[Senate Hearing 117-394]
[From the U.S. Government Publishing Office]
S. Hrg. 117-394
FDA USER FEE AGREEMENTS: ADVANCING
MEDICAL PRODUCT REGULATION AND
INNOVATION FOR THE BENEFIT OF PATIENTS
=======================================================================
HEARING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED SEVENTEENTH CONGRESS
SECOND SESSION
ON
EXAMINING FOOD AND DRUG ADMINISTRATION USER FEE AGREE-
MENTS, FOCUSING ON ADVANCING MEDICAL PRODUCT REGULATION
AND INNOVATION FOR THE BENEFIT OF PATIENTS
__________
APRIL 5, 2022
__________
Printed for the use of the Committee on Health, Education, Labor, and
Pensions
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Available via the World Wide Web: http://www.govinfo.gov
__________
U.S. GOVERNMENT PUBLISHING OFFICE
48-905 PDF WASHINGTON : 2023
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
PATTY MURRAY, Washington, Chair
BERNIE SANDERS (I), Vermont RICHARD BURR, North Carolina,
ROBERT P. CASEY, JR., Pennsylvania Ranking Member
TAMMY BALDWIN, Wisconsin RAND PAUL, M.D., Kentucky
CHRISTOPHER S. MURPHY, Connecticut SUSAN M. COLLINS, Maine
TIM KAINE, Virginia BILL CASSIDY, M.D., Louisiana
MAGGIE HASSAN, New Hampshire LISA MURKOWSKI, Alaska
TINA SMITH, Minnesota MIKE BRAUN, Indiana
JACKY ROSEN, Nevada ROGER MARSHALL, M.D., Kansas
BEN RAY LUJAN, New Mexico TIM SCOTT, South Carolina
JOHN HICKENLOOPER, Colorado MITT ROMNEY, Utah
TOMMY TUBERVILLE, Alabama
JERRY MORAN, Kansas
Evan T. Schatz, Staff Director
David P. Cleary, Republican Staff Director
John Righter, Deputy Staff Director
C O N T E N T S
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STATEMENTS
TUESDAY, APRIL 5, 2022
Page
Committee Members
Murray, Hon. Patty, Chair, Committee on Health, Education, Labor,
and Pensions, Opening statement................................ 1
Burr, Hon. Richard, Ranking Member, a U.S. Senator from the State
of North Carolina, Opening statement........................... 3
Witnesses
Richardson, Liz, Director, Health Care Products Project, The Pew
Charitable Trusts, Washington, DC.............................. 6
Prepared statement........................................... 8
Summary statement............................................ 11
Esham, Cartier, Ph.D., Chief Scientific Officer and Executive
Vice President of Emerging Companies, Biotechnology Innovation
Organization, Washington, DC................................... 12
Prepared statement........................................... 13
Summary statement............................................ 23
Gaugh, David, Senior Vice President, Sciences and Regulatory
Affairs, Association for Accessible Medicines, Alexandria, VA.. 24
Prepared statement........................................... 25
Summary statement............................................ 32
Leahey, Mark, President and Chief Executive Officer, Medical
Device Manufacturers Association, Washington, DC............... 33
Prepared statement........................................... 34
Summary statement............................................ 36
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.
Burr, Hon. Richard:
Letters to and from the FDA.................................. 59
Count of In-Person Medical Product Inspections by Month-FY17
to FY21 (to date).......................................... 128
Smith, Hon. Tina:
Biosimilars Forum Letter..................................... 130
Braun, Hon. Mike:
Letter Requesting a Patient Focused User Fee Hearing......... 131
QUESTIONS AND ANSWERS
Response by Cartier Esham to questions of:
Senator Braun................................................ 132
Senator Romney............................................... 133
Response by David Gaugh to questions of:
Senator Kaine................................................ 134
Senator Romney............................................... 135
Response by David Leahey to questions of:
Senator Burr................................................. 136
FDA USER FEE AGREEMENTS: ADVANCING
MEDICAL PRODUCT REGULATION AND
INNOVATION FOR THE BENEFIT OF PATIENTS
----------
Tuesday, April 5, 2022
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The Committee met, pursuant to notice, at 10:02 a.m., in
room 106, Dirksen Senate Office Building, Hon. Patty Murray,
Chair of the Committee, presiding.
Present: Senators Murray [presiding], Casey, Baldwin,
Murphy, Kaine, Hassan, Smith, Rosen, Hickenlooper, Burr,
Collins, Cassidy, Braun, Marshall, and Scott.
OPENING STATEMENT OF SENATOR MURRAY
The Chair. Good morning. The Committee will come to order.
The Senate Health, Education, Labor, and Pensions Committee
will come to order. And today we are having the first of two
hearings on reauthorizing four Food and Drug Administration
user fee programs. I will have an opening statement followed by
Ranking Member Burr. We will then introduce our witnesses.
After they give their testimony, Senators will each have 5
minutes for a round of questions. Again, while we are unable
yet to have the hearing fully opened to the public or media for
in-person attendance, live video is available on our Committee
website at help.senate.gov. And if you are in need of
accommodations, including closed captioning, you can reach out
to the Committee or the Office of Congressional Accessibility
Services.
Every day, families in Washington State and across the
country count on the Food and Drug Administration to keep them
safe more times than they even realize. Whether we are getting
a meal or a prescription or an ultrasound, or almost anything
in between, we have the FDA to thank for reviewing the data,
inspecting the supply chain, holding companies accountable, and
taking unsafe products off the market.
It is no small task ensuring the safety of nearly 80
percent of our Nation's food supply, inspecting thousands of
food, drug, and device manufacturing sites each year, and of
course, quickly and carefully reviewing the data on new and
potentially lifesaving medical products. As we have seen
throughout this pandemic, this work is incredibly important,
which is why it is also important we reauthorize the user fee
programs, which ensure as FDA gets new drugs or devices to
consider for approval.
As it gets more potentially lifesaving work to do, it also
gets more resources to support that work. Congress has
regularly reauthorized the user fee programs in a bipartisan
way, and I am glad to be working with Senator Burr and our
colleagues on the Committee to get this done once again in a
timely manner. Because it should be unthinkable that after 2
years when FDA's work has been more important than ever, we
would fail to get this done and force the agency to send pink
slips.
Just as it should be unthinkable that we would fail to
learn the lessons of this pandemic, including lessons for FDA,
like how we can get tests to families sooner, or how we can
avoid political interferences like we saw during the Trump
administration, including the reckless push for unproven
treatments like hydroxychloroquine, or how we can improve
transparency and communication to prevent some of the confusion
and frustration we have seen around the timelines for booster
shots and vaccines for younger children.
Beyond pandemic response, it is clear we can't simply
settle for business as usual, because when you look at issues
like the exorbitant cost of prescription drugs, the lack of
diversity in clinical trials, the scourge of opioids and
especially fentanyl, the lack of oversight for dietary
supplements and cosmetics, and how long it took to get
contaminated baby formula off the market, it is clear to me and
to people back in Washington State that business as usual is
not good enough.
We have to make sure the approval process works for
families, not just pharmaceutical companies' bottom lines. That
means better steps to ensure drugs work for everyone, such as
increased diversity in clinical trials and pediatric drug
research. It means ensuring the accelerated approval pathway
benefits patients. And it absolutely means lower costs, because
even a miracle cure is no help if it is too expensive for
people who need it.
We need to fight skyrocketing health care costs with every
tool in our arsenal from stopping pharmaceutical companies who
game the FDA system to block competition and keep cheaper drugs
off the shelves, to bringing down barriers that block cheaper
generics and biosimilars from getting to market, to finally
making good on legislation Congress passed to let hearing aids
to be sold over-the-counter and at lower cost for millions of
people.
I worked with many of my colleagues on this Committee to
pass that into law a half a decade ago, and I am incredibly
frustrated FDA has not been focused on helping so many
Americans. There is just no good reason we are still waiting
for FDA to implement that step and save millions of people
thousands of dollars. We also need to do more to protect
families from dangerous products that have gone for too long
with too little scrutiny.
When it comes to cosmetics, products people put on their
face, rub into their skin, and more, we have discovered known
carcinogens like asbestos and formaldehyde in baby powder,
children's makeup kits, and hair products. And when it comes to
dietary supplements, people across the country who are looking
to make healthy choices are faced with a shelf full of products
that make health claims but lack rigorous oversight.
Yet FDA does not have the authority to collect basic
information about those products or even to know what is on the
market. That makes no sense. People in Washington State and
across the country buy, use, and entrust their health to these
items every day. They deserve to know these products are safe,
vetted, and subject to the same type of careful FDA oversight
people rely on when it comes to food, drugs, and medical
devices. So I hope we will make progress on all of those issues
and more as we rework--as we work to reauthorize the user fee
programs.
All of us on this Committee are grateful for the tireless
work of FDA scientists during this pandemic to review and
authorize safe and effective tests, treatments, and of course,
vaccines for COVID-19. And we are grateful for the constant
work they do to ensure the safety of our food supply, provide
people with the information they need to make healthy choices,
and uphold the gold standard of safety and effectiveness for
drugs and medical devices. But the FDA does not run on
gratitude.
I look forward to today's conversation on the user fee
programs, and to working with my colleagues on bipartisan
legislation that supports and strengthens FDA's ongoing work by
reauthorizing these programs and taking additional steps to
lower drug costs, increase diversity in clinical trials, ensure
the safety of cosmetics and dietary supplements, and more.
With that, I will turn it over to Ranking Member Burr for
his opening remarks.
OPENING STATEMENT OF SENATOR BURR
Senator Burr. Thank you, Madam Chair. And welcome to our
witnesses here today. I look forward to our discussion. Every 5
years, this Committee is charged with evaluating FDA's user fee
programs and the agency's performance in meeting its existing
commitments. At their core, these programs are about bringing
new hope to Americans.
The faster, more predictable, and more accountable the
programs are, the more patients stand to benefit from
lifesaving, innovative drugs and devices. When FDA does not
live up to its commitments, patients are the ones that suffer.
I have served in Congress since 1995, so I have been here for
all but the first user fee process.
Each time, I have gradually added provisions to improve
FDA's accountability to the commitments that FDA makes. Every 5
years, industry agrees to provide more funding under the duress
of negotiating with the regulator. So it is Congress's job to
make sure that those negotiations were not a hostage situation,
and that these arrangements are a good deal for patients and
the industry that brings that hope.
The user fee programs are intended to supplement FDA's
congressionally appropriated resources to speed the review of
medical products and get treatments to patients as quickly as
possible. The user fee agreements negotiated between FDA and
industry partners lay out the process for bringing new products
to market that will treat, prevent, and cure disease. In 1992,
under the first Prescription Drug User Fee Agreement or PDUFA,
the drug application fee was about $100,000.
Today, the drug application fee is $1.3 million. The
medical device user fee agreements were first signed into law
in 2002. In 2007, a 510(k) submission was just over $4,000.
Today, this application costs more than $12,700. When Members
of Congress complain about the cost of prescription drugs or
medical devices, we should evaluate all aspects of the
pipeline, including the cost of development and regulatory
review, to make sure costly and burdensome regulations are not
part of the cost problem.
The enormous growth in the oldest of the user fee programs
underscores my longstanding concerns. In 1993, FDA collected
just over $35 million in annual fees from the Prescription Drug
User Fee Program. Today, FDA collects over $1 billion in PDUFA
user fees annually. Even accounting for inflation, that is an
increase of more than 1,500 percent since the start of the
program.
Yet FDA continues to request more and more resources from
industry, even when they don't meet agreed upon performance
goals. For example, in Fiscal Year 2019 and 2020, FDA missed 12
out of the 14 goals related to scheduled meetings, delaying
needed conversations for innovators to move forward with their
products. As part of the proposed new prescription drug program
commitments, FDA is requesting an additional $324 million over
the 5-year cycle. Let me say that again, $324 million.
The proposed agreement includes $111 million for hiring an
additional 352 people. That is 122 more new hires than the
agency committed to in the last cycle. In fact, across all four
programs, FDA is committing to more than 880 new hires when the
agency has more than 700 vacancies outstanding. Let me say that
again. In fact, across all four programs, FDA is committing to
more than 884 new hires when the agency has more than 700
vacancies outstanding today.
Generic and biosimilar drugs are our best tool at driving
down the cost of prescription drugs and should be a top
priority of the agency. The biosimilar agreement should help
boost the number of biosimilars in the market, including
biosimilars in insulin production. FDA, again, has struggled to
meet some important program goals.
During Fiscal Year 2020, FDA missed its goal to review 90
percent of biosimilar applications within 10 months, only
reviewing 50 percent within that time, and missed 7 out of 15
goals related to product development meetings. Under the
proposed biosimilar agreement, FDA is requesting an additional
$5 million over the 5-year cycle and 15 new hires.
The generic drug program collects more than $494 million in
annual fees and supports more than 2,100 staff positions. Under
the proposed generic drug agreement, FDA is requesting
additional funding of more than $40 million and 128 new hires.
While FDA appears to be on track to meet the majority of its
commitments under the current generic agreement, its
performance has been impacted by COVID-19 in terms of delayed
facility inspections.
As of last August, these inspections challenges had delayed
more than 29 generic drug applications, with many more
applications likely delayed since then. Turning our attention
to the medical device agreement, I have watched this very
carefully and I am concerned. This Committee only recently
received the draft medical device commitment letter.
The final medical device arrangements were due by law to
Congress by January 15th. By the time we receive these final
agreements, the device commitment letter was more than 3 months
late. Under this proposal, FDA is requesting up to $1.9 billion
over the 5-year cycle, nearly $1 billion increase.
This proposed increase is roughly doubling fee collections.
Yet again, the FDA did not meet deliverables under this user
fee program. The FDA missed goals for 510(k) reviews, resulting
in longer review times, failed to explain its reasoning to
sponsors each time it sent a deficiency letter about their
product, and it failed to issue an important digital health
guidance on time. Let me remind my colleagues, these are not
optional actions.
These were requirements, requirements under the last deal
for categories of submissions. For the first 2 years, review
times for premarket approval applications would hold steady at
290 calendar days, and in the last 3 years, review times would
reduce to 285 calendar days. Wow.
However, FDA is significantly walking back its current
commitment to reviewing 510(k) submissions within 180 days.
Instead, FDA is proposing longer review times of 108 days. FDA
Safety and Innovation Act, which we passed in 2012, requires
FDA to review 95 percent of these applications within 90 days.
This agreement almost doubles the user fees and includes longer
review times for some categories of products.
Pay more, get less is not exactly a selling point. MDUFA V
also includes a new pilot program called TAP. This aimed to
initiate early and frequent engagement between FDA and sponsors
of innovative devices. I might say, something already
negotiated in the agreement. As the author of the breakthrough
device pathway, I still can't figure out whether this new
program will offer anything different from FDA's current
activities for breakthrough devices.
The new pilot program is set to grow over the 5-year cycle,
without clear accountability, metrics, or deliverables to help
measure the success of the program. No metrics. The pilot has
the ability to grow to 325 devices, which would cost at least
$477,000 per device. Congress deserves a full accounting of how
FDA plans to spend these resources and operate this new
nebulous program.
I will tell you right now, Congress is going to require
accountability in the new program. With each reauthorization,
FDA receives huge increases in resources despite not fulfilling
or delivering what has previously been promised. And with a
declining percentage of congressional appropriations for the
overall program, FDA is increasingly removing itself from
Congress's reach.
My colleagues should be concerned with this. I question
whether the agreements both passed and proposed reflect a good
deal for patients they are designed to serve. In 2017, during
the user fee hearings in this Committee, I asked each industry
representative testifying about the importance of the user fee
agreements and whether they would support a mechanism to hold
FDA more accountable.
The response was clear, FDA should be held accountable to
its commitments. I look forward to hearing from each of you and
about why you have agreed to these commitments, and how they
would accelerate innovation and lifesaving products for the
American people. I thank the Chair.
The Chair. Thank you, Senator Burr. I would like to ask
unanimous consent to introduce into the record a statement from
the National Organization for Rare Disorders.
Senator Burr. Madam Chair, I would also like to ask
unanimous consent to enter into the record letters that I sent
to then Acting Commissioner Woodcock, requesting information
about the user fee programs and the negotiations for these
proposed new agreements, and the responses I received from the
FDA. One of these letters I sent to the FDA in November last
year, and I am still awaiting a response. I hope to receive
that response soon.
The Chair. So ordered on both.
[The information referred to by Senator Murray was not
submitted:]
[The information referred by Senator Burr can be found on
page 59 in Additional Material:]
The Chair. With that, I want to welcome all of our
witnesses today. Thank you for joining us. Our first witness
will be Liz Richardson, who is the Director of the Health Care
Products Project at the Pew Charitable Trusts. Ms. Richardson,
thank you for sharing your time and expertise with us today.
I look forward to your testimony. Our next witness is Dr.
Cartier Esham, the Chief Scientific Officer and Executive Vice
President of Emerging Companies at the Biotechnology Innovation
Organization. Thank you for joining us today, Dr. Esham. We
look forward to your testimony. I am also pleased to welcome
David Gaugh, who is the Senior Vice President for Sciences and
Regulatory Affairs at the Association for Accessible Medicines.
Mr. Gaugh, I appreciate your being here today to share your
perspectives. Finally, we have Mark Leahey, President and Chief
Executive Officer of the Medical Device Manufacturers
Association. Mr. Leahey, thank you for taking the time to be
with all of us today. Ms. Richardson, you may begin your
opening statement.
STATEMENT OF LIZ RICHARDSON, DIRECTOR, HEALTH CARE PRODUCTS
PROJECT, THE PEW CHARITABLE TRUSTS, WASHINGTON, DC
Ms. Richardson. Chair Murray, Ranking Member Burr, and
Members of this Committee, thank you for the opportunity to
testify today about how the reauthorization of the FDA user fee
agreements can support patients and public health. The Pew
Charitable Trust is a global non-governmental organization that
seeks to improve public policy, invigorate civic life, and
inform the public.
We believe that evidence based policies and investments can
both spur the development of new drugs and medical devices and
ensure effective oversight of these products. Today, I would
like to focus my remarks on the role that the user fee
agreements can play in promoting innovation and supporting a
broad range of public health priorities, ultimately leading to
improvements in patient care and outcomes.
Since 1992, user fees have provided FDA with significant
and sustained resources that have allowed the agency to both
facilitate the development of urgently needed medical products
and to review those products quickly so they can get to the
patients who need them.
This issue is particularly important to Pew's Antibiotic
Resistance Project, which is working to advance policies that
would spur the creation of new antimicrobial products and
establish stewardship programs that would ensure these products
are prescribed only when necessary. Since 2014, FDA has
approved 14 antibiotics, three of which represent a novel drug
class or novel mechanism of action.
These advances are critical as the world faces a dangerous
shortage of antimicrobial products to address both current and
future patient needs. In 2002, Congress also established a user
fee program for medical devices. The fees that FDA collects
under these agreements provide the agency with resources to
review applications and deliver a more efficient oversight
process, one that can adapt to a rapidly evolving device market
where emerging technologies like AI enabled digital health
tools and 3D printing are posing challenges to traditional FDA
oversight.
Pew is currently conducting research to inform how the
agency can better facilitate ongoing innovation while still
providing adequate public health safeguards for these rapidly
changing products. But no matter how the agency decides to
adapt its regulatory approaches, it needs adequate resources to
fund its core activities, and this includes user fees.
A second key aspect of the user fee agreement process is
how each successive reauthorization has provided an opportunity
to advance other priorities that can advance patient health.
For example, in its 2012 PDUFA Reauthorization Bill, Congress
acknowledged the vital need for new antibiotics by enacting the
GAIN Act as part of that package.
The GAIN Act represented an important first step in
launching innovator companies devoted to antimicrobial research
and development, but more work is needed to ensure that these
companies can earn a fair return on investment and continue to
innovate. But to that end, the PASTEUR Act proposes a unique,
only pay for success pull incentive that will strengthen U.S.
preparedness for future pandemics.
We urge Congress to include that measure in its current
PDUFA reauthorization. Pew also believes that reforming
oversight for diagnostic tests, an issue currently addressed in
bipartisan legislation known as the VALID Act, is of critical
importance. As the COVID-19 pandemic has shown, the Nation's
public health depends on rapid access to accurate and reliable
tests that can diagnose disease or identify past infection. But
faulty diagnostic tests can compromise both patient care and
the Nation's response to infectious diseases.
Current gaps in oversight have allowed tests that are
developed and used within the same laboratories, called lab
developed tests, to come to market without FDA approval, even
if those tests are otherwise high risk. Pew believes strongly
that tests should be regulated according to their risk to
patients if they are inaccurate, not according to where they
are developed and used.
By including VALID as part of the MDUFA reauthorization
package, Congress can strengthen and update FDA's oversight of
these critical products to make it more flexible and more risk-
based.
Finally, I want to note that while review times are
important insofar as they speed patient access to potentially
important products, it is critical to remember that true
innovation is not just about getting products to market faster,
it is about developing products that are safer and more
effective than what is already available.
While user fees are important to the efficient function of
FDA, they cannot and should not be a substitute for adequate
appropriations. User fees do not cover all of FDA's essential
functions, such as conducting most post-market oversight
activities or regulating non-drug products, including the large
and ever-growing market of dietary supplements. FDA needs
resources beyond user fees to sustain these core activities.
Because FDA is a public health agency that works to promote
the health of all Americans, the agency should receive public
funds and be accountable to the public, not just to the
industries that it regulates. That being said, I want to
conclude by underscoring again the importance of user fees to
the basic functioning of the FDA.
Given the critical role that the agency plays in protecting
and promoting public health, we urge Congress to reauthorize
these agreements and ensure adequate funding for FDA to carry
out its mission. Thank you for your time and I look forward to
answering any questions.
[The prepared statement of Ms. Richardson follows:]
prepared statement of liz richardson
Chair Murray, Ranking Member Burr, and Members of this Committee,
thank you for the opportunity to testify about the proposed FDA user
fee agreements and how legislation reauthorizing these agreements can
support patients and public health.
Established in 1948, The Pew Charitable Trusts is a global
nongovernmental organization that seeks to improve public policy,
inform the public, and invigorate civic life. Through research and
analysis, Pew's projects work to improve Americans' health and well-
being. We believe that evidence-based policies and investments can help
expand access to life-saving treatments, spur the development of
innovative drugs and medical devices, and provide effective oversight
of the benefits and risks associated with these products.
Today, I would like to talk about how the user fee agreements can
promote innovation and help to ensure the safety and effectiveness of
medical products, ultimately leading to improvements in health.
The User fee Agreements Promote Innovation of Drugs and Medical Devices
Since 1992, user fees paid by the drug and device industry have
provided FDA with significant and sustained resources that allow the
agency to facilitate the development of urgently needed medical
products, and to review those products quickly.
This issue is particularly important to Pew's antibiotic resistance
project, which is working to advance policies that would spur the
creation of new antibiotics and establish stewardship programs to
ensure that antibiotics are prescribed only when necessary in human
health care settings. Since 2014, FDA has approved 14 antibiotics \1\--
three of which represent a novel drug class or mechanism of action--to
treat a variety of life-threatening bacterial infections, including
community-acquired pneumonia and certain abdominal infections. These
advances are critical as the world faces a dangerous shortage of
antibiotics to address current and future patient needs.
---------------------------------------------------------------------------
\1\ K. Talkington. ``Analysis Shows Continued Deficiencies in
Antibiotic Development since 2014'', The Pew Charitable Trusts, last
modified March 9, 2021, https://www.pewtrusts.org/en/research-and-
analysis/data-visualizations/2019/five-year-analysis-shows-continued-
deficiencies-in-antibiotic-development.
Overall, the user fee programs have substantially sped up the
review of new drug applications. In the decade after the first user fee
agreement was passed, the median review time fell by half, from nearly
28 months to less than 14 months. Review times for drugs given priority
status have also fallen significantly. Indeed, a standard review today
is faster than a priority review a decade ago (around 10 months). \2\
---------------------------------------------------------------------------
\2\ https://www.fda.gov/media/102796/
download'msclkid=381a13f5b03e11ec9429b69ceba87906.
In 2002, Congress also established a user fee program for medical
devices. The fees FDA collects under these agreements provide the
agency with additional resources to review applications and better
facilitate the introduction of a wide variety of new medical
technologies. Under the proposed agreement, the total fees collected
are expected to reach at least $1.78 billion, \3\ and if certain
specified goals are met, the agency could collect up to $1.9 billion by
2027, up from about $1 billion in fees authorized under the previous
reauthorization. \4\ These funds help FDA deliver a more efficient and
comprehensive oversight process that is better resourced to protect
consumer safety and adapt to a rapidly evolving device market, where
emerging technologies are posing challenges to traditional FDA
oversight.
