[Senate Hearing 117-]
[From the U.S. Government Publishing Office]
AGRICULTURE, RURAL DEVELOPMENT, FOOD AND DRUG ADMINISTRATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2022
----------
THURSDAY, JUNE 10, 2021
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 10:03 a.m., in room SD-124, Dirksen
Senate Office Building, Hon. Tammy Baldwin (chairman)
presiding.
Present: Senators Baldwin, Hoeven, Moran, Hyde-Smith, and
Braun.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
STATEMENT OF DR. JANET WOODCOCK, ACTING COMMISSIONER,
FOOD AND DRUG ADMINISTRATION
opening statement of senator tammy baldwin
Senator Baldwin. Good morning. I want to welcome everyone
to our first budget hearing of the subcommittee for fiscal year
2022. And Dr. Woodcock, thank you so much for being here this
morning. We are looking forward to your testimony and having a
good discussion about the needs of the Food and Drug
Administration.
The responsibilities at the FDA are vast and have an impact
on every American. That has been made even clearer during our
response to COVID-19. We must continue to invest in safer
drugs, safer medical devices, and the safest food supply in the
world, and for now and for the future.
Dr. Woodcock, I am looking forward to hearing your visions
for the FDA and what this committee can do to support your
vital work. That work begins now, with the fiscal year 2022
budget request that is in front of us. And the request for FDA
includes an increase of $343 million in total budget authority.
This increase touches a wide array of activities at FDA,
including protecting public health, food, and medical product
safety, as well as continuing to address the ongoing opioid
crisis.
I am particularly interested in learning about your
proposed increases for FDA's core safety programs. The budget
request includes significant increases for food and drug
safety, device shortages, as well as a focus on infant health
and nutrition. These are all important investments, and this
subcommittee will play a role in advancing these priorities.
Dr. Woodcock, your job is constantly changing. And I know
it is difficult to try to keep up with all the changes in
research and technology and manufacturing that are going on in
the private sector. To make sure that the vast number of
products FDA regulates are safe, while at the same time not
slowing down the important advancements that will, ultimately,
benefit us all is quiet a tightrope to walk.
I think last year showed the importance of FDA in relying
on sound science when making decisions that impact so many of
us. The work that FDA did to authorize multiple COVID vaccines,
under a short timeframe, guided by science, sound data, and
transparency was truly remarkable. You should be commended for
that, and I look forward to seeing how the FDA will continue to
work to make COVID vaccines more available.
However, I think there is room for improvement. I would be
remiss if I did not briefly mention my continued frustration
with FDA's slow progress on enforcing standards of identity for
milk and dairy products. I recently reintroduced the Dairy
Pride Act, that would require FDA to issue draft guidance on
enforcing these standards.
I would note, yesterday, FDA issued a final rule on the
standards of identity for yogurt. But more work needs to be
done. And so, I hope, as chair of this subcommittee, we can
continue to work together to start making meaningful progress
on this issue of significant importance to my constituency.
Again, I look forward to your testimony and appreciate you
being here today. And with that, I will turn it over to Ranking
Member Hoeven for any opening remarks he may have.
statement of senator john hoeven
Senator Hoeven. Thanks, Madam Chair, and thanks, Dr.
Woodcock, for being here today to discuss FDA's funding parties
for fiscal year 2022. Your many years of public service and
your commitment to promoting health and safety for the American
people is very much appreciated. Thank you.
I would like to reiterate Chairwoman Baldwin's comments
regarding the FDA's COVID response efforts. The Agency has
worked tirelessly to ensure that all medical products,
including COVID-19 vaccines, meet the Agency's standards for
quality, safety, and effectiveness. And your efforts are to be
commended there.
As we dive into this budget request, I want to stress that
FDA has been, and continues to be, the gold standard or food,
drug, and device safety. The rest of the world looks to the FDA
to lead in standard setting and while we can always do better,
it is important to acknowledge that the FDA is leading the way,
in terms of promoting evidence-based scientific advances and
regulatory actions.
Dr. Woodcock, your Agency impacts the daily life of every
American citizen. The FDA has authority over more than $2.5
trillion worth of products used by consumers. Americans expect
that the food that they eat and the drugs that they take will
be safe and effective. The FDA's vast reach covers more than
300,000 foreign establishments and 185,000 domestic
establishments, ranging from food processing plants to
facilities that manufacture lifesaving medications. In addition
to the facilities themselves, the FDA is tasked with the
regulatory responsibility for individual products.
