across the globe are seeking to 
capitalize on America's shrinking competitive advantage in the 
biomedical space.
    In response to that report, we've gotten a glimpse of some 
of the exciting new technologies on the way. We want to make 
sure the FDA is ready for the developments coming, such as 
bioelectric medicine, where nanotechnology sends electric 
signals to restore nerve function; regenerative adult stem cell 
therapies derived and put back into the same patient; and 
therapies based on the whole genome sequence intended to 
prevent any clinical symptoms from ever occurring.
    FDA has quite the task before them to keep up with these 
and many other technologies and to be able to judge the 
benefits. At our first hearing, we heard from Dr. Collins, the 
head of the NIH, and Dr. Hamburg, the former FDA Commissioner. 
Dr. Collins highlighted the need for reforms on the travel of 
NIH scientists and the need for the ability to roll funds over 
from 1 year to the next.
    Dr. Hamburg said that more needs to be done on regulatory 
science, and that FDA needs to be involved earlier in medical 
product development to ensure the most efficient process.
    We know that opportunities exist today: the ability to use 
real world data to improve health, both to shorten the time to 
get to market, and then also to make sure that medical products 
are safe once on the market; the ability to know about a 
disease, including the genetic and molecular impact, and target 
those markers before symptoms are ever present.
    Our task is to help ensure that the exciting new 
technologies being developed and discoveries being made are 
reaching patients and that the NIH is equipped to support the 
early stage research required to make these advancements and 
that the FDA is equipped to handle them.
    I look forward to hearing from the panel how Congress can 
ensure that our biomedical research and review systems are 
ready for these opportunities and have the expertise and tools 
to address the challenges.
    Senator Murray.

                  Opening Statement of Senator Murray

    Senator Murray. Well, thank you very much, Chairman 
Alexander. And thank you to everyone here today, especially our 
witnesses, for joining us.
    I'm very proud to represent a State that is a leader in 
biomedical innovation. I see maintaining our country's central 
role in the life sciences as a top priority, and I believe we 
need to be doing everything we can to make sure the next life-
saving, world-changing cures and treatments are developed right 
here in the United States. The conversation we're having this 
morning about the future of medical innovation for patients and 
families is a really important part of this effort.
    I had the chance to visit the Fred Hutchinson Cancer 
Research Center in my home State of Washington recently. As I 
always am when I visit my State's world-class research 
facilities, I was struck both by how far we've come in terms of 
medical and technological advancement and also by how much more 
there is to discover.
    Over the last half century, our medical system has taken 
huge leaps forward. We've moved from a system in which many 
patients had no idea whether medical products would help them, 
hurt them, or do nothing at all, to one in which FDA-approved 
treatments are the global gold standard for safety and 
effectiveness, a standard that patients and families have come 
to trust when making decisions about their health.
    Clinical research has, of course, been a key contributor to 
this progress. I'm pleased that recently there has been 
increased focus on the need for clinical trials to include 
women, children, and other patients from all backgrounds. This 
is critical, because we need to understand how products work 
for every patient and family. I will continue to make this a 
priority as we look for ways to advance medical innovation.
    Today, medical experts are continuing to push the limits of 
science and technology. We now increasingly have the capability 
to treat patients based on their own unique characteristics and 
medical histories.
    In my home State alone, scientists supported by the NIH are 
exploring ways to stop cancerous cells from metastasizing, 
which is the No. 1 cause of cancer deaths, and develop 3D 
analysis of internal biological surfaces so devices like joint 
replacements can be better integrated into the human body.
    These are just a couple of the many incredible examples of 
scientific work being done today. Our task in Congress and in 
our bipartisan effort to support medical innovation for 
patients is to support this work and ensure that our country 
continues to uphold the highest standards of medical safety and 
effectiveness.
    The two questions I am especially interested in exploring 
today are: What more can Congress do to help get patients the 
best, safest treatments more quickly? In general, what role can 
Congress play in realizing this goal by helping to move the 
ball forward on the most difficult scientific challenges?
    Over the last few years, Congress has put in place tools 
like FDA's breakthrough designation and accelerated drug 
approval, which have helped patients and families get treatment 
more quickly for serious and unmet medical needs.
    One example is FDA's accelerated approval of a new drug to 
treat breast cancer in women. NIH estimates that in 2014, more 
than 230,000 women were diagnosed with breast cancer in the 
United States, and 40,000 died from that disease.
    Until this February, there hadn't been a new drug approved 
for a particularly common form of breast cancer in over 15 
years. FDA granted breakthrough therapy designation to help 
speed development of a new drug, based on preliminary evidence 
that the drug may offer a substantial improvement over 
available therapies. Then, based on a single Phase 2 study of 
165 women, FDA used its accelerated approval authority to 
approve the drug. Now this treatment is available to patients 
while the sponsor completes a Phase 3 study.
    This focus on regulatory flexibility, where appropriate, is 
helping patients and families get the care they need when they 
need it, and I'm hopeful we can continue to make progress on 
this.
    Another area where I hope we can be helpful is finding ways 
to advance the development of new medical products for 
patients. We've heard from Dr. Hamburg that FDA has the fastest 
drug approval times in the world. But the private sector 
development of new medical products can take years before those 
products ever reach the FDA's door.
    I am hopeful that as our discussions continue, we can find 
ways to support efforts to tackle difficult scientific 
challenges in the development process, and, in addition, 
explore innovative ways to determine which products are really 
going to make a real difference for patients and families, and 
weed out products that are not earlier on in the process.
    This would reduce spending on dead ends and bring down 
development costs. And, much more importantly, it would help 
direct private sector resources to the research and development 
that will get the best results for patients and families.
    I look forward to hearing from Dr. Woodcock and Dr. Shuren 
about how FDA's existing tools are working and what other steps 
might be helpful. I am eager to hear from Dr. Austin and Dr. 
Pettigrew about how our work in Congress can help break through 
difficult science in the development process.
    I want to thank again all of our witnesses for coming and 
sharing your expertise with us. I'm confident that with your 
insight, our bipartisan effort to advance innovation for 
patients will be better equipped to help tackle the medical 
challenges our country faces and help families and communities 
stay healthy.
    Thank you very much, Mr. Chairman.
    The Chairman. Thank you, Senator Murray, and as I think the 
witnesses know, this innovation project is a priority of 
Senator Murray and me and this committee. We're working closely 
with the President and with the administration and with the 
House of Representatives, and we expect to have a result 
sometime during this Congress. So your participation is 
welcomed.
    We would appreciate it if you could summarize your remarks 
in about 5 minutes. That way, we can have more conversation. 
I'm delighted to welcome you. Thank you for being here. You've 
got big jobs running important centers.
    First, we'll hear from Dr. Austin. He is Director of the 
National Center for Advancing Translational Sciences, which was 
established in 2011. It's the newest of the 27 NIH institutes 
and centers. It is designed to transform translational science 
so new treatments and cures for disease can be delivered to 
patients faster.
    The second witness is Dr. Roderic Pettigrew. He is Director 
of the National Institute of Biomedical Imaging and 
Bioengineering at NIH. Its mission is to improve health by 
leading the development and accelerating the application of 
biomedical technologies.
    Dr. Janet Woodcock is next. She is Director of the Center 
for Drug Evaluation and Research at the Food and Drug 
Administration, which performs the essential public health task 
of ensuring that safe and effective drugs are available to 
improve the health of people in the United States. She's been 
there for nearly 30 years and has led many of the FDA drug 
initiatives.
    Finally, Dr. Jeff Shuren has been the Director of the 
Center for Devices and Radiological Health at the FDA for over 
5 years. That center is responsible for assuring the safety, 
effectiveness, and quality of medical devices; assuring the 
safety of radiation-emitting products; and fostering device 
innovations. Among his earlier work experience was a year 
detailed to Senator Kennedy's HELP Committee staff. So we 
welcome him back.
    Why don't we begin with Dr. Austin.

 STATEMENT OF CHRISTOPHER P. AUSTIN, M.D., DIRECTOR, NATIONAL 
     CENTER FOR ADVANCING TRANSLATIONAL SCIENCES, NATIONAL 
               INSTITUTES OF HEALTH, BETHESDA, MD

    Dr. Austin. Well, good morning, Chairman Alexander, Ranking 
Member Murray, and distinguished members of the committee. It's 
an honor to appear before you today to discuss these topics, 
because, as Senator Alexander just pointed out, NCATS was 
formed in 2011 to address the systemic issues that we're 
talking about today. These are issues that we deal with, and 
they're very important to us and we work on them every day.
    It's really an honor to be here, not only to represent 
NCATS, but alongside my NIH colleague, Dr. Pettigrew, and our 
colleagues from FDA, Dr. Woodcock and Dr. Shuren, to discuss 
how we stimulate innovation through Federal investments in 
scientific research. On behalf of NCATS and the NIH, I want to 
thank the committee for your continued support.
    I appreciate the opportunity to talk with you about some of 
the innovative and exciting efforts we have ongoing at NCATS to 
improve the process of translating fundamental understanding to 
interventions that will improve the health of patients. Today, 
I'll describe just three examples of the ways that we're doing 
this.
    First, predicting toxicity or adverse events is one of the 
major reasons that drugs fail in development. This is a generic 
problem that bedevils every translational project, no matter 
what the disease is.
    We're tackling this in multiple ways, one of which is 
through the Tissue Chip for Drug Screening program. This is a 
program that you may have heard about. Dr. Collins likes to 
talk about it. It's a collaborative effort with DARPA and with 
the FDA in which bioengineered human-based organs on microchips 
are being developed with the intent to test drug safety and 
effectiveness more rapidly and effectively than current 
methods.
    The chip that I have with me today represents a kidney, and 
it was actually developed at the University of Washington 
together with a company in Seattle called Nortis. NCATS is 
building on its initial phase in which there were 10 different 
organs, the kidney among them, developed.
    We're now funding projects to link these organs together 
with the eventual goal within the next 4 or 5 years of having 
10 organs on a chip, a human on a chip, if you will, and 
possibly even chips from individuals so that one could make a 
chip from each one of us in this room, for instance. Once 
completed, these integrated systems will be used as models for 
disease, as well as, we hope, to predict whether a drug or a 
vaccine or a biologic would be effective in humans and/or toxic 
in humans.
    Another roadblock that I'm sure you've heard a lot about is 
that many drugs make it part of the way down the development 
spectrum, but then they don't progress to actual treatments. 
For either scientific reasons or business reasons, they're 
deprioritized.
    To address this problem, we started a program about 3 years 
ago called Discovering New Therapeutic Uses for Existing 
Molecules. It's an innovative approach to match ideas that 
academic researchers have on how compounds could be used to 
treat currently untreatable diseases. The program matches those 
academic researchers with pharmaceutical industry compounds 
that have already undergone significant research and 
development and are available for testing on those other 
diseases.
    NCATS is celebrating one of the first promising results 
from this program. It's a potential treatment for Alzheimer's 
disease. NCATS-supported researchers through this program at 
Yale collaborated with AstraZeneca researchers to find that an 
experimental compound which was originally developed by 
AstraZeneca as a cancer treatment could be used to treat 
Alzheimer's disease. The compound successfully restored brain 
function in mouse models of the disease, and now the Yale 
researchers are testing it in humans with Alzheimer's to test 
its effectiveness.
    The third example is to address the problem of multisite 
clinical trials, which are the last step needed to bring most 
drugs to market. The current clinical trial system in the 
United States is extremely inefficient. The NCATS Clinical and 
Translational Science Award program is addressing this problem. 
The CTSA sites across the country serve as research hubs to 
support a national network for clinical translational studies.
    One example of how this program is improving the efficiency 
of clinical trials occurred in the aftermath of the 2013 Boston 
Marathon bombing, where doctors from several local hospitals in 
Boston quickly formed a team to design a high-quality, 
multisite study to examine ear injuries as a result of the 
blast. The CTSA hub at Harvard had an agreement in place that 
enabled multiple institutions to rely on a single committee to 
review, approve, and monitor the study. A study involving seven 
sites was able to get going within days instead of the typical 
months that this would require.
    This innovative ability to streamline review of multisite 
clinical studies enables NIH-funded research to generate 
results more quickly without compromising the protection of 
human participants. The CTSA program is also now working on 
improving participant recruitment to clinical trials and to 
leverage electronic health records to speed clinical research.
    NCATS' mission is to catalyze the generation of innovative 
methods and technologies that will advance the development and 
implementation of diagnostics and therapeutics across a wide 
range of diseases and conditions. NCATS looks forward to 
building on these recent successes, such as the ones I've just 
illustrated.
    It's important for you to know that to accomplish this 
mission, because we view translation as a team sport, we 
collaborate on every one of our projects with other partners in 
government, academia, industry, patient organizations. This 
allows us to leverage our expertise and resources with those of 
our partners, thus using taxpayer dollars most effectively to 
bring more treatments to more patients more quickly.
    Finally, a month ago, I had the privilege of hosting 
Senator Mikulski for a tour of our research laboratories 
located in Rockville, MD, which allowed me to show her some of 
the innovative technologies that I've just mentioned. I'd like 
to extend an invitation to the rest of the committee to visit 
and see firsthand the exciting things that NCATS is doing.
    This concludes my testimony, Mr. Chairman, and I look 
forward to your questions.
    [The prepared statement of Dr. Austin follows:]
           Prepared Statement of Christopher P. Austin, M.D.
    Good morning, Chairman Alexander, Ranking Member Murray, and 
distinguished members of the committee. I am Christopher P. Austin, 
M.D., and I am the Director of the National Center for Advancing 
Translational Sciences (NCATS), one of the Institutes and Centers of 
the National Institutes of Health (NIH).
    It is an honor to appear before you today, alongside my NIH 
colleague Dr. Pettigrew and our colleagues from Food and Drug 
Administration (FDA), Dr. Woodcock and Dr. Shuren, to discuss how we 
stimulate innovation through Federal investments in scientific 
research. On behalf of the NCATS and the NIH, I want to thank the 
committee for your continued support and for the opportunity to talk 
about some of the innovative and exciting efforts that NCATS is 
undertaking to improve the process for transforming research 
discoveries into cures so that we can bring more treatments to more 
patients more quickly.
    Recent and rapid discoveries of mechanisms of disease, sequencing 
of the human genome, and advances in technology have led to greater 
scientific opportunities that have the potential to substantially 
improve human health. NCATS is working on innovative ways to improve 
the process for transforming these discoveries into cures so that we 
can bring more treatments to more patients more quickly.
    NCATS defines translation as the process of turning observations in 
the laboratory and clinic into interventions that improve the health of 
individuals and the public--from diagnostics and therapeutics to 
medical procedures and behavioral changes. Translational science is the 
field of investigation focused on understanding the scientific and 
operational principles underlying each step of the translational 
process. NCATS studies translation on a system-wide level. NCATS' 
translational science efforts focus on the entire spectrum of 
translational research--basic research, pre-clinical research, clinical 
research, medical practice, and public health. At all stages of the 
spectrum, NCATS develops new approaches, demonstrates their usefulness, 
and disseminates the findings. Patient involvement is a critical 
feature of all stages in translation.
                    innovation in methods and tools
    The translational science approach generates new technologies and 
data that overcome common roadblocks to translational success, thus 
making the process more efficient and effective for all. One 
technological innovation is a bioengineered system that represents 
human organs, more commonly known as a tissue chip. Through the NCATS 
Tissue Chip for Drug Screening program, a collaborative effort with the 
Defense Advanced Research Projects Agency and FDA, researchers are 
creating human tissue chips that consist of miniature 3D models of 
living organs and tissues on transparent microchips. The chips contain 
living cells and are designed to replicate the complex biological 
functions of specific human organs. The tissue chips are being 
developed to test drug safety and effectiveness more accurately and 
cost-effectively than current methods. NCATS is building on its initial 
success in developing chips that contain single tissue or organ models 
by funding projects to integrate several of the organ-specific chips 
into a full system that represents a ``human on a chip.'' Once 
completed, these integrated systems will be used to predict whether a 
drug, vaccine or biologic agent would be toxic to, or effective in, 
humans.
    NCATS shares its unique research approaches and resources so that 
they can be broadly applied to translational science efforts at other 
public and private sector organizations. In a recent collaboration with 
the National Institute of Neurological Disorders and Stroke, NCATS 
scientists incorporated an innovative approach to find a compound that 
could enhance the activity of the parkin protein, which is implicated 
in Parkinson's disease. Parkin is suspected of playing an important 
role in the removal of faulty mitochondria (a cell's ``powerhouse'') in 
brain cells, but for patients with Parkinson's disease, this 
maintenance mechanism is disrupted. NCATS researchers designed a test 
(called an assay) to measure the activity of the gene for parkin. With 
this assay, the research team is now conducting high-throughput screens 
using the NCATS' chemical libraries to identify compounds that increase 
parkin activity. While specifically designed to address this problem, 
the screening and assay methods designed by NCATS researchers can be 
used by other scientists to solve many other translational research 
problems.
    NCATS also applies innovative methods through its Discovering New 
Therapeutic Uses for Existing Molecules (``New Therapeutic Uses'') 
program. Launched in 2012, this initiative uses an innovative strategy 
that matches the ideas of academic researchers to pharmaceutical 
industry compounds that have already undergone significant research and 
development, and are available for testing on other diseases. To 
accelerate the ``match-making'' process, NCATS developed template 
agreements to streamline the legal and administrative process of 
research collaboration among multiple parties. NCATS is celebrating one 
of the first promising results from this program, a potential treatment 
for Alzheimer's disease. Alzheimer's disease is the most common form of 
dementia, a group of disorders that cause progressive loss of memory 
and other mental processes. About 5 million Americans have Alzheimer's 
disease, and current drug therapies can only ease symptoms of the 
disease without stopping its progression. New treatments--so-called 
disease-modifying therapies--are needed to halt Alzheimer's by 
targeting its underlying mechanisms. Blocking that path to therapeutic 
success is the costly, complex process of drug development. Through the 
New Therapeutic Uses program, NCATS-supported scientists at Yale 
University School of Medicine collaborated with AstraZeneca to find 
that an experimental compound originally developed by AstraZeneca as a 
cancer therapy potentially could be used to treat Alzheimer's disease. 
The compound successfully reversed brain problems in mouse models of 
the condition, and now the researchers are testing it in humans to 
assess its effectiveness. We know that there is more that we can be 
doing to address this disease, and multiple institutes at NIH are 
aggressively pursuing other research on possible clinical therapies and 
a better understanding of the changes in the brain that lead to 
Alzheimer's disease, including through partnerships with the private 
sector. To that end, the President's fiscal year 2016 Budget includes 
$638 million for Alzheimer's disease research.
                  collaboration and patient engagement
    NCATS also applies innovative approaches to translation by 
fostering collaboration and patient engagement. NCATS' Rare Disease 
Clinical Research Network is a highly collaborative network of 22 
clinical research consortia and a data management center. The network 
is composed of approximately 2,600 researchers, including NIH 
scientific program staff, academic investigators, and members of 98 
patient-advocacy groups. Scientists from multiple disciplines at 
hundreds of clinical sites around the world work together with patient 
advocacy groups to study more than 200 rare diseases. Since its launch, 
nearly 29,000 patients have been enrolled in network clinical studies. 
Ninety-one studies are currently under way.
    The NCATS Therapeutics for Rare and Neglected Diseases program 
establishes robust collaborations among NIH, academic scientists, 
nonprofit organizations, and pharmaceutical and biotechnology companies 
to support faster translation of drug discovery and development. When 
successful, these projects are acquired by biopharmaceutical companies 
for further development toward approved treatments for patients.
       a national network for clinical and translational research
    The NCATS Clinical and Translational Science Awards (CTSA) program 
focuses its efforts on addressing the inefficiencies and roadblocks in 
clinical and translational research, from scientific discovery to 
improved patient care. The 62 CTSA sites serve as research hubs to 
support a national network for clinical and translational studies. The 
hubs support collaborations in education and training initiatives, 
share best practices and methods, promote team science, and conduct 
multi-site clinical studies through a shared infrastructure. A good 
example of such collaboration happened in the wake of the April 2013 
Boston Marathon bombing. Doctors from several local hospitals quickly 
formed a team to design a high-quality multi-site study to examine 
blast-related ear injuries. Harvard's CTSA hub had an Institutional 
Review Board reliance agreement in place that enabled these 
institutions to rely on a single committee to review, approve, and 
monitor the study. Therefore, this seven-site study was launched within 
weeks rather than the more typical months. This innovative ability to 
streamline the review of multi-site clinical research studies enables 
NIH-funded research to generate results more quickly without 
compromising the protection of human participants. NCATS has announced 
plans to support the evolution of the CTSA program by soliciting 
innovative approaches to increasing clinical trial efficiency and 
effectiveness, addressing the roadblocks common to clinical studies 
recruitment of research study participants, and supporting 
collaborative innovative research in both translational science and its 
methods.
                               conclusion
    NCATS' mission is to catalyze the generation of innovative methods 
and technologies that will enhance the development, testing and 
implementation of diagnostics and therapeutics across a wide range of 
human diseases and conditions. NCATS looks forward to building on its 
recent successes to bring more treatments to more patients more 
quickly.
    This concludes my testimony, Mr. Chairman. I look forward to your 
questions.