---------------------------------------------------------------------------
\3\ U.S. Food and Drug Administration, ``FDA Statement on Medical
Device User Fee Amendments (MDUFA),'' news release, March 22, 2022,
https://www.fda.gov/news-events/press-announcements/fda-statement-
medical-device-user-fee-amendments-mdufa.
\4\ FIND.
---------------------------------------------------------------------------
Today, for example, health care organizations use AI-enabled
digital health tools for a growing range of clinical, administrative,
and research purposes. FDA has approved or cleared nearly 350 AI-
enabled devices for a broad range of applications. \5\ Nearly 140 of
these approvals or clearances have been granted since the start of
2020, \6\ and the pace of submissions that include an AI component is
only expected to grow over the next 5 years. These tools offer unique
opportunities to improve patient care and health outcomes, but the
volume of applications and the pace at which these products evolve pose
unique challenges to FDA's traditional approach to oversight. These
products will not only need to be reviewed to ensure they are safe and
effective at the time of approval, they also need to be adequately
monitored over time to ensure that they continue to be safe and
effective in the real world, and when used on diverse patient
populations. FDA must have sufficient resources--both through robust
user fee programs and annual appropriations--as well as the internal
expertise and commitment to develop regulatory policies that can
facilitate ongoing innovation while still providing adequate public
health safeguards for these rapidly changing products.
---------------------------------------------------------------------------
\5\ https://www.fda.gov/medical-devices/software-medical-device-
samd/artificial-intelligence-and-machine-learning-aiml-enabled-medical-
devices.
\6\ Ibid.
Similarly, 3D printing is increasingly being used at the point of
care to manufacture a range of products, including anatomical models
used to guide surgery planning and medical devices like surgical
cutting guides. This technology allows for the decentralized
manufacturing of highly customized products--which could 1 day include
implants, pharmaceuticals, and even biological products--that are
manufactured directly within health care facilities. However, 3D-
printed devices--like any medical product--also carry risks, and
existing laws, regulations, and guidance meant to ensure the safety of
devices and drugs do not clearly map to this emerging technology. FDA
needs the resources to be able to adapt its regulatory approach to meet
the demands of the changing field and regulate the increasing number of
sites that utilize the technology in order to ensure that medical
products printed at the point of care are safe and effective.
The User fee Process can Support a Broad Range of Public Health
Priorities
Though the matter of FDA funding is central to the user fee
negotiation process, each successive reauthorization of those
agreements has provided an opportunity for Congress to pass additional
reforms that advance public health. For example, past reauthorizations
led to the establishment of the Sentinel Initiative, provided important
incentives for the development of new antimicrobial drug products,
strengthened FDA's ability to require postmarket trials or labeling
changes in response to safety signals, and facilitated efforts to
better incorporate the patient perspective within the agency's
decision-making process, among many other consequential changes. \7\ We
urge Congress to consider other worthy opportunities to improve public
health during the current reauthorization.
---------------------------------------------------------------------------
\7\ A. Mitchell et al. ``The Prescription Drug User Fee Act'',
Medical Care, Volume 60--Issue 4: 287-293, April 2022, https://
journals.lww.com/lwwmedicalcare/Citation/2022/04000/The-Prescription-
Drug-User-Fee-Act-Much-More-Than.4.aspx.
In particular, the issue of diagnostic test oversight, currently
addressed in bipartisan legislation known as the Verifying Accurate
Leading-edge IVCT Development (VALID) Act, is of critical importance.
As the COVID-19 pandemic has shown, the Nation's public health depends
on rapid access to accurate and reliable tests that can diagnose
disease or identify past infection. But faulty diagnostic tests can
compromise both patient care and the Nation's response to infectious
---------------------------------------------------------------------------
diseases.
Current gaps in oversight have allowed tests that are developed and
used within the same laboratories, called lab-developed tests, to come
to market without FDA approval, even if those tests are otherwise high-
risk. Once used to test for rare diseases for which commercially
manufactured diagnostics were unavailable, these tests have now become
widespread and increasingly complex. However, because there is no
central registration or reporting requirements for these tests, the
exact size of the market is unknown, leaving countless people exposed
to potential harm from unreliable or misleading results.
As Committee Members discussed at a recent hearing, the current
MDUFA reauthorization is an appropriate vehicle for the VALID Act. By
including VALID in the user fees legislation, Congress can strengthen
and update current medical device regulations and enable FDA to adopt a
risk-based approach to diagnostics oversight that balances safety and
innovation.
Congress also acknowledged in its 2012 PDUFA reauthorization bill
the importance of addressing the growing public health threat of
antibiotic-resistant superbugs and the vital need for new antibiotics
by enacting the Generating Antibiotic Incentives Now (GAIN) Act as part
of that package. The GAIN Act represented an important first step that
supported the launch of small biotechnology innovator companies devoted
to antimicrobial research and development.
But on this front, more work is needed. A robust, market-based
subscription model is necessary to ensure that these companies can earn
a fair return-on-investment and continue to innovate. The
sustainability of the antibiotic drug pipeline is absolutely
foundational to modern medicine. To that end, the Pioneering
Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act
proposes a unique, `only pay for success' pull incentive that will
substantially strengthen U.S. preparedness for future pandemics. We
urge Congress to include that measure in its current PDUFA
reauthorization.
The User fee Process is no Substitute for Adequate Funding
Review times are important insofar as they speed patients' access
to potentially important products. The user fee agreements make review
times a performance metric. However, it is critical to remember that
true innovation is not just about getting products to market faster; it
is about developing products that are safer or more effective than
existing drugs and devices. While more challenging to measure than
review times, protecting and promoting health is the ultimate goal of
the FDA.
As important as user fees are to the efficient function of FDA,
they cannot be a substitute for adequate appropriations. User fee
agreements do not cover a broad range of essential health functions,
such as enforcing good manufacturing practices, conducting most post-
market safety activities, and regulating non-drug products, including
food and the large and ever-growing market of dietary supplements. FDA
needs sufficient additional resources beyond user fees to sustain these
critical activities.
Furthermore, FDA is a public health agency that works to promote
the health of all Americans. Because of the public interest in a well-
performing FDA, the agency should receive public funds and be
accountable to the public, not just to the industries it regulates.
Conclusion
In conclusion, I want to emphasize the importance of user fees to
the basic functioning of the FDA. We urge Congress to ensure that FDA
has continued, sustained funding to carry out its important public
health mission.
Thank you for your time and I look forward to answering any
questions.
______
[summary statement of liz richardson]
The Pew Charitable Trusts believes that evidence-based policies and
investments can both spur the development of new drugs and medical
devices, and ensure effective oversight of these products. Since 1992,
user fees have provided FDA with significant and sustained resources
that have allowed the agency both to facilitate the development of
urgently needed medical products, and to review those products quickly.
This issue is particularly important to Pew's antibiotic resistance
project, which is working to advance policies that would spur the
creation of new antimicrobial products and establish stewardship
programs that would ensure these products are prescribed only when
necessary. Since 2014, FDA has approved 14 antibiotics, three of which
represent a novel drug class or new mechanism of action. These advances
are critical, as the world faces a dangerous shortage of antimicrobial
products to address both current and future patient needs.
In 2002, Congress also established a user fee program for medical
devices. The fees that FDA collects under these agreements provide the
agency with resources to review applications and deliver a more
efficient oversight process, one that can adapt to a rapidly evolving
device market, where emerging technologies like AI-enabled digital
health tools and 3D printing are posing challenges to traditional FDA
oversight.
A second key aspect of the user fee agreement process is how each
successive reauthorization has provided an opportunity to advance other
public health priorities. For example, in its 2012 reauthorization of
user fees, Congress acknowledged the vital need for new antibiotics by
enacting the GAIN Act as part of that package. The GAIN Act represented
an important first step, but more work is needed to ensure that drug
developers can earn a fair return-on-investment and continue to
innovate. To that end, the PASTEUR Act proposes a unique, `only pay for
success' pull incentive that will strengthen U.S. preparedness for
future pandemics. Pew urges Congress to include that measure in its
current user fee reauthorization.
Similarly, Pew also believes that reforming oversight for in vitro
diagnostic tests, an issue currently addressed in bipartisan
legislation known as the VALID Act, is of critical importance. The
Nation's public health depends on rapid access to accurate and reliable
diagnostic tests. But current gaps in oversight have allowed tests that
are developed and used within the same laboratories, called lab-
developed tests, to come to market without FDA approval, even if those
tests are otherwise high-risk. Pew believes strongly that tests should
be regulated according to their risk, not where they are developed and
used. By including VALID as part of the MDUFA reauthorization package,
Congress can strengthen and update FDA oversight of these critical
products to make it more flexible and risk-based.
Finally, while user fees are important to the efficient function of
FDA, they cannot be a substitute for adequate appropriations. User fees
do not cover all of FDA's essential functions, such as conducting most
post-market safety activities, or regulating non-drug products,
including food and the large and ever-growing market of dietary
supplements. FDA needs resources beyond user fees to sustain these core
activities. And because FDA is a public health agency that works to
promote the health of all Americans, the agency should receive public
funds and be accountable to the public, not just to the industries it
regulates.
______
The Chair. Ms. Richardson, thank you for your testimony. I
am going to turn it over to Dr. Esham for testimony next. And
then I am going to turn the Committee over to Senator Burr. I
will go vote. There are two votes that are being called and I
will be back shortly. Thank you, Senator Burr.
Dr. Esham.
STATEMENT OF CARTIER ESHAM, PH.D., CHIEF SCIENTIFIC OFFICER AND
EXECUTIVE VICE PRESIDENT OF EMERGING COMPANIES, BIOTECHNOLOGY
INNOVATION ORGANIZATION, WASHINGTON, DC
Dr. Esham. Thank you. Good morning, Chair Murray, Ranking
Member Burr, Members of the Committee. My name is Cartier
Esham, and I am the Chief Scientific Officer at the
Biotechnology Innovation Organization, or BIO. BIO is the
world's largest trade association, representing biotech
companies, academic institutions, and related organizations
across the United States and in more than 30 other nations.
While our membership includes most of the large
pharmaceutical companies, the majority of our members are
small, pre-revenue companies working on cutting edge biomedical
innovations. We appreciate the opportunity to speak with you
today, and we are committed to and working toward modernizing
the clinical development paradigm to one that is more
efficient, more patient centric, more inclusive, and best able
to provide timely availability of next generation medicines
that will improve the lives of patients and their families.
We do urge timely reauthorization of the prescription drug
and biosimilar user fee agreements as they are vital to
advancing these goals and to ensuring the FDA is able to
effectively carry out its vital mission to protect and promote
the public health.
Congress has built a strong foundation over many years with
the enactment of previous user fee agreements and other key
laws that have collectively worked to ensure effective and
timely reviews, improve drug and biologic safety monitoring,
enable the agency to keep pace with medical and scientific
process, and provided the support necessary to ensure that
advanced medicines are provided to patients as quickly and
safely as possible.
The PDUFA and MDUFA User Fee Agreements will build on these
efforts and foster next generation scientific medical advances
that will benefit patients. For example, the PDUFA VII
agreement aligns meeting opportunities with the needs of
complex and innovative clinical development programs that will
support productive scientific dialog and foster early
identification, and better enable timely resolution of those
issues when possible.
This includes the advancement of best practices--best
meeting practices, as it is a shared responsibility between the
biopharmaceutical industry and the FDA to ensure productive and
effective meetings. The commitments in PDUFA will work to
continue to advance the systematic integration of patient
centric perspectives into drug development and review, building
on efforts that began in earnest under the PDUFA V agreement.
They will provide the resources, capacity, and expertise
needed for CBER to manage the exciting and vastly growing
pipeline of cell and gene therapies. They will provide
resources to improve safety monitoring and ensure the FDA is
able to meet the demands and opportunities of the data and
digital age.
Advance evidence collection and analysis approaches--
analytical approaches that are more patient centric, more
informative about health outcomes for all patients. They will
provide resources and drive actions that will work better to
enable the use of advanced manufacturing technologies and
ensure that processes relating to the safe manufacturing of
complex medicines is done in a manner that does not unduly
delay availability of these medicines.
The PDUFA commitments will also include provisions that
will further strengthen the accelerated approval pathway and
the orphan drug designation processes, both of which have been
foundational in enabling the timely availability of medicines
for patients suffering from devastating and life threatening
diseases.
These include provisions that will advance regulatory
understandings about what is necessary to support the
utilization of a surrogate endpoint as a basis for approval and
approve processes to ensure timely or post-market requirement
assessments are made and better enable effective study designs,
as well as improve the ability to engage with the FDA post-
approval to resolve study challenges when they arise and better
support timely determinations of continued scientific validity.
Like PDUFA, BsUFA agreement also works to ensure timely and
productive scientific dialog, and advances regulatory science
in key areas, including supporting the more efficient and
better understood processes for the approval of interchangeable
biosimilars. And they both work to ensure that FDA is best
able--better able to recruit and retain world-class personnel
and effectively manage resources.
Before I close, I would like to take this opportunity to
convey BIO's commitment to improving clinical trial diversity.
In addition to important commitments in the PDUFA VII
agreement, BIO has provided Members of this Committee with
proposals we believe are essential to advancing regulatory
understandings that will drive change and support a clinical
development ecosystem that is more inclusive and representative
of the patients we serve.
Thank you again, and we look forward to working with you on
these reauthorizations and toward advancing a new clinical
development paradigm that is more expansive, more inclusive,
more patient centric, and better enables the timely delivery of
safe and effective next generation medicines that will improve
the lives of patients and their families. Thank you.
[The prepared statement of Dr. Esham follows:]
prepared statement of cartier esham
Introduction
Good morning, Chair Murray, Ranking Member Burr, and Members of the
Committee. My name is Cartier Esham, and I am the Chief Scientific
Officer at the Biotechnology Innovation Organization, or BIO. BIO
appreciates the opportunity to speak with you today about key
priorities we believe will improve regulatory oversight and
transparency, as well as enable biopharmaceutical companies to
modernize the clinical development paradigm to one that is more
patient-centric, efficient, and inclusive. Congress has built a strong
foundation over many years that has served to expedite patients' access
to safe and effective therapies, and helped innovators develop next-
generation medicines that have improved the lives of patients and their
families. We look forward to working with this Committee to continue to
building on these efforts and urge that the Committee proceed with the
timely reauthorization of the Prescription Drug User Fee Act and
Biosimilar User Fee Act to ensure FDA can continue to meet its mission
to protect and promote public health.
BIO is the world's largest trade association representing
biotechnology companies, academic institutions, state biotechnology
centers, and related organizations across the United States and more
than 30 other nations. While our membership includes most of the large,
international biopharmaceutical companies, the majority of our members
are small biotechnology companies working on cutting-edge biomedical
innovations. These companies are pre-revenue and take enormous risks
every day to develop the next generation of biomedical breakthroughs
for the millions of patients suffering from diseases for which there
are no effective cures or treatments today. BIO is proud of their
innovative spirit and dedication to improving the lives of patients and
their families.
Since the initial enactment of the Prescription Drug User Fee Act
(PDUFA) in 1992, user fees have played a key role in ensuring that
effective and efficient regulatory processes keep pace with the
continual advancement of scientific and medical innovation. As a
result, more innovative treatments and therapies are first approved in
the United States, providing our citizens with faster access to
innovative medicines. Additionally, the PDUFA program ensures that FDA
has the resources, capabilities, and processes in place to establish a
clear and direct pathway from initial scientific discovery to
widespread availability of cutting-edge medicines. This benefits not
only regulators, patients, and the biopharmaceutical industry, but also
the entrepreneurial community that makes significant investments in
high-risk, early stage, innovative medicine development. Today, it can
take anywhere from 10 to 15 years at an average cost of approximately
$1 billion or more to advance a single drug or biological product from
a promising idea to an approved product that benefits patients. \1\,
\2\ A well-run and comprehensible pathway to approval is critical to
maintaining U.S. leadership in investment, development, and
availability of next-generation medicines.
---------------------------------------------------------------------------
\1\ Olivier J. Wouters, Ph.D; Martin McKee, MD, DSc; Jeroen
Luyten, Ph.D. Estimated Research and Development Investment Needed to
Bring a New Medicine to Market JAMA. 2020, 323(9).
\2\ Joseph A. DiMasi; Henry G. Grabowskibi; Ronald W. Hansen.
Innovation in the pharmaceutical industry: New estimates of R&D costs.
2016. Journal of Health Economics. 2016, Vol. 47.
The Prescription Drug and Biosimilar User Fee Acts (PDUFA and
BsUFA) have collectively worked to ensure effective and timely reviews,
improve drug and biologics safety monitoring, enable the Agency to keep
pace with medical and scientific advancements, allow for earlier and
more frequent FDA-sponsor engagement to identify and resolve drug and
biologic development challenges, and provide the support necessary to
ensure that advanced medicines are available to patients as efficiently
and safely as possible. These user fee programs, which are reauthorized
by Congress every 5 years, provide FDA with the authority to collect
fees from companies that produce certain human drugs, biologics,
medical devices, and generics. These user fees, in addition to the
resources provided through direct appropriations from Congress, have
ensured that FDA is a global leader in regulatory advancement and
oversight. Last year, 76 percent of novel drugs approved by FDA's
Center for Drug Evaluation and Research (CDER) were approved in the
U.S. before any other country. \3\
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\3\ https://www.fda.gov/media/155227/download.
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User fee programs are not fee-for-service programs, and fees paid
by a company for a medical product application are not tied to the
review of that particular application. Instead, these fees support a
wide range of regulatory programs and ensure FDA has the resources,
capabilities, and processes in place to maintain clear regulatory
pathways and keep pace with medical and scientific innovation. The
PDUFA and BsUFA agreements currently under consideration continue to
advance those goals and activities and include additional commitments
that will strengthen review fundamentals, enhance accountability and
transparency, ensure stable growth of successful existing regulatory
programs, and foster innovative scientific advancements.
Highlighting a few key topics that are most important to BIO, our
member companies, and, most importantly, the patients we serve, we
would like to emphasize the importance of promoting effective
scientific dialog between FDA and sponsors of medical product
development programs, enabling the utilization of regulatory tools that
are more effective and support broader and more meaningful
understandings of clinical outcomes for all patients, the incorporation
of patient perspectives in clinical trials and post-approval data
collection, and the necessity to provide the resources and capacity
needed to meet the demands and opportunities of the digital age. The
COVID-19 pandemic has shown us that decentralized clinical trials,
digital health technology tools, and other innovations utilized during
the pandemic have the potential to improve how we develop medicines
that meet the needs of patients and greatly reduce the burden on
clinical trial participants, especially for those who belong to
historically underserved populations and for those who suffer from rare
diseases, where clinical trial populations are small and geographically
dispersed. We urge an on-time reauthorization of FDA's user fee
programs to allow the enactment of the PDUFA VII and BsUFA III
Commitment Letters that will continue to advance meaningful integration
of the patient voice and experience into drug and biosimilar biological
product development and review processes, build upon important lessons
learned from the pandemic, and pave a path forward to a clinical
development paradigm that is more effective, more informative, and more
inclusive.
Overall Goals for PDUFA VII
Each user-fee Commitment Letter has continued to build upon the
efforts of previous agreements. The following testimony will describe
the content and benefit of critical provisions addressed in seven
primary themes included in the PDUVA VII Commitment Letter:
1. Strengthen scientific dialog and advance innovation
2. Support the next wave of advanced biological therapeutics
3. Enhance patient-centric drug development, review, and
protections
4. Modernize regulatory evidence generation and drug
development tools
5. Enhance innovation in manufacturing and product quality
reviews
6. Advance digital technologies and information technology (IT)
infrastructure
7. Enhance FDA hiring, retention, and financial management
Strengthen Scientific Dialog and Advance Innovation
A goal of PDUFA VII most critical to advancing innovation involves
enhancing and strengthening scientific dialog between sponsors of
applications and FDA. To that end, FDA, for the first time, will
provide consistent timelines for Initial Targeted Engagement for
Regulatory Advice on CBER Products (INTERACT) meetings and expand the
scope of these meetings to include products regulated by the Center for
Drug Evaluation and Research (CDER). INTERACT meetings have been
critical for sponsors of innovative biological products who face unique
challenges that could otherwise delay entry into clinical development.
FDA will also establish a new Type D meeting that enables FDA and
sponsors to engage in more rapid and focused conversations about
innovative approaches or unique challenges that will allow for earlier
resolution of discrete issues. The Commitment Letter also formalizes a
process where sponsors can submit clarifying questions to FDA following
a meeting to ensure alignment on expectations and requirements. We
collectively recognized that establishing and following best practices
for productive meetings is a shared responsibility between
biopharmaceutical companies and FDA.
There are at least 7,000 known rare diseases collectively impacting
over 25 million Americans with new rare diseases identified each year.
Because rare diseases have limited or no treatment options and lack
well-established regulatory precedents, the development and review of
these medicines introduces additional challenges that must be overcome
to deliver new therapies to patients who need them. Key among these
challenges is reaching agreement with regulators about determining the
appropriate efficacy endpoints to support approval of innovative
medicines for rare diseases. The current mechanisms for companies with
rare disease treatments in their pipeline to collaborate with FDA has
not consistently provided avenues for much needed discussions about
these unique issues, which can cause delays in the development and
availability of medicines to these patients who often lack options. The
Rare Disease Endpoint Advancement (RDEA) pilot program in PDUFA VII
will provide avenues for focused engagement opportunities that will
serve to advance and share learnings and enable more efficient drug
development and review process for all rare disease medicines.
The Commitment Letter will establish a Split Real Time Application
Review (STAR) pilot program for certain applications that are intended
to treat a serious condition with an unmet need. The pilot builds on
the concepts that have proven successful for FDA's Real Time Oncology
Review (RTOR) program and expands them to other disease areas to enable
more timely reviews and availability of these medicines to vulnerable
patient populations. The STAR pilot will improve both the stakeholders
and industry's workload management by allowing sponsors of applications
to submit their applications in two parts rather than one, allowing for
earlier review of key components such as proposed labeling, clinical
protocols, and topline efficacy and safety results prior to the final
application submission.
Biopharmaceutical companies and FDA recognize the importance of
post-marketing requirements (PMRs) to ensure timely availability of
information on the safety and efficacy of certain therapies to patients
when further post-approval studies are warranted. PDUFA VII includes
commitments to ensure necessary PMRs are identified and communicated
earlier in the review process and enable the development and
implementation of more thoughtful study designs. This will better
ensure that these PMRs are completed on time and avoids delays in
confirmatory trials. PDUFA VII will also establish stronger processes
for the continued evaluation of PMRs post-approval to ensure
requirements are being met, issues can be resolved, and the studies
remain scientifically valid.
Support the Next Wave of Advanced Biological Therapeutics
Advancing the new wave of biological therapies is a top priority
for BIO member companies. A 2020 analysis by BIO found that there were
231 gene therapy products under development compared to only 93
products in 2015, a trend that is expected to continue in the coming
years. To ensure that new and innovative cell and gene therapy products
are developed and available to patients in a timely manner, the
Commitment Letter will provide FDA with the resources and capacity
needed to address the growing workload of the Cell and Gene Therapy
Program. This will enable FDA to maintain the level of highly trained
and experienced Cell and Gene Therapy staff needed to address CBER's
workload caused by increased regulatory submission volume as projected
over the next 5 years as well as keep pace with scientific and
technological advancements. As part of the commitment, FDA will
facilitate a better understanding of patient perspectives on gene
therapy products, including cell-mediated gene therapy, and provide
greater clarity on expedited pathways for regenerative medicines. FDA
will streamline and harmonize processes, procedures, and interactions
by enhancing, improving, and issuing guidance describing best practices
for communication related to aspects of Cell and Gene Therapy product
development, including the use of novel trial designs.
Enhance Patient-Centric Drug Development, Review, and Protections
One of the most important goals of PDUFA VII involves continuing to
advance the systematic integration of patient perspective data into
drug development and review processes. This work began in earnest under
PDUFA V with the establishment of the Voice of the Patient Program that
supported public meetings where patients provided insights about their
conditions and how they themselves evaluated benefits, risks, and
needs. PDUFA VI advanced this work by holding a series of public
meetings and publishing guidance that provided information about how to
determine the most important impacts to patients, how to measure
disease impact, and how to incorporate Clinical Outcome Assessments
(COAs) into clinical development and review processes.