In delivering these regulatory responsibilities, your
private sector partners expect transparency and certainty from
the FDA. When I speak to small business owners and Ag producers
in North Dakota, their overwhelming concern is that all too
often, overly burdensome regulations coming out of Washington,
DC stifle innovation and hinder their ability to create jobs or
respond quickly to an emergency situation.
While all of this--excuse me, an emerging situation. While
we all support FDA's mission, we must be mindful of these
concerns, now more so than ever. I believe that FDA must avoid
the trappings of a ``one size fits all'' approach to
regulation. And I urge you and your staff to take a commonsense
approach that supports our Nation's innovators, while adhering
to your mission to ensuring safety and efficacy.
So, with that, I look forward to your testimony.
Senator Baldwin. Dr. Woodcock, we would like to hear from
you, now.
Dr. Woodcock. Thank you. Can you hear me?
Senator Baldwin. Try your microphone.
Dr. Woodcock. Can you hear me?
Senator Baldwin. Yes, much better, thank you.
summary statement of dr. janet woodcock
Dr. Woodcock. Turned on. All right, thank you.
Chair Baldwin, Ranking Member Hoeven, and Members of the
Subcommittee, thank you for the opportunity to appear before
you today to discuss the President's fiscal year 2022 Budget
request for FDA.
I would like to begin by thanking the subcommittee for your
continued support of the Agency over recent years. I have gone
over these budgets and it is very--been very helpful, in
particular the past year as the Agency has worked to address
the current COVID-19 public health emergency. And I think the
past year has reinforced the essential role that the FDA plays
in protecting and promoting public health.
I want to thank the entire FDA staff for their unwavering
dedication, commitment, and contribution to public service
through what has been a very stressful time. However, despite
our remarkable progress over the last year, our work is far
from over and our commitment to the mission is unwavering.
The pandemic presented new challenges for the Agency and
has given us an occasion to reflect on our strengths, and
identify areas to improve overall operations and performance,
should this happen again or just in general. The budget I
present to you today will directly support our efforts to
evolve and modernize how we accomplish our mission, our
workforce, and operations.
We are embarking on a multi-year effort to upgrade and
modernize our physical and technological infrastructure,
strengthen our talented workforce, and improve our scientific
capability and regulatory structures. The industries that we
regulate are constantly innovating, as the point was just made,
attracting skilled professionals and upgrading their
technological capabilities. FDA must keep pace with this.
With that in mind, our budget request focuses on
investments in three main categories to support our
modernization. The first is the critical public health
infrastructure. The Agency's infrastructure is fundamental to
every aspect of our work and our budget requests a total of
$185 million to support it. We will invest this money in
several areas, including data modernization, maintenance
repairs to our facility, and expanded laboratory safety
efforts.
I want to take a moment to discuss our data modernization
request in greater detail. While some may not consider data
modernization as exciting as vaccine development or food safety
science, I cannot overstate how critical it is to our success
as an agency. We are requesting $76 million to support much
needed data modernization efforts. As we saw firsthand during
the COVID-19 pandemic, technological advances have and will
continue to revolutionize human and animal health. Scientific
breakthroughs have enabled the development of personalized
therapeutic treatments, advanced manufacturing, and state-of-
the-art solutions such as genomic information, and real-time
analytics.
As a byproduct, the amount and variety of data that FDA
generates, needs, and uses is rapidly increasing. But we are
often hampered by antiquated methods, including inspecting
large volumes of information we get on PDFs, often done by
hand, in order to identify critical safety signals, such as
human and animal drug and device safety concerns or emerging
foodborne outbreaks. The investments requested will modernize
our data infrastructure and allow us to more efficiently gather
data and identify, analyze, and respond to potential problems
more quickly, and to further improve review times for medical
products.
Turning to our second budget category, we are requesting an
increase of $97 million to invest in our core food and medical
product safety programs. Throughout our COVID-19 response, as
you undoubtedly know, medical product supply chain issues have
been a constant challenge, especially at the height of the
pandemic, with critical shortages. We want to continue to play
a role in fixing this issue going forward and are requesting
$22 million to build a resilient supply chain and shortages
program, specifically for medical devices. Medical devices,
including PPE and some other critical items, such as,
ventilators, were often in shortage during this pandemic.
Another vital area, for which we are requesting funding, is
an additional $18 million to expand the Agency's capacity to
review increasingly complex infant formula submissions and
continue to reduce babies' and young children's exposure to
toxic elements in their food. As you all know, nutrition during
pregnancy and early childhood is critically important in
supporting the health and well-being of mothers and their
children. And we think these investments cannot be emphasized
enough.