    The Chairman. Thanks, Dr. Austin.
    Dr. Pettigrew.

   STATEMENT OF RODERIC I. PETTIGREW, Ph.D., M.D., DIRECTOR, 
 NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING, 
          NATIONAL INSTITUTES OF HEALTH, BETHESDA, MD

    Dr. Pettigrew. Good morning, Chairman Alexander, Ranking 
Member Murray, and distinguished members of the committee. It 
is an honor to appear before you today along with my 
distinguished colleagues on this panel, Doctors Austin, 
Woodcock, and Shuren, to discuss some of the tremendously 
exciting innovations made possible by Federal investments in 
biomedical research with a focus on medical impact.
    I want to thank the members of this committee for your 
continued support, for holding this hearing today, and for the 
opportunity to share our work with you. The National Institute 
of Biomedical Imaging and Bioengineering, commonly known as 
NIBIB, conducts research that sits at the intersection of the 
physical sciences, the life sciences, and engineering. 
Together, these disciplines are creating new biomedical 
technologies to improve health.
    We serve as a catalyst for emerging technologies and a 
stimulator of innovation across the NIH in academia and 
industry. I think it is worth noting that our working 
definition of innovation is simply invention put to use. In 
laboratories that we fund across the country, innovative 
research is working on developing breakthrough technologies.
    I'd like to show and tell you about a few of these in a 
brief video. These examples provide a broad view of NIBIB-
supported technologies at various stages of development from 
proof of concept to commercialization.
    [Video Shown.]
    This video entitled ``Eight Awesome Technologies Your Tax 
Dollars are Paying to Create'' provides this overview. The 
first one is a tissue engineered human liver. It looks like a 
contact lens. It can be implanted in a mouse. It grows in a 
mouse and turns the mouse's metabolism into a human-like 
function. It then allows one to evaluate candidate drugs for 
toxicity and biological features.
    This is a hand-held MR assistant which is capable of 
detecting a variety of targets from bacteria to viruses to 
components of cancer cells. This is quite an innovation that 
provides a completely portable, hand-held, take it anywhere you 
can go, fully functional ultrasound system that replaces the 
conventional system that you saw there. It would cost about \1/
20\th of a conventional system, and I have one here in my left 
hand that I'm holding up. This was a partnership with General 
Electric.
    This addresses the devastating problem of paralysis due to 
spinal cord injuries. Implantation of the electrical stimulator 
at the lumbar spine in an epidural type of stimulation allows 
the patients that were treated who were completely immobilized 
for several years to regain voluntary motion as you saw in the 
video.
    This addresses the problem with the availability of organs 
to transplant in patients, extending the time of presentation 
from 1 day to 4 days in order to identify a greater population 
of patients that might benefit from such transplantable organs.
    This addresses a problem with vaccination and makes it a 
simple process that is painless with a vaccine that can be 
delivered in the mail. It uses this biodegradable patch that 
you see here that's the size of a thumb. I actually have one of 
those here. You place it on the skin, press it, and you're 
vaccinated. It is biodegradable and dissolves in about 5 
minutes so you don't have the hazardous waste to be concerned 
about, and it's a stable temperature so you can send it in the 
mail.
    This is an optical needle microscope that is battery 
powered. You place it on the surface. It provides sufficient 
magnification that you can identify healthy cells, distinguish 
those from cancerous or pre-cancerous cells, as being shown 
here, and therefore provides a point of care test for 
identifying cervical cancer and oral cancer, as was done in 
this clinic in Botswana.
    This final example addresses a problem of visualization of 
tumors at the cellular level. This innovation developed by a 
Nobel laureate has a molecule that seeks out cancer cells and 
fluoresces after it enters the cells. You can see the tumor 
there that was florescent. Similarly, for nerves, those are 
demonstrated as well so that the surgeon can be better able to 
distinguish nerves from cancer cells and potential entwining of 
the two.
    Those are examples that illustrate the type of innovative 
technologies that we are developing. In summary, our institute, 
NIBIB, drives innovation. We innovate technologies that expand 
medical knowledge. We innovate diagnostics and therapies for 
this and future generations. We integrate engineering with the 
physical and life sciences to catalyze practical solutions to 
complex biomedical problems.
    Our goal is to accelerate the creation of usable 
technologies to improve human health across the Nation and 
worldwide. I thank you for the opportunity to appear before you 
today, and I look forward to your questions.
    [The prepared statement of Dr. Pettigrew follows:]
        Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D.
    Mr. Chairman and members of the committee: I am pleased to present 
this testimony to you for the hearing on Biomedical Innovation. I am 
Roderic I. Pettigrew, Ph.D., M.D., Director, National Institute of 
Biomedical Imaging and Bioengineering (NIBIB). We are 1 of 27 
Institutes and Centers at the National Institutes of Health. NIBIB is a 
relatively new IC. It was created in December 2000 and we awarded our 
first grants in 2002. NIBIB supports more than 800 grants and the work 
of more than 5,000 researchers, and an Intramural Research Program at 
NIH. At NIBIB we focus on creating biomedical technologies to improve 
health.
    Our mission is to lead the development and accelerate the 
application of biomedical technologies to improve health. We are 
advancing medical care through better understanding, prevention, 
detection, and treatment of disease. We conduct and support emerging 
technology research and development that lead to innovative biomedical 
solutions. Integrating engineering and physical sciences with life 
sciences by building partnerships with industry, academia, and other 
Federal agencies is a high priority for the institute. In this 
testimony I share a few examples from the many exciting NIBIB-funded 
research efforts, which are leading to practical innovations that 
advance public health.
      reversing paralysis through spinal stimulation technologies
    Spinal cord injury can be devastating and affect almost anyone, 
from victims of auto accidents, to athletes, to soldiers on the 
battlefield. An estimated 276,000 people were living with a spinal cord 
injury in 2014. Each year approximately 12,500 new cases occur.\1\
---------------------------------------------------------------------------
    \1\ Spinal Cord Injury Facts and Figures at a Glance. February 
2015. The National SCI Statistical Center, The University of Alabama at 
Birmingham.
---------------------------------------------------------------------------
    Once thought of as an injury with no hope of recovery, a novel 
therapy that involves electrical stimulation of the spinal cord has 
restored function to an unprecedented degree in 7 patients treated to 
date. This is a first-of-its-kind experimental study funded by NIBIB. 
Following treatment, severely paralyzed patients recovered everyday 
bodily functions, including bowel, bladder and sexual function. The 
return of these important basic functions has dramatically improved the 
quality of life of all who were treated. These patients also regained 
the ability to voluntarily stand and achieve limited limb movement, 
providing hope that further recovery may be possible with improvements 
to this treatment approach. Although this research is still in its 
infancy and not yet at the clinical trial stage, it has given real hope 
to people living with paralysis around the world. They have seen the 
positive impact in the small group of study participants and are eager 
to have such technologic advances transform their lives as well.
                    next generation cell engineering
    Our immune systems are highly proficient at attacking and 
destroying anything viewed as foreign when it enters the body. Yet 
cancer cells are largely ignored by the immune system because they are 
derived from our own cells and retain some of the same characteristics. 
A relatively new approach tested through a grant funded by NIBIB, uses 
cell engineering to reprogram the immune system to identify cancer 
cells and destroy them. In a recent advance, researchers have developed 
a vaccine made of nanoscale biomaterials that is injected under the 
skin. Once injected, the nanomaterials form a 3D scaffold, creating a 
relatively large surface area for the immune system to assemble 
``killer'' cells specifically programmed to attack tumors. The power of 
this approach was demonstrated in a mouse model, in which the 3D 
vaccine generated a potent immune response to lymphoma cells and 
inhibited tumor growth. While this study tested the feasibility of a 
single cancer vaccine, the same scaffold could also hold different 
antigens or drugs to treat a range of cancers or infectious diseases. 
This research promises a new class of therapeutic agents which harness 
and enhance the power of our natural defense mechanisms against 
disease.
 advancing precision medicine: early detection of cancer cells at the 
                             point-of-care
    Many therapies today work well for some people, but not for others. 
Matching a treatment to the unique features of an individual's disease 
is the goal of the President's Precision Medicine Initiative. NIBIB is 
supporting research in technology development to realize the vision of 
customized treatment. For example, researchers have developed a 
miniature palm-sized device to isolate rare circulating tumor cells 
from a small routine blood sample. Tested in a proof-of-concept study, 
this novel device was able to isolate breast cancer cells from the 
blood of 36 women. Physicians were then able to grow the tumor cells 
from six of the blood samples in the laboratory to characterize their 
genetic and molecular features and test sensitivities to drugs. A 
subset of these human cells were able to also grow tumors in mice where 
the effectiveness of the selected drugs in inhibiting tumor growth was 
demonstrated. In this initial study, treatments were not given to 
patients; however this approach successfully demonstrated the potential 
to identify a range of genetic changes, or mutations, in an 
individual's cancer cells to enable personalized therapy.
                mobile technology to advance healthcare
    Depending on a variety of factors, such as environmental exposure 
and lifestyle, individuals with the same genetic makeup can have very 
different health outcomes. The use of mobile technology has the 
potential to greatly assist researchers in gaining a better 
understanding of the environmental and behavioral factors that cause 
disease with the goal of preventing or intervening in the process. 
Today, smartphones are natural points of engagement for the large 
percentage of U.S. adults who own them. Interfacing smartphones with a 
variety of biosensors may allow the linkage of an individual's 
electronic medical records and genomic data with information captured 
by the smartphone on environmental exposure and behavior if it were 
done with appropriate security and privacy protections. From measuring 
secondary smoke exposure to counting steps, or testing vision, 
smartphones can record, track, and transmit a significant amount of 
health information. Smartphones can also be used as a tool for 
healthier living. They can be programmed to send automatic reminders to 
take a medication or an alert when a dose is missed. The overarching 
potential application relevant to the Precision Medicine Initiative is 
to link and enrich the genomics and electronic health record data with 
a broad range of medical exposure and lifestyle information. This set 
of ``big data'' can then be evaluated or ``mined'' to identify new ways 
to improve human health.
                            brain initiative
    Approximately 100 billion neurons and 100 trillion connections make 
up the human brain and there is an enormous amount to explore and 
discover in this, the most complex of all human organs. As an institute 
that is very active in the BRAIN Initiative, which has been a priority 
for the President, as outlined in his fiscal year 2016 Budget proposal 
for an additional $70 million, NIBIB supports research that leads to 
the next generation of neuroscience discovery tools and technologies. 
These technologies are being developed to advance our understanding of 
the function of neural circuits and systems in health and disease. In 
one example, researchers are developing a completely new noninvasive 
method for portable 3D human brain visualization called Magnetic 
Particle Imaging. Based on intrinsic bioelectric properties and the use 
of injectable magnetic nanoparticles, this project could provide higher 
imaging clarity and a completely new way to characterize and understand 
changes in brain circuit function in mental and neurological disease.
                               conclusion
    NIBIB drives technological innovation to expand biomedical 
knowledge and create improved diagnostics and therapeutics for this and 
future generations. By integrating engineering with the physical and 
life sciences, NIBIB develops practical solutions to complex biomedical 
problems. These advances are improving human health across our Nation 
and worldwide.

    The Chairman. Thank you, Dr. Pettigrew.
    Dr. Woodcock.

 STATEMENT OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG 
 EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION, SILVER 
                           SPRING, MD

    Dr. Woodcock. Thank you, Mr. Chairman. I'm really pleased 
to be here to discuss the State of medical product development, 
an activity that is so critical to human health, including, in 
our case, at CDER, combating emerging infections like Ebola, 
finding treatments for rare diseases, enabling healthy aging, 
and preventing the development of disease at all.
    CDER, the Center for Drug Evaluation and Research that I 
lead, has a big impact on drug development, both domestic and 
worldwide. I'm pleased to report, as reflected in my written 
testimony, that a large number of innovative new medicines are 
being approved and are in the pipeline. In fact, U.S. patients 
do, in the vast majority of cases, have first access to these 
treatments.
    To ensure continued safety monitoring of these drugs after 
approval, we've developed the cutting edge Sentinel network 
that can analyze information from 178 million Americans' 
medical records without compromising their privacy and watch 
over these new medicines after they're approved.
    Congress has had a big role in these successes, from 
activating the PDUFA program that provides adequate resources 
for FDA to monitoring development of drugs and provide advice 
to developers as well as review the applications in a timely 
manner. Congress also directed establishment of Sentinel for 
safety and in FDASIA started the breakthrough designation 
program that has been highly successful in getting the most 
innovative drugs to patients quickly.
    There are still problems, as already has been mentioned. 
Drug development costs too much and takes too long. This is 
mainly caused by the high failure rate. Even for the drugs that 
make it to human testing, 8 out of 10 of those fail in human 
testing. It's not due to the FDA requirements, but because they 
don't work or because they're too toxic or they're no better 
than existing drugs. The problem is really with failure rate.
    FDA published the Critical Path Report that I actually 
authored in 2004 to bring attention to these problems and start 
working on solutions. There are many steps that have been 
taken. There are many steps that can be taken. For example, 
Chris Austin described what NCATS is doing, which is a focused 
effort on trying to improve the situation. But we do need to 
continue to improve the efficiency of drug development if we're 
going to continue to get drugs to patients rapidly and 
affordably.
    Now, in particular, I thank Senators Hatch and Bennet for 
their leadership introducing the PATH Act to establish a 
limited population antibacterial drug program which could be 
helpful in addressing unmet needs in a very fragile area of 
antimicrobial drug development. I look forward to working with 
the committee as this provision advances. I also look forward 
to working on other aspects of the overall challenges of drug 
development.
    Now, one caveat, as you consider options, is, as we say in 
medicine, first do no harm. When CDER receives a large number 
of unfunded mandates, our attention can be diverted and review 
performance suffers. This happened after the FDA Amendment Act 
in 2007, and I have a chart that we will provide you that shows 
the dip in FDA performance following enactment of that statute.
    As we consider actions to enable innovation, we need to 
make sure that we don't break what is working but that we 
improve on the current system.
    Thank you, and I look forward to your questions.
    [The prepared statement of Dr. Woodcock follows:]
               Prepared Statement of Janet Woodcock, M.D.
    Mr. Chairman and members of the committee, I am Dr. Janet Woodcock, 
Director of the Food and Drug Administration's (FDA) Center for Drug 
Evaluation and Research (CDER). I am privileged to have the 
responsibility to oversee much of FDA's efforts to review the safety 
and efficacy of new pharmaceuticals. Thank you for having me here today 
to give you my views on current efforts and areas for improvement.
    When I came to FDA in the 1980s, the process by which FDA approved 
new drugs for marketing to patients was under considerable criticism--
for being slow, for lagging behind other countries, and for lacking 
transparency to, and collaboration with, the developers of new drugs.
    Today, thanks to the efforts of those across the Agency, our 
Nation's drug review process reveals a very different picture--we are 
delivering new, lifesaving therapies to patients faster than any other 
developed country and more expeditiously than ever before. In 2014, 
almost two-thirds of the novel (``new molecular entity'') drugs 
approved by CDER (26 of 41, 63 percent) were approved in the United 
States before receiving approval in any other country. In addition, we 
have significantly strengthened the drug safety surveillance system in 
the United States, modernized drug review processes, and introduced new 
genomic and related sciences into the drug evaluation process.