During PDUFA VII, FDA will continue this critical work by
continuing to strengthen capacity and knowledge through the expansion
of training opportunities for FDA staff and ability to better engage
external methodological experts. FDA will seek public input on
methodologies and approaches for the submission of high-quality patient
perspective data designed to inform benefit-risk assessments and
inclusion of information in the label. PDUFA VII will provide
supplementary support to FDA's development of a publicly available
virtual catalog of Standard Core Sets of COAs and related endpoints
that will help make possible the broader utilization of patient
perspective data in clinical product development. FDA will also seek
public input on which diseases areas have the greatest need for
Standard COA development. Additionally, FDA will work to increase
shared understandings about how patient preference studies can inform
meaningful benefit-risk assessments in therapeutic areas, which is of
very high value to the patient community.
Modernize Regulatory Evidence Generation and Drug Development Tools
Advancing innovative, patient centric drug development tools, and
modernizing the regulatory evidence generation paradigm is a top
priority for BIO member companies. Advancements in science and
technology offer real opportunities to reduce patient burden, improve
ability to recruit and conduct effective clinical trials and provide
more informative analyses of benefit and risk pre and post approval.
PDUFA VII will continue to build on several key initiatives that were
launched under PDUFA VI. Under this Commitment Letter, FDA will advance
the use of real-world evidence (RWE) to support approval of labeling
claims, approval of new indications and to satisfy post approval study
requirements. The agreement establishes an Advance RWE pilot program
that will provide shared learnings with the public and inform the
publication of guidance increasing broad knowledge about how and when
RWE can be utilized in future applications.
Complex innovative trial designs can be more efficient, improve
patient outcomes, and produce high-quality information faster compared
to traditional trial designs. PDUFA VII will continue both the Complex
Innovative Trial Design and Model-Informed Drug Development (MIDD)
pilot programs which enable the utilization of these tools and
approaches more broadly. Additionally, the Agreement will enhance the
drug development tool (DDT) qualification pathway for biomarkers by
retaining and enhancing staff capacity and piloting processes that
enhance the review of biomarker qualification submissions. High quality
biomarkers can accelerate and enable drug development in areas of unmet
need, improve clinical trial feasibility and efficiency thus continued
improvement of the qualification pathway is beneficial to regulators,
the research and development community, and patient communities.
To enhance FDA's drug safety system, PDUFA VII provides resources
and processes that will enable the adoption of new scientific
approaches designed to improve the utility of existing tools for the
detection, evaluation, prevention, and mitigation of adverse events.
PDUFA VII will modernize and improve Risk Evaluation and Mitigation
Strategies (REMS) approaches and processes through new guidance
documents and timelines for feedback to companies on REMS
methodologies. Newly allocated resources will expand and optimize FDA's
electronic safety data base (the Sentinel program) including supporting
the integration of Sentinel and BEST (Biologics Effectiveness and
Safety) systems, and FDA will advance knowledge about how Sentinel data
can be used for regulatory purposes (e.g., PMRs, PMCs and labeling) and
how real-world evidence (RWE) may be used for evaluating the
effectiveness of medicines. Collectively, these improvements and
advancements in FDA's drug safety system will improve patient
protections and utilization of this vast data resource to gain deeper
insights about the benefits and risks of medicines for all patients.
Enhance Innovation in Manufacturing and Product Quality Reviews
One of the critical needs for PDUFA VII was to advance innovation
in manufacturing and inspection review processes and improve the
ability to get medicines to patients in a timely manner. A rate-
limiting step for the past several years has been discussions and
resolution of chemical manufacturing and control (CMC) issues,
especially for innovative biologic therapies and treatments. FDA will
improve the timeliness and effectiveness of CMC communications through
training and updating CDER and CBER guidance designed to enable more
consistent review of high-quality information requests from sponsors.
FDA will also engage a third party to assess, seek public comment, and
provide recommendations about how these processes can be optimized to
support modernization of CMC-related processes.
To address the outsized hindrance of timely availability of
innovative treatments for serious and life-threatening diseases
undergoing expedited reviews due to CMC issues, FDA will publish new
internal documents to better align CMC communications and processes to
meet the desired timelines for approval decisions more consistently.
The FDA will also establish a CMC Development and Readiness Pilot
(CDRP) in both CDER and CBER to provide additional opportunities for
engagement between FDA and sponsors that will help companies meet
critical CMC milestones. Learnings from this pilot and an associated
public workshop will inform a strategy document describing the Agency's
plans to revise processes and information about submission strategies
to accelerate CMC development.
Over the past several years there have been significant scientific
advancements about how to effectively and efficiently manufacture high-
quality complex medicines. PDUFA VII will work to identify and remove
current barriers to the utilization and adoption of advanced
manufacturing technologies. FDA will conduct a workshop where best
practices, case studies, and regulatory strategies will be shared and
discussed, including how to assess innovative technologies across
platform products and sites. We are pleased that this Committee
included a focus on manufacturing in the PREVENT Pandemics Act, and BIO
supports the pathways for reviews of technologies established under
Sections 506 and 518 of that bill which will enhance these PDUFA goals
and facilitate the adoption of advanced manufacturing.
During the COVID-19 pandemic, regulators, biopharmaceutical
companies, and other key stakeholders from around the world held
discussions about how best to ensure the continued availability of
medicines and meet the needs of providing COVID vaccines and treatments
to all in need. Among the results of those discussions were the
increased utilization, when appropriate, of alternative tools such as
use of information shared by trusted foreign regulatory partners and
record requests for assessing manufacturing facilities. PDUFA VII will
continue the advancement of those lessons learned by issuing draft
guidance about when and how these types of alternative approaches may
be utilized beyond the pandemic.
Advance Digital Technologies and Information Technology (IT)
Infrastructure
It is of vital importance that support be provided to FDA to
increase its capacity and ability to meet the demands and opportunities
of the data and digital age. Increasing utilization of cloud
technologies is necessary for FDA to meet the growing needs, demands,
and advantages of modern-day development and review of innovative
medicines. Today's medical product applications have large and/or
complex data sets that require high-quality repository and analytical
capabilities. PDUFA VII activities and resources, collectively, will
enable FDA to make the necessary changes to meet these needs. These
advancements will serve to improve the quality of applications
submitted to FDA and improve our ability to better understand the
benefits and risks of medicines to all patients before and after they
are approved.
First, FDA will continue to meaningfully advance its Data and
Technology Modernization Strategy to improve both FDA's enterprise
needs and to advance key PDUFA objectives such as completing transition
to a cloud-based system. FDA also committed to regular engagement with
the biopharmaceutical industry to provide progress updates, share
learnings, and discuss challenges in meeting PDUFA VII goals and
advancing objectives outlined in the Data and Technology Modernization
Strategy.
Second, FDA will launch a series of demonstration projects in
collaboration with external partners to improve the core capabilities
necessary for reviewing data captured via digital technology tools. We
expect continued growth in the utilization of digital technologies as
they offer the ability to reduce burdens on patients in clinical
trials, better assess clinical outcomes for all patients, and more
efficiently collect high-quality data and evidence to support approvals
and inform life-cycle management of medicines. Findings and planned
next steps from these demonstration projects will be shared with
biopharmaceutical companies and made available to the public on FDA's
website.
Third, critical IT modernization and capacity needs for the review
of Biologic License Agreements will be provided to CBER to meet the
demands of current and future applications that are projected to
increase significantly over the next 5 years. In coordination with the
Data Technology Modernization Strategy described above, CBER will
develop a specific multi-year modernization roadmap to chart specific
steps necessary for CBER to meet current and projected needs necessary
to continue to successfully carryout its mission.
Enhance FDA Hiring, Retention, and Financial Management
PDUFA VII continues to build upon the resource management and
fiscal accountability provisions included in PDUFA VI. For example, the
time reporting system initiated under the previous Agreement will be
optimized to allow for time and associated costs to be reported and
examined on a more continual basis. Additionally, to strengthen fiscal
and staff resource management, accountability, and transparency, PDUFA
VII will continue to mature the resource capacity planning system that
includes a publication of an updated implementation plan describing how
resource capacity planning and time reporting will be improved and
implemented over the coming 5-year PDUFA cycle. A third-party
assessment of the capacity planning system will be conducted and inform
the 5-year fiscal planning activities. Recommendations and findings of
this assessment will be included in the annual financial reports.
Additionally, FDA will maintain a stronger operating reserve to ensure
they are better able to mitigate against disruptions to funding
resources and continue to carry out mission critical activities.
Ensuring FDA can recruit and retain world-class personnel is the
bedrock for maintaining U.S. regulatory leadership around the world.
PDUFA VII continues to provide resources and tools to better enable FDA
to attract and retain leading medical and scientific professionals.
Specifically, PDUFA VII provides FDA with resources to conduct a third-
party assessment of hiring and retention to identify challenges and
provide recommendations for the Agency. These recommendations will be
made available to the public where FDA will also share its plans to
address issues raised.
BSUFA III Highlights
The Biosimilar User Fee Agreement (BsUFA) contains several
commitments that have the same goals and objectives as those included
in PDUFA VII, including: maintaining and improving performance goals
for the effective and timely review of biosimilars, improving
scientific dialog and meeting best practices, modernizing IT
capabilities, advancing utilization of RWE to assess safety and support
regulatory decision-making, and strengthening the ability to recruit
and retain world-class personnel. Below I will highlight a few key
beneficial provisions included in the BsUFA III Commitment Letter most
important to our member companies and the patients we serve.
Improving Scientific Dialogue
Ensuring timely scientific dialog throughout the review process is
a top priority for BIO member companies. BsUFA will improve the ability
to engage in timely and focused discussions through the creation of new
and improved meeting opportunities. Specifically, FDA will now provide
a new meeting structure that enables FDA and sponsors of applications
to engage in focused conversations on a narrow set of issues. BsUFA III
also reforms the biosimilar initial advisory (BIA) \4\ advisory meeting
process to better manage FDA workload and ensure productive discussions
about whether licensure of a biosimilar is feasible, and if so, plans
and expectations for the development of that biosimilar.
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\4\ A BIA meeting is an initial assessment limited to a general
discussion regarding whether licensure under section 351(k) of the PHS
Act may be feasible for a particular product, and if so, general advice
on the expected content of the development program.
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Improving Review Processes of Biosimilar Supplemental Applications
The BsUFA III agreement will bring more predictability and
efficiency to the review of supplements. Specifically, there will be
timelines and goals established for 6 different types of supplement
categories. These commitments will increase efficiency, consistency,
and predictability of biosimilar supplemental applications and provide
patients with timelier access to these medicines.
Advancing the Development and Review of Interchangeable Biosimilars
BsUFA III will continue to support more efficient and better
understood processes for the approval of interchangeable biosimilars.
FDA will hold a scientific workshop to discuss shared learnings and
remaining challenges to the development of interchangeable biosimilars
that will help FDA determine what additional steps need be taken to
support the development and availability of these medicines (e.g.,
additional guidance or research). Following the workshop, FDA will
publish a strategy document describing the specific actions FDA will
implement to facilitate development of interchangeable biosimilars.
To advance regulatory science in this field, FDA will pilot a
regulatory science program that is designed to advance the development
of interchangeable products and improve the efficiency of their
development. Specifically, this pilot program will work to improve
knowledge about how data (including RWE) can be utilized to meet safety
standards for determining interchangeability and what methodologies can
be utilized to assess the potential impact of differences between
proposed interchangeable biosimilars and their reference products. The
findings and shared learnings from this pilot program will greatly
advance the development, review, and availability of interchangeable
biosimilar medicines.
Interchangeable Biosimilar Labeling and Manufacturing Guidance
Under BsUFA III, FDA will publish guidance that will serve to
improve communication of important biosimilar labeling information to
patients and their caregivers and better facilitate resolution of
manufacturing issues. Specifically, FDA will publish a guidance on
labeling for interchangeable biosimilars, a guidance on promotional
labeling and advertising considerations for interchangeable biosimilar
products, and a guidance on what information is needed to support post-
approval manufacturing changes to approved biosimilar and
interchangeable biosimilar products. Collectively, these will serve to
provide a greater understanding of what is required for efficient
review and approval of changes to labels and manufacturing processes.
Priorities for Advancing Medical Product Regulation and Innovation for
the Benefit of Patients
BIO strongly supports the objectives and activities outlined in the
PDUFA VII and BsUFA III commitment letters. These commitments, in
addition to other key pieces of legislation and initiatives from
Congress and the pharmaceutical industry, will facilitate innovation
that benefits all patients served by our member companies. The
testimony below outlines additional priorities that we believe will
support this objective.
Building a New Clinical Development Paradigm: More Inclusive, More
Patient Centric and More Informative About Clinical Outcomes for All
Patients
BIO is committed to enhancing clinical trial diversity, and we
included this commitment as part of our BIOEquality Agenda launched in
2020. The COVID-19 pandemic highlighted the urgent need to remove
barriers and advance solutions that enable clinical trials to be more
representative of the patients being treated. Scientific advancements
are providing opportunities to establish clinical development and post-
approval data collection approaches that can improve our understanding
of clinical outcomes for all patients. The PDUFA VII Commitment letter
will provide resources, capacity, and the development of guidance that
will significantly advance regulatory certainty and promote the
acceptance of real-world data/evidence (RWD/RWE) and digital health
tools (DHTs) like remote monitoring devices, cell phones, and smart
watches that are essential in more broadly enabling the utilization of
decentralized or non-traditional clinical trial locations.
BIO stands ready to work with Congress, the Administration, and
stakeholders to create a more expansive, inclusive, and sustainable
clinical development ecosystem. We need to modernize the regulatory
system to accept innovative tools and approaches that enable increased
participation in clinical trials from underrepresented communities and
the ability to collect data that improve our understanding of clinical
outcomes for all patients. In addition to important legislation
addressing these issues that will be discussed today, BIO has provided
this Committee with legislative proposals we believe are essential to
removing barriers and establishing a regulatory framework that is more
inclusive and representative of the patients we serve.
The lack of reliable data sources capturing U.S. demographics is a
challenge that must be resolved. Incomplete or outright missing
demographic data for many disease areas leads to poorly or inaccurately
informed enrollment targets and action plans during drug development.
While FDA regulations require sponsors to present a summary of safety
and effectiveness data by demographic subgroups within their trials, it
is difficult to compare this data to epidemiological data to understand
whether enrollment targets are representative of the disease
population. Sponsors also lack certainty regarding innovative clinical
trial designs that could improve trial diversity. Traditional clinical
trial designs are typically geographically centralized around academic
medical centers and associated with significant burden for patients,
such as multiple mandatory visits to the clinic. This creates
significant challenges when recruiting individuals who are
geographically dispersed, unable to travel, or unable to take leave
from work. By contrast, modern trial designs that embrace innovative
tools and methods, like digital health technologies, decentralized
clinical trials, and RWD/RWE, have demonstrated success in facilitating
trials and driving diverse enrollment throughout the COVID-19 pandemic,
\5\ but companies currently lack a regulatory framework to fully
leverage such techniques and tools.
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\5\ https://jamanetwork.com/journals/jamanetworkopen/fullarticle/
2789002.
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We need to re-examine and update approaches to and criteria for the
establishment of inclusion and exclusion criteria and advance
approaches to data collection for approved medicines that enhance our
understanding of benefits and risks for all patients and enable that
information to be more transparent and available to patients and their
care givers. Our proposal requires public meetings with comment periods
and the publication of guidance on each of these topics that together
will work to remove present-day barriers and establish a regulatory
framework that promotes inclusive and representative clinical
development and review processes.
To help build a more expansive, inclusive, and sustainable clinical
trial network infrastructure, BIO also recommends that HHS conducts a
series of public roundtable discussions that converge stakeholders from
FDA, NIH, CDC, community organizations, industry, and clinical research
organizations (CROs) to discuss, develop, and implement recommendations
that will serve to create a more expansive and inclusive clinical
development infrastructure. Roundtable discussion topics could include
establishing a publicly available data base of well-indexed active
clinical trialists, establishing clinical trialist training programs
and mentoring networks for investigators/trialists serving
underrepresented communities, and establishing a publicly available
data base of community engagement organizations supported by NIH. HHS
should also establish new or leverage existing programs for a federally
funded clinical trial investigator fellowship pilot program for women,
members of the LGBTQIA+ community, and racial and ethnic minorities to
help increase participation of underrepresented populations in clinical
trials.
To promote diversity and inclusion for workforce development in the
STEM community, BIO also recommends requirements for FDA and NIH to
improve transparency around hiring, retention, and promotion practices
within their organizational leadership and scientific workforces.
Requirements should outline clear objectives for staff and leadership
diversification and include a regular reporting cadence to Congress on
metrics related to progress on these objectives. Such provisions would
work synergistically with human resources (HR) authorities established
by the 21st Century Cures Act of 2016 that enable FDA to build and
maintain a talented workforce that keeps pace with rapid scientific and
technical advancements in the biopharmaceutical industry. These H.R.
authorities grant FDA increased flexibility to streamline the hiring
process for recruits with specific scientific, technical, and
professional occupations. They also established a new pay authority
enabling FDA to compete with the private sector and academia when
recruiting and retaining highly qualified candidates for these key
positions. Together, these activities would strengthen the Federal
public health workforce in terms of talent, expertise, and diversity.
We acknowledge that removing regulatory barriers and enhancing and
developing data sources and infrastructure will not address all
existing barriers to inclusive clinical trial participation, including
language and health literacy disparities and historical mistrust of
certain clinical research tactics and ethics. We have established a
website, The Power of Participation (www.ctpop.org), for patients,
designed to help assess and locate clinical trial opportunities and
identify patient and community organizations they may find helpful. We
remain committed to working with stakeholders across the public health
spectrum to provide meaningful educational materials for all patients.
Accelerated Approval Brings Life Changing Treatments to Patients who
Urgently Need Them
BIO continues to strongly support the Accelerated Approval Pathway
(AAP) for reviewing safe and effective therapies that address critical
unmet patient needs in serious and life-threatening disease states.
This pathway has proven to be very effective in addressing some of the
most pressing public health needs and has been foundational to
extending and saving countless lives since its enactment. As of June
2021, 269 new drugs or biologics to treat serious or life-threatening
diseases or conditions with high unmet medical needs have been approved
through this pathway, extending, and in certain cases, saving patients'
lives by providing novel therapies earlier than would have been
possible using the traditional pathway. \6\ Medicines approved through
this pathway meet FDA's well-established approval standard of safety
and effectiveness. The AAP is essential to providing timely access to
treatments where there is an unmet need and for patients who lack
therapeutic options.
---------------------------------------------------------------------------
\6\ https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-
approvals.
Since the AAP was established in 1992, \7\ the pathway has led to
the approval of treatments that have significantly improved the care of
patients suffering from many different diseases, including rare
cancers, Human Immunodeficiency Virus (HIV), bacterial infections,
multiple sclerosis, sickle cell disease, and other serious and life-
threatening conditions. The AAP encourages scientific and medical
advancement by allowing the use of surrogate or intermediate clinical
endpoints that are reasonably likely to predict clinical benefit to
support approval. Prior to the establishment of the AAP, patients with
HIV recognized the need for a new pathway as the development of
treatments using traditional endpoints of disease progression and death
were prohibitory to providing access to much needed treatments for
patients suffering from this deadly disease. The AAP enabled the
approval of the first HIV/AIDS treatment based on the use of surrogate
endpoints (viral load and CDR count) which served to prolong and save
the lives of millions of patients. The PDUFA VII agreement includes
commitments that will strengthen the AAP, such as advancing surrogate
endpoint development through the RDEA Pilot Program and providing
avenues for earlier and more timely discussions on the design of post-
market requirements to avoid delays in confirmatory trials. (PMRs),
which are critical to confirming the clinical benefits of products
receiving accelerated approval. \8\ The Commitment Letter will also
serve to advance regulatory understandings about when and how RWE may
be used to support PMRs that may significantly improve the ability to
complete PMRs in a more effective and efficient manner, modernizing the
conduct of confirmatory trials required by the AAP.
---------------------------------------------------------------------------
\7\ In 1992, and partially codified in 1997, FDA instituted the
Accelerated Approval regulations (21 CFR 314 Subpart H and 601 Subpart
E) to formalize the process for approving drugs to treat serious
conditions that filled an unmet medical need based on a study of
surrogate endpoints.
\8\ Sponsors planning to use surrogate endpoints as primary
efficacy endpoints also gained an opportunity to consult with FDA
earlier in the drug development process through Type C Surrogate
Endpoint meetings established during PDUFA VI.
Patients have consistently voiced their support for the use of AAP
over the last 30 years. We have all seen how this pathway has led to
more timely access to treatments that improve, extend, and save lives
and has been foundational to continued advancements in the treatment of
serious and life-threatening diseases. BIO looks forward to working
with the Committee to ensure that the Accelerated Approval Pathway is
working efficiently, effectively, and as intended.
Closing Comments
BIO member companies are committed to advancing innovation on
behalf of all patients, especially in areas of unmet medical need. Our
members constantly adapt to keep pace with technological and scientific
advancements that create opportunities to develop new therapies for
patients without any other options. The regulatory framework
established and refined over multiple reauthorization cycles by
Congress, including Members of this Committee, enables our member
companies to collaborate with the academic, advocacy, and patient
communities to develop innovative solutions to health challenges that
have historically left patients with little to no hope.
In 2021 alone, FDA approved 60 new therapeutic products between
CDER and CBER, including treatments to prevent and mitigate the impact
of COVID-19. 27 of these new drugs were first-in-class, up from 21
first-in-class approvals in the previous year. There were 26 approvals
for rare disease treatments that received orphan drug designations.
\9\, \10\ FDA staff adapted to unforeseen challenges to fulfill their
mission to protect and promote public health, and industry continues to
adapt as well. In addition to efforts from regulators, these life-
changing and life-saving approvals would not have been possible without
unwavering commitment by our member companies to create innovative
treatments and ensure that they reach the patients who urgently need
them. The biopharmaceutical industry supports and shares FDA's mission
to protect and promote public health by ensuring access to safe and
effective drugs and biological products for patients, and this shared
commitment enabled continued progress toward this mission despite
unprecedented obstacles posed by the pandemic. This reauthorization is
an opportunity to build on lessons learned from responding to the
COVID-19 public health emergency and incorporate these innovations into
the regulatory paradigm.
---------------------------------------------------------------------------
\9\ https://www.fda.gov/media/155227/download.
\10\ https://www.raps.org/news-and-articles/news-articles/2022/1/
fda-approved-more-first-in-class-drugs-more-with-a#:-:text-
Other%20drugs%20approved%20by%20CDER,treatment%20options%20for%20rare%20
diseases.
Companies continue to invest in and develop advanced manufacturing
technologies that offer the promise of increased capacity and
efficiency to help expedite production, enhance product quality, and
address shortages of essential medications. Innovation in new drug and
biologic development has been robustly incentivized by the modern drug/
biologic regulatory framework at FDA, and BIO continues to work with
Members of Congress to tackle unprecedented technical and regulatory
challenges like those associated with investment in advanced
manufacturing technologies and tools to modernize medical product
---------------------------------------------------------------------------
development and distribution.
Drug development for patient populations with unique needs, such as
the pediatric community, remains a priority for BIO and our members,
and we celebrate the many successes that benefit our youngest patients
stemming from these efforts. Today, we have numerous therapies with
pediatric indications, including for neonates, that are making a
measurable difference for these patients and their families. We have
seen advancements across a range of conditions, including recent drug
approvals in sickle cell, cystic fibrosis, pediatric rheumatologic
conditions, and even Ebola, and we are optimistic about the
breakthroughs to come. BIO is committed to building on this progress by
delivering more innovative medicines to pediatric patients.
PDUFA VII and BsUFA III include provisions to enhance drug
development with the goal of advancing novel therapies for patients,
including in disease areas with an unmet medical need and which have
proven to be more challenging areas for developing therapies, like rare
diseases and pediatrics. Leveraging advances in science, enhancing the
application of drug development tools, and modernizing clinical trials
are critical to continuing to improve the drug development paradigm and
regulatory processes for these medicines so we can better serve these
patients and their families.
These commitments will build on the numerous provisions Congress
has enacted over the years to help foster the development of promising
therapies for children, including the Best Pharmaceuticals for Children
Act (BPCA) and the Pediatric Research Equity Act (PREA). The most
recent PDUFA reauthorization bill (The FDA Reauthorization Act of 2017)
included new requirements for pediatric studies of certain cancer drugs
that FDA is in the process of implementing. The initial impact of that
legislation is beginning to work through the development cycle and BIO
and its member companies will continue to work with FDA to ensure
effective implementation of these programs.