But the importance of nutrition and food safety extend well
beyond childhood. We are equally committed to making sure the
food each of us eats everyday is safe, as well, and foodborne
illnesses remain a significant public health challenge. So, we
are still facing these illnesses. The availability of safe and
nutritious foods across the population is a key element of
ensuring equitable health outcomes. Our budget seeks to address
this challenge through a requested increase of $45 million, to
further implement our New Era of Smarter Food Safety Blueprint.
And finally, our third and last category relates to public
health issues confronting the nation today. While COVID
pandemic has predominated, these other health challenges have
not vanished. We request an additional $61 million to further
our efforts, specifically requesting $38 million to support the
development of opioid overdose reversal treatments and better
guidance for clinicians, advance the development authorization
of digital health medical devices, and treatments to address
opioid disorder, to establish satellite laboratories at our
international mail facilities so we can better screen for
illicit opioids through the mails.
And we are also committed to modernize FDA's inspectional
activities. To support this inspection work, our budget
requests an increase of $19 million, which will allow us to
maintain staff that we hired with supplemental funding and
increase our foreign inspection teams.
And finally, I am pleased to request an increase of $4.7
million to enhance FDA's ability to support and expand health
equity and combat health disparities.
Finally, FDA also protects Americans from tobacco-related
death and disease by regulating these products. We propose an
additional $100 million in user fees to enhance product review
and all the activities that go along, including enforcement.
This increased funding will strengthen our actions to combat
youth use of tobacco products.
I would like to close by thanking this subcommittee again,
for your continuing support of the agency. As a gold standard
for protecting public health, we are trusted by Americans and
admired around the world for our work ensuring safety,
efficacy, and security of our Nation's medical products and our
food supply.
Thank you for inviting me and I look forward to answering
your questions.
[The statement follows:]
Prepared Statement of Dr. Janet Woodcock
Chair Baldwin, Ranking Member Hoeven, and Members of the
Subcommittee, thank you for the opportunity to appear before you today
to discuss the President's fiscal year 2022 Budget (Budget) request for
the Food and Drug Administration (FDA or the Agency).
I would like to begin by thanking the Subcommittee for your
continued support of the Agency in recent years, and in particular the
past year as the Agency has worked to address the current COVID-19
public health emergency. The funding increases that the Subcommittee
provided to FDA have been essential to the Agency fulfilling its
critical mission.
Today, I am pleased to present FDA's fiscal year 2022 Budget
Request. Our program level request totals $6.5 billion, which is
comprised of $3.6 billion in discretionary budget authority and $2.9
billion in user fees. This is an increase of eight percent, or $477
million above the fiscal year 2021 Enacted level. The Budget requests a
net budget authority increase of $322 million, which reflects $343
million in requested increases and scheduled adjustments of -$21
million to reflect the authorized level for 21st Century Cures and the
one-time funding provided in fiscal year 2021. The Budget focuses on
necessary investments in three main categories: (1) critical public
health infrastructure; (2) core FDA safety programs; and, (3) public
health issues confronting the nation today.
critical public health infrastructure
FDA's Budget requests an increase of $185 million to support our
critical public health infrastructure. This infrastructure is
fundamental to every aspect of our work. Challenges faced during the
current pandemic have reinforced the need to ensure that the Agency is
making consistent, smart investments with respect to our physical and
technological infrastructure so that we are prepared to effectively
fulfill our core mission and tackle unpredictable public health crises.
With that in mind, the Agency's infrastructure request includes
critically important investments in data modernization, maintenance and
repairs to our facilities, expanded laboratory safety efforts, and an
increase in internal capacity to support our workforce of over 18,000,
including targeted investments in the Office of Chief Counsel,
cybersecurity, IT equipment replacement, and business functions within
the Office of Operations. A few of these investments requested in this
year's Budget are highlighted in more detail below.
data modernization
The Budget requests an increase of $75.9 million to support FDA
data modernization efforts. As witnessed firsthand during the COVID-19
pandemic, technology has and will continue to revolutionize human and
animal health. Scientific breakthroughs have enabled the development of
new, more personalized therapeutic treatments, advanced manufacturing,
and state-of-the-art solutions such as blockchain, genomic information,
and real-time analytics. As a byproduct, the amount and variety of data
that FDA generates, needs, and uses is rapidly increasing at
exponential rates. However, the Agency utilizes antiquated methods,
including inspecting large volumes of PDFs, often ``by hand,'' in order
to identify critical safety signals, such as human and animal drug and
device safety concerns or emerging foodborne outbreaks.