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              factors speeding drug review and development
    No single action or programmatic change has brought us to where we 
are today; rather, it has been a steady program of improvements, new 
investments through PDUFA, new authorities and other factors. These 
improvements were based upon both externally and internally identified 
gaps, so that now we have more predictable review times, additional FDA 
resources to adequately address the workload from applications, and 
additional interaction between FDA staff and drug manufacturers to 
ensure promising drugs reach patients quickly.
                   prescription drug user fee program
    The approval by this committee of the Prescription Drug User Fee 
Act of 1992 (PDUFA) has been one of the most important components of 
our improvements in review times. As its name suggests, PDUFA provided 
funds in the form of user fees for FDA to hire sufficient staff to 
undertake the growing workload of applications to market new drugs in 
the United States. But it had much broader implications. It established 
the principle that timely review was important, not just to 
manufacturers, but also to patients, and that FDA should commit to 
conducting those reviews in a predictable manner.
    I became Director of CDER not long after PDUFA's enactment and was 
determined from the start to ensure that the program was run in a 
business-like fashion, with use of modern project management 
techniques, establishment of specific goals, and accountability on the 
part of review staff and managers to adhere to those goals. The result 
has been a concerted effort across the Center with steady lowering of 
review times, greater predictability for industry, and most 
importantly, faster patient access to new therapies.
    So, I thank the committee for the user fee program. It has helped 
revolutionize our Nation's drug review process speeding access to new 
drugs and without compromising the Agency's high standards for product 
safety, efficacy, and quality. In 2014, CDER met its PDUFA goal dates 
for 98 percent of the novel drugs we approved (40 of 41).
    In addition to PDUFA, there have been a number of other important 
initiatives that have contributed to our progress in achieving these 
goals, including expedited FDA review programs, greater collaboration 
with industry, and the use of surrogate endpoints to advance drug 
development.
                     expedited fda review programs
    FDA's expedited review programs were established in recognition of 
the need to find ways for therapies intended for serious conditions in 
patients with unmet medical needs to get into the hands of patients and 
health professionals more quickly.
Accelerated Approval
    Around the time of PDUFA's passage, FDA created an ``Accelerated 
Approval'' program to permit certain drugs intended to treat serious 
and life-threatening medical conditions to be approved on the basis of 
a ``surrogate endpoint''--that is, using a biomarker or measure that is 
``reasonably likely'' to predict clinical benefit instead of directly 
measuring benefits to patients. As a condition of accelerated approval, 
sponsors must conduct or complete required post-approval studies to 
confirm that the drug actually helps people. Surrogate endpoints serve 
as stand-ins for clinical endpoints that measure the real benefits of 
drugs: whether a patient actually feels better or can function better, 
or lives longer. Surrogate endpoints generally allow clinical studies 
to be conducted in smaller populations of individuals over shorter 
periods of time, reducing both the time and cost of drug development. 
More information about how surrogate endpoints and other biomarkers are 
being used to advance drug development is included below.

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    CDER has approved over 90 new drug and biologics applications more 
rapidly because of the Accelerated Approval program. In 2014, CDER 
approved 8 of the 41 novel drugs approved (20 percent) under FDA's 
Accelerated Approval program.
Priority Review
    Drugs with the potential to deliver a significant improvement in 
safety or effectiveness over existing therapy for serious or life-
threatening illnesses may also be designated for ``priority review.'' 
Priority review drugs receive a shortened, 6-month FDA review goal. For 
example, from the beginning of 2008 through the end of 2014, 93 novel 
drugs and biologics approved by CDER received the shortened, 6-month 
review dictated by priority-review designation. In 2014, 25 of the 41 
novel drugs approved by CDER were designated Priority Review.

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Fast Track
    Another expedited program that helps reduce the time to market for 
drugs being developed for serious and life-threatening illnesses is 
known as ``fast track.'' Fast-Track designation generally may be used 
for drugs intended to treat a serious condition where nonclinical or 
clinical data demonstrate the drug's potential to address an unmet 
medical need.
    When a drug receives Fast-Track designation, FDA works closely with 
its sponsor to facilitate submission of the drug development plan, the 
design of clinical trials, and to identify any other data necessary to 
support FDA approval of the drug. Moreover, once the sponsor begins to 
develop the data to support approval, it can submit that data for 
``rolling review.'' Rolling review allows a sponsor to submit portions 
of a marketing application in advance of the entire application, rather 
than submitting all portions of the marketing application at once, 
which is the usual process.
    Seventy-six novel drugs and biologics were approved by CDER from 
2008 to 2014 with Fast-Track designation. Seventeen of the 41 novel 
drugs (41 percent) approved by CDER in 2014 were designated as Fast 
Track.

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Breakthrough Therapy Designation
    In 2012, Congress provided the ``Breakthrough Therapy'' designation 
as another new tool for expediting important new advances in therapy 
for serious and life-threatening illnesses.
    Breakthrough therapy designation may be granted for a drug that is 
intended to treat a serious condition, where preliminary clinical 
evidence (i.e., in people) indicates that the drug may demonstrate 
substantial improvement on one or more clinically significant endpoints 
over available therapies. Such breakthrough therapies, like drugs that 
receive Fast-Track designation, receive intensive guidance from FDA, to 
help sponsors better tailor their drug development program and, thus, 
maximize the prospects for a rapid and successful path to approval. In 
addition, breakthrough therapy drugs receive an organizational 
commitment from FDA's senior managers and experienced review staff to 
collaborate in advancing the review of these potentially high-impact 
drugs.
    As of April 16, 2015, CDER and the Center for Biologics Evaluation 
and Research (CBER) have designated more than 84 new therapies as 
breakthrough therapies, and 24 have received marketing approval. 
Moreover, initial experience with the breakthrough process has yielded 
more rapid FDA review times in many cases and shortened overall 
development times for these therapies. Continued success of the 
breakthrough therapy drug program is expected as a result of FDA's 
intensive collaboration with new drug sponsors. CDER designated 9 of 
the 41 novel drugs (22 percent) approved by the Center in 2014 as 
breakthrough therapies.

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                  greater collaboration with industry
    The movement toward greater collaboration between industry and FDA, 
embodied in such initiatives as the Breakthrough Therapy program, is 
reflected throughout our efforts and is one of the more significant 
changes that has occurred during my time at FDA. In recent years, 
meetings between FDA and industry have become routine and have proven 
to be invaluable in improving communication about planned clinical 
trials, development milestones, and data requirements.
    The impact of improved FDA/industry communication is becoming 
increasingly evident. Recently, FDA took a look at the development 
times of new drugs that were approved with the benefit of pre-
Investigational New Drug (IND) meetings and compared them to the 
development times for drugs that were approved without such meetings. 
The results were quite remarkable. For instance, for all new drugs 
approved between 2010 and 2012, the average clinical development time 
was more than 3 years faster when a pre-IND meeting was held, than it 
was for drugs approved without a pre-IND meeting. A 2014 article in The 
Lancet, ``Biomedical research: increasing value, reducing waste'' 
(January 11, 2014), noted that 85 percent, or $200 billion, of annual 
global spending on research is wasted on badly designed studies, and I 
believe that greater industry-FDA collaboration can significantly 
reduce such wasted effort.
    Another result of improved collaboration between industry and FDA 
is a substantial reduction in the number of application review 
``cycles.'' The phenomenon of ``multiple review cycles'' occurs when a 
sponsor submits a marketing application for approval and FDA does not 
approve the drug during the first-review cycle. The most efficient 
outcome for both the Agency and industry is for an application to 
receive approval on the first-review cycle, if the drug is ultimately 
approvable. Not receiving FDA approval on the first cycle means that 
the sponsor must go back and take steps to collect additional data or 
address a deficiency in their marketing application and then resubmit 
their application, which FDA must then review again. But achieving 
first-cycle approval requires a well-prepared application with no major 
deficiencies.

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    As a result of better collaboration between industry and FDA, which 
has helped companies identify the data and analyses needed for approval 
before the application is submitted, first-cycle approvals, which until 
recently occurred for fewer than half of all novel drug submissions, 
are now exceeding 70 percent. For example, CDER approved 78 percent of 
the 41 novel drugs it approved in 2014 on the first cycle. This 
translates into reduced costs for industry and earlier patient access 
to new therapies, as illustrated by the charts. The early and frequent 
communications that characterize some of the expedited development 
programs were not possible before user fees were established, so, once 
again, I commend this committee for the authorization--and 
reauthorization--of the user fee program.

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         using surrogate endpoints to advance drug development
    As noted above, FDA routinely permits the use of surrogate 
endpoints as the basis for Accelerated Approvals, when the surrogate is 
reasonably likely to predict clinical benefit in a serious or life-
threatening disease that lacks good therapies. However, when scientific 
study has progressed sufficiently to establish the correlation between 
the surrogate endpoint and clinical benefit, the surrogate endpoint 
then may be relied upon as the basis for traditional approval, thereby 
negating the need for the confirmatory studies requirement, to which 
drug sponsors are subject, under Accelerated Approval. For example, 
reducing elevated blood pressure levels is a well-known surrogate 
endpoint to reflect reduction in cardiovascular outcomes such as 
stroke. Over many years, FDA has allowed the traditional approval 
pathway to be used in approving a wide range of blood pressure 
medicines, thereby dramatically expanding options for fighting stroke 
and other related cardiovascular conditions.
    During the last 5 years (2010-14), out of a total of 197 novel 
drugs and original biologics approved across FDA, 84 (43 percent) 
relied upon a surrogate endpoint for approval. A table listing the 
surrogate endpoints relied upon for these 84 approval determinations 
(covering both traditional approvals and accelerated approvals) is 
attached as an appendix.

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              a growing record of action on new therapies
    Each of the improvements noted above has contributed to speed both 
the development and the review of new therapies to prevent and fight 
disease. This past year provides an example of how those improvements 
are working; FDA approved 51 novel drugs and original biologics, 41 by 
CDER, 10 by CBER. Additionally, 21 of these 51 novel drugs were for 
orphan diseases.
    The lag in approval times compared to approvals in other countries 
that existed many years ago has been reversed. Today, FDA approves 
drugs faster on average than all other developed nations: 40 days 
faster than Japan; 70 days faster than Canada; and 174 days faster than 
the European Union (EU). As the British-based Centre for Innovation in 
Regulatory Science recently reported, over 75 percent of the new drugs 
approved by Japan, EU, Canada, Australia, Switzerland, and FDA, from 
2004 to 2013, were approved first by FDA. Yet, another independent 
analysis concludes that FDA continues to lead the EU and other advanced 
regulatory authorities in the introduction of novel drugs, as shown by 
the following graph.

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    The most important effect of this progress is that American 
patients with untreatable or poorly treated diseases are receiving the 
newest therapies rapidly and well before their counterparts in other 
nations. In addition, the major enhancements that FDA has made in the 
drug safety surveillance system means that American patients can also 
be confident that these newly approved drugs continue to have intense 
scrutiny after they are marketed in the United States to detect any 
unexpected side effects and allow for quick and appropriate FDA action.
                            the path forward
    Despite the progress that has been made, and as this committee has 
noted, there are hurdles to overcome, if we are to ensure continued 
U.S. leadership in the biomedical sciences. While Congress and FDA have 
worked successfully together to greatly reduce FDA review times, many 
of the serious challenges for drug development occur before FDA review 
even begins. If the explosion in basic scientific knowledge is going to 
efficiently translate into the treatments and cures patients need, we 
must work together to overcome critical infrastructure and scientific 
hurdles that prevent the advances we all desire. In January 2015, the 
Administration unveiled the Precision Medicine Initiative, a vital new 
research effort to catalyze improvements in targeting treatment to the 
right patient at the right time. Launched with a $215 million 
investment in the President's 2016 Budget, the Precision Medicine 
Initiative promises to arm clinicians with new tools, knowledge, and 
therapies that will work best for each patient. Below, I have described 
a few specific areas which advance the development of new therapies for 
patients.
Reducing Clinical Trial Costs
    First, the cost of clinical trials continues to grow and is the 
greatest source of cost increases in medical product development. 
Today, developers of a new medicine spend many millions of dollars 
planning a clinical trial, developing an elaborate trial 
infrastructure, finding and enlisting investigators, conducting the 
trials, and managing the trial data. Each time a new drug is tested, 
the process is repeated, at great expense, only to dismantle the 
infrastructure when the study is completed.
    We believe that there are ways to greatly improve clinical trial 
efficiency, such as widespread use of clinical trial networks and 
master protocols, and we would like to work with you to examine those 
possibilities.
Enhancing the Science of Biomarkers and Other Tools
    Second, the science of identifying and evaluating the utility of 
biomarkers and other scientific tools must be greatly enhanced. These 
tools can be used to predict and evaluate the effects of candidate 
drugs, both before clinical testing, and in people. Biomarkers are 
technically defined as physical, biochemical, or genetic 
characteristics that are objectively measured and evaluated as 
indicators of health, disease, or in assessing the response to a 
therapeutic intervention. In other words, biomarkers are the results of 
tests done on the body, such as blood sugars or a chest x-ray. 
Biomarkers have many uses in drug development, such as identifying 
appropriate patients to enroll in a clinical trial, performing safety 
monitoring, and selecting therapy for treating specific patients. 
Hundreds of biomarkers are used today in drug development. However, 
biomarkers based on new scientific understanding have been slow to come 
into clinical use, largely because the evidence supporting their 
validity has been lacking. The lack of new, well-understood biomarkers 
also impacts drug development, these new tests could speed evaluation 
of drug performance, including drug safety, and prediction of 
effectiveness. Similar to the problems with clinical trials, the 
scientific infrastructure for evaluating the validity of new biomarkers 
has not kept pace with the need for this activity.
    Typically, drug sponsors interact with FDA about new biomarkers 
during clinical drug development, when an IND has been filed for a new 
molecule. These discussions are confidential, and while new biomarkers 
may be used in a specific drug development program, they are not 
necessarily subject to broad scientific scrutiny. To address this 
situation, CDER recently established a Biomarkers Qualification 
Program. In this program, biomarkers that have demonstrated performance 
for a certain use are designated by FDA as qualified biomarkers, and 
can be used during the regulatory process by any developer for that 
specific context of use. These qualified biomarkers are only a subset 
of the biomarkers FDA has used in the review process.
    FDA recognizes that there is still confusion about how new 
biomarkers can be qualified through this process. Some believe that 
many biomarkers are ``stalled'' in the qualification process. The 
actual case is that most of the programs in the biomarker qualification 
process are still in the evidence-gathering stage--which may take 
considerable time due to the need for more development work within the 
scientific community.
    However, it is important to note that biomarkers do not need to go 
through this formal qualification process, and most do not. As 
mentioned previously, FDA has the ability to work directly with drug 
sponsors who wish to utilize various new biomarkers within their drug 
development program. For example, sponsors can propose a surrogate 
endpoint--one type of biomarker--to be used in clinical trials based 
upon the scientific communities' existing knowledge about the 
particular surrogate endpoint. A sponsor can request FDA's agreement on 
this surrogate endpoint through the ``Special Protocol Assessment'' 
process that is embodied in the PDUFA program. These product-specific 
surrogate endpoints are one example of biomarkers that do not need to 
pass through our formal qualification process in order to be used to 
support drug development and review. Biomarkers are also important in 
the growing field of so-called ``personalized'' or ``precision'' 
medicine, in which drugs are targeted at a genetically determined or 
other disease characteristic that only occurs in a subset of people 
with the disease. Targeted drug development is one of the most 
promising areas for future drug therapy. Patients are chosen for 
treatment based on specific test results (such as a genetic test or 
other biomarker), indicating that the patient's disease (tumor, 
hepatitis C, cystic fibrosis) is likely to respond to the drug.
    In the early 1990s, targeted therapies represented only 5 percent 
of FDA's new drug approvals. In recent years, roughly one-quarter of 
the drug approvals has been supported by targeted drug development 
programs, and that rate appears to be growing over time. Important, 
new, recently approved, targeted cancer treatments include: Mekinst 
(trametinib) and Tafinlar (dabrafenib) for forms of melanoma; Imbruvica 
for forms of lymphoma and leukemia; and Zykadia (ceritnib) for a form 
of lung cancer. The development of such targeted therapies is clearly 
expanding rapidly. Similarly, targeted treatments for other diseases 
have been approved, including treatments for cystic fibrosis and 
ground-breaking treatments for hepatitis C that are potentially 
curative for the majority of treated patients. As targeted therapies 
become ubiquitous, advances in standardizing and increasing our 
understanding of the biomarkers that enable use of these therapies will 
be necessary.
Harnessing Evidence from Clinical Experience
    Another source of information about drug effects is evidence from 
clinical experience (called ``real world evidence'' or ``big data,'' by 
some). I have aggressively developed FDA's Sentinel Initiative, a 
national electronic system that is transforming FDA's ability to track 
the safety of drugs and biologics once they reach the market. Sentinel 
enables FDA to actively query diverse health care data sources--such as 
electronic health record systems, administrative and insurance claims 
data bases, and registries--to evaluate possible medical product safety 
issues quickly and securely. The Sentinel Initiative is one of the 
largest uses of this type of information in health care and is proving 
vital for monitoring safety and analyzing safety signals. But the 
science of using evidence from clinical experience to establish product 
effectiveness, e.g., to evaluate new uses of drugs, is still in its 
infancy. So we must first develop the methodologies needed to harness 
its promise.
Strengthening Patient Engagement
    The final example focuses on making patient experience more central 
to drug development. FDA recognizes that patients living with a chronic 
disease are experts in the effects of that disease and its current 
treatments. As you know, the FDA Safety and Innovation Act (FDASIA) 
instructed the Agency to begin a process for incorporating more patient 
experience into drug development, and we have had numerous public 
meetings to gain important insights from patients. But we recognize 
that information needs to be collected in a structured and 
representative way to be most useful in drug development. I hope that 
we can work with you to further the movement toward patient-focused 
drug development in your upcoming legislation.
                               conclusion
    There are other areas in which we hope to work with you as well, 
including modernizing drug manufacturing, encouraging the development 
of new antibiotics, and improving the processes for FDA review of drug/
device combination products. I believe all of the challenges I have 
described above are ones on which FDA, the drug industry, and patient 
groups have common interests. We look forward to working with Congress 
to address these challenges in ways that will serve patients and 
pharmaceutical innovation well.
    Thank you again for inviting me to share my views today.
                                 ______
                                 
                               Attachment
            novel drugs--approved using surrogate endpoints*

                  (January 1, 2010-December 31, 2014)

    Before the U.S. Food and Drug Administration (FDA) approves a drug 
or biologic, the product must show substantial evidence of 
effectiveness in clinical trials and that the benefits outweigh the 
risks. Clinical trials measure benefit using clinical endpoints, 
surrogate endpoints, or other types of measurements. Clinical endpoints 
measure how a patient feels or functions better, or lives longer. 
Surrogate endpoints are biomarkers, such as a laboratory test, 
radiographic image (e.g., x-rays, MRIs), and physical sign (e.g., blood 
pressure), that substitute for clinical endpoints in certain 
circumstances.
---------------------------------------------------------------------------
    * In the last 5 years, FDA approved 197 novel drugs and biologics; 
84 relied upon surrogate endpoints.
---------------------------------------------------------------------------
    A surrogate endpoint may serve as the basis for traditional 
approval when it is known, through scientific study, to predict 
clinical benefit. A surrogate endpoint may serve as a basis for 
Accelerated Approval when it is reasonably likely to predict a drug's 
intended clinical benefit. Drugs approved under Accelerated Approval 
are subject to the requirement of post-approval confirmatory trials.
    From 2010-14, FDA approved 197 novel drugs, known as new molecular 
entities (NMEs), and New Biologic Approvals that include both New Drug 
Applications (NDAs) and Biologic License Applications (BLAs). The 
following table shows the 84 NME drugs and original biologics approved 
during that time period that relied upon a surrogate endpoint for an 
approval determination (i.e., traditional approval or Accelerated 
Approval). Many of these drugs have orphan designation, which means 
that they are intended to treat rare or uncommon diseases.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    The Chairman. Thanks, Dr. Woodcock.
    Dr. Shuren.