The Orphan Drug Act (ODA) is a critical tool used to incentivize
the expensive and heavily uncertain investment necessary to bring
therapeutics for rare and orphan diseases to market. It is difficult to
identify a more successful and consequential regulatory incentive than
the ODA. Before it passed, there were merely a handful of treatments
for rare disease patients. Today, we have hundreds of life changing
treatments for these patients with countless more in the pipeline. We
celebrate scientific progress that has led to innovative medical
product development alongside patients, parents, and caregivers who
have new treatment options, and sometimes even cures, that were
previously unthinkable. While there is now immense hope for even the
rarest diseases, many more are still waiting. There are thousands of
identified rare diseases afflicting patients across the globe, many of
which still have no alternative or meaningful treatments on the market.
Given the tremendous risk, capital, and time it takes to discover and
develop such medicines, the rare disease development paradigm should be
handled with the utmost care and with significant consideration for
potentiality of unintended consequences.
BIO strongly supports timely enactment of the PDUFA VII and BsUFA
III Commitment Letters. The resources provided will serve to maintain
FDA's global leadership and enable the Agency to keep pace with the
medical and scientific advances of today and tomorrow. We look forward
to working with Congress to advance proposals that support a new
clinical development paradigm that is more expansive, inclusive, and
patient-centric and continues to incentivize the development and timely
delivery of next-generation medicines that save and improve the lives
of patients and their families.
______
[summary statement of cartier esham]
My name is Cartier Esham, and I am the Chief Scientific Officer at
the Biotechnology Innovation Organization, or BIO. BIO appreciates the
opportunity to speak with you today about key priorities we believe
will improve regulatory oversight and transparency and enable
biopharmaceutical companies to modernize the clinical development
paradigm to one that is more patient-centric, efficient, and inclusive.
We look forward to working with this Committee to build on the strong
foundation forged by Congress over many years that has expedited
patients' access to safe and effective therapies and helped innovators
develop next-generation medicines that have improved the lives of
patients and their families. We urge that the Committee proceed with
the timely reauthorization of the Prescription Drug User Fee Act
(PDUFA) and Biosimilar User Fee Act (BsUFA) to ensure FDA can continue
to meet its mission to protect and promote public health.
We emphasize the importance of promoting effective scientific
dialog between the FDA and sponsors of medical product development
programs, enabling the utilization of regulatory tools that are more
effective and support broader and more meaningful understandings of
clinical outcomes for all patients, the incorporation of patient
perspectives in clinical trials and post-approval data collection, and
the necessity to provide the resources and capacity needed to meet the
demands and opportunities of the digital age and the next wave of
advanced biologic therapies. The COVID-19 pandemic has shown us that
decentralized clinical trials, digital health technology tools,
utilization of real-world data and evidence, and other innovations have
the potential to improve how we develop innovative medicines.
Incorporating these lessons learned into the regulatory framework
enables the biopharmaceutical industry to better meet the needs of
patients, improve care, and greatly reduce burden on clinical trial
participants, especially those who belong to historically
underrepresented populations and those who suffer from rare diseases,
where clinical trial populations are small and geographically
dispersed.
BIO is committed to enhancing clinical trial diversity, and we
included this commitment as part of our BIOEquality Agenda launched in
2020. We stand ready to work with Congress, the Administration, and all
stakeholders to create a more expansive, inclusive, and sustainable
clinical development ecosystem. In addition to important legislation
addressing these issues that will be discussed today, BIO has provided
this Committee with legislative proposals we believe are essential to
removing barriers and establishing a regulatory framework that is more
inclusive and representative of the patients we serve by building
reliable demographic and epidemiological data, modernizing inclusion/
exclusion criteria, utilizing clinical trial modernization efforts as a
tool to improve diversity, formalizing scientific workforce
diversification, and other key actions.
Further, we strongly support the Accelerated Approval Pathway (AAP)
for reviewing safe and effective therapies that address critical unmet
patient needs in serious and life-threatening disease states. The AAP
has proven essential in addressing some of our most pressing public
health needs and has been foundational to extending and saving
countless lives since its enactment. We emphasize the role it plays in
providing timely access to treatments when there is an unmet medical
need and patients lack therapeutic options.
We urge an on-time reauthorization of FDA's user fee programs to
allow the enactment of the PDUFA VII and BsUFA III Commitment Letters
that will continue to advance meaningful integration of the patient
voice and experience into drug and biosimilar biological product
development and review processes, build upon important lessons learned
from the pandemic, and pave a path forward to a clinical development
paradigm that is more efficient, more effective, more informative, and
more representative of the patients we serve.
______
Senator Burr. Cartier, thank you. David, the floor is
yours.
STATEMENT OF DAVID GAUGH, SENIOR VICE PRESIDENT, SCIENCES AND
REGULATORY AFFAIRS, ASSOCIATION FOR ACCESSIBLE MEDICINES,
ALEXANDRIA, VA
Mr. Gaugh. Chair Murray, Ranking Member Burr, and Members
of the Committee, thank you for the opportunity to testify
about the critical role of GDUFA and BsUFA, and which they hold
in increasing patient access to more affordable generic and
biosimilar medicines. My name is David Gaugh, Senior Vice
President for Sciences and Regulatory Affairs at the
Association for Accessible Medicines.
I am a licensed pharmacist with many years of experience
with a generic and biosimilar industries. I represent the
industry in the initial development and in both subsequent
renewals of generic and biosimilar user fee agreements. AAM's
biosimilar council strongly support congressional
reauthorization of GDUFA and BsUFA as negotiated and without
changes.
Timely approval of the FDA user fee agreements ensure
patients will continue to benefit from new, more affordable
generic and biosimilar medicines. Over the last 10 years, GDUFA
and BsUFA significantly increased the resources available to
FDA for the review of applications. The benefits of this is
clear.
A record number of generic drugs were approved in 2017,
2018, and 2019, and a total of 34 biosimilars have been
licensed to date. A direct result of this increased competition
is lower prescription drug costs for the American patients.
Since 2012, patients in the U.S. health care system have saved
more than $2 trillion, including $469 billion from new generics
and more than $12 billion from biosimilars.
GDUFA III and BsUFA III build upon the successes of the
last decade. The user fee agreements incorporate lessons
learned, include enhancements to ensure the timely review of
applications, and will provide FDA with sufficient resources
over the next 5 years. GDUFA III and BsUFA III are the
culmination of months of negotiations, have been subject to
public review and comment, and represent a careful balance
between stakeholders.
My written statement details many improvements negotiated
in GDUFA III and BsUFA III but let me highlight a couple.
First, complex generics are generic versions of brand name
drugs that have complex active ingredients or drug device
combinations, for example. These drugs are more difficult to
develop due to the part--due in part to the lack of FDA product
specific guidance.
GDUFA III includes commitments to facilitate the
development and publication of product specific guidance for
complex generics. These commitments will increase transparency
and developers' understanding of FDA's expectations to allow
for a more predictable review process. Inspections.
Generic and biosimilar developers support FDA's inspection
program. One of the original purposes of GDUFA was to provide
resources for FDA to conduct risk based facility inspections.
GDUFA III enhances the efficiencies of the inspection process
by helping ensure re-inspections occur within a specified
timeframe. In addition, under BsUFA III, FDA commits to
increasing guidance on its use of alternative tools to request
records for documentation.
BLA supplements. Biosimilar developers can submit
supplements to modify an approved BLA. For example, updating
labeling with new study information or changes to indications.
Under pursue BsURA III, FDA commits to accelerating
supplemental reviews for safety labeling, for extrapolation,
for label carve in, carve out, and also for new data.
Interchangeability. As of March 2022, FDA has licensed two
interchangeable biosimilars. BsUFA III will help manufacturers
to develop more interchangeable biosimilars through the newly
negotiated regulatory science demonstration projects.
These demonstration projects will also evaluate mechanisms
to streamline overall biosimilar development. In closing, we
strongly support the timely reauthorization of GDUFA and BsUFA.
We look forward to working with Members of both parties to
accomplish this goal. Thank you for the opportunity to testify,
and I look forward to answering any questions you might have.
[The prepared statement of Mr. Gaugh follows:]
prepared statement of david gaugh
Chair Murray, Ranking Member Burr and Members of the Committee:
Thank you for holding today's hearing on the reauthorization of the
Food and Drug Administration's (FDA) user fee programs and for the
opportunity to testify about the critical role the Generic Drug User
Fee Amendments (GDUFA) and the Biosimilar User Fee Act (BsUFA) hold in
increasing patient access to more affordable generic and biosimilar
medicines. My name is David Gaugh, Senior Vice President for Sciences
and Regulatory Affairs at the Association for Accessible Medicines
(AAM). I am a licensed pharmacist with more than two decades of
experience working in and around the generic and biosimilar medicines
industry, and I represented the industry in the initial development and
in both subsequent renewals of the generic and biosimilars user fee
agreements.
AAM and its Biosimilars Council are the Nation's leading trade
association for the manufacturers and distributors of FDA-approved
generic and biosimilar prescription medicines. Today, generic and
biosimilar medicines comprise 90 percent of prescriptions in the United
States at only 18 percent of total drug spending. \1\ AAM's members
provide more than 52,000 jobs at nearly 150 facilities and manufacture
more than 60 billion doses of generic medicines in the United States
every year. \2\ Our core mission is to improve lives by advancing
timely access to high-quality, more affordable safe and effective
generic and biosimilar medicines.
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\1\ AAM, ``The U.S. Generic & Biosimilar Medicines Savings
Report,'' October 2021 (link).
\2\ ``A Blueprint for Enhancing the Security of the U.S.
Pharmaceutical Supply Chain,'' October 2021 (link).
In today's testimony, I will highlight the success of the FDA's
generic and biosimilars programs in significantly increasing patient
access to lower-cost medicines and, in turn, dramatically lowering the
cost of prescription drugs for America's patients and our health care
system over the last 10 years; outline the improvements made to the
public-private partnership embodied in GDUFA III and BsUFA III; and
discuss how congressional approval of the FDA user fee programs for the
next 5 years (FY2023-2027) will benefit patients and increase their
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access to more affordable treatments.
AAM and its Biosimilars Council strongly support congressional
reauthorization of GDUFA and BsUFA as negotiated and without changes.
Timely approval of the FDA user fee agreements ensures patients will
continue to benefit from new, more affordable generic and biosimilar
medicines. The GDUFA III and BsUFA III commitment letters were
carefully negotiated to balance program enhancements and resource
requirements provided to FDA. The agreements include a year-over-year
capacity planning adjuster (CPA) that allows FDA to automatically add
additional full-time equivalent (FTE) resources when increased workload
criteria exceed expectations. Therefore, AAM would have concerns about
adding policies into the reauthorization package that require
additional FTEs to implement if the package does not also include
corresponding appropriations. Adding such policies would increase
industry's year-over-year costs beyond what was negotiated and agreed
to with FDA.
GDUFA and BsUFA at 10 Years
Ten years ago, Congress created the FDA's user fee programs for
generic and biosimilar medicines when it enacted GDUFA and BsUFA as
part of the FDA Safety and Innovation Act of 2012. For generic drugs,
the number of applications submitted to the FDA had increased
substantially since enactment of the Hatch-Waxman Act. Prior to GDUFA,
FDA's review of abbreviated new drug applications (ANDA) was often slow
and unpredictable. For biosimilar medicines, FDA's licensure pathway
for these new treatments had been created in 2010 as part of the
Biologics Price Competition and Innovation Act (BPCIA). With passage of
the first GDUFA and BsUFA iterations in 2012, Congress helped ensure
FDA would have sufficient resources to carry out its mission.
Congressional authorization of the FDA's generic and biosimilars
user fee programs in 2012 and reauthorization in 2017 substantially
increased the resources available to the Agency to review applications.
More than $4 billion in supplemental user fees from generic and
biosimilars developers was and will be provided as a result. \3\
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\3\ AAM Analysis of FDA's fiscal year 2014--fiscal year 2020 GDUFA
and BsUFA Financial Reports and Five-Year Financial Plans (2021
Update). FDA's reports are available at https://www.fda.gov/about-fda/
user-fee-reports/user-fee-financial-reports.
[GRAPHIC] [TIFF OMITTED] T8905.002
.epsWith the additional resources, FDA was able to increase
efficiencies and approval of generic drugs increased significantly,
with full and tentative approvals exceeding 1,000 in fiscal years 2017,
2018 and 2019. The median number of ANDA approvals has increased over
time as a result of GDUFA I and GDUFA II. \4\ The partnership between
FDA and the generic industry has enhanced the overall stability and
predictability of the GDUFA program and accelerated the timely review
of ANDAs, increasing access to quality affordable generic medicines.
---------------------------------------------------------------------------
\4\ AAM Analysis of the FDA Office of Generic Drug Annual Reports
(2015-2020) and Activities Report of the Generic Drug Program (FY13-
FY15, fiscal year 2021). FDA's reports are available at https://
www.fda.gov/drugs/generic-drugs/annual-reports.
[GRAPHIC] [TIFF OMITTED] T8905.001
.epsFollowing the creation of the biosimilars pathway and
subsequent development of the biosimilars program, FDA licensed the
first biosimilar in 2015 and has now licensed 34 biosimilars in the
U.S. \5\ Biosimilar medicines are safe, effective and more affordable
treatments for patients and, with 21 products launched and available to
patients, biosimilars are already delivering on their promise of lower
costs and expanded patient access to care.
---------------------------------------------------------------------------
\5\ Biosimilars Council, ``FDA Biosimilars Approvals,'' March 2022
(link).
[GRAPHIC] [TIFF OMITTED] T8905.003
.epsWith FDA approval, the introduction of new generic and
biosimilar medicines leads to competition in the pharmaceutical
market--and the result is a significant reduction in the cost of
prescription drugs for patients. Experience shows drug prices decline
rapidly when generics enter the market. \6\ According to FDA, prices
fall as generics enter the market--by an average of 39 percent when
there is only one generic and by nearly 80 percent when four or more
generics enter the market. \7\ Evidence with biosimilar medicines is
similar with an average cost savings of nearly 50 percent. \8\
Importantly, biosimilar competition also results in lower brand
biologic costs--by more than 25 percent on average. \9\
---------------------------------------------------------------------------
\6\ IMS Institute for Healthcare Informatics, ``Price Declines
after Branded Medicines Lose Exclusivity in the U.S.,'' January 2016
(link).
\7\ FDA, ``New Evidence Linking Greater Competition and Lower
Generic Drug Prices,'' December 2019 (link).
\8\ AAM Analysis of Average Sales Price Files, January 2022.
\9\ Ibid.
---------------------------------------------------------------------------
Over the last 10 years, generics and biosimilars provided more than
$2 trillion in savings--including $469 billion from new generics and
more than $12 billion from biosimilars--to patients and the U.S. health
care system. \10\ In addition to the cost savings provided, patient
access to life-saving treatments is broadened as the price of medicine
falls. A recent analysis of Medicare Part D from the Congressional
Budget Office noted ``the number of standardized prescriptions
dispensed for generic drugs more than doubled from 2009 through 2018.''
\11\
---------------------------------------------------------------------------
\10\ Ibid., AAM Generic & Biosimilar Savings Report.
\11\ CBO, ``Prescription Drugs: Spending, Use, and Prices,''
January 2022 (link).
[GRAPHIC] [TIFF OMITTED] T8905.004
.epsGDUFA and BsUFA aim to put FDA's generic and biosimilar drug
programs on firm financial footing by enabling FDA to assess user fees
to fund critical and measurable enhancements and, in turn, bringing
greater predictability and timeliness to the review of applications. As
a direct outcome, the generic and biosimilars drug programs have
increased patient access to safe, effective and affordable quality
medicines.
GDUFA III Enhancements
FDA plays a critically important role in making lower-cost, high-
quality generic medicines available to patients. FDA reviews ANDAs
submitted by generic drug manufacturers (ANDA sponsors). To receive FDA
approval, data submitted in an ANDA must generally demonstrate that the
generic drug is bioequivalent to the Reference Listed Drug (RLD), more
commonly known as the innovator or brand product.
The GDUFA commitment letter specifies various fees the FDA sets and
can collect from manufacturers, such as ANDA applications, Drug Master
Files (DMF), and facility and program fees. \12\ The fees paid by the
generic drug industry aid FDA's ability to meet agreed-upon performance
goals and commitments, such as timely reviews and other regulatory
activities. FDA also provides annual reports to Congress on its
performance. \13\ The increases in transparency and communication are
important to FDA's ability to meet the commitments, which enhance the
overall stability and predictability of the GUDFA program.
---------------------------------------------------------------------------
\12\ AAM, ``The Generic Drug User Fee Amendments (GDUFA III),''
October 2021 (link); FDA, ``GDUFA Reauthorization Performance Goals and
Program Enhancements Fiscal Years 2023-2027,'' October 2021 (link).
\13\ FDA, GDUFA Performance Reports, fiscal year 2015--fiscal year
2020 (link).
The negotiated GDUFA III performance goals will further strengthen
and build upon the progress made and lessons learned from GDUFA I and
GDUFA II. Let me take a moment to highlight five areas--advancing
approvals, complex generics, inspections, suitability petitions and
sustainability--where we believe the FDA's generic drug program will be
enhanced with congressional ratification of GDUFA III.
Advancing Approvals
GDUFA III includes important performance goals that will maintain
FDA's rigorous ANDA review standards, building upon and improving the
review process to increase timely patient access to high-quality,
lower-cost generic medicines. For example, the newly negotiated
provision known as ``imminent action'' will allow the FDA to extend a
goal date by up to 60 days if, in FDA's judgment, an approval or
tentative approval of the application is imminent. This commitment will
mitigate the need to add additional review cycles unnecessarily and
delay approvals over minor, easily resolvable issues.
Complex Generics
Complex generics are generic versions of brand-name drugs that have
complex active ingredients, routes of administration, drug-device
combinations or formulations. These drugs are more difficult to develop
due in part to the lack of FDA product-specific guidance. Congress and
FDA helped spur competition for complex products by including
provisions in the previous user fee authorizations to increase product-
specific guidance publication and meetings with FDA during the product
development phase. GDUFA III builds on this success through performance
goals to facilitate the development and publication of product-specific
guidances for complex generic products--increasing transparency and
understanding of FDA's expectations to allow for a more predictable
review process.
Inspections
Generic and biosimilar developers support FDA's inspections
program. One of the original purposes of GDUFA was to provide resources
for FDA to conduct facility inspections. Under the inspections process,
FDA typically inspects a facility and identifies deficiencies. The
facility has a specified timeframe to address and correct the
identified deficiencies and subsequently request a reinspection from
FDA. In some cases, extended time passes from when a facility performs
the corrective actions to resolve the deficiencies and the time period
when FDA can reinspect. Delays in reinspection lead to significant
delays in the review process. GDUFA III enhances the efficiencies of
the inspection process by helping ensure reinspection occurs within a
specified timeframe.
Suitability Petitions
Suitability petitions are required to be submitted to FDA when a
generic drug manufacturer intends to seek approval of an ANDA for a
drug that differs from the reference brand product in terms of the
active ingredient (for a combination product), route of administration,
strength and/or dosage form. Current law requires FDA to grant or deny
suitability petitions within 90 days from petition submission. That
deadline, however, is rarely met. This results in delays to generic
market entry. GDUFA III includes performance goals and resources to
facilitate the FDA's ability to conduct a timely review of suitability
petitions. These new resources will help FDA meet these goals,
including conducting completeness assessments within 21 days from
petition submission and using agreed upon metrics to prioritize
petition reviews.
Sustainability of Resources
Under GDUFA II, FDA committed to developing a Resource Capacity
Planning (RCP) capability to optimize resources and better anticipate
future resource needs. GDUFA III provides an additional tool to further
enhance the utility of the RCP to allow FDA to better forecast resource
needs via the Capacity Planning Adjustment (CPA). The CPA will help
promote sustainability for both FDA and industry by allowing FDA to
increase full-time employee needs as workload increases. In turn, the
CPA will provide predictability for generic developers through a 3
percent cap to prevent significant fluctuation in fees and minimize the
financial barriers for smaller generic manufacturers.
BsUFA III Enhancements
Similar to FDA's generic drug program, FDA helps ensure that
America's patients can gain access to high-quality, more affordable
biological products in the form of biosimilars. FDA reviews abbreviated
biologics license applications (BLA) submitted by biosimilar
developers. In order for a biosimilar to be licensed, data submitted in
a BLA must demonstrate the biosimilar drug product is ``highly
similar'' to the brand-name reference biologic and there are no
clinically meaningful differences in safety, purity or potency.
BsUFA allowed FDA to assess and collect fees from developers and
manufacturers that submit BLAs for FDA's review. The negotiated
commitments enhance and improve the review process to facilitate timely
access to biosimilar medicines and ensures the Agency has the necessary
resources to fulfill the agreed upon commitments. FDA also provides
annual reports to Congress on its performance. \14\
---------------------------------------------------------------------------
\14\ FDA, BsUFA Performance Reports, fiscal year 2013--fiscal year
2020 (link).
The negotiated BsUFA III performance goals will further strengthen
and build upon the progress made and lessons learned from BsUFA I and
BsUFA II. \15\ Let me highlight several enhancements to FDA's
biosimilars program: supplement reviews, meeting management, regulatory
science and interchangeability, inspections, use of carryover funds and
IT modernization. I will briefly describe each.
---------------------------------------------------------------------------
\15\ AAM, ``Key Elements of BsUFA III,'' September 2021 (link);
FDA, ``Biosimilar Biological Product Reauthorization Performance Goals
and Procedures Fiscal Years 2023 Through 2027,'' September 2021 (link).
---------------------------------------------------------------------------
BLA Supplements
Biosimilar developers can submit supplements to modify an approved
BLA, for example, updating labeling with new safety information or
changes to indications. Under BsUFA III, FDA commits to accelerating
supplement reviews for safety labels, extrapolation, label carve-in and
carve-outs and new pharmacokinetic data.
Meeting Management
Biosimilar developers participate in meetings with FDA to gain
insight into the agency's expectations and perspectives on different
issues. These meetings help facilitate a predictable and efficient
review process. BsUFA III includes commitments to: add a new type of
meeting to get feedback on focused questions; make meetings more
efficient; help provide FDA with sufficient information in advance of
meetings; and obtain rapid clarification of meeting minutes.
Regulatory Science and Interchangeability
As of March 2022, FDA has licensed two interchangeable biosimilars.
In order to achieve the interchangeable designation, a biosimilar must
produce the same clinical result as the brand-name biologic. With the
interchangeable designation and subject to state law, a pharmacist may
dispense an interchangeable biosimilar when a brand-name biologic is
prescribed without intervention from the provider. BsUFA III will help
manufacturers to develop more interchangeable biosimilars through the
new Regulatory Science Program's demonstration project. These
demonstration projects will also evaluate mechanisms to streamline
overall biosimilars development. Findings from the demonstration
projects will inform a comprehensive strategy to advance
interchangeability and the development of future guidance documents.
Remote Inspections
FDA uses alternate tools to conduct inspections and supplement its
ability to assess manufacturing facilities remotely. Due to the COVID-
19 pandemic, FDA used these alternate tools to request records and
documentation from its regulatory partners. Under BsUFA III, FDA
commits to issuing guidance on the use of alternative inspection tools.
Use of Carryover Funds
Any remaining user fees collected by FDA but not yet spent are
carried over to the next year. Under BsUFA III, FDA commits to reducing
the carryover balance from 39 weeks to 21 weeks over a 3-year period.
IT Modernization
FDA continues to modernize the Agency's IT capabilities. BsUFA III
will further FDA's efforts. For example, FDA will modernize and move
the Electronic Submissions Gateway to the cloud to help improve
transparency and communication.
COVID-19 and FDA's Use of Remote Inspections
Given congressional interest about lessons learned from the COVID-
19 pandemic and this Committee's leadership in driving forward
solutions to prepare the country for future public health emergencies,
I do want to take a moment to share the experience of AAM's members in
regard to FDA inspections over the last 2 years. Manufacturing facility
inspections are an essential part of evaluating applications to market
all FDA-approved pharmaceuticals, including brand-name, generic, and
biosimilar medicines. When FDA does not conduct inspections in a timely
manner, approvals and patient access to new treatments, as well as more
affordable options, can be delayed.