In response, the Budget requests investments to modernize the
Agency's data infrastructure. The request includes two components--an
Agency-wide component ($44.5 million) and complementary program-
specific investments ($31.4 million). Combined, this funding will allow
FDA to more efficiently gather data; identify, analyze and respond to
potential problems more quickly; and, to further improve review times
for medical products.
buildings and facilities infrastructure
The Budget requests an increase of $37.5 million for FDA's owned
and leased facilities' needs. FDA's facilities requirements during any
given year are diverse and cover 77 FDA-owned buildings at six
locations across the U.S. and Puerto Rico and approximately 265 leased
buildings, including 53 laboratories. Repairs and upgrades needed at
these facilities vary from basic maintenance to complex laboratory
retrofits. This requested increase will allow FDA to better operate,
maintain, and secure its owned and leased facilities, as well as make
necessary repairs and improvements at both the FDA White Oak Campus and
FDA owned buildings across the country. FDA's current backlog of
maintenance and repairs at our owned locations is greater than $220
million and places a considerable strain on the Agency's ability to
execute its mission. Maximizing the public health value of FDA funding
is paramount and we will continue to prioritize our facility
investments to ensure that our owned and FDA-occupied facilities are
efficient, cost-effective and meet the demands of FDA's expanding
workload and workforce.
core fda safety programs
FDA's responsibilities continue to expand and grow in complexity
due to advances in food and medical product technology, globalization
of supply chains, increasingly complex and diverse data sources, and
emerging scientific approaches. The nation relies on FDA to provide
rigorous and transparent scientific review, a predictable and
responsive regulatory structure, comprehensive inspections at domestic
and foreign food and medical product manufacturers, and expert staff to
provide support for these activities. The Budget requests an increase
of $97 million to invest in core food and medical product safety
programs to reduce the number of foodborne illnesses through
implementation of the New Era of Smarter Food Safety Blueprint; improve
maternal and infant nutrition and health; address emerging food-related
chemical and toxicological issues; strengthen oversight of animal
foods, strengthen and monitor the device supply chain; and increase
drug safety surveillance and oversight. A few of the investments
requested in this year's Budget are highlighted in more detail below.
maternal and infant nutrition and health initiative
Nutrition during pregnancy and in early childhood is critically
important in supporting the health and wellbeing of mothers and their
children and key to promoting health equity. Nutrients vital for brain
development and growth must be provided in adequate amounts during
early years, whereas certain dietary constituents should be limited,
and some should be avoided altogether to prevent potentially
irreversible harm. Infants, young children, and the developing fetus
are especially vulnerable to toxic elements (e.g., lead, cadmium,
arsenic, and mercury) due to small body size and rapid growth and
development.
With its available regulatory tools and authorities, the FDA is
uniquely positioned to advance work that promotes healthy dietary
patterns and consumption of essential nutrients for pregnant women,
infants and young children, while mitigating risk of dietary exposure
to toxic elements harmful for growth and development in early life. As
such, the Budget requests $18 million to support work that advances
both nutrition and food safety at the Center for Food Safety and
Applied Nutrition (CFSAN). The funding will support three components:
(1) Enhancing Infant Formula Premarket Review; (2) Addressing Toxic
Elements in foods commonly consumed by babies and young children; and
(3) Promoting Dietary Patterns Recommended by the Dietary Guidelines
while Mitigating Risk of Exposure to Dietary Toxicants. This funding
will expand the Agency's capacity to review the increasing number,
size, and complexity of infant formula submissions and will push to
reduce exposure to toxic elements from foods eaten by babies and young
children to as low as possible.
medical product supply chain
The COVID-19 pandemic has exposed great weaknesses in the medical
product supply chain's dependence on foreign medical products. To
ensure the U.S. is properly prepared now, and in the future, we must
take action to secure our medical product supply chain, including
related ingredients and components.
The Budget requests an increase of $21.6 million for a new
Resilient Supply Chain and Shortages Program at the Center for Devices
and Radiological Health (CDRH). This funding will provide resources to
establish a permanent program for U.S. supply chain resilience for
medical devices for the first time. The funding will help to stand up
this program that will focus on strengthening the domestic supply chain
through investments in preventive measures, identifying potential
medical product supply short-falls, continuing surveillance, and rapid
intervention.