 STATEMENT OF JEFFREY E. SHUREN, M.D., J.D., DIRECTOR, CENTER 
      FOR DEVICES AND RADIOLOGICAL HEALTH, FOOD AND DRUG 
               ADMINISTRATION, SILVER SPRING, MD

    Dr. Shuren. Mr. Chairman and members of the committee, 
thank you for the opportunity to testify today.
    Medical technology is transforming the way America 
practices medicine and making a difference in patients' lives. 
Expediting patient access to new medical devices is critical 
but only if that technology is safe and effective. We know that 
unnecessary regulatory burden can drive innovators to seek more 
favorable environments, which can impact timely patient access 
to potentially lifesaving therapeutics.
    We also know that lax oversight can lead to patient harm. 
Medical devices that have not been shown to be safe and 
effective can hurt American patients and can drive up 
healthcare costs.
    In 2010, FDA's medical device program faced severe 
problems. Some consumer, patient, payer, and practitioner 
groups thought we weren't doing enough to assure patient 
safety, while industry felt that we had raised the safety and 
effectiveness bar too high and that we were taking far too long 
to review new device submissions. In fact, from 2000 to 2010, 
measures of device review performance showed steadily worsening 
performance year after year.
    Recognizing the need to address these concerns and 
strengthen the device program, CDRH began to make systematic 
changes to our policies, processes, and management oversight. 
Since then, the performance of the device program has been 
steadily improving.
    For example, since 2010, we've reduced the average total 
review time of 510(k)'s for moderate-risk devices by 10 percent 
and cut the number of pending submissions by about 30 percent. 
For PMAs for high-risk devices, we've cut the average total 
review time by 26 percent and are on track to reduce it by one-
third, and we've cut the number of pending submissions by 43 
percent.
    For De Novos, a pathway for innovative lower risk devices, 
we've cut nearly 2 years off the review process and seen almost 
a doubling of De Novo requests. At CDRH, we have focused our 
strategic priorities on reducing the time and cost of bringing 
devices to market so that companies will bring their devices to 
the United States first while still meeting the U.S. safety and 
effectiveness standard.
    One of our priorities is to strengthen the clinical trial 
enterprise. We've already reduced the median time to full 
approval of a clinical trial by almost 1 year and are poised to 
meet our goal of reducing the median time from 442 days to 30 
days, and our first cycle approval times for clinical trials 
has increased ninefold.
    We've recently launched a pathway for breakthrough devices 
called the Expedited Access Pathway program. This program 
provides manufacturers the opportunity to ship the collection 
of some data where we otherwise require premarket to the post-
market setting. Post-market data includes information gathered 
as a part of routine clinical practice, such as through device 
registries and electronic health records. In fact, we are 
already relying on registry data to approve expanded device 
indications.
    If our proposal for a national surveillance system for 
medical devices is fully implemented, we can further reduce 
premarket data requirements through greater reliance on post-
market data collection and, just as important, improve patient 
safety. Last year, we created a multi-stakeholder planning 
board which included patients, practitioners, payers, and 
industry. The board recently released their recommendations for 
implementing the system.
    CDRH also believes that patients should have a say in our 
review decisions. We've begun our initiative to utilize patient 
preference data in our review of a device's benefits and risks. 
Just recently, CDRH used such data in the approval of the first 
device to treat obesity since 2007.
    Flexibility already built into the existing statutory 
framework for medical devices allows us to adapt to emerging 
technologies. For example, over the past few years, we decided 
to no longer oversee many lower risk software medical devices 
we previously regulated. We recognize that our oversight is 
best suited for higher risk functions, and by removing our 
oversight in the low-risk digital area, we are able to help 
stimulate the development of health-related mobile apps.
    In response to the emergence of next-generation sequencing 
platforms, we have leveraged data from curated data bases 
rather than require new clinical studies to help bring 
innovative tests to market. We recently proposed a new 
regulatory model for next-generation sequencing tests that 
would routinely rely on evidence generated by the clinical 
community rather than on company-sponsored clinical studies.
    Today, the medical device program is in a better place to 
protect and promote public health than when I testified before 
you in 2011. But we know we still have more to accomplish.
    It is my hope that whatever this committee decides to do--
and we appreciate the opportunity to work with you--it does not 
impede the strong progress we have made nor lose sight of the 
tremendous effort and dedication of the medical device program 
staff and managers.
    Mr. Chairman, I commend the committee's efforts and I'm 
pleased to answer questions the committee has.
    [The prepared statement of Dr. Shuren follows:]
            Prepared Statement of Jeffrey Shuren, M.D., J.D.
    Chairman Alexander, Ranking Member Murray, and members of the 
committee, I am Jeffrey Shuren, Director, Center for Devices and 
Radiological Health (CDRH) at the Food and Drug Administration (FDA). I 
am pleased to be here today to discuss FDA's work to promote patient 
access to innovative medical devices while ensuring appropriate patient 
protections.
                              introduction
    Advances in medical technology are transforming established medical 
practice and bringing completely new models of treatment, prevention, 
and diagnosis to patients right now. New devices include not only 
improvements over existing technology--devices that make less-invasive 
treatments possible and provide new options to patients whose condition 
would have been considered untreatable in the past--but also 
technologies that will be keystones in emerging fields, such as 
precision medicine. Genetic testing offers the promise of targeting the 
right treatment to the right patients, reducing ineffective treatment 
decisions, and speeding the delivery of therapies that work. Health 
information technology can empower people with chronic diseases to 
manage their own health and well-being by putting medical ``apps'' 
right into the hands of patients. FDA has responded to the promises--
and challenges--posed by these devices with flexible, risk-based 
approaches to its oversight role and with strong performance in 
bringing new, safe and effective products to market.
    At the same time, FDA needs to ensure it is delivering on its 
oversight role. This role requires that FDA facilitate patient access 
to new medical technology while providing the oversight to minimize 
unnecessary risks and ensure devices provide clinical benefit. At one 
end of the spectrum, unnecessary regulatory burden could drive 
innovators to seek more favorable environments, potentially depriving 
American patients of timely access to needed therapeutic and diagnostic 
devices. At the other end of the spectrum, lax oversight could lead to 
patient harm from devices that have not been tested and shown to be 
safe and effective, and affect the marketplace by reducing confidence 
in the health care system that devices will do what they are intended 
to do without harming the patients they are intended to benefit. A 
flexible, risk-based approach to oversight of medical technology is 
critical to striking the right balance.
    FDA's existing framework establishes flexibility that has allowed 
FDA to develop innovative approaches to medical device oversight, 
approaches that reduce unnecessary burden without compromising 
assurances that devices marketed to American patients are safe and 
effective. Improvements to FDA's device program have already resulted 
in decreased review times and timely patient access to important new 
devices. And while other changes are too new to evaluate, early signs 
are positive and point to additional improvements in timely access for 
U.S. patients to safe and effective devices.
                                 ______
                                 
                         Glossary of Key Terms
    510(k)--An application to FDA for market clearance of Class II 
devices and a small number of Class I devices. The manufacturer must 
demonstrate that the device is ``substantially equivalent'' to a 
legally marketed device. FDA currently reviews 510(k)s for fewer than 
10 Class III devices that were legally marketed before 1976. FDA is in 
the process of reclassifying or finalizing calls for PMAs for these 
devices.
    De Novo--A premarket request for FDA to classify a novel device 
into Class I or Class II.
    IDE--Investigational Device Exemption: An application to conduct 
studies on human subjects.
    MDUFA--Medical Device User Fee Act: An agreement between FDA and 
industry that FDA will take certain actions and attain performance 
goals in exchange for industry user fees.
    PMA--Premarket Approval Application: The application to FDA for 
Class III devices. The manufacturer must demonstrate a reasonable 
assurance of safety and effectiveness to gain approval of a PMA.
                                 ______
                                 
          the u.s. regulatory environment for devices: 2010-15
Performance of FDA's Device Program
    In the early part of this decade, many policymakers and FDA 
stakeholders called for reform of FDA's device program, arguing that 
FDA regulation was driving companies to relocate overseas or market 
their devices abroad before introducing them in the United States. To 
support their arguments, critics pointed to contemporary surveys of 
device manufacturers and FDA's own data showing a decline in the 
performance of its premarket program from 2000 to 2010. Although FDA 
raised questions about the methodology used in some of these 
studies,\1\ the underlying premise that industry's perception of FDA 
oversight can affect decisions about introducing new technology in the 
U.S. marketplace is important. This premise, as well as FDA's own 
awareness of the Agency's worsening performance numbers, moved FDA to 
implement a number of new policies and programmatic changes over the 
past 5 years to improve its performance and to adapt its oversight to 
the global marketplace, and to new technologies. Added funding and 
increased capacity, as the result of the 2012 reauthorization of MDUFA 
also helped reverse the direction of the Agency's medical device 
premarket program.\2\
---------------------------------------------------------------------------
    \1\ These arguments often rely on studies published early in this 
decade to support these assertions--the methodology of which FDA has 
questioned. See Letter from Jeanne Ireland, Assistant Commissioner for 
Legislation, FDA, to Ranking Member Henry A. Waxman (July 11, 2011) 
http://democrats.energycommerce.house.gov/sites/default/files/
documents/Waxman-FDA-Concerns-Regarding-Makower-Study-of-Medical-
Device-Regulation-2011-7-18.pdf.
    \2\ FDA estimates that it has added at least 190 of the planned 240 
staff authorized by MDUFA III, since the end of fiscal year 2011. These 
additional staff members have contributed to FDA achieving the new 
performance goals under MDUFA III.
---------------------------------------------------------------------------
    Today, the performance of FDA's device program has significantly 
improved. FDA is on track to meet all of its MDUFA performance goals 
related to device review, and premarket performance measures of FDA's 
device program show marked improvement since the start of the current 
decade on several measures related to how quickly devices come to 
market in the United States.
    FDA is making progress in bringing down total review times for 
510(k) submissions, de novo requests, IDEs, and the higher risk PMA 
applications. While data is not complete for the years 2013 and 2014 
because some applications remain open, existing data show improvements 
on several important measures:\3\
---------------------------------------------------------------------------
    \3\ Appendix A provides additional data showing the current 
performance of FDA's device program, including data over several years 
that show the course of improvement over the past 5 years.

---------------------------------------------------------------------------
     Time to decision on device submissions has decreased:

          510(k)s: The vast percentage of device premarket 
        submissions received by FDA in any given year are 510(k)s. In 
        fiscal year (FY) 2010, it took 116 days for a total time to 
        decision on a 510(k). By fiscal year 2014, total time had 
        dropped by 10 percent to about 105 days (these figures compare 
        review times when 75.8 percent of submissions are closed).
          PMAs: Original PMAs generally account for only about 
        1 percent of all device applications received by FDA. Average 
        total time to decision in fiscal year 2014 has decreased to 236 
        days from 320 days at its peak in fiscal year 2009, or an 
        improvement of 26 percent (these figures compare review times 
        when 41 percent of applications are closed). Once all fiscal 
        year 2014 applications are closed, we project performance will 
        meet or exceed fiscal year 2012 levels, which would be at least 
        a 32 percent improvement since 2009.
          IDEs: Median total time to full IDE approval decision 
        has decreased from 442 days in fiscal year 2011 to 101 days in 
        fiscal year 2014, reducing the time it takes to bring a new 
        medical device to market by nearly a full year. The number of 
        IDE studies requiring more than two cycles to full approval has 
        been reduced by 34 percent.
          De novo: The average total time to final decision for 
        de novo requests (510(k) plus de novo review) submitted after a 
        device was found to be not substantially equivalent through the 
        510(k) process has been reduced from 992 days in fiscal year 
        2010 to 300 days in fiscal year 2014.

     Another measure of the performance of the medical device 
program is that FDA is working with industry to ensure that submissions 
are complete and ready for review. As a result, the percentage of 
submissions that are cleared and approved has increased since 2010:

          The percentage of 510(k)s cleared increased from 73 
        percent to 84 percent.
          The percentage of PMAs approved increased from 59 
        percent to 86 percent.

     The number of pending submissions at the end of a year has 
significantly decreased since 2010:

          The number of 510(k) submissions has been reduced by 
        30 percent.
          The number of PMA submissions pending has been 
        reduced by 43 percent.

    Our experience also suggests that there is marked improvement in 
the medical device industry's perception of FDA. In 2014, CDRH made 
providing excellent customer service a strategic priority and launched 
an effort to improve customer service that included staff training, 
surveys to assess interactions with customers and measure customer 
satisfaction, and, based on feedback from customers, actions to improve 
the quality of CDRH actions and services. CDRH's 2014 results show 83 
percent satisfaction. While customers include everyone who interacts 
with FDA's medical device program, CDRH's results generally appear to 
track our experience.
                     framework for device oversight
    The basic framework under which FDA oversees devices was put in 
place almost 40 years ago, when Congress enacted the Medical Device 
Amendments of 1976 (MDA). The MDA established a flexible framework for 
FDA's oversight of medical devices and required that FDA tailor its 
oversight of devices to the degree of risk presented. Although the 
framework established under the MDA recognizes that medical devices 
inherently carry risk, the MDA did not mandate that FDA eliminate risk. 
Rather, FDA applies only the level of oversight necessary to establish 
a reasonable assurance of safety and effectiveness for devices. Under 
this framework, only about half of all devices are subject to any 
premarket review by FDA, and, of the devices that are subject to 
premarket review, FDA reviews clinical data for fewer than 20 percent 
because there are other, less-burdensome means to determine that there 
is a reasonable assurance that a device is safe and effective.\4\
---------------------------------------------------------------------------
    \4\ The 20 percent includes in vitro diagnostics (IVD) devices, 
which typically contain test results based on human-derived samples. 
When IVDs are excluded, the number of submissions with clinical data 
drops to fewer than 10 percent.

    FDA oversight of devices is tailored to three risk-based 
---------------------------------------------------------------------------
classifications:

     Class I, or low-risk devices:  FDA does not review any 
premarket information for Class I devices, with the exception of a 
small subset of Class I ``reserved'' devices. Class I makes up about 50 
percent of all medical devices. An example of a Class I device is an 
elastic bandage.
     Class II, or moderate-risk devices:  FDA generally reviews 
510(k) submissions for these devices, which requires a demonstration of 
substantial equivalence to a legally marketed device. About 80 percent 
of all 510(k)s contain only non-clinical data. Examples of Class II 
devices include glucose test strips and infusion pumps.
     Class III, or high-risk devices:  FDA generally reviews 
PMAs containing clinical and non-clinical data to determine whether 
there is a reasonable assurance of safety and effectiveness for these 
devices. FDA generally reviews about 40 PMAs a year. Examples of PMA 
devices include heart valve replacements and diagnostic tests used to 
select ovarian cancer patients for a drug regimen.

    FDA's evidentiary standard for premarket review of devices is valid 
scientific evidence, a standard established by Congress in 1976 that 
still sets the benchmark for evidence to support premarket submissions. 
This benchmark ensures that the evidence is of sufficient quality that 
it can be relied on to determine whether or not a device should be 
approved or cleared. Although valid scientific evidence includes 
randomized-controlled clinical trials, the overwhelming majority of 
devices come to market based on non-clinical data, small clinical 
studies, or both. The valid scientific evidence standard encompasses 
many other forms of evidence, such as bench testing, journal articles, 
observational data, and foreign studies.
    In vitro diagnostic (IVD) devices have been regulated by FDA under 
its risk-based device framework since the inception of the device 
program. Diagnostic tests can be used in the context of acute 
outbreaks, such as the recent Ebola outbreak, and in the diagnosis and 
treatment, including management, of chronic diseases like cancer and 
diabetes. Success in combating these diseases depends on diagnostic 
tests that can accurately detect them and be used to select and manage 
treatments. A case in point is the widespread use of glucose meters and 
diabetes test strips. These devices can empower people with diabetes to 
manage their diseases independently, but only when the devices are 
accurate. In recent years, test reports of falsely high and low blood 
sugar levels have led to multiple recalls of these products over 
concerns that false readings could lead to incorrect treatment 
decisions; in particular, insulin administered in response to falsely 
high measures of blood sugar could lead to acute hypoglycemia, coma, 
and even death, if left untreated. The American Diabetes Association 
issued a statement of strong support of FDA oversight of these tests, 
stating:

          The American Diabetes Association strongly endorses [FDA] 
        oversight of test strip manufacturers[]. The Association 
        applauds the FDA's requirements that all test strips meet 
        existing FDA standards for medical devices, since those 
        standards are designed specifically to require the greatest 
        accuracy in readings when an error would place a patient's 
        health and life in danger.\5\
---------------------------------------------------------------------------
    \5\ http://professional.diabetes.org/News_Display.aspx?CID=93129.