During the last 2 years, there have been significant disruptions to
the inspections program. In March 2020, FDA announced that it was
suspending domestic and foreign inspections due to the COVID-19
pandemic. The Agency focused only on ``mission-critical'' inspections,
a narrow category that does not include inspections tied to most drug
applications. As the pandemic subsided in mid-2021, FDA attempted to
resume all domestic inspections. However, with the rise of the Omicron
variant in December 2021, FDA reverted to performing only mission-
critical inspections and did not resume a normal domestic inspection
schedule until February 2022.
These inspection disruptions have had a significant effect on our
members' ability to obtain timely approval of more affordable generics
and biosimilars. By FDA's account, as of the end of fiscal year 2021--
the most recent data available to AAM at the time of this hearing--52
human drug application decisions remain ``delayed solely due to a
pending inspection or facility assessment.'' \16\ The tally of 52
likely underestimates the extent of the delays, as it excludes
applications that might have had a minor issue unrelated to an
inability to inspect. Inspections for biosimilar applicants are also
impacted, including biosimilars for brand-name biologics like Humira.
\17\ Prompt inspection of such facilities is urgently needed.
---------------------------------------------------------------------------
\16\ FDA, ``An Update to the Resiliency Roadmap for FDA
Inspectional Oversight,'' November 2021 (link).
\17\ Center for Biosimilars, ``FDA Delays Review of Alvotech's
AVT02 Adalimumab Biosimilar Candidate,'' September 2021 (link).
Under existing authorities FDA has several alternatives to
physically inspecting facilities, including: (1) obtaining inspection
records remotely; (2) requesting information and records from
applicants, facilities, and other inspected entities; (3) conducting
remote interactive evaluations (real-time video interactions with
facilities that cover the same ground as inspections); and (4) relying
on inspections conducted by trusted foreign regulatory authorities
under the Mutual Recognition Agreements (MRA). FDA, however,
infrequently uses these alternatives. For example, FDA informed AAM
that, as of December 2021, it had conducted only five remote
---------------------------------------------------------------------------
interactive evaluations.
AAM recognizes the important role inspections play in FDA's ability
to assess the overall quality of applications. Our members also share
the Agency's concerns about public health and preventing the spread of
COVID-19 among FDA and manufacturing facility employees. The
interruptions caused by COVID-19, however, delayed and denied patients
prompt access to new therapies and generic and biosimilar choices that
would lower drug costs. If new COVID-19 variants emerge, or if there is
a future pandemic, FDA's inspections could be paused again.
AAM believes FDA should expand the use of remote interactive
evaluations and use them more frequently in place of a physical
inspection, in addition to using alternative tools in place of an in-
person inspection to verify corrective actions for a site that had
received a warning letter. Specifically, we recommend requiring FDA to
evaluate alternatives when an in-person inspection is not possible.
Should FDA determine that an alternative to an in-person inspection
cannot be used, the Agency should be required to inform the applicant
which alternatives were considered and the reasons why an in-person
inspection was deemed necessary. We believe this additional
transparency and accountability will encourage FDA to perform its
critical mission without delay, while preserving the Agency's
discretion and judgment to require in-person inspections when
necessary.
Conclusion
Patient access to generic and biosimilar medicines has never been
more critical. Over the last 10 years, GDUFA and BsUFA significantly
increased the resources available to FDA for review of generic and
biosimilars applications. The benefit of this partnership between FDA
and industry is clear: record levels of generic drugs were approved in
2017-2019, and more than 30 biosimilar medicines were licensed. The end
result is lower prescription drug costs for America's patients. Since
the establishment of FDA's generic and biosimilars programs in 2012,
patients and the U.S. health care system have saved more than $2
trillion--including $469 billion from new generics and more than $12
billion from biosimilars. Congressional passage of GDUFA and BsUFA,
along with their reauthorization in 2017, made this possible.
GDUFA III and BsUFA III build on this success. The user fee
agreements incorporate lessons learned, include enhancements to ensure
the timely review of applications and provide FDA with sufficient
resources over the next 5 years (FY23-27). GDUFA III and BsUFA III are
the culmination of months of negotiations, have been subject to public
review and comment, and represent a careful balance between
stakeholders. AAM and its Biosimilars Council strongly support
congressional reauthorization of GDUFA and BsUFA as negotiated and
without changes. Timely approval of the FDA user fee agreements ensures
patients will continue to benefit from new, high-quality and more
affordable generic and biosimilar medicines. We look forward to working
with Members of both parties to accomplish this goal.
Thank you again for the opportunity to testify on this important
issue. I look forward to answering your questions.
______
[summary statement of david gaugh]
The Association for Accessible Medicines (AAM) and its Biosimilars
Council, represented by David Gaugh, Senior Vice President of Sciences
and Regulatory Affairs, will provide testimony on the importance of
timely reauthorization of GDUFA and BsUFA to continued patient access
to high quality, more affordable generic and biosimilar medicines. Mr.
Gaugh's testimony highlights the success of FDA's generic and
biosimilar programs in significantly increasing patient access to
lower-cost medicines and, in turn, dramatically lowering the cost of
prescription drugs for patients over the last 10 years. Since 2012,
more than $4 billion in funding has been provided under GDUFA (70
percent) and BsUFA (60 percent) to help ensure FDA has sufficient
resources to review and approve applications. As a result, FDA approval
of generic drugs increased significantly with full and tentative
approvals exceeding 1,000 in fiscal years 2017, 2018 and 2019. The
first biosimilar was approved in 2015 and now 34 biosimilars are
approved in the U.S. These approvals increased competition from
generics and biosimilars and led to significant savings to patients and
the health care system--more than $2 trillion in savings over the last
10 years. The GDUFA III and BsUFA III agreements includes enhancements
with the goal of: advancing approvals; ensuring timely inspections;
improving review of complex generics; streamlining suitability
petitions; providing for BLA supplement reviews; addressing
interchangeability; and ensuring the efficient of resources.
______
Senator Burr. David, thank you very much. Mark, the floor
is yours.
STATEMENT OF MARK LEAHEY, PRESIDENT AND CHIEF EXECUTIVE
OFFICER, MEDICAL DEVICE MANUFACTURERS ASSOCIATION, WASHINGTON,
DC
Mr. Leahey. Thank you, Ranking Member Burr. Thanks again to
Chair Murray and Members of the Committee for the invitation to
testify today. My name is Mark Leahey, and I am the President
and CEO of the Medical Device Manufacturers Association, a
national trade association representing hundreds of medical
technology companies.
MDMA was founded in 1992 to be the voice of the innovative
and entrepreneurial sector of our industry. According to the
Department of Commerce, 98 percent of medical technology
companies have fewer than 500 employees and 80 percent have
fewer than 50 employees.
These small companies drive the majority of innovation in
med-tech. Our industry is dedicated to one mission, to
alleviate human suffering and improve patient care. Perhaps no
recent example is more profound than what innovators have done
since the outset of the COVID-19 pandemic.
In addition to the extraordinary efforts of our industry
and health care professionals, I would also like to take a
moment to acknowledge the dedicated professionals at FDA who
are 24-7 on COVID and non-COVID medical technologies to improve
patient care during the pandemic, their efforts ensure that
patients have timely access to safe and effective products. The
MDUFA V draft agreement that we are discussing today and the
historic increase in user fee funding that it contains
demonstrates our commitment to provide additional capacity and
expertise to further advance FDA's mission.
MDUFA V provides over $2 million in investible funding to
FDA. As a point of reference, MDUFA I totaled approximately
$150 million. While each MDUFA typically provides the resources
to fund approximately 200 new hires, under MDUFA V, FDA will be
able to hire at a minimum 273 FTEs and up to 387 new FTEs.
This represents a historic increase in both overall funds
and people, and it is our expectation that this will be the
last major investment needed for the MDUFA program, and that
moving forward, any necessary increases will be much more
modest and targeted. MDUFA V also establishes more transparency
around the use of funds, including ensuring that annual hiring
targets are met.
FDA will also conduct an H.R. assessment during MDUFA V to
identify how many MDUFA funded vacancies exist. Beyond the
financial and accountability provisions that MDUFA V contains,
performance goals associated with De Novos and PMA Total Time
to Decision also improve over the course of the agreement.
One goal that was elusive under MDUFA IV was the total--
510(k) total time to decision goal in Fiscal Year 2022 of 108
days. COVID did impact FDA capacity, including the ability to
meet certain B MDUFA IV goals.
Under MDUFA V, the 510(k) total time to decision goal will
improve each year, hopefully achieving 108 days by Fiscal Year
2026. Also for the first time the agreement incorporates add on
payments that will provide the agency up to $150 million in
additional funding above the baseline in the final year of the
agreement if FDA meets modest but important performance goals
in the first 2 years of the agreement.
The United States medical technology ecosystem is the envy
of the world, and this is in no small part due to FDA's gold
standard of reviewing the safety and efficacy of medical
devices. The billions of dollars in user fees provided by
industry under this agreement will enable FDA to hire hundreds
of new reviewers and scientific experts, strengthening the
agency's ability to maintain its strong track record.
This agreement also makes additional investments to enhance
device safety. This includes increased funding to better
incorporate the patient perspective in the product evaluation
process, as well as funding to improve the use of real world
evidence.
The agreement also contains resources to pilot the Total
Product Lifecycle Advisory Program, also known as TAP, a top
priority for FDA during these negotiations. Medical
technologies that serve patients with unmet needs unfortunately
can take longer to navigate the regulatory process.
This is often due to the complexity and novel approach that
breakthrough devices encompass. Innovators participating in the
Safer Technologies Program, or STeP, will also be eligible for
the TAP pilot. TAP is designed to allow FDA and sponsors to
share early feedback to improve the process.
Based upon the data and independent assessment of the
pilot, industry and FDA will determine whether to continue,
expand, or terminate the TAP pilot during the MDUFA V
negotiations--VI negotiations, excuse me. In conclusion, this
is a historic investment in the FDA and will be critical over
the coming years to meet the goals and milestones within the
user fee agreement to help ensure that the United States
remains the global leader in medical technology development.
It is also critical that Congress continues its vital
oversight role and provides the necessary appropriations to FDA
to achieve its mission. MDMA and our members remain committed
to working closely with you to reach our shared goal of
providing safe and effective medical technologies to patients
and providers in a timely manner.
Thank you once again, Chair Murray, Ranking Member Burr,
and Members of the Committee, for the opportunity to testify,
and I welcome your questions.
[The prepared statement of Mr. Leahey follows:]
prepared statement of mark leahey
Thank you Chair Murray, Ranking Member Burr and Members of the
Committee for this opportunity to testify today. My name is Mark Leahey
and I am the President and CEO of the Medical Device Manufacturers
Association (``MDMA''), a national trade association representing
hundreds of medical technology companies. MDMA was founded in 1992 to
be the voice of the innovative and entrepreneurial sector of our
industry. While the industry is broadly represented throughout the
United States, one of the unique components of this vibrant part of
America's innovation ecosystem is that the majority of companies are
small businesses. According to data from the Department of Commerce,
over 98 percent of med tech companies have fewer than 500 employees,
and more than 80 percent have less than 50 employees, yet they are the
major source of innovation and America's competitive advantage in
medical technology. Our industry is dedicated to one mission: to
alleviate human suffering and improve patient care.
Our industry has a proud tradition of answering the needs of
patients and providers, and perhaps no example is more profound than
what innovators have done since the outset of the COVID-19 pandemic.
Whether it was respiratory technologies, diagnostics, advanced patient
monitoring, or personal protective equipment, the medical technology
industry worked tirelessly to help the United States and the entire
world to confront this challenge, and they continue to do so today. In
addition to the extraordinary efforts of this industry and health care
professionals, I would also like to take a moment to acknowledge the
dedicated professionals at the FDA who worked 24/7 on COVID and non-
COVID medical technologies to improve patient care during the pandemic.
Their efforts ensured that patients had timely access to safe and
effective medical technologies.
MDUFA V--A Historic Investment
The MDUFA V draft agreement that we are discussing today, and the
historic increase in user fee funding that it contains, demonstrates
our commitment to provide additional capacity and expertise to further
advance FDA's mission.
MDUFA V provides over $2B in investable funding to FDA. As a point
of reference, MDUFA I totaled approximately $150M over the 5-years of
the program. While each MDUFA typically provides funding for an
additional 200 new hires, under MDUFA V, FDA will be able to hire a
minimum of 273 FTEs and up to 387 new FTEs to support the MDUFA
program. This represents a historic increase in both overall funds and
people, and it is our hope and expectation that this will be the last
major investment needed for the MDUFA program and that moving forward,
any necessary increases will be much more modest and targeted.
With these significant investments, MDUFA V also establishes more
transparency around the use of the funds, including ensuring that
annual hiring targets are met. FDA will also conduct a H.R. assessment
during MDUFA V to identify how many MDUFA funded vacancies exist.
Currently, CDRH is only able to track MDUFA IV and later FTEs. Public
reports in 2016 indicated MDUFA funded vacancies exceeded 25 percent,
and innovators want to ensure that the additional capacity we are
funding through user fees is realized in the new additional hires and
backfilling any vacancies that arise.
Beyond the financial accountability and transparency provisions
that MDUFA V contains, performance goals associated with De Novos and
PMA Total Time to Decision (TTD) also improve over the course of the
agreement. One goal that was elusive under MDUFA IV was the 510(k)
Total Time to Decision Goal in fiscal year 2022 of 108 days. As was
mentioned earlier, COVID did impact FDA capacity, including the ability
to meet certain MDUFA IV goals. Under MDUFA V, the 510(k) TTD goal will
ramp down each year, hopefully achieving 108 days by fiscal year 2026.
Also, for the first time, the agreement incorporates add on payments
that will provide the agency up to $115 million in additional funding
above the baseline in the final years of the agreement if FDA meets
modest but important performance goals in the first 2 years of the
agreement.
Maintaining FDA's Gold Standard
The United States medical technology ecosystem is the envy of the
world, and this is in no small part due to the FDA's gold standard of
reviewing the safety and efficacy of medical devices. The billions of
dollars in user-fees provided by industry under this agreement will
enable FDA to hire hundreds of new reviewers and scientific experts
strengthening the agency's ability to maintain its strong track record.
The agreement also makes targeted investments to enhance device safety.
This includes increased funding for patient perspective and engagement
in the product evaluation process to better incorporate their
experiences, as well as new funding to improve the use of real-world
evidence in the review process.
The agreement contains resources to start a pilot for the ``Total
Product Lifecycle Advisory Program,'' also known as ``TAP.'' Medical
technologies that serve patients with unmet needs unfortunately can
take longer to navigate the regulatory process, despite the fact that
these patient populations often have no other alternatives. This is
often due to the complexity and novel approach that breakthrough
devices encompass. Beyond breakthroughs, TAP will support devices
developed to significantly improve the safety of currently available
devices and diagnostics under the Safer Technologies Program (STeP).
FDA was very vocal during negotiations about the importance of piloting
the TAP concept. TAP is designed to allow FDA and innovators to share
early feedback to improve this process. Based upon the data and
assessment of the TAP pilot, industry and FDA will determine whether to
continue, expand or terminate the TAP pilot during MDUFA VI
negotiations.
Conclusion
As we all know, America's medical technology ecosystem was not
built overnight. It took decades of work between countless
stakeholders, including Congress, the FDA, innovators, physicians,
patient groups and more to design the regulatory pathways that has
resulted in the gold standard of safety and efficacy. At the same time,
we all recognize that this is a delicate balance to ensure that the
right policies are in place to support innovation, and to spur the next
generation of cures, therapies and diagnostics that so many patients
are relying on. As I noted, this is a historic investment in the FDA,
and it will be critical over the coming years to meet the goals and
milestones within this user fee agreement to help ensure that the
United States remains the global leader in medical technology
development. It is also critical that Congress continues its vital
oversight role, and providing the necessary resources and investments
to FDA for it to achieve its mission. MDMA and our members remain
committed to working closely with you to reach our shared goal of
providing safe and effective medical technologies to patients and
providers in a timely manner. Thank you once again Chairwoman Murray
and Ranking Member Burr for your passionate leadership on this
important work, and I look forward to answering any questions that the
Committee Members might have.
______
[summary statement of mark leahey]
I am the President and CEO of the Medical Device Manufacturers
Association (``MDMA''), a national trade association representing
hundreds of medical technology companies. MDMA was founded in 1992 to
be the voice of the innovative and entrepreneurial sector of our
industry, including the small companies who make up the majority of the
industry and drive medical innovation.
The device industry's singular mission--to alleviate human
suffering and improve patient care--has been on display since the
outset of the COVID-19 pandemic. Whether it was respiratory
technologies, diagnostics, advanced patient monitoring, or personal
protective equipment, medical technology innovators worked tirelessly--
partnering with the dedicated professionals at the FDA--to help the
U.S. and the world confront the pandemic.
MDUFA V_A Historic Investment--The MDUFA V draft agreement provides
$2B in user fees enabling the FDA to hire a minimum of 273 FTEs and up
to 387 new FTEs to support the MDUFA program. By comparison, MDUFA I
totaled approximately $150M and subsequent MDUFA's typically provided
funding for 200 new hires. It's our expectation that this will be the
last major investment needed for the MDUFA program and that moving
forward any necessary increases will be much more targeted.
MDUFA V also includes provisions to help ensure that annual hiring
targets are met. Currently, CDRH is only able to track MDUFA IV and
later FTEs. Public reports in 2016 indicated MDUFA industry-funded
vacancies exceeded 25 percent, and it's essential that FDA hits the new
hiring targets and backfills any vacancies.
Beyond the financial accountability and transparency provisions in
MDUFA, performance goals associated with De Novos and PMA Total Time to
Decision (TTD) also improve over the course of the agreement. One goal
that was elusive under MDUFA IV was the 510(k) Total Time to Decision
Goal in fiscal year 2022 of 108 days. COVID did impact FDA's ability to
meet certain MDUFA IV goals. Under MDUFA V, the 510(k) TTD goal will
ramp down each year, hopefully achieving108 days by fiscal year 2026.
Also, for the first time, the agreement incorporates add on payments
that will provide the agency up to $115 million in funding above the
baseline in the final years of the agreement if FDA meets modest
performance goals in the first 2 years of the agreement.
Maintaining FDA's Gold Standard--The United States medical
technology ecosystem is the envy of the world, and this is in no small
part due to the FDA's gold standard of reviewing the safety and
efficacy of medical devices. The billions of dollars in user-fees
provided by industry under this agreement will enable FDA to hire
hundreds of new reviewers and scientific experts, strengthening the
agency's ability to maintain their strong track record. The agreement
makes targeted investments to enhance device safety including increased
funding for patient perspective and engagement in the product
evaluation process, as well as new funding to improve the use of real-
world evidence in the review process.
The agreement contains resources to start a pilot for the ``Total
Product Lifecycle Advisory Program,'' also known as ``TAP.'' Medical
technologies that serve patients with unmet needs unfortunately can
take longer to navigate the regulatory process, despite the fact that
these patient populations often have no other alternatives. Beyond
breakthroughs, TAP will support devices developed to significantly
improve the safety of currently available devices and diagnostics under
the Safer Technologies Program (STeP).
Conclusion--It took decades of work between countless stakeholders,
including Congress, the FDA, innovators, physicians, patient groups and
more to design the regulatory pathways that has resulted in the gold
standard of safety and efficacy. At the same time, we all recognize
that this is a delicate balance to ensure that the right policies are
in place to support innovation, and to spur the next generation of
cures, therapies and diagnostics that so many patients are relying on.
It is also critical that Congress continues its vital oversight role,
and provides the necessary resources and investments to FDA for it to
achieve its mission.
______
The Chair. Thank you very much. And thank you to all of our
witnesses, and we do apologize having a vote, Members in and
out, but we do have your written testimony and appreciate,
again, all of you being here. We will now begin a round of 5-
minute questions. I ask my colleagues to keep track of your
clocks always and stay within the 5-minutes. Prescription drug
prices in the United States continue to skyrocket. In 2020, our
Nation spent over $535 billion on pharmaceuticals.
That number is rising. That is really outrageous. We have
too many Americans who we know are choosing between paying
their rent or mortgage and getting a lifesaving medicine.
According to the Urban Institute, in 2018, nearly 13 million
adults delayed getting or did not get needed medications
because of the high cost, and Congress just really has to
address this.
Families really need us to take some bold steps to get this
problem under control like giving Medicare new power to
negotiate and force drug companies to bring down prices and
stopping the games pharmaceutical companies play to keep their
prices high, for example, creating a tangle of patents that
block competition.
I want you all to know I remain committed to working with
all of my colleagues in Congress, on both sides of the aisle,
to bring down prices and make sure prescription medication and
lifesaving treatments are not just available, but accessible
and affordable. Now, while FDA does not regulate drug prices,
it does have a role in increasing access to lower cost generics
and biosimilars, which can increase competition and drive down
prices.
But for that to work, we have to build off the steps we
took in the Lower Health Care Costs Act by doing more to stop
pharmaceutical companies from gaming the system with sham
petitions, exclusivity, parking, and other tactics that block
cheaper generic drugs, and increase transparency and
information sharing that can help bring more affordable
generics and biosimilars to the market.
Mr. Gaugh, how do the generics and biosimilar user fee
programs help increase competition and expand patient access to
critical drugs without sacrificing safety, efficacy, or
quality?
Mr. Gaugh. Thank you for the question. Yes, we have spent a
significant amount of time in GDUFA III to get enhancements
that we felt we had left on the table, if you will, in GDUFA
II. So in that prospect, we have a 10 month time point within
which the FDA is going to take an action on a product. We found
that in that 10 month time point, at a certain point in time,
we can get toward the end and run out of time, which means we
get a complete response letter for that product.
In GDUFA III, we put forward an imminent action capability.
So when the FDA knows that the product is about to be approved
or could be approved with just a short period of time, they can
take the imminent action route, which gives an additional 60
days for review. And while it is now a 12 month clock, it is
also a first cycle approval.
If it went into a second cycle approval, that would be
months down the road. So it would be at least 6 to 9 to 12
months delay. And this will help get access to the American
public more quickly.
The Chair. What barriers exist for generic applicants in
demonstrating their products have the same ingredients as more
expensive brand name drugs, and how do we address those
barriers?
Mr. Gaugh. Well, there is one area that we refer to is Q1,
Q2. And in Q1, Q2, that is a qualitative and quantitative
analysis of the product. So we know what the active ingredient
is when we are reverse engineering the product, if you will.
What we don't know is the inactive ingredients or the
concentrations of those inactive ingredients.
Prior to 2017, when we had those issues come up, we would
submit a control correspondence to the FDA, they would tell us
what that product is, the inactive ingredient, and then we
would look at ranges of what the concentration were and the FDA
would say, usually high or low.
After 2017, that was changed. They no longer will tell us
what the product is, nor give us a plus minus on the
concentration. And when we put a control correspondence in to
ask those questions, we can only have three products in that
control correspondence.
If we don't guess right on the first time, it goes back for
the next, and the next, and the next. So it is more of a
guessing game and that delays even longer.
The Chair. Okay, thank you. Dr. Esham, we have seen
pharmaceutical companies abuse the citizen petition process to
delay cheaper drugs from competitors. In fact, the FTC and FDA
have both called out that behavior, with FDA arguing that those
shenanigans present obstacles to the availability of follow on
drugs. Isn't it right that the citizen petition process should
not be used to reduce choice for consumers?
Dr. Esham. Let me just start by saying that we do believe
that the citizen petition process is an important mechanism not
only for the public to express its views to the FDA, but also
for the FDA to hear stakeholder perspectives on scientific,
technical, and regulatory topics. We do understand that our
colleagues at FDA have expressed concerns about situations
where a company might try to use this process to block generics
or follow-on biologics from entering the market.
We also understand that they do conduct their own research.
And while process requirement is associated with the 505(q),
petitions have the potential to add some burdens to the generic
drug review process. Citizen petitions have really delayed
specific generic drug approvals.
That being said, if this is an issue that the Committee
would like to explore, we stand committed to working with you
and other stakeholders.
The Chair. Okay. Appreciate that.
Senator Cassidy.
Senator Cassidy. Ms. Richardson, and Mr. Gaugh, I will
probably hit you afterwards. Some go to the doctor, eye doctor,
he gives me a prescription for something which is four times a
day, eye drop for the pain, and it cost me like $50 bucks.
Except they can't find it. The only thing I find is something
which is taken twice daily.
Same active ingredient, which cost me $400. Now that
clearly is not innovation. It is not a once monthly depo shot
to prevent pregnancy or once daily shot for HIV. It is
something which allows them to remove the generic so that
instead of paying $50 bucks, the patient is now paying $400.