FDA is also requesting an additional $2.3 million for medical
product supply chain efforts by the Center for Veterinary Medicine
(CVM) to strengthen its data analytics capacity to help identify and
anticipate the effects of the public health emergencies on the animal
drug supply. Finally, FDA is requesting an increase of $5.6 million for
Drug Safety Surveillance and Oversight activities for the Center for
Drug Evaluation and Research (CDER).
public health issues confronting the united states
In addition to strengthening our fundamental infrastructure and
supporting our core medical product and food safety programs, in the
upcoming year we must also focus on the most pressing public health
issues facing our country.While the COVID-19 pandemic has dominated
headlines over the past year, other longstanding health challenges have
surged back into the spotlight and our Budget requests an additional
$61 million to further our efforts to address these public health
challenges. Funding will support several activities, including, efforts
to increase safe and secure inspections, promote health equity, and
address the opioid crisis. A few of these investments requested in this
year's Budget are highlighted below in more detail below.
safe and secure inspections
FDA's inspectional activities, coordinated by the Office of
Regulatory Affairs (ORA), play a crucial role in te mission of the
Agency to protect consumers and enhance public health by ensuring
access to FDA regulated products and minimizing risk associated with
those products. ORA inspects regulated products and manufacturers,
conducts sample analyses of regulated products and reviews imported
products offered for entry into the United States. To support our
critical inspection work in the upcoming fiscal year, our Budget
requests an increase of $18.8 million to ORA's base funding to support
for our inspections program.
With support from COVID-19 supplemental funding, ORA is working on
COVID-19 recovery activities including inspectional modernization,
preparing to adjust staffing and onboarding new staff to support onsite
inspections. The resources requested as part of the fiscal year 2022
Budget will allow ORA to maintain the staff hired with supplemental
funding and increase our foreign inspection teams. We are also actively
working to expand upon the use of remote assessment tools where
appropriate, such as remote livestreaming video of operations,
teleconferences, or screen sharing. These remote assessments, used in
combination with other tools, enable the FDA's investigators to assess
the level of compliance and process control at sites.
expand health equity and health disparity efforts
I am pleased to request an increase of $4.7 million to enhance
FDA's ability to support and expand health equity and health disparity
efforts. The COVID-19 pandemic is only the latest example of the
disproportionate impact public health problems have on minority and
underserved communities. This funding will allow FDA to expand
culturally and linguistically tailored communication and outreach
efforts, establish new scientific initiatives, support novel health
disparity and health equity focused intramural and extramural research,
advance activities that enhance meaningful inclusion of minority
populations in clinical trials, and understand and address health
disparities. In addition, the funding will allow FDA to increase
engagement with Historically Black Colleges and Universities, Minority
Serving Institutions, and other collaborators to address gaps and needs
of underserved communities, and develop FDA-wide training programs that
focus on the reduction of health disparities and advancement of health
equity.
ending the opioid crisis
FDA will continue to address the opioid crisis that has only been
exacerbated by the COVID-19 pandemic. As part of HHS's Department-wide
initiative to Advance the Goal of Ending the Opioids Crisis, in fiscal
year 2022 FDA requests an increase of $38 million to support activities
in CDER, ORA, and CDRH. As part of the initiative, CDER will receive
$26 million to support development of opioid overdose reversal
treatments and treatments for Opioid Use Disorder (OUD). CDER will,
among other activities advance the development and adoption of
evidence-based clinical practice guidelines for acute pain conditions;
assess feasibility to integrate opioid Risk Evaluation and Mitigation
Strategies (REMS ) education into IT health systems/Electronic Health
Records and explore use of health IT systems to support goals of REMS,
such as prescriber education; and continue to support opioid research
efforts. Within CDRH, $2 million will be invested in efforts that will
allow FDA to advance the development, evaluation, and market
authorization of digital health medical devices that help address OUD.
Finally, of the $38 million increase, the Budget will provide ORA
$10 million to establish satellite laboratories at the Agency's
International Mail Facilities (IMFs). FDA staff are assigned to nine
IMFs throughout the U.S., Puerto Rico and the U.S. Virgin Islands and
are responsible for monitoring mail importations of FDA regulated
products by conducting comprehensive examinations of packages suspected
of containing drugs to determine if those drugs should be refused
delivery to the U.S. consumer. The Budget request will also fund
permanent staffing at the IMFs by scientists along with expanding ORA's
use of analytical tools for screening entries, expand the current IMF
initiative to interdict shipments of opioids, unapproved foreign drugs,
counterfeit pharmaceuticals and health fraud related shipments, and
support Pharmacy Compounding and Outsourcing Facility inspections,
which include an inspectional assessment for compounding or repackaging
of opioid products.
conclusion
I would like to close by thanking the Subcommittee again for your
continued support of the Agency. As the gold standard for protecting
and promoting public health, FDA is trusted by Americans and admired
around the world for our work ensuring the safety, efficacy, and
security of our nation's medical products and the safety of our food
supply. Once again, thank you for inviting me. I look forward to
answering your questions.