    For IVD devices, a reasonable assurance of safety and effectiveness 
means that a test has analytical and clinical validity. ``Analytical 
validity'' assesses how well the test detects or measures certain 
markers in human specimens. ``Clinical validity'' assesses whether the 
marker has clinical significance, such as correlation with disease or 
the ability to predict a therapeutic response to a drug. As FDA's 
recent announcement--that it intends to exempt carrier screening tests 
from premarket review--shows, the level of data FDA requires to show 
analytical and clinical validity for IVD devices depends largely on 
risks from the device.
    The central features of FDA's device program--a risk-based 
framework that tailors oversight to device risk; a flexible review 
standard that requires a reasonable assurance of safety and 
effectiveness; and an adaptive but scientifically grounded evidentiary 
standard of valid scientific evidence--have served the public well. 
While there have been multiple amendments to FDA's original authority, 
providing new premarket pathways and enhancing FDA's post-market 
oversight, the framework put in place by the MDA continues to provide 
the tools to assure safety and effectiveness of therapeutic and 
diagnostic devices while allowing FDA to adapt its oversight to the 
demands of rapidly evolving medical technology.
      adapting fda's oversight role to current challenges: 2010-15
    The new policies and programmatic changes FDA has implemented in 
the past 5 years respond to the needs of American patients to have 
timely access to high-quality, and safe and effective devices, and to 
challenges created by rapidly evolving fields of medical innovation. 
These initiatives have had far-ranging objectives, from providing FDA 
review staff with new tools to assess the benefits as well as the risks 
of a device to American patients to promoting regulatory certainty and 
empowering patients to manage their well-being. Among these initiatives 
are process improvements and policy changes to its oversight of 
clinical investigations of devices.
Streamlining Clinical Trials
    In 2014, FDA established a Clinical Trials Program to coordinate 
its oversight of clinical studies of devices; provide interventions if 
a review of an application to conduct a clinical investigation of a 
device (Investigational Device Exemption or IDE) takes more than one 
cycle; offer more opportunities for interactions with sponsors; expand 
training for review staff; and establish new or modified policies in 
this area. For example, recognizing that devices that are studied in 
the United States in the early stages of clinical assessment are more 
likely to reach U.S. patients sooner in pivotal trials and as marketed 
devices, FDA implemented a pilot program in 2011 to encourage early 
feasibility studies, or early stage clinical studies, of devices in the 
United States. In 2013, FDA issued final guidance on early feasibility 
studies;\6\ under this program, FDA may accept a higher degree of 
uncertainty during the device development process to facilitate 
important early clinical evaluation of promising technologies. As a 
result, we are beginning to see an increase in companies submitting 
IDEs for early feasibility studies in the United States and more 
approvals of such IDEs. In the past 2 years, we have reduced the median 
time to approval for early feasibility studies by 70 percent, from 226 
days in fiscal year 2013 to 66 days in fiscal year 2015.
---------------------------------------------------------------------------
    \6\ Investigational Device Exemptions (IDEs) for Early Feasibility 
Medical Device Clinical Studies, Including Certain First in Human (FIH) 
Studies: Guidance for Industry and FDA Staff (October 1, 2013), 
available at http://www.fda.gov/downloads/medicaldevices/
deviceregulationand
%20guidance/guidancedocuments/ucm279103.pdf.
---------------------------------------------------------------------------
    Devices that are studied in the United States in the early stages 
of development are more likely to reach U.S. patients sooner in pivotal 
studies and as marketed devices. In the past 15 fiscal years, for those 
original PMAs whose approval was based on FDA-approved pivotal clinical 
studies, 94 percent (283 out of 300) of these approvals were based on a 
single pivotal clinical study. More recently, in the past 5 years, the 
number has increased to 98 percent (82 out of 84). Of the 82 FDA-
approved original PMAs whose approval was supported by a single pivotal 
clinical study, 32 (39 percent) included studies enrolling subjects 
outside of the United States. For IVD devices, where clinical studies 
are typically conducted in at least three sites, sponsors generally 
choose to have one of those sites inside of the United States to 
address differences between the United States and other countries in 
how medicine is practiced, patient populations, and disease 
progression.
    FDA is facilitating and encouraging the use of innovative clinical 
trial designs and statistical methods such as adaptive clinical trials 
and Bayesian statistics. By incorporating existing clinical information 
about devices into statistical analyses, adaptive clinical trials such 
as the Bayesian approach can support a marketing application for a 
device based on shorter and smaller clinical trials. In 2010, FDA 
published a guidance document on how Bayesian methods can be used to 
design and analyze data from medical device clinical trials.\7\ FDA's 
efforts to promote the appropriate use of adaptive trial designs to 
support premarket device applications date to the late 1990s\8\ and in 
recent years, many devices have come to market based on adaptive trial 
designs. For the period from 2007 to May 2013, FDA received 250 
submissions that were adaptive, most of which were pre-submissions and 
IDEs. About 30 percent of these used Bayesian methodologies. In 
addition, there were 17 PMAs and PMA Supplements that used adaptive 
clinical trials from 2007 to May 2013, eight of which used Bayesian 
methodologies.
---------------------------------------------------------------------------
    \7\ Guidance for the Use of Bayesian Statistics in Medical Device 
Clinical Trials (February 5, 2010), available at http://www.fda.gov/
medicaldevices/deviceregulationandguidance/guidance
documents/ucm071072.htm.
    \8\ Gregory Campbell (2011) Bayesian Statistics in Medical Devices: 
Innovation Sparked by the FDA, Journal of Biopharmaceutical Statistics, 
21:5, 871-87, DOI: 10.1080/10543406.2011
.589638. This article refers to 16 approved PMAs that relied on 
Bayesian analysis and one cleared 510(k); there have been several 
additional device approvals since 2011, but an exact number is not 
available.
---------------------------------------------------------------------------
    These programmatic improvements and policy changes have already 
yielded results in significantly reduced time to approval of IDEs and 
increasing approval rates. While the full effect of these programmatic 
improvements on U.S. health care will not be known for several years, 
streamlined processes for initiating device studies in the United 
States and reductions in the time to approval for U.S. clinical studies 
are promising developments in the effort to ensure U.S. patients have 
timely access to medical devices of public health importance.
Flexible decisionmaking
    In recent years, FDA has also implemented a series of new premarket 
policies that build on the risk-based framework established by the MDA. 
While these policies are relatively new, and the programmatic effects 
cannot yet be measured, many of the policies have affected important 
review decisions, impacting public health by speeding access to new 
safe and effective devices.
    Benefit-Risk: FDA's standard for premarket review of high-risk 
devices has always required the Agency to weigh the benefits of a 
device against its risks. For the past 3 years, however, FDA has used a 
more flexible, patient-centric, and transparent benefit-risk framework 
to evaluate devices. Under this framework, developed with public 
feedback, reviewers weigh a number of factors to arrive at a decision 
of whether the benefits of a device outweigh its risks, including: the 
type, magnitude, and duration of a risk or benefit, the probability 
that a patient will experience the risk, patient tolerance for risk, 
availability of alternative treatments, and the value the patient 
places on treatment. Under this approach, devices that present a small 
but real likelihood of preventing serious disability or death could, 
with appropriate risk mitigation such as labeling, reach the market 
despite greater uncertainty about its risks. Also, in appropriate 
cases, FDA may defer some data otherwise collected premarket to the 
post-market setting to promote timely access to the benefits of devices 
of public health importance, provided there is still a reasonable 
assurance of safety and effectiveness. FDA currently applies this 
benefit-risk framework to all reviews of high-risk and novel lower-risk 
devices.\9\
---------------------------------------------------------------------------
    \9\ Factors to Consider When Making Benefit-Risk Determinations in 
Medical Device Premarket Approval and De Novo Classifications (March 
28, 2012), available at http://www.fda.gov/downloads/medicaldevices/
deviceregulationandguidance/guidancedocuments/ucm296379.pdf.
---------------------------------------------------------------------------
    Patient Preferences Initiative: Increasingly, patients seek to be 
involved in decisionmaking about their own health. Recognizing the 
importance of considering patients' views in deciding how the probable 
risks and benefits of medical technology should be weighed, in 2013 FDA 
launched the Patient Preferences Initiative. The initiative seeks to 
incorporate valid scientific evidence of patient preferences on the 
benefit-risk tradeoffs of medical devices into premarket review and 
other decisionmaking by FDA's device program. For example, a team of 
FDA scientists published an article with leading behavioral economists, 
illustrating how patient preferences can inform medical device approval 
decisions.\10\ The authors successfully tested a new method for 
capturing patient sentiment and translated it into a decisionmaking 
tool for incorporating patient preferences into clinical trial design 
for obesity treatments. They were able to estimate the tradeoffs in 
risks that obese patients are willing to accept in exchange for a 
certain amount of weight loss, and the minimum number of pounds they 
would have to lose to tolerate the risks of a weight-loss device. FDA 
used the results of this study to inform the product approval decision.
---------------------------------------------------------------------------
    \10\ Marin P. Ho, et al., Incorporating Patient-Preference Evidence 
into Regulatory Decision-Making, Surgical Endoscopy DOI 10.1007/s00464-
014-4044-2 (2015).

---------------------------------------------------------------------------
    Use of Patient Preferences to Approve a New Weight- Loss Device

    In 2015, FDA approved a new weight-loss device--the Maestro 
Rechargeable System, a new therapeutic option for certain obese 
patients. The decision to approve the device was based in part on the 
patient preference data, which showed that a substantial portion of 
obese patients would accept the risks associated with a surgically 
implanted device if they lost a sufficient number of pounds. Maestro is 
the first FDA-approved obesity device since 2007.

    Expedited Access Program: In 2014, FDA proposed a program for 
expedited patient access to devices that are of potential significant 
public health benefit because they are intended to treat or diagnose 
patients with life-threatening or irreversibly debilitating conditions 
whose medical needs are unmet by current technology--what some have 
called ``breakthrough devices.'' Under this program, FDA would provide 
earlier and more interactive engagement with sponsors of such devices, 
including the involvement of senior management and a collaboratively 
developed plan for collecting the scientific and clinical data to 
support approval--features that, taken together, should provide 
patients with earlier access to safe and effective medical devices. The 
program would target devices with potentially high impact on patient 
health because, for example, they fulfill an unmet need by offering an 
important advantage over existing devices. To promote earlier patient 
access, some data collection for devices marketed under this pathway 
might be moved from pre- to post-market, provided there is still a 
reasonable assurance of safety and effectiveness concerning the device. 
FDA issued final guidance\11\ in April 2015. The Expedited Access 
Pathway program went into effect on April 15, 2015.
---------------------------------------------------------------------------
    \11\ http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/Guidance
Documents/UCM393978.pdf.
---------------------------------------------------------------------------
    regulatory science: new uses of evidentiary and analytical tools
    FDA has also invested in several new regulatory science programs 
over the past several years to reduce the time and cost but not the 
quality of data development for devices. These programs promote the 
development and use of tools, analytical methods, and data sources in 
premarket applications to bring safe and effective devices to market 
faster and at less cost.
Medical Device Development Tools (MDDTs)
    An MDDT is a scientifically validated tool--a clinical outcome 
assessment (e.g., patient-reported or clinician-reported rating 
scales), a test used to detect or measure a biomarker, or a non-
clinical assessment method or model (e.g., an in vitro, animal, or 
computational model) that aids device development and regulatory 
evaluation. In August, 2014, FDA announced a pilot program under which 
anyone can submit scientific information to FDA to ``qualify'' an MDDT. 
Once qualified, MDDTs can be used to support premarket applications. In 
practice, this can enable sponsors to support a PMA, de novo request, 
or a 510(k) using smaller and shorter clinical trials. The MDDT program 
builds on FDA's successes, developing computational models like the 
Virtual Family (VF), a set of highly detailed, anatomically correct, 
computational whole-body models, designed to mimic humans of both sexes 
at various stages of growth.

    Regulatory Science--The Virtual Family (VF)

    FDA collaborated with researchers and industry to create the VF, a 
set of four highly detailed, anatomically correct whole-body models of 
an adult male, an adult female, and two children. Currently, the VF 
models are used for electromagnetic, thermal, acoustic, and 
computational fluid dynamics (CFD) simulations--simulations that can 
supplement or replace data from clinical investigations of devices. At 
the end of 2014, the VF was used in more than 120 medical device 
submissions to FDA and was cited more than 180 times in peer-reviewed 
literature. Recently the Virtual Population 3.0 became available. The 
VF are available free of charge to researchers for use in device 
development.
Medical Device Innovation Consortium (MDIC)
    In 2012, FDA and LifeScience Alley (a biomedical trade association) 
co-founded a new nonprofit partnership--the Medical Device Innovation 
Consortium--the first public-private partnership (PPP) whose mission is 
to advance medical device regulatory science. MDIC is a collaboration 
among Federal agencies, industry, nonprofit organizations, and patient 
advocacy organizations, and provides a venue for leveraging of 
resources, people, and intellectual capital to find solutions to common 
challenges in the precompetitive space. MDIC supports the development 
of non-clinical device development tools that can reduce the need for 
or size of clinical studies to support market approval as well as steps 
to reduce the time and cost of clinical trials. MDIC has several active 
project focus areas, including the following:

     Patient-centered Benefit-Risk: This project focuses on 
developing scientifically robust ways to measure patient perspectives 
on the benefits and risks of medical devices, and a framework for 
incorporating patient perspectives into device development and 
regulatory decisionmaking.
     Clinical Trials Innovation and Reform: MDIC is working 
with FDA, NIH, industry, academia, and patient groups to explore ways 
to improve the efficiency and cost-effectiveness of medical device 
clinical trials while maintaining data quality. The goal is to 
streamline the clinical trial process and restore the United States to 
the country of first choice to conduct clinical research for medical 
technology innovation. The project aims to innovate and reform the U.S. 
clinical trial process by defining and tackling top barriers to 
efficient design and conduct of medical device clinical trials.
     Computer Modeling & Simulation: The goal of this project 
is to reduce the time and cost of bringing devices to market while 
improving patient safety by advancing the science around computer 
modeling and simulation for medical devices. These models, when of 
sufficient quality to be considered ``regulatory grade,'' can be used 
to assess device performance, thus reducing or obviating the need for 
other more expensive or burdensome types of scientific evidence (such 
as human clinical studies).

    MDIC's collaborations focus on advancing regulatory science to 
propel device development through the regulatory process and to market, 
resulting in smarter regulation and earlier patient access to safe, 
effective, and high-quality devices.
                            real-world data
    In September 2012, FDA published a report, ``Strengthening Our 
National System for Medical Device Postmarket Surveillance,'' which 
proposed a National Medical Device Surveillance System (MDS) for 
improving and addressing the limitations of our current system for 
monitoring medical device safety and effectiveness. This report 
recommended establishing a national infrastructure for gathering and 
analyzing real-world data, or data collected as part of routine 
clinical practice and patient experience. The purpose of such a 
national system is to identify potential safety signals in near real-
time; better understand the benefit-risk profiles of medical devices on 
the market; and facilitate the clearance and approval of new devices, 
or new uses of existing devices.
    In the past year, FDA has achieved tremendous progress laying the 
groundwork for the MDS. FDA has begun implementing the unique device 
identification (UDI) rule for the highest risk devices, including 
development of a Global UDI Data base (GUDID) as the repository for 
information that unambiguously identifies devices through their 
distribution and use. By promoting incorporation of UDIs into 
electronic health information (such as electronic health records, or 
EHRs, and device registries), a vast quantity of untapped real-world 
data from clinical experience with devices housed in EHRs and other 
electronic information sources may become available for use in 
understanding the benefit-risk profiles of medical devices. In 
addition, FDA continues to build registry capabilities both 
domestically (such as the National Breast Implant Registry) and 
internationally (such as the International Consortium of Vascular 
Registries). FDA established a Medical Device Registry Task Force 
consisting of key registry stakeholders as part of the Medical Device 
Epidemiology Network (MDEpiNet) Program, a collaborative program that 
FDA co-founded to develop new and more efficient methods to study 
medical devices and to enhance FDA's ability to more fully understand 
the safety and effectiveness of medical devices after they are 
marketed. FDA commissioned the Engelberg Center for Health Care Reform 
at the Brookings Institution to convene and oversee deliberations of 
the Medical Device Postmarket Surveillance System Planning Board. In 
February 2015, the Planning Board issued a report, ``Strengthening 
Patient Care: Building an Effective National Medical Device 
Surveillance System,'' outlining recommended steps toward the 
development, oversight, and effective use of medical devices, while 
supporting improvements in patient safety and health outcomes.
    FDA's work in developing registries has relieved post-market burden 
by allowing device sponsors to submit data from registries instead of 
conducting their own new post-market studies. FDA is also pursuing 
strategies to use data from the most robust registries in the premarket 
context, and has already relied on registry data to expand access to 
transcatheter aortic valve replacement devices.

    Use of Real-World Evidence to Expand Use of Minimally Invasive 
Heart Valve Replacement

    Before 2014, transcatheter aortic valve replacement, a minimally 
invasive alternative to open heart surgery, was indicated only for 
patients with aortic stenosis for whom open heart surgery was too 
risky, who were yet healthy enough to undergo certain placement 
procedures. At the same time, clinical experience indicated this device 
could offer good outcomes to inoperable patients with no other options. 
In 2014, FDA expanded approval for the Edwards Sapien Transcatheter 
Aortic Valve Replacement to patients deemed inoperable without 
requiring controlled clinical trials of the new use. FDA approved the 
expanded indication based on registry data from clinical use of the 
device.
Adapting to New Technology
    FDA's device program aims to be adaptive in responding to new 
technologies. Recent policies have focused FDA oversight of health IT 
on medical devices that present greater risks, with the goal of 
permitting access to a range of products while ensuring the safety and 
effectiveness of medical devices--a subset of mobile medical apps that 
present a greater risk to patients if they do not work as intended--
such as those that provide or assist health care practitioners with 
treatment and diagnosis. FDA's device program is leading the 
development of clear, streamlined pathways for technologies that are 
pivotal to the success of precision medicine, such as companion 
diagnostics and Next-Generation Sequencing devices. The approach to 
oversight in these areas demonstrates the adaptability of the existing 
regulatory framework.

     Mobile Medical Applications and Other Health IT: As the 
number and functionality of mobile applications, or apps, exploded in 
recent years, in 2013, FDA announced a policy under which FDA intended 
to focus its regulatory oversight on those mobile medical apps that 
pose the greatest risk to consumers and exercise enforcement discretion 
for the majority of mobile apps as they pose minimal risk to consumers. 
FDA followed this policy with a preliminary health IT report produced 
in collaboration with the Office of the National Coordinator and the 
Federal Communications Commission, as required by the Food and Drug 
Administration Safety and Innovation Act (FDASIA) of 2012;\12\ this 
report outlines a series of recommendations and actions for the public 
and private sectors to take in this dynamic area of health IT to avoid 
duplicative regulation, while promoting innovation and protecting 
patient safety. The agencies accepted public comment on this report to 
inform its development. Recently, FDA has issued guidance under which 
FDA clarified that it intends to exercise enforcement discretion for 
medical device data systems,\13\ a form of health IT that, while low 
risk, is widely used in the delivery of health care. With these 
actions, FDA helped to make clear the narrow arena of health IT where 
the Agency intends to continue its oversight--namely, the space 
occupied by the riskiest forms of medical software--while clearly 
stating its intention to not focus its oversight over a broad range of 
other medical device software products.
---------------------------------------------------------------------------
    \12\ See FDASIA Health IT Report (April 2014), available at http://
www.fda.gov/downloads/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/UCM391
521.pdf.
    \13\ Medical Device Data Systems, Medical Image Storage Devices, 
and Medical Image Communications Devices: Guidance for Industry and FDA 
Staff (February 9, 2015), available at http://www.fda.gov/downloads/
medicaldevices/deviceregulationandguidance/guidancedocuments/ucm
401996.pdf.
---------------------------------------------------------------------------
    FDA recently proposed a similar policy for all low-risk devices 
used to promote health and well-being and to help individuals with 
chronic disease maintain wellness. The policy extends to products used 
to promote physical fitness, maintenance of a healthy weight, 
relaxation, and similar states of well-being, so long as the product 
does not present inherent risks to users. As with FDA's recent policies 
concerning health IT, FDA proposed this policy to provide greater 
certainty to product developers and users that FDA intends to focus its 
oversight in these emerging areas of product development on medical 
devices that present more than low risk.