How do we differentiate true innovation from faux
innovation, which frankly works to the detriment of the
consumer?
Ms. Richardson. Thank you very much for the question,
Senator. I have to confess that the question of measuring
innovation is not something that Pew has done any research on
or is currently focused on, although certainly as a patient and
as a consumer, it is on my mind all the time. Every time I go
to the doctor----
Senator Cassidy. Let me go to Mr. Gaugh. Mr. Gaugh, how do
we measure innovation? It is something because I am a big
believer that innovation needs to be rewarded and that we need
to have that profit motive for people to innovate. But I am
also recognizing that it is gamed at times so that, I call it
faux innovation, is merely gaming the patient. How would you
respond?
Mr. Gaugh. Thank you, Senator Cassidy. So you bring up a
great point, and we have always believed and felt that the
generic and biosimilar industry does promote innovation and
moves the innovator companies to better products, different
products. But there is still some gaming that goes on to your
point.
Whether it is a single daily dose or it used to be three
times a day goes to a single. That is not necessarily an
innovation, but it is really hard to judge how you stop that
gaming, if you will.
Senator Cassidy. Okay. Ms. Esham--Dr. Esham, I am sorry.
Clearly, we want to bring drugs to market more quickly, and
there is this discussion of using the accelerated approval with
this reliance upon post-market data. Now, tell me, just kind of
from your perspective, what various sources of post-market data
could be used to evaluate whether something is a true innovator
value and improves patient outcomes to make sure that whatever
we are using it for is bringing value to the patient.
Dr. Esham. Certainly. I would say that when we entered into
the PDUFA agreements, we did recognize the need for improving
how we design, have conversations pre-approval about post-
market requirements associated with--that are always required
with accelerated approval, and improving processes post-
approval to ensure that we are able to address challenges as
they arise and not just let them hang there and, not know a
path forward.
The processes improvements in the commitment letter we do
think will be helpful. In addition, I think more specifically,
probably to your question, is advancing the ability to utilize
patient registries, real world evidence that we do believe have
the potential to offer more efficiencies and realistic pathways
toward completing those requirements.
Senator Cassidy. These are patient registries that you are
establishing, or will this be borrowed from some master
registry of EHRs, etcetera?
Dr. Esham. I don't think it is an either, or, but happy to
meet with you and your staff and discuss in more detail if that
would be helpful.
Senator Cassidy. Okay. Mr. Leahey, I am concerned--the
cybersecurity. Now, there is a lot of stuff, a lot of medical
devices that are going to be increasingly cyber, correct?
Mr. Leahey. Yes.
Senator Cassidy. Senator Baldwin and I have a bill called
the Patch Act, which requires a premarket demonstration of
cybersecurity measures and post-market updates for any issue
discovered. Can you tell me a little bit of how the
manufacturers are thinking about cybersecurity in the context
of hospital networks or individuals who may be affected?
Mr. Leahey. Thank you, Dr. Cassidy. As you noted, devices
are becoming more interoperable each day. And MDMA as part of
the HCC. It is a private, public partnership with HHS, FDA,
hospitals, insurers working to address these issues.
Fortunately, we haven't seen any issues directly related to
compromising the devices themselves.
But as you noted with the ransomware and other issues,
these have certainly become challenges. So in 2019, the HHSC
published the Medical Cybersecurity Joint Security Plan to
provide device makers with a playbook on how to develop best in
class cyber management.
But clearly, much more work needs to be done, and we look
forward to working with you and your colleagues to making sure
that again, as technologies evolve, we make sure that the
hospital system, the patients are ultimately protected within
these cyber threats.
Senator Cassidy. Thank you. I yield.
The Chair. Senator Kaine.
Senator Kaine. Thank you, Chair Murray. And thanks to our
witnesses. Five years ago, when Congress last addressed user
fee reauthorization, I asked Dr. Woodcock of the FDA a question
on the availability of biosimilar drugs. This is something that
Senator Collins and I have done some work on, together with the
Biologic Patent Transparency Act.
Dr. Woodcock told me then that biosimilars were being
analyzed and improved at that time, and that would set a
standard for future biosimilars to come to market. She also
shared that as of that time, 2017, the FDA had approved four
biosimilars. I don't think they were yet on the market. They
had 13 pending applications and that there were 64 biosimilars
in development.
Mr. Gaugh, in your testimony, you stated there are now 34
biosimilars approved by the FDA, 21 of which are on the market
and available to patients, many others in development. Could
you talk about how the advancements over the last 5 years have
brought more biosimilars to market, have increased the number
of available biosimilars to address the rising costs of
prescription drugs, and how patients have benefited from the
growth in this industry?
Mr. Gaugh. Thank you, Senator Kaine. Yes, your points are
exactly right. So we started the biosimilar program in
basically 2012, when legislation was put in place in 2010, but
the guidance first came out in 2012 with the FDA, that gave us
the pathway for biosimilars.
Since that time, we have approved 34--or the FDA has
approved 34, as you just noted, and 21 on the market. But there
has been a significant cost savings to the patients for that.
So in the biosimilar realm, it is a cost savings of roughly 50
percent. Also, something that you don't see on the generic side
is that the innovator price has come down about 25 percent on
those products.
Having that access has provided cost savings for the
patients. You noted 64 program development back in 2017. There
is now 97 that we know of that are in development. So it is
continuing to grow and expand, and BsUFA III is addressing
several of the enhancements, if you will, from BsUFA II to
BsUFA III that will improve that through meetings, through
supplement review process and being more timely, and some
things about inspections.
Senator Kaine. Excellent. Thank you. Dr. Esham, I have a
question for you about treatment for rare diseases. It is clear
that sponsor companies that want to address treatments for
these diseases face a number of challenges, particularly the
limited number of patients with these types of conditions.
However, it is not a limited number of people who suffer from
rare disease conditions.
There are about 7,000 known rare diseases, and they
collectively affect over 25 million Americans. You also state
in your written testimony that the current mechanisms for
companies with rare disease treatments and their pipeline to
collaborate with FDA have not consistently provided avenues for
such needed discussions.
Could you talk a little bit about the provisions of PDUFA
VII that would allow for better collaboration between the FDA
and sponsor companies in the rare disease treatment area?
Dr. Esham. Yes. First, thank you for that question. And
again, I think we are all very excited about the progress we
have made, but there is just much more work to be done here in
this--in terms of providing treatments for rare diseases. I
think there are a number of provisions that collectively we
believe will work to improve regulatory clarity and
understanding for rare diseases.
That includes the Rare Disease Endpoint Advancement Pilot
Program, which is really designed to pilot engagements with
sponsors to increase our understanding about what is needed to
develop and support utilization of an endpoint for the basis of
approval for rare diseases.
Those learnings will be shared across industry, academics,
researchers, and the entire research and development ecosystem.
There are also provisions that I think will be particularly
important for rare diseases, and that is the ability to have
focused meetings on complex and unique challenges, both at
preclinical as well as during development that I think will
be--offer a chance to really address those unique challenges.
As well as some of the provisions designed to ensure that
there is a better utilization of innovative clinical trial
designs. And that is just to name a few. I don't want to run
out of my time, but collectively again, we did try to work to
make sure that there was the ability to engage at the right
time and have those discussions in advanced innovation for
these treatments.
Senator Kaine. Thank you. Mr. Gaugh, I am going to submit a
question for the record about interchangeable biosimilars that
I would direct to you, but I will put that in for the record.
Chair Murray, I yield back.
The Chair. Thank you.
Senator Collins.
Senator Collins. Thank you, Madam Chair. Before I turn to
my questions, let me thank the Chair and the vice Chair for
their hard work on this issue and to express the hope that a
bill that Senator Feinstein and I have worked on for some time,
that has to do with personal care products, can also be
considered.
Chair Murray brought that up in her opening statements, so
I just wanted to mention it. Dr. Esham accelerated approval is
a critical regulatory pathway that provides timely review of
treatments for patients with serious and life threatening
conditions for which there is an unmet need.
Sponsors must meet, as I understand it, the same
substantial evidence standard as traditional approval, but they
can rely on a surrogate endpoint that predicts a clinical
benefit rather than measuring that clinical benefit directly.
Obviously, clinical outcomes can take significantly more time
to manifest. And an example is that tumor size is often used as
a surrogate in oncology.
It can be measured much earlier than mortality and is
reasonably likely to predict an effect on that devastating
clinical outcome. Understanding that science does not move at
the same pace across all disease areas, why hasn't this pathway
been used to the same degree in fields like neurology or for
rare diseases?
Dr. Esham. I really appreciate this question, and you are
correct. We know that historically over 60 percent of
accelerate approvals to date have been for oncology
indications, and that is wonderful. There are multiple factors
as to why this has been the case, including the maturity of an
investment in oncology basic research.
There has also been incredible collaborations between
doctors, academics, patient organizations, the pharmaceutical
industry, and the regulatory leaders that have resulted in the
identification of surrogate endpoints and other informative
biomarkers and subsequent validations.
Again, we can't underscore--I can't undervalue the
leadership that is really important in this, both within the
industry research and the regulatory agency. And we have long
advocated for broader utilization of this pathway across more
therapeutic areas. We do think that it would be helpful for the
FDA to hold disease specific or disease or therapeutic area
specific meetings or promote that multi-stakeholder dialog on
appropriate biomarkers and clinical endpoints.
It is our hope that the Rare Disease Pilot Program that I
have referred to earlier will also advance our learnings about
how to approach--it is not just looking at an individual
endpoint, it is thinking of the how, what is needed, how do you
think about developing evidence, and how will that evidence be
evaluated, that we think will hopefully drive more innovation
and utilization of this pathway to, as you say, provide more
timely access to these medicines that are--just really
devastating.
Senator Collins. You have mentioned the Rare Disease Pilot
Program, and I want to follow-up on that issue with you as
well. More than half of the 400 million people in the world who
are affected by rare diseases are children, and about one-third
of those children will sadly die before the age of five.
Drug development is hamstrung by the fact that we simply do
not have well characterized the endpoints for most rare
diseases. The PDUFA agreement establishes the Rare Disease
Endpoint Advancement Pilot Program, which would enable FDA and
industry to collaborate to develop more meaningful, consistent,
and relevant endpoints for clinical diseases.
I am thinking of diseases like Duchenne muscular dystrophy,
for example. It is difficult to precisely measure progression
of the neurological and neuromuscular effects associated with
many of these diseases, and thus it can be difficult to
determine a treatment's impact.
This pilot program that you referred to is limited to a few
select applicants, but how can we share the lessons learned
through this pilot to ensure that other rare disease drug
applications can build on its findings?
Dr. Esham. Very important point to raise. And I will note
that when we worked with the FDA to develop this pilot program,
it was modeled after what we view as a successful pilot program
for complex innovative clinical trials and modeled for drug
development that used the same model of having only a limited
number of applications that went through the pilot program, but
that the learnings if you go through that program, the FDA has
the ability to share those learnings to the entire stakeholder
community.
It was very specifically modeled after that. We have seen
that be successful and create opportunities for learnings
across the academic, medical research, and biopharmaceutical
industry.
It is our expectation that the minimum of the three public
workshops will serve that. But we do expect more engagement and
more shared learnings in other venues of scientific dialog that
occur on a normal basis.
Senator Collins. Thank you.
The Chair. Senator Hassan.
Senator Hassan. Well, thank you, Madam Chair. And I want to
thank you and the Ranking Member for holding this hearing, and
I want to thank all of our witnesses for being here today. Dr.
Gaugh, let me start with a question to you. While Americans
struggle to afford lifesaving drugs, brand name manufacturers
continued to increase prices.
Generic competition can help drive down drug prices now. So
how do new generic drugs affect brand name prices? And how much
do generic drugs save consumers each year?
Mr. Gaugh. Thank you for the question. So significant
savings is brought forth by the generics. If you look at the
numbers, over the last 10 years, we have saved $2 trillion, and
$469 billion of that was in new generics that came to market.
It is a significant improvement in the increase for the
patients. We find that when one generic drug is approved, the
price comes down about 50 percent--the generic price comes down
50 percent, excuse me, not the brand. And with four or more, it
is more like 80 to 85 percent. So it is a significant increase
in savings to the American patient and U.S. health care
systems.
Senator Hassan. Thank you. Also another question to you,
Mr. Gaugh. For some medications with serious safety concerns,
FDA requires manufacturers to set up risk evaluation and
mitigation strategies, otherwise known as REMS programs. REMS
helps to minimize the risk associated with these medications
and make them safer for the public and for patients.
For example, a REMS program may require prescribing
clinicians to receive training on the risks of a drug and to
perform monthly lab tests. Even though REMS programs are meant
to protect patient safety, some brand name manufacturers have
patented these programs to prevent generic competitors from
entering the market.
Mr. Gaugh, how have brand-name manufacturers use REMS
patents to delay the launch of generic drugs? And how have
these delays affected drug prices?
Mr. Gaugh. Thank you. Thank you for the additional
question. So REMS is a very important program. As you
mentioned, it is about safety for patients, and it is a very
restricted program in its set up. I would almost make it akin
to new drug IRBs when they are doing the study process, so it
has to be patient specific, signed off, and given.
REMS has really had two problems with, the first one was we
as the generics, as we reverse engineer, need the product that
we are reverse engineering to make that. The CREATES Act help
solve that because we were being blocked from even getting the
drug. We weren't a patient. We couldn't sign up for it. We
wouldn't get it. So that has now been changed.
But what is new is what you just brought up, and that is
the patenting of the REMS programs. And so if the REMS program
is actually patented, then I, as a generic company, can't get
on that REMS structure to be able to bring my product to
market. So it is a further delay of not months, but years.
Senator Hassan. And it is using the notion of patient
safety to delay the development of additional drugs that could
bring down the cost.
Mr. Gaugh. Absolutely.
Senator Hassan. Yes. Okay, last question for you, sir.
There is a long history of brand name manufacturers playing
games with the law to delay and block the launch of generic
drugs. As a result, patients pay more at the pharmacy counter
with some rationing life medications because they can't afford
them.
I would expect that every single Senator on this Committee
has heard stories from their constituents about their decisions
to ration their drugs and the impact that has on their health.
Mr. Gaugh, how are brand name manufacturers manipulating the
system to limit generic competition?
Mr. Gaugh. We just talked about two of those methods. And
Dr. Cassidy brought up the point about some quasi-innovation,
if you will, moving a product from twice a day to one today,
for example. And that in and of itself is not necessarily
innovation. It is an improvement.
But in that particular case, the physicians and the
pharmacists can overturn that by having the patient go ahead
and take the twice daily at the lesser price than once daily at
the higher price point level.
Senator Hassan. Thank you. I yield my time.
The Chair. Senator Burr.
Senator Burr. Thank you, Madam Chair. Cartier, again,
welcome. More than 278 therapies have been approved under the
accelerated approval pathway over the 30 year history, saving
and improving thousands of lives.
This pathway has been the subject of recent scrutiny. But
it is a successful and important tool for the FDA to bring game
changing innovation to patients faster. What promise does the
accelerated approval pathway provide for companies investing in
novel treatments and particularly treatments for rare diseases?
Dr. Esham. Thank you, Senator. The role of this program
played in improving care for patients suffering from serious
and life threatening diseases when their needs are not being
met or where precedents are little or do not exist, or are not
well known, cannot be overstated. And we have seen this be very
successful in driving innovation and investment in oncology and
infectious diseases.
It is our hope that we expand utilization of this pathway
across more therapeutic areas, including for rare diseases. It
is critical for continued innovation--continued investment and
innovation in these disease areas that are complex and where
there are little or evolving precedents, which is the case in
many rare diseases.
It is also foundational to advancing scientific
understandings that allow us to continue to innovate and
continue to improve care for these complex and devastating
diseases. And so if it did not exist or it is not able to
function as intended, the path forward for timely access to
improved care for these devastating diseases will be limited
and delayed.
Senator Burr. May I ask you, how could we ensure the
accelerated approval pathway is used to create new
breakthroughs in more fields like neurology?
Dr. Esham. Great question. And there are provisions in the
PDUFA VII commitment that we think will strengthen the pathway,
such as the ability to engage with the FDA early to discuss
what is needed to support the use of a novel surrogate
endpoint. And as we have discussed previously, there is also
the rare disease endpoint pilot program, which should lead to
broader understandings about how to approach and develop
support for the utilization of a surrogate endpoint to support
approval.
There are also process provisions--process improvements to
try to improve what the approach will be to accomplish post-
approval requirements. Which again, in neurology, that is an
assessment that you make before you endeavor into a clinical
development program.
The more that we can improve those processes, enable
utilization of things like real world evidence to enable them
to be more realistically completed and in a more efficient
timeline, will also be quite helpful, I think, in driving more
investment and research and utilizing the accelerate approval
more broadly.
Last, just one quick thing, can't underestimate the
importance of multi-stakeholder engagement with regulators to
really identify new surrogates and advance their utilization.
Senator Burr. Thank you. Mark, FDA is proposing longer
review times for 510(k) devices. FDA committed to review
510(k)'s within 108 days in Fiscal Year 2022, and I understand
that FDA is not currently meeting that goal. What does it mean
for a small company when FDA misses these goals, and what does
it mean to patients?
Mr. Leahey. Obviously meeting goals are critical to timely
patient access and to small companies, the predictability. The
small companies don't have a number of products to subsidize
delays, so it is critically important. COVID was certainly an
impact, but we need FDA to get back on track and meeting that
shared outcome goal of 108 days as quickly as possible.
Senator Burr. Why did FDA agree, and why did the industry
agree to longer review times of 128 days on 510(k)'s and
provide the agency with so much more money?
Mr. Leahey. There is no doubt this is a significant
increase in funding. And as I said in my opening testimony,
this doubling of fees is certainly not sustainable. As MDMA is
representing small companies, it is of great concern.
But we do recognize the challenges that FDA went through
during COVID, and this investment is obviously put forward to
get them back on track, and there are additional accountability
measures to make sure that these metrics are met going forward.
Senator Burr. Just so I and my colleagues understand
better, I went through a litany in my opening statements of the
deficiencies in what FDA committed to and what they missed. And
they missed resoundingly in things like meeting with
applicants, explanations and deficiencies letters. Is this
really a difficult thing, or is this just a choice by FDA to
stiff somebody on meeting them, even though there is a
requirement to do it?
Mr. Leahey. I can just say from our Members' perspective,
the quality of the journey is so much more important than the
time. If you have high quality inputs and timely interaction,
you get there.
Obviously, it has been disappointing that simply providing
the rationale for a deficiency is something that we have to
bake into a commitment. And it is not just part of the basic
offering. But we are where we are, and we hope that we have a
productive and effective meeting for V.
Senator Burr. I thank all of you. Thank you, Madam Chair.
The Chair. Senator Smith.
Senator Smith. Thank you, Madam Chair and Ranking Member
Burr, and I really appreciate this Committee and all of your
testimony. Madam Chair, I would like to request unanimous
consent to submit into the record a letter from the biosimilars
forum expressing support for the biosimilar user fee agreement
and urging additional action to address the impact of the
pandemic on approvals of low cost biosimilar products like
biosimilar insulin.
The Chair. Without objection.
[The information referred to can be found on page 130 of
Additional Material:]
Senator Smith. Thank you. I think we all agree that these
FDA user fee agreements are critical for supporting the FDA's
work, and I want to just note that I worked with Senator
Cassidy to move forward legislation to streamline the process
for bringing biosimilar products to the market.
I want to thank Senator Hassan for her questions about how
that streamline process and bringing biosimilars, bringing
generic drugs to market helps to contribute to our goals of
lowering costs for Americans, which is very much on the minds
of my constituents. Mr. Gaugh, I want to ask you about
something specific to the therapeutic equivalence ratings.
According to the FDA, complex generic products, I mean,
there are so called because they have complex active
ingredients, routes of administration, drug device
combinations, or formulations. So in short, these drugs are
more difficult for generic manufacturers to develop. Examples
might include inhalers, or topical ointments.
These complex generic products face regulatory challenges
compared to other generics. It is harder for them to be
assigned a therapeutic equivalence or TE rating from the FDA.
In fact, it can take years to get a rating if they ever get a
rating at all.
This TE rating is important because it lets
pharmaceuticals--pharmacists, excuse me, automatically
substitute a lower cost generic product for a brand name
product at the pharmacy counter so patients can get cheaper
medicines.
Mr. Gaugh, could you please describe for us why it is
harder for certain complex generic manufacturers to receive
this TE rating, what medicines are impacted by this issue, and
what we can do to make this process more efficient?
Mr. Gaugh. Thank you for the question. And there are
different categories of generics, including and most often
complex generics that have to use a 505(b)(2) pathway for
approval. So it is not the normal generic pathway, if you will.
That approval pathway does not give 100 percent therapeutic
equivalence.
The FDA does not grant 100 percent therapeutic equivalence
when the product is approved. Therefore, we have to go back to
the FDA, as you mentioned, through a citizen's petition process
to get the FDA to grant that. That can take years for that to
happen. And to your point, if it is not granted, it is not
therapeutically equivalent and therefore the pharmacist cannot
automatically substitute it.
That is an area that we hope to work with Congress on, with
this Committee on to get that changed and get the citizens
petitions moving in a more quick process.
Senator Smith. And is the solution to that to get those
citizens petitions moving more quickly? Is that what you see?
Mr. Gaugh. Well, there is also some other rule, regulation
processes that the FDA can put in place for that as well.
Senator Smith. Thank you. So I am working with Senator
Cassidy on legislation that would require the FDA to provide a
TE rating at the request of an applicant on a much quicker
timetable. And I look forward to working with the Chair and
Ranking Member as we move forward with these user agreements.
Ms. Richardson, I have a question for you. I appreciate how
your written testimony highlights that these user fee
agreements are important for streamlining the review of medical
products. But the FDA's role is not just about bringing
products to market faster.
As you note, the FDA is a public health agency that works
to promote health of all Americans. So could you just expand
upon the recommendations that you have made that the FDA should
be receiving public funds and be accountable to the public
through these user free processes?
Ms. Richardson. Thank you very much for that question,
Senator. As I noted in my remarks and really just want to
reemphasize, user fees are essential to the functioning of the
FDA, but they are dedicated to specific functions like
expedited review.
That is very useful, but it is limited because there are so
many other areas that FDA's mission--of FDA's mission that
don't enjoy that kind of support. They don't cover food, they
don't cover supplement oversight, they don't cover a lot of the
agency's post-market oversight activities like inspections.
Appropriations really are essential to fully support FDA's
public health mission in the years ahead. So thank you again
for the question. I welcome the opportunity to underscore how
important it is to ensure adequate appropriations for the
agency.
Senator Smith. Thank you. And do you have any specific
recommendations for how we should improve the use of free
agreement process to better engage Americans in that process?
Ms. Richardson. That is not an area that Pew works on,
although I do know there have been suggestions about increasing
transparency, right. I know that there were some issues with
posting of meeting minutes, things like that. So I am sure that
there are some solutions that FDA would be more than happy to
consider, but I don't have any more specific recommendations.
Senator Smith. Thank you very much. Thank you, Madam Chair.
The Chair. Thank you.
Senator Marshall.
Senator Marshall. Thank you, Madam Chair. If I could have a
moment of privilege first and just start by congratulating my
University of Kansas Jayhawks on their fourth national
championship, and I would be remiss for not congratulating my
friends from North Carolina on a great game, one of the
greatest games in NCAA history, and just Kansas so much as a
special connection to North Carolina, going back to Dean Smith
being a player for KU in the early 1960's. So congratulations
to our amateur sports and my Jayhawks. Thank you.
Madam Chair, I want to start off by talking about the
importance of innovation. I have always said that innovation
would do more to drive the cost of health care down than any
legislation that we can write. And I was so excited when
biosimilars came on the market and I thought that competition
would drive the cost of insulin down.
Unfortunately, brand name manufacturers have found out ways
to prevent this competition, these new biosimilars to come to
market. And it is so frustrating. We have a saying back in
Kansas that pigs get fat and hogs get slaughtered. And my point
is that these middlemen and big pharma is getting hogwash. That
they are--they can't have it both ways. You can't want
protection from price fixes or price costs, but you can't--but
you don't allow innovation.
You can't allow it to work both ways. And my first question
is going to be for Mr. Gaugh. Right now, we are seeing with
these brand name manufacturers using inactive ingredients now
to keep biosimilars to come to market. And I think of Humira
using the size of a needle to keep something from coming to
market.