Senator Baldwin. Thank you, Dr. Woodcock. I have a number
of questions that dive deeper into some of the things that you
have already described in your testimony, and broad ranging
issues in the Food and Drug Administration.
I am going to start with the issue of strengthening the
domestic supply chain for some of the things needed in this
pandemic, but also, could need in the future. I was very
concerned last year about--and I have been for a long time,
about our overreliance on foreign manufacturers for critical
medical supplies and pharmaceuticals. It is vital that we work
to make these supplies in America. To do that, we need to make
sure that there are policies in place at the FDA that make it
more attractive for companies to make their products here, in
the United States.
In setting up a new pharmaceutical manufacturing facility,
36 months may elapse between the start of construction and the
first product being released to the market, 10 months of which
may be spent awaiting regulatory review. What does the FDA need
from Congress in order to streamline and prioritize inspections
and approvals for new domestic facilities?
Dr. Woodcock. FDA has been working for some time on
improving manufacturing and getting to advanced manufacturing,
which we think, for pharmaceuticals, is the way we will be able
to bring manufacturing back into this country. Advanced
manufacturing does not use the methods that have been used for
100 years, but uses advanced continuous methods, both for
synthesis of compounds and making the final dosage form.
These methods and the factories that relate to them, are
very innovative and actually can be brought up much more
speedily because of the methods that they use. They use
computer control, rather than paper records. They do not stop
for testing, and so forth. They are much smaller. They have
better environmental footprints. And so, many of those
obstacles--those regulatory obstacles are diminished.
However, we must, the FDA, must make a new regulatory
framework for this type of advanced manufacturing and we are
working on that. We are working on creating, between drugs and
biologics centers, a new, sort of, Center of Excellence that
will help bring these facilities along.
In addition, the Administration has announced investments
as part of their efforts to both boost U.S. jobs and
manufacturing and to deal with critical supply chain issues,
and pharmaceuticals is one of those. So, they plan to invest in
manufacturing science in the United States, so that we can get
to this advanced stage of manufacturing. And FDA's role will be
to have new regulatory standards that apply to these advanced
methods. And we have actually asked for, and you all have
provided, some money for our field organization, for example,
to get training on these new methods so that the entire FDA is
ready for these methods. And it is encouraging them.
Senator Baldwin. Thank you. As a follow up, for many years
FDA has been working to develop a framework for conducting
quality management maturity assessments of manufacturers, and a
rating system to incentivize industry investments. What do you
see as the overlap between a quality rating system for
manufacturers and this larger effort that we are talking about,
to bring manufacturing back to the U.S.?
Dr. Woodcock. I believe that the modern manufacturing
methods will--and this is a technical opinion of mine, boosted
by many other people who are very good in this area, that they
will naturally have a better-quality maturity, all right,
because a computer-controlled process that has very small
tolerances, will achieve tighter specifications, higher
quality. So, the quality maturity measures will be somewhat of
a little bit of a stick, I think, and the ability to do
advanced manufacturing is, sort of, a carrot in the United
States. And so, I think these two efforts will be synergistic.
Senator Baldwin. Thank you. Senator Moran.
Senator Moran. Thank you, Chairman. Dr. Woodcock, thank you
for your presence here. I am going to try to ask you three
questions and then, give you a compliment.
As food evolves, and the chairman mentioned this in her
opening statement, the FDA standards of identity needed to keep
pace, to avoid hindering research and development, to make sure
we get the most nutritious and healthy foods. That consumers
are knowledgeable about what they are buying is really
important. But the FDA's process that is bureaucracy is, in my
view, updating standards of identity.
And while there was, perhaps, a bit of a compliment to the
FDA, in its announcement yesterday in regarding--in regarding
identity of yogurt, what I understand is that the industry
first petitioned for an update in the yogurt standards in 2000
and FDA issued a proposed rulemaking in 2009 and only finalized
the new identity yesterday. Updating a single standard of
identity for a popular food item should not take 21 years.