     Companion Diagnostics: Companion diagnostic tests play an 
important role in promptly determining which therapies are safe and 
effective for a particular patient and are a key component of precision 
medicine. FDA has approved 20 companion diagnostic tests, all of them 
within the PDUFA performance goals for the corresponding drug or 
biological product, ensuring the timely marketing authorization of 
both. In 2014, FDA issued guidance\14\ describing a clear marketing 
pathway for developers of companion diagnostic tests and pharmaceutical 
manufacturers, receiving strong support from both pharmaceutical and 
conventional test manufacturers for providing regulatory clarity in 
this rapidly advancing area of medicine. Companion diagnostics approved 
by FDA in recent years include the BRACAnalysis CDxTM test, 
a laboratory-developed test that aids in determining which ovarian 
cancer patients are more likely to respond to the drug 
LynparzaTM (olaparib), based on certain BRCA variants; the 
THxIDTM BRAF Kit, which detects certain mutations in 
melanoma tissue samples to aid in selecting patients for drug therapy 
with Tafinlar (dabrafenib) or MekinistTM (trametinib); and 
the therascreen KRAS RGQ PCR Kit, a test that screens out colorectal 
cancer patients with genetic mutations known to predict a 
nontherapeutic response to the biological products Erbitux (cetuximab) 
and Vectibix (panitumumab).
---------------------------------------------------------------------------
    \14\ In Vitro Companion Diagnostic Devices: Guidance for Industry 
and Food and Drug Administration Staff (August 6, 2014), available at 
http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/UCM262327.pdf.
---------------------------------------------------------------------------
     Next-generation Sequencing: Many newly developed genomic 
diagnostic tests rely on next-generation sequencing (NGS), an advanced 
technology, which is becoming a keystone of precision medicine. NGS 
tests can rapidly generate an unprecedented amount of genetic data for 
each patient. Most IVD devices are used to detect a single or a defined 
number of markers to diagnose a limited set of conditions; in contrast, 
a single NGS test can identify thousands or millions of genetic 
variants that can be used to diagnose or predict the likelihood of an 
individual developing a variety of diseases. FDA has provided marketing 
authorization for an NGS test for cystic fibrosis using innovative 
approaches to establishing the test's effectiveness. As part of the 
President's Precision Medicine Initiative FDA will develop a new 
approach for evaluating Next Generation Sequencing technologies to 
facilitate the generation of knowledge about which genetic changes are 
important to patient care and foster innovation in genetic sequencing 
technology, while ensuring that the tests are accurate and reliable.

    Next-generation Sequencing: Cystic Fibrosis (CF)

    FDA authorized marketing for the Illumin MiSeqDx Cystic Fibrosis 
System in vitro diagnostic test, which detects 139 genetic mutations 
that are relevant to whether an individual will develop CF or transmit 
the CF genetic mutation to his or her children. FDA worked with the 
test developer to apply novel approaches to establishing clinical 
validity by using publicly available, quality-weighted human reference 
genomes (databases) that were created through collaboration between FDA 
and the National Institutes of Standards and Technology (NIST), and 
analytical validity by using data showing the test could accurately 
detect a representative sample of variants,

    FDA recently published a white paper outlining a possible approach 
to review of this technology that would greatly reduce burden by 
leveraging data in existing high-quality curated genetic data bases as 
an alternative to conducting new clinical trials and by reviewing 
analytical performance for only a subset of variants. FDA has received 
positive feedback from thought leaders in this area for identifying 
ways to adapt its review practices to this important new 
technology.\15\
---------------------------------------------------------------------------
    \15\ Lander, Eric S., Cutting the Gordian Helix--Regulating Genomic 
Testing in the Era of Precision Medicine, NEJM2015, DOI: 10.1056 p. 
150.
---------------------------------------------------------------------------
                               conclusion
    This is a time of remarkable advances in medical device technology, 
advances that can extend lives, and minimize suffering for American 
patients. New technologies hold out promise for empowering patients in 
their own health care decisionmaking and for delivering precision 
treatments that are truly targeted to individuals. At the same time, 
the promise of advances in medical technology will only be realized if 
the patients and providers who use them are confident that they are 
safe and can do what they are intended to do.
    FDA's device program has evolved alongside changes in medical 
technology and in the global marketplace. FDA has implemented several 
new policies and programmatic improvements to ensure American patients 
have timely access to devices without compromising standards of safety 
and effectiveness. Devices are coming to market more quickly, and more 
devices that go through FDA's premarket program are being approved and 
cleared for marketing. In addition, FDA has made its review of 
investigational devices more efficient and expeditious, streamlining 
the pathway to conducting clinical investigations in the United States.
    The improvements in FDA's device program have occurred under a 
long-standing framework that tailors FDA oversight to a device's risks 
and benefits. This framework provides flexibility to adapt to new 
technology and to consider a variety of different forms of evidence. At 
the same time, the framework establishes a standard for devices 
marketed to American patients: there must be a reasonable assurance of 
safety and effectiveness for devices, demonstrated by valid scientific 
evidence. We believe this framework serves the public well, allowing 
FDA to meet the demands of rapid innovation and a changing global 
marketplace, while promoting public confidence in high-quality, safe, 
and effective devices.
    Thank you for the opportunity to testify today about the steps FDA 
is taking to foster innovation. I am happy to answer questions you may 
have.
                                 ______
                                 
        Appendix A. Medical Device Premarket Program Performance
                               mdufa iii
    Performance Goals: Preliminary data for MDUFA performance goals 
through September 30, 2014, indicate that FDA is on track to meet all 
of its performance goals while maintaining a high workload. In fiscal 
year 2014, FDA received over 6,000 submissions for PMAs, PMA 
supplements, 510(k)s, de novos, and HDEs.
    The 4th quarter MDUFA III Performance Report presents preliminary 
performance for the fiscal year 2013 and fiscal year 2014 MDUFA III 
submissions. Further details can be found in the MDUFA III Quarterly 
Performance Reports available on FDA's MDUFA III website. (Table 1)
---------------------------------------------------------------------------
    \16\ Current Performance presents the percentage of actions that 
FDA completed within the review-time goal as of September 30, 2014.
    \17\ Review Progress presents the number of submissions that had 
actions taken in fiscal year 2014, plus submissions pending but overdue 
as of September 30, 2014, whether or not they met the MDUFA goal date, 
out of all MDUFA cohort submissions.

   Table 1.-- Fiscal year 2014 MDUFA III performance for selected submission types,  as of September 30, 2014.
----------------------------------------------------------------------------------------------------------------
                                                 Performance      Current
                                                  Goal [In    Performance\16\     Review Progress\17\ [Percent
                                                  percent]      [In percent]               complete]
----------------------------------------------------------------------------------------------------------------
PMA, Panel-Track PMA Supplements, and
 Premarket Reports:
  Substantive Interaction.....................           75               95   37 of 45 (82 percent)
  Decision with no Advisory Committee input...           80              100   7 of 43 (16 percent)
  Decision with Advisory Committee input......           70                    0 of 2
180-Day PMA Supplements:
  Substantive Interaction.....................           75               94   127 of 178 (71 percent)
  Decision....................................           90              100   78 of 178 (44 percent)
Real-Time PMA Supplements:
  Decision....................................           90               99   272 of 333 (82 percent)
510(k) Premarket Notifications:
  Substantive Interaction.....................           75               97   2,739 of 3,166 (87 percent)
  Decision....................................           93               99   1,811 of 3,133 (58 percent)
CLIA Waivers:
  Substantive Interaction.....................           95              100   14 of 14 (100 percent)
  Decision for dual submissions ((510(k) and             90                    0 of 1 (0 percent)
   CLIA waiver).
  Decision with no Advisory Committee input...           95              100   8 of 14 (57 percent)
  Decision with Advisory Committee input......           95                    0 of 0
----------------------------------------------------------------------------------------------------------------

                premarket notification (510(k)) program
    Average Time to Decision for 510(k)s: Total time to decision 
includes the time spent by FDA reviewing the application as well as the 
time spent by the submitter responding to questions from FDA. 510(k) 
average total time to decision has decreased since its peak in fiscal 
year 2010. (Chart 1) fiscal year 2013 and fiscal year 2014 cohorts are 
not yet fully closed; as of December 31, 2014, the fiscal year 2013 
510(k) cohort was 99.2 percent closed and 2014 cohort was 75.8 percent 
closed. Comparison of receipts cohorts at the same closure\18\ levels 
show a 16 percent decrease in total review time (Chart 2) between 
fiscal year 2010 and fiscal year 2013 and a 10 percent decrease in 
total review time between fiscal year 2010 and fiscal year 2014. (Chart 
3) The fiscal year 2013 cohort had the same average total time to 
decision as fiscal year 2014 at the 75.8 percent level of closure.
---------------------------------------------------------------------------
    \18\ Use of closure level provides a means for fair ``apples to 
apples'' comparisons, as performance is compared using the same 
percentage of work completed in a given year.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    Organizationally, CDRH medical device premarket review offices are 
divided into review divisions, which are comprised of review branches. 
FDA is also closing the gap between the premarket review branches with 
the fastest and slowest review times. In 2003, the lowest performing 
branch reached 34 percent of its 510(k) MDUFA decisions within 90 FDA 
Days. In fiscal year 2013 and 2014, most branches were reaching 
decisions within 90 FDA days 90 percent of the time or better.
    Substantially Equivalent (SE) Determinations and Pending 
Submissions: Improvements to the 510(k) program have increased the 
number of submissions determined to be substantially equivalent (SE) 
since 2011 (decision cohort). The number of submissions determined to 
be SE in fiscal year 2014 is 10 percent greater than in fiscal year 
2010. The impact of CDRH improvements is further observed in the number 
of pending 510(k) submissions, which has been reduced by 30 percent 
from its highest level in fiscal year 2010.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    510(k) Refuse to Accept (RTA) Program: Under the RTA Program FDA 
conducts an early review against specific acceptance criteria to assess 
whether the submission meets a minimum threshold of acceptability and 
should be accepted for substantive review. The assessment of the 
completeness of the 510(k) occurs during the early acceptance review, 
while the assessment of the quality of the submitted information occurs 
during the substantive review. Since the initiation of the Refuse to 
Accept (RTA) program on January 1, 2013, the RTA rate has been 
decreasing from 58 percent during the second quarter of fiscal year 
2013 to 39 percent during the last quarter of fiscal year 2014. (Chart 
6)
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    Training and increased FDA and Industry experience regarding the 
RTA process have contributed to the decreased rate while improving the 
quality of 510(k) submissions. FDA is undertaking a process improvement 
exercise to further reduce the RTA rate and improve consistency of this 
program. Overall acceptance rate, when RTA 1st and 2d cycles are 
combined, was 84 percent in fiscal year 2013 and 90 percent in fiscal 
year 2014.
              premarket approval application (pma) program
    Average Time to Decision for PMAs: Average time to decision has 
decreased since its highest point in fiscal year 2009. (Chart 7) As of 
December 31, 2014, the fiscal year 2012 original PMA cohort was 98 
percent closed, the fiscal year 2013 cohort was 72 percent closed and 
the fiscal year 2014 cohort was 41 percent closed. Comparison of 
receipt cohorts at the same closure levels show a 32 percent decrease 
in total review times (Chart 8) between fiscal year 2009 and fiscal 
year 2012 when the cohort is 98 percent closed, 3 percent decrease in 
total review times between fiscal year 2009 and fiscal year 2013 (Chart 
9) when the cohort is 72 percent closed, and a 26 percent decrease in 
total review times between fiscal year 2009 and fiscal year 2014 (Chart 
10) when the cohort is 41 percent closed. Examination of the 
applications included in these cohorts, detected a correlation between 
average total time to decision and panel meetings (see further 
explanation below).
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    FDA is also closing the gap between the divisions with the fastest 
and slowest review times. Performance has decreased significantly, from 
a difference in total average days to final decision between the 
highest and lowest performing divisions of 633 days in fiscal year 2008 
to 197 days in fiscal year 2014.
    Effect of an Advisory Panel Meeting on Average Total time to 
Decision: As part of the review process, FDA may present a PMA to an 
expert advisory panel for its recommendations. Medical device advisory 
committees provide independent, professional expertise and technical 
assistance on the development, safety and effectiveness, and regulation 
of medical devices. PMAs that undergo an advisory panel review have 
different performance goals than PMAs that do not go to an advisory 
panel because holding an advisory panel meeting adds more time to a 
review. Examination of the fiscal year 2013 cohort shows the highest 
percentage of PMAs undergoing an advisory panel review since 2007, 
which led to what appears to be an increase in review times. But when 
``apples-to-apples'' comparisons are made, total review times continue 
to show a decrease.
    PMAs that undergo an advisory panel review typically take longer to 
reach a final decision, as accounted for in MDUFA III performance 
goals. Because the average total time includes both PMAs that go and do 
not go to an advisory panel meeting, the spike in review time for 
fiscal year 2013 reflects the significantly higher percentage of 
applications with an advisory panel meeting (33 percent). (Chart 11) 
However, when comparing reviews times of PMAs with a panel meeting 
(Chart 12) across different years and PMAs without panel meetings 
across different years, we continued to see improved performance in 
fiscal year 2013 for both categories of PMAs. In addition, the percent 
of PMAs that will undergo advisory panel review in fiscal year 2014 is 
considerably less than fiscal year 2013. A decrease in the percent of 
PMAs which will go to an advisory panel meeting in fiscal year 2014 
along with other program improvements lead us to expect lower average 
total review times in fiscal year 2014.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    Approved and Pending PMAs: Improvements to the PMA program have 
resulted in an increase in the number of applications approved since 
2011 (decision cohort). The number of applications approved in fiscal 
year 2014 was 27 percent greater than fiscal year 2010. (Chart 13)

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    Note that the fiscal year 2015 cohort only includes 3 months of 
data. The impact of CDRH improvements is further observed in the number 
of pending original PMAs, which has been reduced by 43 percent from its 
highest level in fiscal year 2010. (Chart 14)

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

                            de novo program
    Average Time to De Novo Granting: Improvements to the de novo 
program have resulted in a 70 percent reduction in the average total 
time to decision for these submissions. Average total time to final de 
novo decision for devices with post-NSE de novo requests (includes FDA 
and Industry days for 510(k) NSE review and post-NSE de novo review) 
has been reduced from 992 days in fiscal year 2010 to 300 days in 
fiscal year 2014. Average total time to decision for direct de novo 
requests are even lower than for de novo requests using the post-NSE 
review pathway. (Chart 15) While time to decision has significantly 
decreased since fiscal year 2010, the number of de novo requests 
received has almost doubled (25 de novo requests in fiscal year 2010 
versus 46 and 41 in fiscal year 2013 and 2014, respectively).

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

             investigational device exemption (ide) program
    IDEs Approved within Two Cycles: Improvements to the IDE Program 
(e.g., establishing a formal Clinical Trials Program, process 
improvements, policy changes, extensive training for CDRH review staff 
and the device industry, and new guidance documents) have greatly 
shortened the time for an IDE to reach approval, so that a clinical 
trial can begin. The number of IDE studies that get fully approved 
within two cycles has increased significantly. The percentage of fully 
approved IDE studies within one cycle has increased ninefold compared 
to fiscal year 2011 and the percentage fully approved within two cycles 
has increased fourfold compared to fiscal year 2011. (Chart 16) In 
fiscal year 2014, 63 percent of IDEs submitted were approved within 2 
cycles.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    Median Days to IDE Full Approval: The median number days to full 
IDE approval has decreased from 442 in fiscal year 2011 to only 101 in 
fiscal year 2014, reducing the time it takes to bring a new medical 
device to market by nearly a full year. (Chart 17)

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    Clinical Studies: Devices that are studied in the United States in 
the early stages of development are more likely to reach U.S. patients 
sooner in pivotal studies and as marketed devices. In the past 5 fiscal 
years, 82 FDA approved original PMAs were supported by a single pivotal 
IDE study. Of those, 32 (39 percent) included studies enrolling 
subjects outside the United States. For in vitro diagnostic devices 
(IVD), where clinical studies are typically conducted in at least three 
sites, sponsors generally choose to have one of those sites inside the 
United States to address differences between the United States and 
other countries in how medicine is practiced, patient populations, and 
disease progression.
    FDA is facilitating and encouraging the use of innovative clinical 
trial designs and statistical methods such as adaptive clinical trials 
and Bayesian statistics. For the period from 2007 to May 2013, FDA 
received 250 submissions that were adaptive, most of which were pre-
submissions and IDEs. About 30 percent of these used Bayesian 
methodologies. In addition, there were 17 PMAs and PMA Supplements that 
used adaptive clinical trials from 2007 to May 2013, eight of which 
used Bayesian methodologies.
                         customer satisfaction
    Industry Customer Service Rating for Premarket Program: Excellent 
customer service means understanding and addressing, as appropriate, 
stakeholders' and colleagues' needs through active listening, problem 
solving, seeking out the ideas of others, explaining the rationale for 
our decisions and requests for information, learning from our mistakes, 
and doing our best. Providing excellent customer service improves our 
interactions supports better regulatory outcomes, thereby improving 
patient health.
    By providing excellent customer service, we do not alter our 
regulatory obligations. Customer service does not mean letting unsafe 
or ineffective devices on the market--rather it involves identifying 
and meeting our customers' needs, as appropriate, while achieving our 
mission and vision.
    The experience of receiving excellent customer service can 
encourage device makers to choose the United States first when bringing 
their products to market; in turn, U.S. health care providers gain 
access to the technologies that they need to administer quality health 
care to patients. In June 2014 CDRH began measuring customer 
satisfaction and established a goal of 70 percent satisfaction by the 
end of 2014. The Center's performance was 83 percent (95 percent 
confidence level and 2 percent margin of error). The performance of the 
premarket program was 86 percent satisfaction (95 percent confidence 
level and 3 percent margin of error). Among its industry stakeholders--
industry, industry consultants, and industry trade associations--was 
even higher, 89 percent (95 percent confidence level and 4 percent 
margin of error). (Chart 18)

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    The Chairman. Thank you very much.
    Senator Roberts has an important engagement in a few 
minutes. I'm going to call on him at this time.