I would ask both sides of the aisle, the staff to start
looking into if we get rid of the rebates, that is what is
going to solve this problem. If we get rid of the middlemen
rebates, that is what is going to drive the price of insulin
down. And if we put a price fixed at $35, a price cap, all that
is going to do is drive up the cost of health care for
everybody else in the plan.
It is just basically given the middleman a license to
charge whatever they want to, even though the person that is
getting the insulin is going to be capped with an out-of-pocket
expense. It is going to drive the cost of prescriptions up for
everybody else in the plan. So I am all about promoting
competition.
Mr. Gaugh, what--in the review of this reauthorization,
what can we do to make it better for patients to have faster
access to generics and biosimilars without compromising
innovation?
Mr. Gaugh. Thank you for the question. And so we did build
in several enhancements in both GDUFA and BsUFA to help move
that along more quickly. I talked earlier about the imminent
approval in the GDUFA realm.
In the BsUFA realm, in the biosimilars--which we now have
two interchangeable insulins that are in or one insulin that is
in the market, so that is out there for competition and
hopefully that will help bring----
Senator Marshall. Have we done everything we can, or do we
need to do more?
Mr. Gaugh. There is always more that we can do. Absolutely,
yes. So we built that in with meeting management and supplement
reviews.
Senator Marshall. Thank you. Dr. Esham, my next question
for you. It takes 10 years and $1 billion to get a new product
to market and often maybe a 1 or 2 percent chance it ever
actually reaches the market. The reauthorization process of
these new drugs, authorizing these new medications, we talk
about that process, but I want to back up in the research going
on here. So often we are using animal models, which are like
night and day to the real world when it comes to human biology.
What we see in the animals, consequently, typically, not
uncommonly, doesn't apply to humans. There is something now
called where we can use human cells with bioprinting.
For instance, if we know a medication that is going to be
metabolized through the liver, we would test it with human
liver cells. Do you see any way that we can start implementing
that technology in helping the process of approval for new
medications?
Dr. Esham. Thank you, Senator. And first, let me say again,
congratulations. As a University of Kentucky fan, I really hope
that I believe that at some point. I will get there. But to
your point, in all seriousness, we actually have a very active
group of scientists in what we call our bio-safe working group
that has been publishing papers on advancing non-human primate
ability to use utilize alternative tools to primates for
preclinical work.
We certainly see a lot of innovation in this space that you
have mentioned, and we would be happy to bring our scientists
to meet with you and discuss in detail their potential. But the
bottom line is, yes, we do think we can continue to innovate
here and be much more--less dependent on primates----
Senator Marshall. Speed up the process and hopefully make
it safer. Both.
Dr. Esham. Yes----
Senator Marshall. That is a win, win.
Dr. Esham [continuing]. However they have--the goal is to
fail earlier or fail better and then advance most
optimistically.
Senator Marshall. Quickly to Mr. Leahy. I am a big fan of
using real world evidence. And how does the FDA currently
lack--does the FDA currently lacks the expertise and
infrastructure to interpret real world data? And what can we do
to make that situation better?
Mr. Leahey. Well, absolutely. This is critically important
to leverage that, as you noted, information out there in the
world to help accelerate additional patient access. Under MDUFA
IV, we invested tens of millions of dollars to help build the
real world evidence capacity in a private public, partnership.
We are continuing that investment in MDUFA V to help both
private, public partnerships enhance their capabilities and
also make sure that FDA have the personnel to take that
information and leverage that for the purposes of application.
Senator Marshall. Thank you so much, Madam Chair. I yield
back.
The Chair. Thank you. I will turn it over to Senator Casey.
I am going to go vote and I will be back.
Senator Casey. Chair Murray, thanks very much. I have a
question for Dr. Esham and Ms. Richardson. Doctor, I want to
start with you. Patients with rare diseases and conditions
often face their diagnosis with either a limited or no
treatment options.
I was glad to see PDUFA VII, the commitment letter, have
dedicated pages to advancing the development of drugs for rare
diseases, including a commitment for FDA's rare disease team
staff to be more closely involved in training, outreach, and
application review. With their expertise, what--I should say,
while their expertise is very valuable, I am not--I am sure you
will agree that they are the voice and the unique experience of
patients with rare diseases must be heard within FDA.
In your written testimony, you discuss the Rare Disease
Endpoint Advancement Pilot Program in PDUFA VII. I know Senator
Collins made reference to this on. Page five of your testimony,
you say, and I am quoting, ``key among these challenges is
reaching agreement with regulators about determining the
appropriate efficacy endpoints to support approval of
innovative medicines for rare diseases.''
How can we ensure that firsthand knowledge and expertise of
this small group of patients, for whom the drugs are ultimately
intended, are considered in developing endpoints that are
meaningful for these patients?
Dr. Esham. Thank you for that question, and it is quite
important. And, when--back in PDUFA V, when we, the commitment
sort of started that voice of the patient meetings, I think
that is where we learned really what mattered to patients, and
more importantly, learned that we were often wrong about how to
interpret their needs.
In addition to that pilot program, when you think about
what is needed to support, what evidence is needed to support
the utilization of surrogate endpoint, it is our hope that
there will be--that the utilization of patient perspective data
will be incorporated into that assessment, either for the
assessment--the evaluation of the benefit, risk evaluation or
as support as an endpoint.
Again, it is our hope, desire, and we will certainly be
advocating for inclusion of those perspectives into the
learnings of that pilot program.
Senator Casey. Thanks, doctor. Ms. Richardson, I want to
thank you for raising the issue of antimicrobial resistance.
The Committee has taken steps in previous user fees
reauthorizations to encourage the development of new
antimicrobial drugs to mitigate the serious impact of
antimicrobial resistance.
In 2012, we had the GAIN Act, for example. Yet the
realities here, the financial realities of developing these new
agents remain very challenging. And investment, as well as
research, as well as drug development are not keeping pace with
the need.
I know that the Pew Charitable Trust has been an important
partner in a proposal that I have been working on with Senator
Cassidy, the Disarm Act, which would use reimbursement tools
through CMS to help stabilize the market for novel
antimicrobial agents. Can you talk about why these multiple
approaches are necessary?
Ms. Richardson. Yes, Senator, and thank you for that
question. I absolutely agree with you that antimicrobial
resistance is a public health crisis, and no single solution is
going to fix the problem. We need creative ideas that can
realign current market incentives to encourage drug developers
to stay in this business, right.
Large companies are exiting the market. Small companies are
going bankrupt. It is just a tough business model. And so we
need to provide new types of incentives to antibiotic drug
developers so that this absolutely crucial antibiotics pipeline
doesn't dry up completely. So your legislation, the DISARM Act,
is certainly part of that solution, as well as the PASTEUR Act,
which is authored by Senators Bennet and Young.
We support both DISARM and PASTEUR, and we believe the
solution to the broken antibiotic pipeline, it will require
multiple creative solutions on both the legislative and the
regulatory fronts.
We hope Congress will remain open to considering additional
options like DISARM, and we support the PASTEUR Act as an
immediate opportunity for policymakers to make progress in
fixing the market.
The PASTEUR Act has an innovative only pay for success
subscription approach that will stimulate the antibiotic drug
pipeline and help ensure that patients will have access to
these lifesaving drugs when they need them. Thank you, again,
for that question.
Senator Casey. Thank you. Thanks very much, Mr. Chairman.
Senator Burr. Senator Murphy.
Senator Murphy. Thank you very much, Mr. Chairman. Thank
you all for your testimony. I have been in and out of the
hearing today, but I look forward to reviewing the record. I
wanted to talk a little bit about the issue of mental health
drug discovery. And I will maybe sort of ask this question to
you, Dr. Esham, but others I am glad to hear from.
It is interesting, when you look at some of the data about
recent drug discovery, it just doesn't seem that the
development of new drugs in the mental health space is keeping
up with the need.
I was taking a look at recent records from the FDA on novel
drug approvals from 2015 to 2022, and there is about 333
approvals during that 8 year time span. And let me just sort of
give a--my best attempt at an apples to apples comparison. Of
those 333, 90 were cancer drugs.
About 40 percent of Americans over the course of their
lifetime will be diagnosed with cancer. And so I am glad that
there were 90. But 46 percent of Americans at some point over
their life will have a diagnosable mental illness. And yet of
those 333 drugs, only 12 of them were mental health drugs.
You hear this pretty routinely from the medical community
that we just aren't keeping pace with the need when it comes to
drug discovery in the mental illness space. So let me just sort
of ask the sort of broad question here, how do we get your
members, how do we get the private sector more interested in
developing novel pharmaceuticals for mental health conditions?
What are the barriers and are there public policies you would
recommend to this Committee?
Dr. Esham. Thank you for that question. I think it is fair
to state that none of us are--believe that we are anywhere near
the level of innovation in mental health, providing innovative
treatments for those suffering from mental health, anywhere
near where we want to be.
There are--I will point you and your staff, your office and
your staff to some reports that we did over the course of
years, kind of looking at the challenges of highly prevalent
chronic diseases. And we did one specifically in 2018 on
depression, sort of as an example on the mental health space,
to try to understand what was going on and sort of what looks
like an inverse investment in public health need trend lines.
I think that there are some challenges in understanding the
underlying causes of these diseases. There are challenges in
developing and implementing clinical--effective clinical trial
designs. And there are also challenges on the access coverage
side. And so, it is a, unfortunately in the space I think it is
all of the above more often than not.
But we would be happy to bring in some scientists and
researchers from our companies working in this space to really
kind of dove into the details here. But I think that clearly
some pretty collaborative multi-stakeholder dialog is really
needed here.
Senator Murphy. Well, I will be glad to do that. And I will
just note for the Committee, one part of your answer, you
referenced an uncertainty about reimbursement, which is true
generally in the mental health space.
We have been working very hard on this Committee over the
years to make sure that there is parity between reimbursement
for mental health and for physical health. I am interested to
know whether that exists on the drug reimbursement side. I
doubt it is as dire as it is on the sort of in-person treatment
side, but I look forward to follow-up with you on that. Mr.
Leahey, I wanted to ask you a question with my remaining time
about the state of clinical trials and clinical research.
I heard Senator Murray references in her opening
statements. But there, as you know, is a concern that trials
and research often don't represent the democratic diversity of
the populations that are going to ultimately benefit from these
drugs and devices.
We have seen how COVID clearly had a disproportionate
impact on racial ethnic minorities, and it has, I think,
spurred a conversation about how we make sure that there is
broader representation in those that are part of these trials.
Is that a question one that you are grappling with, that
your members are grappling with? Why is it important that, and
do you think it is important that we make sure that there is
broad demographic representation amongst the populations who
are part of the research and the trial process?
Mr. Leahey. Thanks, Senator, for that question. And
absolutely, MDMA and our member companies support diversity in
clinical trials and agree that the trial enrollment should
accurately reflect the intended patient population. And we look
forward to working with Congress and FDA to ensure that
proposals are thoughtfully structured to achieve this
objective.
Senator Murphy. Just why is it important?
Mr. Leahey. Ultimately, it is because it is about the
patient. We want to make sure that these drugs, devices all are
tested in populations and age demographics, racial dynamics to
ensure that, again, they meet the mark of having the safety and
effectiveness for those who are intended to help.
Senator Murphy. Right. Thank you. Thank you, Mr. Chairman.
Senator Burr. Thank you, Senator.
Senator Braun.
Senator Braun. Thank you. The FDA user fee program was
established to provide a predictable and accountable regulatory
framework that supports expedited FDA review and approval of
safe and effective treatments for patients. The user fee
process has given lip service to the patient's voice in the
conversation.
PDUFA commitment letter includes a number of provisions to
address unmet medical needs and advance rare disease endpoint
development. The purpose of today's hearing is to discuss
advancing medical product regulation and innovation for the
benefit of the patient.
There should be a witness here, I think, that would be from
the patient's perspective. There is not. There should also be a
representative from the rare disease community, which I have
wrestled with since I have been here on for families that have
issues, where the diagnosis is bleak, and time is the most
important thing. They are not represented, either.
In fact, there is not one hearing scheduled for this that
brings in that patient voice. I would like to submit to the
record a letter I sent to the HELP Committee yesterday
requesting a patient focused user fee hearing.
Senator Burr. Without objection.
[The information referred to can be found on page 131 in
Additional Material:]
Senator Braun. In general, the Members of this Committee
are given 5 minutes to talk about whatever they want to. Today,
I had planned to show a video. There is really nothing in the
rules that says I can't do that. We use video aids often here.
But it hasn't been done before. A lot of things I have tried to
do over 3 years I have been here is to fix the things that
haven't been done before to give the patient, to give the
constituent a better outcome.
In this case, it is Ala, a happy go lucky girl who dreams
of 1 day becoming a scientist. Without the necessary FDA
reforms, timely access to promising therapies, that is not
going to happen. Won't be able to achieve that goal. Her
parents share a similar grief knowing that they won't see their
daughter graduate from college or walk down the aisle. The
average survival time for this particular ailment is only a
year.
Imagine from the patient, the family, are they interested
in the cumbersome process that we always want to keep as a gold
standard, but that doesn't necessarily mean you don't change it
to adapt, keeping those standards in place to the
particularities of this and many other ailments. The video
highlighted the patient perspective and the need for the FDA to
reform its process there.
As a U.S. Senator, I have been proud since I have been here
to represent Main Street, to represent the voice that is not
heard, to represent the patient and the family that wonders
why. No rules have prevented it, yet we couldn't show it today.
I think it is kind of sad when you have got a hearing and
that all kinds of different ways to make your point are
generally available, and here, maybe because of the poignancy
and the fact that it is coming from the patient who drives this
process, maybe that is too much for us to bear when we keep
giving it lip service and do nothing about it.
I have had the Promising Pathways Act out there, sponsored
by many on this Committee, and it is just saying one thing,
give some hope to these families that there is more than just
what we have been doing for decades, which is a process we call
the gold standard, but yet it lets so many individuals feel
that they are not having their voice heard. I think as elected
officials, we got to always point out something that we would
rather see change in the process.
That is what I am doing here today. I think the Committee
should have allowed it, but when that doesn't happen, you go to
plan B. You can find that video on my Senate account, my
Twitter profile at Senator Braun, and you will find that video
is worth a thousand words, if not more, of what we will hear
today, because it speaks to the frustration that people across
the country feel when it comes to this particular issue. Thank
you for listening.
Senator Burr. Thank you, Senator Braun. And before I move
on, let me just say this Committee and many committees in
Congress have held specific hearings over the years with rare
disease individuals. That is not out of the ordinary.
One of the reasons that Pew is here, Pew represents the
patients, the folks that don't have the opportunity to be here,
the multiple categories. It is not one, it is hundreds of
thousands of individuals.
We are grateful for Pew's participation in this. It is my
hope that we will be able to satisfy your needs--I am not
speaking for the Chair, but I will leave that up to her,
because I think there is value to that.
But there is much more value outside of the user fee
agreements. This is a small part of the access that they don't
have today that they need in the future. And the No. 1 thing is
innovating at what today's pace will allow us to do so that we
would begin to bring those breakthroughs. So I thank you.
Senator Rosen.
Senator Rosen. Well, thank you, Chair Burr, Ranking Member
Burr, and of course, Chair Murray. Thank you all for being
here, for the important work you do and participating today. I
want to move on to something, of course, that is in everybody's
thought every day is cybersecurity and getting hacked.
We have medical devices and I want to address medical
device cyber security because cyber-attacks really remain a
major threat to the health care sector, particularly as bad
actors like Russia are beginning to target or threatening to
target our domestic industries.
That is why I recently introduced bipartisan legislation
with Senator Cassidy that improves collaboration among agencies
to improve cybersecurity in the health care sector, sharing
that threat information, and providing cybersecurity training
to medical professionals. It is really important.
But however, as we work to increase the cybersecurity of
our hospitals, our health care systems as a whole, we must also
ensure there aren't cybersecurity gaps with our medical
devices, our pacemakers, for example. As more and more medical
devices become connected to networks, they are accessible
online, they become more vulnerable to cyber-attacks. It
impacts patient safety. It impacts their health, and the
vulnerability of the entire health system to which the devices
connect.
Mr. Leahey, the current FDA guidance for the medical device
cybersecurity is from 2018. It is in the process of being
updated. Can you speak about the importance of timely Federal
cybersecurity guidance, how nimble we have to be as technology
just continues to outpace our ability to protect it?
Mr. Leahey. Absolutely. Thank you, Senator, for that
question. And cyber is a top priority for our members. As we
spoke with Dr. Cassidy earlier and you noted the
interoperability of these technologies, how they interface with
other technologies with hospital systems is of paramount
importance.
I think that, fortunately, thus far there haven't been any
devices that have been compromised that impact patients'
safety. But as you noted, the ransomware, the security threats
and how that impacts hospitals on the system is very important.
We have actually been active members of the HCC, the
private public, partnership with FDA, HHS, hospital systems,
insurers, innovators all together, sharing information in real
time because this is something that is ever evolving. And in
2019, the HHSC published the MedTech Cybersecurity Joint
Security Plan to provide device makers a playbook. As you
noted, there is a guidance being updated.
This is something that we have to have real time
conversations with all the stakeholders so that we are ahead of
the curve. And we are committed to doing that and working with
you and other Members of the Congress to ensure that we have
the proper protocols in place.
Senator Rosen. Thank you. I just introduced a bill for HHS
and DHS to work with hospital systems just for what you are
speaking about, ransomware, cyber-attacks, and really
considering them critical infrastructure. But I would like to
build a little bit upon what Senator Murphy was talking about,
next clinical trial diversity, and more specifically, gender
diversity, how it relates to women.
Because, Ms. Richardson, in 2015, FDA released a women's
health research roadmap as a strategy for science and
innovation to improve the health of women. And so among the
topics included are improving clinical trial design and
evaluating differences between men and women, how they respond
to drugs and medical technologies.
Again, we are talking about roadmaps, we are talking about
being nimble. Is it time for the FDA to update this roadmap so
that women are included more broadly? And what actions do you
recommend the FDA take to improve this?
Ms. Richardson. Yes. Thank you so much for that question,
Senator. As I noted in my testimony, one of the benefits of the
user fee renegotiation process is that it provides FDA with an
opportunity to think really clearly and concretely about where
it wants to focus attention over the next 5 years.
Not just on reducing review timelines or meeting
procedures, but where it really wants to focus its policies.
And I think, of course, that could involve a renewal of the
women's health roadmap, which I believe was housed within the
Office of Women's Health. One of the core focus areas of the
roadmap was to support studies to advance the understanding of
how sex differences affect the safety and effectiveness of
emerging technologies like AI enabled devices and 3D printing.
That has been a real area of focus for Pew and our research
lately. I know that office has funded some important research
in that area. But I think that in addition to additional
research funding, it would be helpful for the agency to focus
on how that research gets translated into policy at the level
of the centers, which is where the rubber meets the road policy
wise. That is where it really happens.
CDRH, for example, recently announced strategic priorities
that would focus on over the next 3 years, and health equity
was a core focus area. As a part of their process, I think it
will be important for them to focus on women's health in
addition to other populations that may be underrepresented in
clinical trials or in real world datasets, which includes not
just women, of course, but also minority populations.
Thank you very much for that question.
Senator Rosen. Thank you. Mr. Chairman, I see I am out of
time, but I would have asked Dr. Esham about health equity and
how the use of telemedicine, satellite sites, health centers,
rural health clinics, we can improve diversity in clinical
trials for urban and rural, for women and people of color. All
of that really matters. Will ask for your response----
Dr. Esham. Will be happy to engage with you in detail
following the hearing. Thank you.
The Chair. Thank you very much. And I was out of the room
for the discussion before, but I really do understand the
desire to bring in the voices of patients. And both Ranking
Member Burr and I are very focused on keeping patients at the
center of this conversation. I actually think every Member of
this Committee believes what is best for patients and their
families absolutely needs to be at the center of any discussion
on medical advancements and innovation.
Like everybody, I have heard from patients across my state
who are forced to choose between paying for medicines or paying
for rent. I am sure we have all heard those. And it really is
imperative that patient's voice be heard at every step of
medical product development, from new research to pricing, user
fee reauthorization, and I hope we can all work together to
make sure that as this process goes forward, we can ensure that
their voices are heard.
With that, I will turn it over to Senator Baldwin for her
questions.
Senator Baldwin. Thank you, Madam Chair. As Chair of the
Appropriations subcommittee that provides funding for the Food
and Drug Administration, I am well aware of the resource
constraints that the agency is under. We recently worked on a
bipartisan basis to increase FDA funding for Fiscal Year 2022,
including for food safety activities, medical product safety,
infrastructure and cross-cutting initiatives.
Still, I know that with current budget constraints, the
increase will not be enough. Ms. Richardson, can you describe
some of the agency's obstacles when it comes to critical
operations and hiring necessary additional staff?
Ms. Richardson. Yes, happy to. I will say that this is not
an area that Pew has spent a lot of time focused on. And when
it comes to hiring, I do know that, as I think Senator Burr
pointed out, the agency has a lot of open positions.
They have a lot of trouble hiring. I do know that one
proposal that FDA has supported in the past and continues to
support is direct hiring authority Pew doesn't take a position
on that, but I think it is certainly worth considering,
personally.
Senator Baldwin. Thank you. Over the past week, NPR has
been sharing stories of individuals diagnosed with cancer
attributed to asbestos exposure. One possible source of that
exposure is baby powder, which is a personal care product
regulated by the FDA. The stories of these cancer patients are
harrowing, but they also point to the fact that when it comes
to personal care products, as widespread as make-up, deodorant,
and lotion, we have really failed to protect consumers. Mr.
Leahey, how many employees does FDA have assigned to work on
medical devices?
Mr. Leahey. That is a question we asked during the
negotiations. I know in the Congressional report, the 2021
Financial Report to Congress, I think there are about 1,800 or
so FTEs related to the device review process. I think there are
a few hundred more--hundreds more, but that is about 1,800 I
would say.
Senator Baldwin. Okay. Mr. Gaugh, how about the number for
generics and biosimilars?
Mr. Gaugh. There are about 1,600 for generic and
biosimilars that are paid for by the user fee dollars. 1,550
for the generic side and about 50 for the biosimilar side.
Senator Baldwin. Dr. Esham, how many FDA employees work on
drugs and biologics?
Dr. Esham. When--at the end of December 2021, I believe the
CDER had around over 5,300 employees and CBER had around 1,200,
a little over 1,200 employees. I would say the majority of
those, probably in some way, work on the review of drugs and
biologics.
Senator Baldwin. Thank you. In contrast, the FDA has only
30 full time employees that work on personal care products, 30.
And I don't believe that is acceptable. FDA needs more
resources and more authorities to ensure that personal care
products are safe, and cosmetics reforms--reform needs to be a
part of this package. I yield back.
The Chair. Thank you very much. That concludes our hearing
today, and I want to thank all of our colleagues for their very
thoughtful questions. I want to thank all of our witnesses, Dr.
Esham, Mr. Gaugh, Mr. Leahey, and Ms. Richardson for sharing
your time and your expertise.
I am looking forward to continuing our work to reauthorize
the FDA's user fee programs in the coming weeks to ensure the
agency has the resources to support its vital work. With that,
the Committee stands adjourned.
ADDITIONAL MATERIAL
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Biosimilars Forum,
Washington, DC 20006,
April 4, 2022.
Hon. Patty Murray, Chair,
Hon. Richard Burr, Ranking Member,
U.S. Senate Committee on Health, Education, Labor, and Pensions,
428 Dirksen Senate Office Building,
Washington, DC 20510.
Re: FDA User Fee Agreements: Advancing Medical Product
Regulation and Innovation for the Benefit of Patients.
Dear Chair Murray and Ranking Member Burr and Members of
the Committee:
On behalf of the Forum members, I would like to thank you
for considering this letter in advance of the hearing ``FDA
User Fee Agreements: Advancing Medical Product Regulation and
Innovation for the Benefit of Patients.''
The Biosimilars Forum is the non-profit trade association
representing the companies with the most significant U.S.
biosimilars development portfolios, including: Biogen,
Boehringer Ingelheim, Coherus BioSciences, Organon Inc., Pfizer
Inc., Samsung Bioepis, Sandoz, Teva, and Viatris. This letter
represents the views of our members, all of whom manufacture or
market biosimilar products in the US as well as other parts of
the world.
Biosimilars have the potential to provide very significant
health care savings in the U.S. Without robust competition,
innovator biologics will continue to represent approximately 40
percent of total prescription drug spending while they
represent only 4 percent of the medicines prescribed to
patients. Biosimilars provide competition to allow Americans
access to lower-cost biologic alternatives, and their timely
licensure and launch is vital to ensuring patient access to
lower cost biologic medicines.