A company in my state of Kansas, with a--recently
petitioned the FDA to update the standard identity for
margarine. It is a critical for the Agency not to take years
for to modernize the standard of identity for margarine, as
was, unfortunately, the case in yogurt.
In the past, we heard these bottlenecks were due to lack of
resources. As a result, Congress, this committee, this
subcommittee has provided increases in FDA's Office of
Nutrition and Food Labeling, the past three Appropriations
cycles. I have been involved in that process. Dr. Woodcock,
just reassure me that steps are being taken to improve the
process for reviewing and modernizing identity standards.
Dr. Woodcock. Yes, they are and yes, I agree that is too
long for modernization. However, I will tell you my technical
assessment is that, certainly the Center for Food Science and
Applied Nutrition did not have enough staff on this to get the
job done, previously. And currently, still do not have enough
staff, because there are 280 standards. Each one need to be
done by rulemaking.
Senator Moran. Does your budget request solve that problem?
Dr. Woodcock. It does not solve it but we--I think many of
our data efforts, and so forth, will help. We are exploring
more innovative methods, which they call horizontal standards,
which I would say are cross-cutting. For example, ultra-
filtrated milk to put into standardized cheeses would go across
a number of cheese standards. And so, you could put that in,
modernize all of those at once, without having to go through
rulemaking for each of the standards. So, they are exploring
additional methods that would get this process moving more
quickly.
Senator Moran. Well, it strikes me as odd as asking to
modernize something when the answer on how to modernize it
takes so long, that by the time the answer is given, it is no
longer modern.
Dr. Woodcock, it currently takes three to 5 years for new
animal feed ingredients to be approved. In fiscal year 2020, I
worked to secure increased funding for the FDA to hire
additional personnel to review feed ingredient approvals. I
offer to continue to work with you to pursue that, to decrease
the amount of time it takes to bring a new ingredient to
market.
I also want to flag a policy concern with the approval
process. The livestock industry is looking to offer solutions
in meeting the challenges related to climate. However, the
current FDA policy interpretation regulates certain feed
ingredients, which could reduce greenhouse gas emissions and
benefit the environment, as animal drugs instead of feed
ingredients.
It is my understanding that the FDA's Center for Veterinary
Medicine policy manual dictates these decisions, and it has not
been updated since 1998. I just ask for your commitment, again,
to address this issue in a way that is timely and beneficial.
Dr. Woodcock. Thank you. I certainly will give you that
commitment. We have approved one product, such as this, for
decreasing emissions from animals or their waste, and we are
working very diligently and closely with manufacturers who are
working in this space. But I certainly will be glad to look
into this more.
Senator Moran. Thank you. Let me also suggest the
compliment in the 30--I am sorry, I have 30--I had four minutes
and 30 seconds to issue my concerns and 30 seconds to give you
the FDA compliment.
I have paid a lot of attention to research in regard to
Alzheimer's and I want to express my gratitude for the
decisions that the FDA made, just in recent days, and I think
this--again, it is talking about the timeliness, and certainly
the process matters, but I am convinced that with more timely
approvals, that there will be more private investment in
research to find these lifesaving and live improving drugs.
The FDA has a role. While we have been very generous as an
Appropriations Committee and a Congress in supporting the
research that goes on at NIH, a lot of research goes on
elsewhere and the reward from that research comes in a drug
that is approved for the market. And so, sending a message to
the market that there is a process by which there is a reward,
a return on investment, is very valuable--I suppose you could
say to the company, but much more important to me is to the
individuals who suffer from Alzheimer's and their families.
Dr. Woodcock. Thank you.
Senator Moran. Thank you.
Senator Baldwin. Senator Hyde-Smith. And I will just
announce that there will be additional rounds of questions as
senators would like.
Senator Hyde-Smith. Thank you, Senator Baldwin, and thank
you, Dr. Woodcock, for being here today.
My first question, the FDA frequently touts expanded
generic drug approvals as an accomplishment. But I am concerned
that the FDA is lagging in approvals for complex, generic
drugs. One example is Restasis, an expensive drug that millions
of Americans rely on that costs the U.S. healthcare system more
than $2 billion annually. And I can tell you that this drug
costs Medicare beneficiaries a pretty penny. I am very familiar
with many people that have those teeny, tiny tubes of Restasis
that cost a lot of money.
But more than 7 years after companies filed applications to
develop a lower cost generic of this drug, the FDA has still
not approved a single application. As a result, patients are
still paying the increasingly high brand name drug price for
Restasis.
Will you commit to prioritizing the review of complex
generic drug applications and ensuring that patients receive
timely access to more affordable medications?