                      Statement of Senator Roberts

    Senator Roberts. Mr. Chairman, I thank you, and I apologize 
to my colleagues. I have several questions I'd like to submit 
for the record.
    I just want to say that I share Senator Murray's concern 
with regard to the fact that with the FDA, as the agency has 
grown with large new requirements to publish regulations for 
food, tobacco, other things, we have seen additional delays in 
getting guidances and regulations necessary for medical product 
innovation and the public health finalized and approved. I know 
they'll have good answers as to how they are prioritizing their 
work with these new authorities.
    I also want to note that in Kansas, we've seen the medical 
research and development field expand greatly in recent years, 
anchored by a research hospital and medical school at the 
University of Kansas, the home of the ever-fighting and 
optimistic Jayhawks. The recent National Cancer Institute 
designation for KU has created nearly $1 billion in economic 
activity and over 1,800 jobs locally. I am very confident we 
will continue to lead in this area.
    I thank the chairman for his indulgence and the patience of 
my colleagues. Thank you.
    The Chairman. Thank you, Senator Roberts, for your succinct 
statement.
    We'll now move to 5 minutes of questions for committee 
members, and I'll begin.
    Dr. Woodcock, you said something very important about the 
mandates from 2007. We know in this committee that--I mean, we 
are a feast of well-intentioned good ideas here, and they come 
from all directions, from the right and the left. We see that 
in higher education, where a number of us have invited the 
higher education community to talk to us about simplifying 
regulations, and they came back with 59 specific 
recommendations.
    Our purpose here is to enable you, not to slow you down. We 
want to align Federal policies--and that means our laws and our 
regulations--with an opportunity for more, not less, safe 
innovation.
    I would invite each of you to form your own internal red 
team for red tape, and if you see things that are in the law or 
in regulation or even that the Office of Management and Budget 
makes you do that you think are nonproductive, let us know, 
because this train is going to get to the station. We're 
working with the House and the President, and this is an 
opportunity to clear the clutter out of the way and to take 
advantage of a rapidly changing landscape.
    Now, Dr. Austin, we've heard a lot about the valley of 
death. I had some Vanderbilt researchers explaining that to me 
the other day. More money obviously would help. You talked 
about it some. What else can we do to shorten the period from 
discovery to medicine cabinet and this middle ground where so 
many--8 out of 10--medicines fail for business reasons or for 
medical reasons? Is there anything else we should do?
    Dr. Austin. Thank you for the question. First, it is 
important to say that there--as it will not surprise you to 
learn--are many, many more of those valley of death crossing 
projects that we have proposed to us than we can possibly fund. 
The number is currently 96 percent that we cannot fund.
    It's important to realize that--to see change that's 
happened since I was in training 30 years ago, there were tens 
of opportunities to intervene in a rapid way for patients with 
untreatable diseases. Now that's in the thousands. The 
opportunities have really exploded.
    The Chairman. If 8 out of 10 don't succeed, if that's 
anywhere close to right, are there any other steps you can take 
to reduce that number with whatever dollars you have?
    Dr. Austin. Yes, and to give you some examples, one beyond 
the direct support is that these projects traditionally have 
been done in a rather disparate fashion. This requires a team 
to do this. It requires people of different expertises, often 8 
or 10 different expertises, and different sectors, so academia, 
biotech, pharma, VC, patient groups, regulators, and, 
traditionally, they've tended to work in silos.
    It is one of the reasons why everything NCATS does is done 
as a collaboration. What we find is what our mothers told us, 
that many hands make light work, and if you put together a 
team----
    The Chairman. Collaboration is one answer. Anything else?
    Dr. Austin. I can't let this go by without mentioning the--
--
    The Chairman. If you can do it in 25 seconds, I would 
appreciate it so I can go to another question.
    Dr. Austin. The administrative limitations that Dr. Collins 
has talked about, the travel, the hiring issues. Those are big 
issues for us because of the----
    The Chairman. I have encouraged Dr. Collins literally--I 
had a good visit with him last week--to form a red team for red 
tape and give us a list. We know that some of those things are 
your fault, and some of them are our fault.
    Dr. Austin. Yes.
    The Chairman. Some of them is the Office of Management and 
Budget. We can put the spotlight on all of them, and we'll try 
to change the ones that we can that get in the way of your good 
work.
    Dr. Woodcock and Dr. Shuren, I have just a few seconds 
left. We hear that in Europe, it's easier for regulators to 
take advantage of outside expertise. As the world changes and 
so much is going on in the area in which you work, surely you 
can't have enough smart people inside the system to make all 
the decisions you need to know. Are there things we can do to 
make it easier for you to appropriately involve experts from 
outside your agencies to help you deal with these issues?
    Dr. Shuren. Well, in trying to address that, we set up what 
we call a network of experts. We are leveraging the networks 
already existing in healthcare professional and scientific 
organizations. I'd say our biggest holdup is some questions 
rely on confidential information that's in the possession of 
the company and it's theirs to own. And because we can't share 
that information, we can't leverage those experts as well as we 
could. That is a limitation.
    The Chairman. Thank you very much.
    Senator Murray.
    Senator Murray. I want to start by mentioning two letters 
that I sent to the FDA about the serious outbreak in my State 
linked to the use of special medical scopes. I acknowledge that 
after my first letter, FDA took several actions to help protect 
patients.
    Dr. Shuren, I know your center's staff is working to 
provide me with information about the agency's full review of 
this situation, a review Commissioner Hamburg committed to me 
in March. I want to underscore again today how important that 
review is so that we can work to prevent outbreaks like that 
from happening ever again.
    Dr. Shuren. We take it very seriously, too, and we'll be 
getting back to you shortly. We're also continuing to look for 
ways to provide more information out to the public as we 
continue to work with the companies, with the healthcare 
professionals, with hospitals, with the CDC and others. Next 
up, just to flag for everyone, there will be an advisory 
committee meeting on May 14 and 15 to discuss many of these 
important scientific issues.
    Senator Murray. Very good. Thank you very much for that.
    Dr. Woodcock, we've heard testimony about the extraordinary 
time and expense it takes to develop a new lifesaving drug, 
from having an idea to FDA approving a product for patients. 
We've heard many ideas about why this is the case and how to 
improve things, like better drug development tools like 
biomarkers.
    How do you think we can cut down on the cost and time it 
takes to develop new lifesaving products?
    Dr. Woodcock. The limitations, as I said in my oral 
testimony, are really related primarily to the science. We have 
been working for quite some time on improving the 
infrastructure that is used to move these products along and to 
evaluate them. I do think what NCATS is doing is extremely 
important, because they're doing a focused scientific effort.
    It's developing new biomarkers, in which we're engaged with 
many consortia on; developing clinical trial networks so that 
each clinical trial isn't set up separately at great expense 
and time and then taken down, and 8 out of 10 times, nothing 
comes of it because the drug fails. Also streamlining 
electronically how we collect data from clinical trials and 
elsewhere, and we're making tremendous advances on that and the 
standards.
    Now, what NCATS is doing and other people are working on is 
the predictive toxicology, because I believe what Senator 
Alexander was referring to in a great sense--this valley of 
death--relates to the academic community who have wonderful 
ideas, but they don't have the funding to advance their ideas 
beyond the laboratory stage and into people, because you have 
to do the safety testing. You can't just put laboratory 
chemicals into people. You have to evaluate them.
    We need a more streamlined way, a common way, perhaps, that 
these could be evaluated and get into early clinical testing 
and how to get the expense down on that, or to fund it in some 
way, or provide more funding. As Dr. Austin said, there is very 
little funding that can be provided by NCATS to help all these 
scientists around the country take their ideas beyond the 
laboratory stage.
    I think there are quite a number of things that can be 
done, but I wouldn't underestimate the difficulty of doing each 
one of them. They are scientific problems, and they need 
collective solutions.
    Senator Murray. Thank you.
    Dr. Shuren, in order for FDA to operate with speed and 
efficiency needed to review new products and protect public 
health, FDA must be staffed by some of the top scientists in 
the United States. Commissioner Hamburg talked to us about the 
challenges the agency faces in hiring and retaining qualified 
personnel to support your mission. Can you tell us whether 
you've encountered similar challenges?
    Dr. Shuren. All the time. I have great staff, but we have a 
very hard time recruiting and particularly retaining people. 
It's because, for one, I can't pay a competitive salary to 
industry. I can't attract people or--I train people. We are the 
training ground for industry. I train them. They become more 
marketable, and they leave and they get salaries of two or more 
times what they're getting paid today.
    The other is if you come from industry, a lot of times your 
retirement is in stock just for that company. I can't wall them 
off. They have to divest that stock, and as a result, I've had 
great people say, ``I'd come, but I can't because this is my 
family's future.''
    We have a high workload. This is something we deal with 
through user fees. But, if you combine the high workload with 
the less pay, then it is hard to get people, and that's why I 
always have a high staff turnover. As a result, it hurts 
companies. In the middle of a review, your lead reviewer or 
your medical officer leaves, and I don't have a deep bench in 
my center. It's a small center.
    Senator Murray. Industry steals your employees but they 
need you.
    Dr. Shuren. That's exactly right, and we've got to change 
that, because it best serves not just industry, but it 
ultimately serves patients, and that's what this is all about.
    Senator Murray. Dr. Woodcock, I assume you see the same 
thing?
    Dr. Woodcock. Absolutely. I mean, our scientists need to go 
toe to toe with the best industry scientists, and yet when my 
people leave, for either academia or industry, they typically 
may double their salaries from what they're getting at CDER.
    Senator Murray. Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Murray.
    Senator Scott.

                       Statement of Senator Scott

    Senator Scott. Thank you, Mr. Chairman.
    Thank you to the panel for participating in this hearing, 
and, certainly, your task is a daunting task without any 
question. We look forward to being as helpful as we can.
    Over the last year, I had an opportunity to meet an 
incredibly young health advocate from Summerville, SC, a guy 
named Zion Thomas, who is often referred to by his nickname, 
The Mayor. He is an 11-year-old kid who has more energy and 
more charisma than most of us sitting around the table, except 
for his doctor and Elizabeth over there, of course. No offense, 
of course, to Senator Alexander.
    [Laughter.]
    The challenge when you start calling names is that you find 
yourself in trouble and digging a deep hole with a shovel that 
you won't put down. Anyway, I will tell you that Zion continues 
to be one of the strongest advocates for health issues because 
he, from the age of 6 months, has been in and out of the 
hospital because of the impact of sickle cell on his life and 
on his family's, and all its challenges.
    I'm happy to report that South Carolina has done a pretty 
good job, and, specifically, the Medical University of South 
Carolina, which has opened a sickle cell treatment clinic that 
has been a breath of fresh air for Zion and his entire family. 
Despite the fact that sickle cell disease impacts close to 
100,000 people in the United States, there is still no cure, 
and only one drug has been approved by the FDA to treat the 
symptoms of the disease.
    The problem I see is that I know that companies are working 
very hard to find that cure for kids like Zion but, 
unfortunately, they continue to hit road blocks along the way. 
Part of the road blocks has been the approval process, 
according to some of the companies, with the FDA.
    The main frustration I hear--and not simply from those 
companies trying to develop cures for sickle cell, but just 
companies going through the approval process--is that the 
agency can't quite articulate to the drug companies exactly 
what they are looking for from the clinical trials process in 
order to advance the drugs toward final approval.
    Dr. Woodcock, what is the FDA doing now to ensure that 
companies understand through communication between the FDA and 
those companies what is necessary and what the results should 
be along the way in multiple trials?
    Dr. Woodcock. We have negotiated under the PDUFA program 
something called a special protocol assessment. We have 90 
days, I think it is, or maybe less, to get back to the company. 
If they have a list of questions they've submitted to us--Do 
you agree with this trial? Will this trial be sufficient to 
support approval? Do you agree with these endpoints? Do you 
agree with these inclusion criteria, et cetera, et cetera?--we 
get back to them in writing, whether we agree or not. And if we 
don't agree, we negotiate with them until we get an agreement.
    We've done over 1,000 of these special protocol 
assessments. This is a very valuable tool under the user fee 
program for the companies to get predictability about what the 
FDA would like them to do in order to get onto the market.
    I think as a result of that and our program of meeting with 
companies during the development process, we have a very high 
what's called first cycle approval rate. In other words, when 
the companies submit an application to us, almost 80 percent of 
the time, we're able to approve it. If it's going to be 
approved, we're able to approve it, during that cycle, because 
they know what they're supposed to send us, and they're able to 
fulfill our requirements.
    I agree with you, especially for the smaller companies, 
that they still feel uncertain and they want that clarity. That 
process is available to all.
    Senator Scott. Thank you.
    The Chairman. Thank you, Senator Scott.
    We have Senator Warren, Senator Cassidy, and Senator 
Bennet.
    Senator Warren.

                      Statement of Senator Warren

    Senator Warren. Thank you, Mr. Chairman.
    This committee is beginning to develop legislation to 
accelerate the development of new cures and treatments. To do 
that effectively, we must start with where medical innovation 
comes from. Real innovation comes from NIH. A recent analysis 
by Harvard researchers found that most of our truly 
transformative drugs are based on insights gained through 
federally funded research.
    Another analysis found that two-thirds of the 21 highest 
impact drugs approved between 1965 and 1992 stem directly from 
public sector research. The private sector commercializes these 
discoveries, but they would never happen in the first place 
without strong government support.
    Now, the industry knows this. The Biotechnology Industry 
Organization testified that, ``There is no private sector 
alternative for much of the basic research that NIH supports.'' 
John Castellani, President and CEO of PhRMA, has said that,

          ``Government-supported basic research is one key to 
        how we collectively progress in discovering novel 
        compounds for addressing patients' unmet medical 
        needs.''

    Dr. Austin, do you agree that many of the drugs on the 
market today are based on scientific insights gained through 
NIH or other publicly funded research?
    Dr. Austin. Absolutely. It's a fact.
    Senator Warren. It's a fact. Good. We'll go with that.
    Dr. Pettigrew, in addition to providing the basic science 
used to develop new drugs, can you describe other ways that we 
benefit from NIH-funded research?
    Dr. Pettigrew. Thank you for the question, Senator. I think 
the issue here really is impact, as you pointed out. This is a 
process that is a continuum. It starts with basic science. The 
objective of basic science is to understand the laws of nature, 
and with that understanding, we are more informed about how 
things work and what goes wrong. That leads to fashioning 
solutions to these problems, and then those solutions have to 
be translated.
    The other things that we do at the NIH is to integrate that 
knowledge with our ability to invoke the practical solutions 
and design them through engineering and the physical sciences 
along with the life sciences to fashion such solutions to the 
kinds of problems you identified.
    Senator Warren. Dr. Austin, would you like to add anything 
to that?
    Dr. Austin. A couple of things. The first is that--and I 
can speak from both sides of this, because I'm a basic 
researcher by training, but I'm also a clinician, and I also 
spent many years in the pharmaceutical industry. I've seen all 
sides of it.
    Fundamental science is the seed corn on which all 
interventions are based. It is necessary, but almost never 
sufficient. This is a very long process of going from--what 
fundamental science does is fundamentally to figure out how 
something works normally, and when it breaks, why does it 
break.
    Then the issue is how to fix it, and how to fix it actually 
requires a quite different skill set in any field, from 
figuring out why it's broken, and translation is really to fix 
it, and that's a completely different field. Sometimes there's 
a feeling that the intervention to improve what's broken 
happens kind of naturally, and it's well worked out about how 
to do this, and we know how to do it.
    The fact is, as Dr. Woodcock was saying, our understanding 
of this process is extremely poor. The science underlying the 
translational process is extremely poor, and our operational 
structures to do it are extremely poor. So I would say, yes, 
basic science is the seed corn of everything, but it requires 
enormous energy to get through the next 10 or 15 years to 
actually have an intervention which improves human health. 
That's what we're working on.
    Senator Warren. Dr. Woodcock, I see you nodding yes. Would 
you like to add an amen to that?
    Dr. Woodcock. Well, I think Dr. Austin put it extremely 
well. It's very under-appreciated, and I'm sure you all have 
researchers coming to you--because I do all the time--saying, 
``I discovered this. It should be treating people tomorrow.'' 
All right? Actually, then, when you think it takes 15 years to 
get from a discovery to actually treatment, people really don't 
understand what goes in between there.
    There's an enormous amount of work and effort, and, 
frankly, at that stage, at the ``I have a discovery'' stage, 
it's 10,000 compounds getting down to one that actually gets 
approved. And that isn't because of FDA requirements. That's 
because of the scientific process.
    Senator Warren. Let's just stay focused on that about the 
scientific process, then, if we're talking about innovation. We 
have to be blunt. Medical research funding in this country is 
in crisis. Since 2003, the NIH budget has not even kept pace 
with inflation. Its purchasing power is down about 25 percent. 
To increase medical innovation, the NIH needs more resources. 
We've got to keep this pipeline going.
    Last week in the New York Times, Newt Gingrich said that 
when it comes to breakthroughs that could cure--not just treat, 
but cure--the most expensive diseases, government is unique. It 
alone can bring the necessary resources to bear, and it is 
ultimately on the hook for the cost of illness. It is 
irresponsible and short-sighted, not prudent, to let financing 
for basic research dwindle.
    I agree. If we want medical innovation in this country, we 
need to double down on support for NIH. If we want to improve 
the quality of life for Americans and reduce Federal healthcare 
spending, we need to double down on NIH spending.
    This committee has a chance to make a real difference, Mr. 
Chairman, but that chance begins with support for the NIH. 
Thank you.
    The Chairman. Thank you, Senator Warren.
    Senator Cassidy

                      Statement of Senator Cassidy

    Senator Cassidy. Dr. Woodcock, I asked Dr. Hamburg just 
before she left, but I wasn't really quite sure I could 
comprehend the answer. The Manhattan Institute did an FDA 
report card finding wide variance in performance among the 
agency's drug review divisions. For example, median drug 
approval in the fastest division, oncology, was two to three 
times faster than neurology, cardiovascular, and renal. 
Neurology took nearly 600 days to approve a new drug. 
Cardiovascular took 400. Oncology and antiviral took slightly 
less than 200. These high performers, oncology and antiviral, 
actually have a higher workload than the other divisions.
    Now, I've learned in life that leadership often plays a 
role. Given the problems that you and Dr. Shuren--presumably, 
those are common in both. What metrics do we have on these 
divisions? How do we explain the difference? How do we minimize 
it?
    Dr. Woodcock. Well, I think that report was highly 
misleading. First of all, CDER met all PDUFA goals. They have 
six timelines for getting back to companies with a full review, 
and all those divisions met their timelines. I can tell you, 
though, if the Nation had declared a war on neurodegenerative 
disease at the same time they declared a war on cancer, we 
wouldn't be having this conversation.
    Senator Cassidy. Now, let me ask--and I agree with you. We 
need a war on neurodegenerative disease. Believe me. I'm with 
you. That said, it does suggest that the workload at the 
antiviral and the oncologic divisions is actually higher, and 
yet they have approval times that are one-third of those of the 
others.
    Dr. Woodcock. Yes, and they----
    Senator Cassidy. Then we have had a war on cardiovascular 
disease, and that's one of the divisions that does poorly.
    Dr. Woodcock. Well, does poorly. All right. When 
cardiovascular disease--we have a large number of treatments 
available for myocardial infarction. I won't go into this in 
great detail, but, we have a large number of available 
therapies. These are comparative trials that are done. They 
often involve 25,000 patients or more.
    To review that level--and they often have very small 
incremental benefits, like 0.1 percent improvement in mortality 
or stroke or something like that. That's quite a different 
issue than, like, what Senator Murray was talking about--breast 
cancer, where that drug doubled the time that it took for the 
tumor to start growing again.
    These are apple and orange comparisons, I believe. And I 
will tell you that I was at the center a decade and a half ago 
when the oncology division was routinely criticized over and 
over and over again for not approving cancer drugs fast enough. 
Now, because of advances in genetics, we actually understand 
the molecular basis----
    Senator Cassidy. May I interrupt just for a second?
    Dr. Woodcock. Yes.
    Senator Cassidy. Again, I have limited time. I don't mean 
to be rude. One marker that kind of sorts things out sometimes 
is your turnover in each division. Obviously, if there's more 
turnover--and you alluded earlier, you and Dr. Shuren--turnover 
can play a factor. Are the turnovers in the divisions constant? 
Are they all similar?
    Dr. Woodcock. Well, I would say in the neurology division, 
due to the problems that Dr. Shuren was alluding to in hiring 
and competitiveness of our salaries, we are really down on 
neurologists. We're having a desperate time getting enough 
neurologists, because the good news is that research in 
neurodegenerative diseases is actually picking up. We've had 
some turnover in that division with retirements of people who 
have been there a long time, and we cannot really recruit 
neurologists. This is a huge issue for us.
    Senator Cassidy. I got you--and not to cut you off.
    Dr. Austin, I walked in from another hearing as you were 
speaking about these consortiums and some of the problems 
thereof. I'm really interested about the intellectual property 
rights as we go forward. I have an article from 2012, 
``Recalibrating Intellectual Property Rights to Enhance 
Translational Research Collaborations.'' It makes sense to me 
that if you have a consortium, and you come up with an 
invention, someone has to figure out who owns the IP.
    Dr. Austin. Yes.
    Senator Cassidy. That in itself--you've got to use somebody 
else's IP, which--I've learned a new term--if it's a platform, 
they can choke off the research if the licensing fee is too 
high. I'm actually seeing people in the audience nod their 
heads. What thoughts do you have? Do we need to do something 
legislatively about this IP? Because I do get a sense that this 
is a choke point going forward.
    Dr. Austin. The good news is--I can tell you from our 
perspective--we have never had a project fail because of IP.
    Senator Cassidy. I was told that industry is going to be 
different than government. Government tends to make it work 
better. Industry is going to be the sticky wicket.
    Dr. Austin. About half of our projects are with companies, 
and we have--probably the reason that we have made this work is 
that we view this area that you're describing as an area of 
innovation. Science is not the only area that needs innovation. 
Novel public-private partnership models is also a model of--a 
way that we innovate.
    If we have time, I could tell you about some of the 
examples that we've developed and that are----
    Senator Cassidy. I'm out of time, so let me ask you this 
quickly. Do we need to do something legislatively, or is this 
something that you all are going to be able to figure out? 
Because otherwise, there's going to be bipartisan agreement in 
addressing an IP issue that's going to thwart cost-effective 
relations----
    Dr. Austin. This is something that I'd have to consult with 
my NIH colleagues and get back to you with.
    Senator Cassidy. Please. If all of you would do that--I 
mean, you know better than we. We are willing to help you. I 
don't understand IP, but the Chairman is a lawyer, and he tells 
me he can handle it.
    I yield back. Thank you.
    The Chairman. That's a very helpful question, and we would 
appreciate a response on that.
    Senator Bennet