The Biosimilars Forum is supportive of the negotiated BsUFA
III agreement, and we believe it represents important progress
in facilitating timely access to safe and effective biosimilar
medicines for patients. We are pleased the commitment letter
codifies review timelines for labeling supplements, provides
meeting management enhancements, and promotes best practices of
communication between FDA and sponsors.
The Forum is particularly pleased that the BsUFA III
program will include a regulatory science program that can help
bring more biosimilars to market faster. Since the BPCIA was
enacted over a decade ago, there have been many advances in the
science of developing biological drugs. The regulatory science
program will provide FDA and industry the ability to
incorporate the latest scientific innovations into biosimilar
development and regulation.
Although we are very satisfied with the progress
represented in the BsUFA III commitment letter, we want to
stress that the pandemic has impacted biosimilars and patient
access disproportionately hard for almost 2 years. COVID-19 has
stalled onsite inspections for biosimilars delaying their
approvals.
While biosimilar inspections have been delayed over the
past 2 years, on-time actions for the GDUFA and PDUFA programs
have averaged over 90 percent; and the BsUFA program, plunged
to 75 percent during Quarter 4 of fiscal year 2020, and further
dropped to 67 percent during Quarter 1 of fiscal year 2021 and
it remains at 67 percent today. In addition, per the Agency's
May 2021 Roadmap for FDA Inspection Oversight, biosimilar
inspections are not, considered to be ``mission critical'' and
thus are not prioritized. This has the ultimate outcome of
slowing timely approvals of biosimilars. We would like to ask
the FDA for clarity to sponsors and the public as to the
estimated timelines the FDA believes it will take to address
the backlog in inspections and reviews and why biosimilars are
not prioritized or treated equitably.
For the BsUFA III Commitment Letter to be a success the
inspection backlog for biosimilars must be addressed and remote
inspections be implemented consistently across all programs,
biosimilars cannot remain a low priority for the Agency.
The Forum is encouraged by FDA's commitment to hire and
retain sufficient numbers and types of technical and scientific
experts to efficiently conduct reviews and applauds the
agency's efforts to improve its use of data and technology.
Industry understands FDA staff works on numerous types of
applications, a small cadre of focused Biosimilar staff could
help expedite the assessment and inspection process for
Biosimilars. We will work with the FDA to determine how can we
allocate reviewers specifically for BsUFA goals.
As we head into BsUFA III we look forward to working with
the Agency to implement the commitment letter to the mutual
benefit of biosimilar sponsors and FDA. We are committed to
developing a robust biosimilar industry in the US, and to help
the BsUFA program further develop over the next 5 years. We are
at a critical inflection point for the biosimilars industry and
we believe that enhancing the process for biosimilar
development, review and educating the public of the importance
of biosimilars is critically important to sustaining and
cementing the biosimilar pathway for years to come, but as you
all know, more needs to be done outside of BSUFA to help us all
achieve our goal of lowering the costs of medicines and
improving patient access to biosimilars.
To conclude, thank you for the opportunity to provide this
letter. The Forum strongly supports efforts to advance the
FDA's biosimilars program. We need to see the FDA prioritize
biosimilar inspections and continue their work to streamline
the development of biosimilars as well as advance the guidances
we need. Policies that support timely approval of biosimilars
will ensure that patients have more access to high quality,
safe, effective, and affordable biological therapies.
Sincerely,
Juliana M. Reed,
Executive Director.
------
Senator Mike Braun,
Washington, DC 20510,
April 4, 2022.
Hon. Patty Murray, Chair,
Hon. Richard Burr, Ranking Member,
U.S. Senate Committee on Health, Education, Labor, and Pensions,
428 Dirksen Senate Office Building,
Washington, DC 20510.
Dear Chair Murray and Ranking Member Burr:
As Senate hearings begin tomorrow on the U.S. Food and Drug
Administration (FDA) user fee renewal, I write to urge you to have a
patient-focused hearing that allows the rare disease community to
testify at Senate Health, Education, Labor, and Pensions (HELP)
Committee. Simply put, the user fee renewal process will not be
successful if it ignores the end users of the medicines in the hearing
process, or rubberstamps a proposal without patient input.
The overarching mission of the FDA user fee program is to provide a
predictable and accountable regulatory framework that supports
expedited FDA review and approval of pharmaceuticals and medical
devices, ensuring Americans receive access to safe and effective
products. Recognizing the importance of incorporating patient voices in
the review and approval of medical products, the FDA, medical
industries, and Congress have taken steps to encourage patient-focused
drug and device development. Integrating patient perspectives with drug
development is especially important for patients with rare, lesser
known, progressive, and serious diseases and conditions, as well as for
diseases with unmet clinical. It is therefore critical that the FDA
user fee program incorporate patient experiences and perspectives,
especially patients with rare diseases and unmet needs.
In September 1992, Congress passed the Prescription Drug User Fee
Act into law, authorizing the FDA to collect fees from pharmaceutical
companies to review their product applications for approval. Since its
enactment, Congress has reauthorized the user fee program every 5
years, and is responsible for reauthorizing the program for the sixth
time in September 2022. Over the last 30 years, the user fee program
has expanded to include medical devices, generic drugs, and
biosimilars. Importantly, the user fee program reauthorization process
has evolved into an opportunity for Congress to direct FDA and medical
industries to implement new policies for the benefit of patients,
including 21st Century tools and techniques to address rare disease
drug development.
While the FDA, medical industries, and Congress have made great
improvements to include patients and patient perspectives in the user
fee program, there is still more to be done to ensure that patients
with rare diseases receive representation and consideration for the
September 2022 user fee reauthorization. For example, during the 2012
and 2017 user fee reauthorization process, the Senate HELP Committee
invited a witness to provide the patient perspective and testimony, in
addition to witnesses from the pharmaceutical and medical device trade
associations, at user fee reauthorization hearings. I commend the
Committee for its efforts to ensure patient representation in user fee
reauthorization discussions and hearings. However, I am concerned about
the lack of representation of patients with rare diseases at upcoming
HELP hearings, especially given the considerable number of provisions
related to rare disease drug and device development included in FDA and
industry's final user fee agreements for 2022.
In general, rare and lesser known diseases present a unique set of
challenges, particularly for drug and device development, clinical
trial design, and patient access to therapies, that are not commonly
experienced during traditional product development. For example,
clinical trials for rare disease drugs often struggle to recruit and
maintain a patient sample size large enough to generalize the data, as
well as lack biomarkers and endpoints to adequately demonstrate
efficacy. Despite increased efforts to address these issues and
expedite approval of rare disease treatments, more than 90 percent of
rare diseases have no treatment. \1\ Unfortunately, the current
regulatory framework for rare disease product development has failed to
support efficient development, review, and approval of treatments for
rare diseases, further preventing patients from access to therapies.
---------------------------------------------------------------------------
\1\ Nord, ``New Report Finds Medical Treatments for Rare Diseases
Account for Only 11 percent of U.S. Drug Spending; Nearly 80 percent of
Orphan Drug Products Treat Rare Diseases Exclusively,'' Mar. 4, 2021,
https://rarediseases.org/new-report-finds-medical-treatments-for-rare-
diseases-account-for-only 11-of-us-drug-spending-nearly-80-of-orphan-
products-treat-rare-diseases-exclusively/#:-
:text=Approximately%207%2C000%20known%20rare%20diseases,rare%20diseases%
20 have%20no%20treatment.
The FDA user fee program and reauthorization has helped modernize
FDA regulatory requirements, establish new approval pathways, and
improve the Agency and development process in tandem with medical and
technological advancements to ensure expedited approval of products
that benefit patients across the United States and globally. The FDA
and industry fmal agreements reflect a shift in FDA and industry
priorities to encourage and advance rare disease product development
and accessibility. As a result, it is imperative that Senate ensures
the rare disease community is represented by a witness in the on-going
user fee reauthorization discussions held in the Senate HELP Committee
to ensure the translational success of new policies incorporated into
---------------------------------------------------------------------------
the final user fee agreement.
For these reasons, I request that the Senate HELP Committee provide
a full patient representative hearing from the rare and life
threatening disease community in order to advance medical product
regulation and innovation for the benefit of patients, including those
diagnosed with rare diseases. I appreciate your attention to this
request, and my staff and I are willing to help you both organize this
hearing.
Sincerely,
Senator Mike Braun.
______
Questions for the Record
Response by Cartier Esham to Questions From Senator Braun, and Senator
Romney
senator braun
The PDUFA commitment letter stresses the importance of new programs
to allow earlier patient access to therapies that address unmet medical
needs and advance rare disease endpoint development.
Question 1. What challenges exist in FDA's current framework for
rare disease drug development? Does the PDUFA agreement go far enough
to provide the necessary regulatory flexibilities to address these
challenges?
Answer 1. Due to the smaller than average patient populations
affected by rare diseases, study recruitment, retention, and other
factors that can inhibit adequate endpoint measurement, thus limiting
drug development in these spaces. BIO supports the PDUFA VII Rare
Disease Endpoint Advancement (RDEA) Pilot Program and its goal to
advance and facilitate the development and timely approval of drugs and
biologics for rare diseases, including rare diseases in children. The
RDEA pilot is modeled after the Complex Innovative Trial and Model
Informed Drug Development programs initiated under PDUFA VI, which
provide foundational experience for a potentially successful rare
disease pilot.
The RDEA Pilot's aim to accept a proposal for a development program
for a common disease that includes innovative or novel endpoint
elements can allow for new rare disease treatments that utilize the
most cutting-edge and patient-centric study designs to reach the right
patients.
Given the FDA Pilot's small allotment of a maximum three
participating sponsors per year, we look forward to engaging with the
Agency regarding the best ways to glean useful and broadly applicable
data to inform our members, and most importantly, yield faster and
better results for our rare disease patient community.
Overall, we are optimistic that the RDEA pilot can provide
learnings to the biotech and greater R&D community regarding surrogate
endpoint use in rare disease drug development.
senator romney
U.S.-China Competition--FDA approval of a new drug or device does
not grant the U.S. exclusive access to that drug or device. Companies
aren't prohibited from also applying for approval in other countries,
where regulatory bodies may move comparatively faster to approve new
products.
Question 1. Aside from the consumer health benefits, how does
timely FDA approval promote American interests?
Answer 1. BIO agrees that the timely approval of safe and effective
medical products by FDA can mean the difference between death,
disability, relief, or potentially a cure for American patients with
urgent medical needs who lack other treatment options. We agree that
beyond consumer health benefits, timely FDA approval promotes American
interests in areas outside of patient outcomes.
FDA approval is often considered the ``gold standard'' globally
with respect to regulatory authority and rigor due to stringent safety
and efficacy standards. This reputation of regulatory excellence and
consistency has policy implications; for example, the US engages in
Mutual Recognition Agreements (MRAs) with almost 30 other countries,
allowing for a degree of reciprocity and data sharing between trusted
health authorities if FDA deems those authorities capable of conducting
inspections that meet US standards. In 2021 alone, almost half (27/60)
of FDA's new drug approvals in the Center for Drug Evaluation and
Research (CDER) and the Center for Biologics Evaluation and Research
(CBER) were first-in-class. That same year, 76 percent of novel drugs
approved were approved in the US before any other country. \1\, \2\
Approval by FDA can indicate likelihood for approval by other health
authorities. For example, a study indicated that FDA and the European
Medicines Agency (EMA) had 91-98 percent concordance in decisions on
marketing approvals between 2014 and 2016. \3\ Approval in multiple
markets translates into more revenue for US-based sponsors, increasing
their ability to conduct research and development on new innovative
treatments to help more patients.
---------------------------------------------------------------------------
\1\ https://www.fda.gov/media/155227/download.
\2\ https://www.raps.org/news-and-articles/news-articles/2022/1/
fda-approved-more-first-in-class-drugs-more-with-
a#::text=Other%20drugs%20approved%20by%20CDER,treatment%20options.
\3\ Kashoki, M., Hanaizi, Z., Yordanova, S., Vesely, R., Bouygues,
C., Llinares, J. and Kweder, S.L. (2020), A Comparison of EMA and FDA
Decisions for New Drug Marketing Applications 2014-2016: Concordance,
Discordance, and Why. Clin. Pharmacol. Ther., 107: 195-202. https://
doi.org/10.1002/cpt.1565.
In addition to economic and financial benefits, timely FDA approval
yields earlier availability of US-generated real-world evidence and
real-world data (RWE/RWD). As soon as patients have access to new
treatments, American academic institutions, health systems, software/
technology companies, and other stakeholders can begin to harness and
apply clinical outcome data generated by the use of these novel
products. In addition to supporting regulatory submissions and
decision-making, increased availability of RWE/RWD improves health
equity for Americans. Such data enable the utilization of decentralized
and non-traditional clinical trial locations, allowing for increased
diversity in clinical trials that can improve our understanding of
---------------------------------------------------------------------------
clinical outcomes for all American patients.
Question 2. How does timely approval affect the rate and
willingness of U.S.-based firms to invest in research and development?
Answer 2. Bringing a drug to market in the US is associated with
significant time, effort, resource expenditure, and risk for American
companies. It can take anywhere from 10 to 15 years at an average cost
of approximately $1 billion or more to advance a single drug or
biological product from a promising idea to an approved product that
benefits patients. \4\, \5\ Timely review and approval helps mitigate
risks and opportunity costs associated with regulatory submissions for
American firms.
---------------------------------------------------------------------------
\4\ Olivier J. Wouters, Ph.D; Martin McKee, MD, DSc; Jeroen
Luyten, Ph.D. Estimated Research and Development Investment Needed to
Bring a New Medicine to Market JAMA. 2020, 323(9).
\5\ Joseph A. DiMasi; Henry G. Grabowskibi; Ronald W. Hansen.
Innovation in the pharmaceutical industry: New estimates of R&D costs.
2016. Journal of Health Economics. 2016, Vol. 47.
Every day that an approval is delayed translates into unrealized
revenue for the sponsor of an application. Small companies with limited
research and development budgets, or even new companies that are pre-
revenue, are disproportionately impacted by such delays. These firms
might only have the resources, staff, and facilities to manage a single
product in their pipeline at a given time. Delayed approval results not
only in financial impact but can also chill innovation efforts due
solely to resource constraints. As approval timelines shorten, US-based
firms are more likely and more able to invest in biopharmaceutical
---------------------------------------------------------------------------
research and development.
Question 3. How does U.S.-based research and development investment
in medical products (drugs and devices) compare to Chinese-based
investment?
Answer 3. The biopharmaceutical industry is one of the largest
economic sectors domestically and globally. A recent study indicated
that total US medical and health research and development reached
$245.1 billion in 2020. Specifically, US private industry accounts for
66 percent of these investment dollars at $161.8 billion. \6\ During
that same year, Chinese pharmaceutical research and development reached
$187 billion. \7\
---------------------------------------------------------------------------
\6\ U.S. Investments in Medical and Health Research and
Development 2016-2020. Research! America. (n.d.). Retrieved April 29,
2022, from https://issuu.com/researchamerica.
\7\ Zhang, W. (2022, January 27). China: Pharmaceutical R&D
spending 2023. Statista. Retrieved April 29, 2022, from https://
www.statista.com/statistics/1202091/china-pharmaceutical-randd-
spending/.
According to census data from datacommons.org, American and Chinese
populations in 2020 were 329.5 million and 1.402 billion, respectively.
Using private industry spending data, we can estimate per capita
research and development spending at $49.1 in the US and $62.1 in
China.
______
Response by David Gaugh to Questions From Senator Kaine, and Senator
Romney
senator kaine
Mr. Gaugh, in your testimony you shared that as of March 2022, the
FDA has licensed two interchangeable biosimilar products. We know that
interchangeable biosimilars must produce the same clinical result as
the brand-name biologic and that a pharmacist may dispense an
interchangeable biosimilar when a brand-name biologic is prescribed
without intervention from a provider. As you shared in the hearing, the
development of biosimilars, and interchangeable biosimilars, has worked
to reduce the price that patients pay at the drug counter. We also know
this is a relatively new space and that we are still learning more
about the best science and oversight in the development of these
products.
Question 1. Mr. Gaugh, which provisions of the BsUFA III agreement
will help manufactures quickly develop additional interchangeable
biosimilar products?
Answer 1. Following enactment of the BPCIA in 2010, the first
biosimilar was licensed by FDA in 2015. Today, a total of 35
biosimilars including two interchangeable biosimilars--are now licensed
in the United States. Biosimilar medicines are safe, effective and more
affordable treatment options for patients than their brand-name
counterparts. Biosimilars are already delivering on their promise of
lower costs and expanded patient access to care with average prices of
nearly 50 percent less than their reference biologics at time of the
biosimilar's launch. Biosimilars represent much needed competition to
the specialty medicines that now account for more than 55 percent of
all drug spending.
The interchangeable designation permits a pharmacist to dispense,
subject to state law, an interchangeable biosimilar when a brand-name
biologic is prescribed without intervention from the provider. It
requires a biosimilar developer to demonstrate the same clinical result
for its medicine as the brand-name biologic. It is important to note
that the interchangeable designation is unique to the Unites States and
is not an indication of superior quality.
As part of the industry's negotiations with FDA, enhancements were
made to help facilitate more timely patient access to interchangeable
biosimilars. BsUFA III will help manufacturers to develop more
interchangeable biosimilars through the new Regulatory Science
Program's demonstration project. These demonstration projects will also
evaluate mechanisms to streamline overall biosimilars development. In
our view, the findings from these demonstration projects will inform a
comprehensive strategy to advance interchangeability and the
development of future guidance documents.
We appreciate your interest and attention to the important role
biosimilar medicines--and, in particular, interchangeable biosimilars--
can play in lowering prescription drug costs. We would welcome the
opportunity to further discuss how Congress could take steps to reduce
the clinical burden on biosimilars and interchangeable manufacturers to
ensure more timely patient access to low-cost medicines.
senator romney
U.S.-China Competition--FDA approval of a new drug or device does
not grant the U.S. exclusive access to that drug or device. Companies
aren't prohibited from also applying for approval in other countries,
where regulatory bodies may move comparatively faster to approve new
products.
Question 1. Aside from the consumer health benefits, how does
timely FDA approval promote American interests?
Answer 1. In addition to the consumer health benefits, timely FDA
approval of generic and biosimilar medicines benefits America's
interests through increased market-based competition and lower health
care costs. Experience shows drug prices decline rapidly when generics
enter the market. According to FDA, prices fall as generics enter the
market--by an average of 39 percent when there is only one generic and
by nearly 80 percent when four or more generics enter the market.
Evidence with biosimilar medicines is similar with an average cost
savings of nearly 50 percent. Importantly, biosimilar competition also
results in lower brand biologic prices--by more than 25 percent on
average for brands with biosimilar competition.
Over the last 10 years, generics and biosimilars provided more than
$2 trillion in savings--including $469 billion from new generics and
more than $12 billion from biosimilars--to patients and the U.S. health
care system. In addition to the cost savings provided, patient access
to life-saving treatments is broadened as the price of medicine falls.
A recent analysis of Medicare Part D from the Congressional Budget
Office noted ``the number of standardized prescriptions dispensed for
generic drugs more than doubled from 2009 through 2018.'' And
biosimilars have already resulted in more than 10 million additional
patient days of treatment.
GDUFA III and BsUFA III, as negotiated, will further these
interests. Both GDUFA and BsUFA aim to put FDA's generic and biosimilar
drug programs on firm financial footing by enabling FDA to assess user
fees to fund critical and measurable enhancements and, in turn,
bringing greater predictability and timeliness to the review of
applications. As a direct outcome, the generic and biosimilars drug
programs increase patient access to safe, effective and more affordable
quality medicines.
Question 2. How does timely approval affect the rate and
willingness of U.S.-based firms to invest in research and development?
Answer 2. Timely approval of generic and biosimilar medicines by
FDA increases the likelihood generic and biosimilar developers will
invest in bringing more affordable medicines to market going forward.
AAM's member companies invest significant resources in building and
operating U.S.-based facilities and in bringing generic and biosimilar
medicines through FDA's approval process to market. Manufacturing sites
can cost as much as $1 billion to build in the U.S. In addition, the
development and approval of biosimilar medicines, for example, require
8-10 years at a cost of $100 to $250 million.
GDUFA III and BsUFA III ensure FDA has sufficient resources for
review of generic and biosimilars applications, while building on the
success and incorporating lessons learned over the last 10 years. As
described in more detail in my written statement, GDUFA III and BsUFA
III include a number of enhancements to ensure the timely review of
applications over the next 5 years (FY23-27). Timely approval of the
FDA user fee agreements ensures America's patients will continue to
benefit.
Question 3. How does U.S.-based research and development investment
in medical products (drugs and devices) compare to Chinese-based
investment?
Answer 3. We do not have any data on how U.S.-based investment in
the research and development of generic and biosimilar medicines
compares to Chinese-based investment.
______
Response by David Leahey to Questions From Senator Burr
senator burr
Question 1. Aside from the consumer health benefits, how does
timely FDA approval promote American interests?
Answer 1. There is broad bipartisan agreement on the importance of
American patients gaining first access to American medical
technologies, a goal shared by innovators, FDA and most importantly,
patients. In addition to the health benefits, a timely and efficient
FDA review of medical technologies strengthens the entire medical
device ecosystem. Physicians, surgeons and all healthcare professionals
are able to work collaboratively with innovators to improve existing
technologies, as well as develop the next generation of cures,
therapies and diagnostics here in the United States. Unnecessary
regulatory delays also drive capital to markets outside the United
States and weaken our Nation's global leadership in device innovation.
It's in our collective public health, economic and national security
interests that the U.S. remains the most attractive country in the
world for medical device development and manufacturing.
Question 2. How does timely approval affect the rate and
willingness of U.S.-based firms to invest in research and development?
Answer 2. FDA has made significant progress since 2009. At that
time, FDA's performance slipped and as a result venture investments
fled the device markets. Thankfully, Congress intervened and passed key
reforms to improve FDA's review programs. FDA, to their credit, has
made improvements since then, and our expectation is that the $2B in
new resources provided under the MDUFA V agreement--a doubling of fees
from the current MDUFA--will build on this progress. Still, the harsh
reality remains that every dollar spent on research and development
carries risk, and many ventures fail. Ongoing improvements in
transparency, consistency and accountability at FDA will help ensure
that research and development investments in new medical technologies
continue.
Question 3. How does U.S.-based research and development investment
in medical products (drugs and devices) compare to Chinese-based
investment?
Answer 3. While there has always been shifts in venture capital
investments and others who support the medical technology ecosystem,
there has been an alarming trend of the majority of investments being
made in later stage companies. This is certainly necessary and
beneficial to patient care, but it is critical that investments are
also being made in early stage companies and startups. Reports show
that there are ongoing increases in these types of investments in China
with direct support from the Chinese government. In fact, the People's
Republic of China identified medical technologies as a critical sector
of investment as part of their Made in China 2025 industrial policy to
grow indigenous industries. Keeping the Chinese market open to U.S.
exports is critical to U.S. manufacturers, but improvements to the
regulation and reimbursement of medical technologies in the United
States will protect our Nation's leadership position in this vibrant
industry.
Question 4. How confident are device manufacturers these
adjustments will incentivize the FDA to meet its own commitment's?
Answer 4. The milestones and commitments contained in the MDUFA V
draft agreement are designed to help ensure that the investments being
made by industry will strengthen patient care and innovation. As the
agency works to maintain its gold standard of providing safe and
effective medical technologies to the public, we are confident that the
structure of the agreement before Congress will achieve our shared goal
of protecting the United States' leadership position in medical
technology innovation. Ongoing congressional oversight will also play a
central role to ensure that these important goals are met.
Question 5. How confident are device manufacturers that the FDA's
methods for measuring and reporting on hiring goals will provide both
accurate and reliable data?
Answer 5. During the MDUFA V negotiations, it was concerning to
learn that FDA was unable to identify how many MDUFA I-IV funded
positions were vacant. FDA did implement a tracking system for MDUFA IV
hires and has committed to an independent assessment during MDUFA V to
better assess workforce tracking and management. Given the significance
increase in funding under MDUFA V, it is a reasonable expectation that
FDA will do more to ensure timely hiring for new positions and existing
vacancies during MDUFA V and beyond. The results of the independent
assessment, coupled with FDA's annual financial report to Congress,
should provide more transparency into these workforce issues and any
gaps that need to be filled.
______
[Whereupon, at 11:49 a.m., the hearing was adjourned.]
[all]