                      Statement of Senator Bennet

    Senator Bennet. Thank you, Mr. Chairman, and thank you for 
holding this important hearing. I thank all the panelists.
    Dr. Woodcock, I was hoping you could touch briefly on what 
we've learned through the new breakthrough therapy process 
that's been set up at the FDA. I want to thank you for working 
with us on that bill. When Peggy Hamburg was here, she 
testified that 23 of the 55 drugs approved during her time as 
Commissioner of the FDA came through the breakthrough therapy 
process. So something must be working.
    As you know, Senators Burr, Hatch, and I also recently 
introduced a parallel bill on the device side, and I wonder 
whether you, Dr. Shuren, could also comment on the potential 
for that. What are the pitfalls? What are the limitations, but 
also the successes?
    Dr. Woodcock.
    Dr. Woodcock. Well, this program has been much more active 
than we expected. We expected, based on historical trends, that 
we would see one or two breakthrough drugs a year. We've 
designated, since the program was enacted, 84 drugs. Not all of 
them are going to make it, and I think that's the major 
pitfall. We don't want to raise the hopes of desperate 
patients, and then only to have that drug fail.
    People have to be clear that when we designate a 
breakthrough, it doesn't mean it's going to work at the end of 
the day. However, we have approved 24 of these, and the track 
record is very good, that, usually, that early clinical 
indication is right.
    The interesting thing about breakthrough--and I think the 
most important thing--is it has shortened the development time. 
That's really a first time. These other things have focused on 
FDA review. For a priority drug, FDA review is 6 months or 
less. There's not much to come and go on there.
    We have the 15 years of drug development time, and the 
breakthrough designation--by FDA working very closely with the 
companies, we've had companies come up and testify and so forth 
that up to 2 years has been cutoff of that development time. I 
think it's a successful program.
    It is, again, stressing, where staff, to Senator Cassidy's 
point--many of them are antivirals and oncology drugs because 
the science is advanced due to HIV and the war on cancer. We 
understand those diseases better and we're able to actually 
develop better therapies. However, the good news is we've had 
designations in psychiatry and we've had designations in 
serious dermatologic conditions and rare diseases of children 
and so forth, and we can only hope that those bear fruit as 
well.
    Senator Bennet. What explains--you said you thought maybe 
we would have one or two designated, and now we've got 80 
designated and 24 approved. What explains that delta between 
what we thought was going to happen and what actually has 
happened?
    Dr. Woodcock. I believe there's been an inflection point in 
drug development. You know, everyone was very upset about drug 
development. It was slowing down in the early 2000s and mid-
2000s.
    Really, what happened is the companies started investing in 
innovation, and it's the advances in science--what Senator 
Warren was talking about--that are paying off in certain 
fields. We know enough that we can--Chris was talking about the 
fixes to the problems. We know better what to target and how to 
do that.
    For antivirals, for cancer drugs, we can actually get drugs 
that are highly effective. Most of the older drugs maybe only 
work--6 percent improvement or something like that. These 
breakthroughs we're seeing--we're seeing curative therapies in 
some cases.
    Senator Bennet. Dr. Shuren, could you talk a little bit 
about the potential in the medical device side and what some of 
the things we should be thinking about are as we explore this?
    Dr. Shuren. The potential here is tremendous, and we're 
very excited to have a breakthrough device program at the 
center. We started piloting this approach back in 2001 as the 
Innovation Pathway. In fact, one of the products that came 
through had funding support from NIH, and I think that's a nice 
example where, for government, we might be able to marry up 
this investment in important technology and then move it 
through the regulatory process in a much more streamlined 
fashion, with collaboration between NIH and FDA.
    While we just launched that program the other week 
formally, based on our experiences, I want to first of all say 
thank you to you and Senator Burr and Senator Hatch for the 
opportunity to work with you in providing some suggestions in 
legislation to help sort of codify and maybe move that program 
forward more expeditiously.
    Senator Bennet. Mr. Chairman, I'm out of time or about out 
of time. I just want to make one observation. When I first got 
here 6 years ago, I used to say that it was nobody's day job in 
Washington to figure out how we are going to keep a thriving 
bioscience industry here in the United States.
    I think it would only be fair to say we have made a 
tremendous amount of progress in the last number of years in 
part because of the leadership at the FDA. I'm grateful for it. 
I think we have a long way to go, but I think we are certainly 
moving in the right direction.
    The Chairman. Thank you, Senator Bennet.
    Senator Isakson.

                      Statement of Senator Isakson

    Senator Isakson. Thank you, Chairman Alexander.
    Dr. Woodcock, I was at the Association of County 
Commissioners convention in Georgia last Sunday. That may seem 
to be irrelevant to this hearing. Ross King is the association 
director for the county commissioners of Georgia. His daughter, 
Jackie King, died last year. She died of melanoma. In her 2-
year fight against melanoma, she joined up with me to help 
promote the Sunscreen Innovation Act which we passed here about 
6 months to a year ago.
    My question to you is this. The surgeon general has issued 
a call to action on skin cancer. More Americans have skin 
cancer than lung cancer, prostate cancer, breast cancer, and 
the others combined. It costs us $8.1 billion a year.
    One of the cancers that comes directly from the sun is 
melanoma, which is the deadliest of all cancers. I have had 
two, which, fortunately, I got in time. It's a very deadly 
cancer. It's what Jackie King died of.
    Why is it that now that we've passed the Sunscreen 
Innovation Act, which directed the FDA to look at these 
ingredients in over-the-counter drugs that are approved in 
foreign countries, that are innovative and helpful in 
sunscreen--why do you continue to delay in taking action? Some 
of those have been pending for 12 years.
    Dr. Woodcock. We have taken the actions directed by the 
Sunscreen Innovation Act. The way the process is set up for the 
monographs for how over-the-counter ingredients are regulated--
we have followed that process. That process calls for data 
submission prior to the finalization of the monograph for 
products. That is the scheme that is currently in effect.
    Senator Isakson. If you carried that scheme to its 
conclusion, when will we have some results?
    Dr. Woodcock. Well, it would require the manufacturers to 
submit the data that we have asked them to submit about the 
safety of these additional sunscreens to the FDA, and then we--
the monograph process is a regulations process. We have to 
propose and finalize regulations for each segment of any 
monograph, and there are multiple categories.
    There are 88 categories of over-the-counter drugs, I 
believe, that we need--to go through this process. Some of them 
are in final form. The sunscreen one is not.
    Senator Isakson. The monograph is not in final form?
    Dr. Woodcock. Right.
    Senator Isakson. Is that because you don't have what you 
need from the manufacturers of the ingredients?
    Dr. Woodcock. In part, and in part it's because the 
monograph process follows a sort of stately progression, and as 
the science evolves, the process of proposing and finalizing 
regulations always seems to lag behind the scientific changes 
that occur. We're always trying to catch up. We started on the 
monograph for sunscreens in the 1970s, and we're still working 
on it.
    Senator Isakson. Well, it's been a long time, and it's time 
to bring some of it to a conclusion. I know you can't answer 
this off the top of your head, but if you would, let me know or 
let the committee know what the progress is on the sunscreen 
ingredients, if there are any manufacturers who are delinquent 
in getting you the information that you need. Please let us 
know, because I would like to do everything we can to promote 
them getting all the information in so you can do it in a 
timely fashion--finish your monograph.
    Dr. Woodcock. I totally agree, and we will be happy to get 
back with you.
    In fact, I introduced the regulation that allows these 
other ingredients to be considered in the monograph process in 
the late 1990s so that we could put more ingredients into this 
process.
    Senator Isakson. All right. I'm getting ready to show my 
ignorance because my staff is always smarter than I am, and 
I've just been handed a note, so I'm going to ask this 
question. If it's a dumb question, my staff got me to ask it.
    [Laughter.]
    And since it's my staff, I know it's not a dumb question. 
The bill changed the law and gave sunscreen a separate order 
process. Is that correct?
    Dr. Woodcock. That's correct for the time and extent, to my 
understanding, but not for the final process.
    Senator Isakson. Has that time and extent been expedited?
    Dr. Woodcock. To the extent we were able to under the new 
law, we've obeyed all the provisions.
    Senator Isakson. Because that's really what led to the 
whole Sunscreen Innovation Act, because one of those time and 
extent applications was 12 years old and still did not have 
action. I'm not trying to pick on you, but it's a big 
important--anybody that's lost a child to melanoma or anybody 
that's suffered from skin cancer knows how important it is.
    Dr. Woodcock. You are not picking on me, and I share your 
frustration about the monograph process. It is not very 
functional in today's world.
    Senator Isakson. Well, I'll pick on Dr. Shuren for 1 
second.
    Dr. Shuren, we sent you a letter about a year ago asking 
about the draft guidance. Right before the May 10th hearing, 
you submitted a partial list of the amount of draft guidance 
that FDA had issued. This Friday, we got the rest of that list 
to the committee, and I have it before me. It lists whether 
you're going to withdraw draft guidance, finalize draft 
guidance, or reissue draft guidance.
    My question is just--and you don't really need to respond 
to this except to respond in writing. Will you let us know when 
you plan to take those actions on finalization, revision, or 
withdrawal? There are 144 pending draft guidances for the 
agency right now. We'd like to know what the timing of those is 
going to be.
    Dr. Shuren. I know we'll get back from the agency.
    I can say for the device program, we're withdrawing 30 from 
last week. The 43 remaining--the 40 we will finalize within the 
next 18 months, and the majority of those are actually less 
than 5 years.
    The other thing I'll point out is we put in performance 
goals in December of last year about finalizing draft 
guidances, commitments that we will finalize 80 percent within 
3 years, 100 percent by 5 years, or reissue or withdraw. That's 
our starting point, and we hope to make greater progress from 
there, too.
    Senator Isakson. Thank you very much.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Isakson.
    Senator Murray, do you have any closing comments or 
questions?
    Senator Murray. Well, Mr. Chairman, thank you for this 
hearing. I thought it was really excellent. I do have a few 
more questions. I will submit them for the record to get 
responses.
    I thought this was a great hearing. We've got a lot of work 
in front of us, but I think, working in a bipartisan way, we 
can move forward, and I appreciate your work on this.
    The Chairman. Thanks, Senator Murray.
    Dr. Woodcock, you said the monograph process--you seemed to 
suggest the monograph process is outdated. Who requires it? Do 
we require it, or do you require it?
    Dr. Woodcock. The monograph process was a workaround around 
the 62 amendments which required efficacy data for all drugs 
that would be on the U.S. market. It wasn't known, but there 
were up to 500,000 over-the-counter drugs which apparently came 
from about 200 active ingredients.
    The Chairman. Well, let me ask this. If you were the king 
or the queen, would you change it?
    Dr. Woodcock. Yes. I would have a more effective process to 
finalize the monographs and also keep them up to date with 
modern science, because at the time it was done, it was thought 
we could just put a monograph out, and then we'd be done. We've 
learned things like the toxicity of Tylenol, acetaminophen----
    The Chairman. Would that require a change in the law?
    Dr. Woodcock. It would require something.
    The Chairman. Would you please give our staff technical 
advice about what that change might look like?
    Before I conclude, I see Senator Casey is here. He was here 
earlier, so let me call on him now, and then we'll conclude the 
hearing after that.

                       Statement of Senator Casey

    Senator Casey. Mr. Chairman, thank you. I want to thank you 
and the Ranking Member for the hearing. I know I've been in and 
out, so I'll be within my time limit for sure.
    Dr. Woodcock, I wanted to start with you with a question, 
but I first wanted to ask you--I notice you went to Penn State? 
Are you a Pennsylvania native?
    Dr. Woodcock. I am.
    Senator Casey. Where are you from?
    Dr. Woodcock. Hollidaysburg, PA.
    Senator Casey. Blair County.
    Dr. Woodcock. Absolutely, yes.
    Senator Casey. I just wanted to get that on the record.
    Dr. Woodcock. Idyllic childhood.
    Senator Casey. I wanted to ask you, in the context of rare 
pediatric diseases--I understand that FDA recently awarded the 
third and final priority review voucher as authorized under 
FDASIA. I wanted to ask you, in particular, regarding this 
question. What are the three products that were approved and 
awarded that priority review voucher--or vouchers, I should 
say, plural. I don't know if you have that.
    Dr. Woodcock. I do have that here somewhere, because I 
think that is important. There was one for a tropical disease. 
There was--hold on. I'm sorry. We can get back to you on that. 
Yes, we did--here they are. Vimizim for Morquio Type A 
syndrome; another one called Unituxin for pediatric people with 
high-risk neuroblastoma; and then recently Cholbam, cholic acid 
for bile acid disorders and peroxisomal disorders.
    Those are obviously very rare diseases where there was not 
very much satisfactory treatment available. That's really good 
news.
    Senator Casey. I appreciate that, and maybe we'll followup 
with some questions about companies that are interested in 
seeking a priority review voucher. That would be helpful, and 
we can submit these for the record.
    I want to thank you for that. I just have a last question, 
I guess, for Dr. Austin regarding the so-called tissue chip.
    Let me just ask a preliminary question. Is the product safe 
now for use in humans?
    Dr. Austin. No. That's an important question. This is a 
research project at this point. This project only started 3 
years ago. It's made much more rapid headway than I 
anticipated, at least. It is very much in the testing-
validation stage now. We are working very closely--and have 
from the beginning--with colleagues from the FDA about this.
    Perhaps within 3, 4, or 5 years, we'll be at the point 
where this might be able to be used for some conditions of 
qualification. But, there's a lot more work to go.
    At this point, the most immediate applications--and we're 
beginning to see this already--a number of these chips are 
being used actually in research applications to be able to 
understand human diseases and why they happen and how they 
might be fixed in a way that works better and more quickly than 
animal models. For regulatory applications, the requirements 
are simply much more stringent. We're definitely working in 
that direction and working hand-in-glove with the FDA, but we 
have a ways to go.
    Senator Casey. I'll leave the rest of the time. I want to 
thank our witnesses for being here. I also want to, Mr. 
Chairman, thank you and the Ranking Member, and I'll refer back 
to something Senator Warren said and that a number of us have 
been saying for a number of years. We have to get more 
researchers to NIH for all the reasons that were cited, and, 
frankly, we're years behind in doing that.
    Thank you very much.
    The Chairman. Thank you, Senator Casey, and thanks, Senator 
Warren.
    Let me thank the witnesses. You have distinguished careers. 
You run immensely important centers and, in one case, an 
institute. You know the ways of Washington. I mean, if we 
wanted to talk about Obamacare or right-to-work laws, we could 
have a big fight on this committee.
    Senator Murray and I aren't interested in a big fight on 
this subject. We're interested in getting a result, and we're 
not here to make it harder for you to do your job. We're here 
to enable you to do it better.
    We would like to know from you, specifically, what we can 
do to make it easier for you to align Federal policies with 
innovation so that we can get discoveries and treatments all 
the way through the process into the medicine cabinets so they 
can help Americans. We know that part of that has to do with 
funding, and we'll discuss that, and we'll deal with that in 
the Appropriations Committee and to some extent here.
    There are bound to be other specific things that, with your 
experience, you sit there some days and say, ``Why do I have to 
do this when I could do it better? '' For example, if the 
monograph is outdated, and if there's a way to fix it, we'd 
like to know how to fix it.
    If it makes a difference at NIH, as Dr. Collins says it 
does, to give you a chance to take the funding that we 
appropriate for 1 year and roll it over to the next year, as we 
do with some agencies, then please put that on your list. In 
other words, we would like to invite you to give the bipartisan 
working group that Senator Murray and I have formed specific 
suggestions from your agencies about what we can do to enable 
you to do your job.
    We don't want to produce a bill that reduces your 
productivity. We'd like to increase it. You know what you're 
doing much better than we know what we're doing. We'll still be 
appropriately critical. We'll have our questions. We're here to 
enable you, and we invite that.
    The time for receiving that is the next few months, because 
right now, we're working on elementary and secondary education. 
We're doing pretty well with that. We're going to move next, as 
a major priority, to the Higher Education Act, and in the 
meantime, we're getting ready for this. As I said earlier, 
we're working on a parallel track with the House. We're working 
with President Obama, who is very interested in the precision 
medicine initiative, as all of you know.
    This is an invitation that I hope you won't pass up. We 
thank you for your service, and we look forward to your further 
comments.
    The hearing record will remain open for 10 days. Members 
may submit additional information for the record within that 
time if they would like.
    Thank you for being here. The next HELP Committee health 
hearing will be on May 5th. The committee will stand adjourned.
    [Whereupon, at 11:27 a.m., the hearing was adjourned.]

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