Dr. Woodcock. Absolutely. That is one of our highest
priorities within the drug center, as well as getting
biosimilar applications out there to lower costs for biological
products when they are legally available. And they are spending
a lot of work on research for complex generics and for
biological products, so that we can actually get more
affordable versions out on the market.
Senator Hyde-Smith. Yeah, because it is really burdensome
for so many people there. And I led a bicameral letter to you
in April, expressing serious concerns with the recent FDA
recent decision to not enforce the risk evaluation and
mitigation strategy for Mifepristone--am I saying that right--
the chemical abortion drug, for the remainder of the public
health emergency. And the FDA decision is alarming because this
drug is dangerous. The limited data we do have shows
unacceptable rates of complication for women and girls.
Specifically, more than 20 percent of reported complications
were life-threatening or resulted in death. And over 70 percent
of reported complications required follow up surgeries,
including total hysterectomies.
I am particularly struck by the inconsistency of FDA's
actions. For instance, the FDA and CDC imposed a clause on the
Johnson & Johnson COVID vaccine, after reports of blood clots
in some women. At the same time, FDA is expanding the approval
for chemical abortion pills that have much, much higher risk of
blood clots than the J&J vaccine.
Your response to my letter, which I received just this
morning, a few hours ago, states that FDA will be undertaking a
further view of the issue. In my letter to you, I encouraged
you to mandate the collection of complete and accurate
information on all adverse events related to this drug. And
will you commit to requiring this data be collected, so that
FDA has complete data for its review for this abortion pill?
Dr. Woodcock. Well, I can certainly--I will have to look at
the conditions of the REMs as far as which event--all serious
events need to be reported to the FDA. So, let me look into
that. But it may well be that, if a person has a headache
after, you know, using this drug, that that may not have to be
reported. Because it is a serious self-limited event.
Senator Hyde-Smith. Twenty percent, though, you know, that
is pretty serious for the life threatening or resulted in
death. And I am going to follow up with you to provide some
studies on the adverse events that I would like to ensure the
FDA reviews.
Dr. Woodcock. Certainly.
Senator Hyde-Smith. Chair Baldwin, I would also like to ask
consent to include those studies in the record for this
hearing.
[The information follows:]
[article 1: medical abortion: what physicians need to know]
[article 2: deaths and severe adverse events after the use of
mifepristone as an abortifacient from september 2000 to february 2019]
Senator Baldwin. Without objection.
Senator Hyde-Smith. Thank you.
Senator Baldwin. Senator Hoeven.
Senator Hoeven. Thank you, Madam Chairman. Chair Baldwin
and I, along with the chair and ranking member on the House
side, wrote to you recently regarding FDA's drug inspection
program backlog and the importance of resuming both domestic
and foreign inspections. And we did provide additional
resources to you, you know, obviously as part of the COVID
pandemic legislation, including the facilitation and conduct of
inspections relating to the manufacturing of vaccines,
therapeutics, and devices, delayed or cancelled for reasons
related to COVID.
So, how does FDA plan to deploy those resources to resume
the inspection program and ensure applications are not further
delayed?
Dr. Woodcock. First of all, FDA was able to act upon over
90 percent of all applications--premarket applications that
came in during this period, so far. So, with a combination of
our usual processes and inspections for mission critical
products, we were able to get a lot of products out.
We only had 68 product applications that are waiting for an
inspection because we cannot do an inspection. For example,
right now we cannot do an inspection in India. And if we
determined we had to do a physical inspection to approve the
product, whatever it might be, then we must do a physical
inspection. On the other hand, we are not turning those
applications down. We are simply waiting until a time would
come that we could actually go into that country and actually
accomplish an inspection.
As far as most of the inspections you are referring to, the
backlog, most of them are what we call surveillance
inspections. There are plant, food processing facilities, other
areas, that are currently operating, and we inspect them on a
schedule, every so often, on a risk base or statutory base. And
what happened during COVID is, we could not get into a lot of
those plants because we could not travel.
And so, if you think about a rubber band with marks on it,
and this is how often we would like to inspect that plant, what
has happened is we have stretched that rubber band. And for
every plant there is going to be a little bit more--there is
going to be more time between inspections than there ordinarily
is.
So, that is one part of the answer, if that makes sense to
you.
Senator Hoeven. Mm-hmm.
Dr. Woodcock. Okay. The second part of the answer is, a lot
of the money we are asking for here, we really need an overhaul
of how we operate our inspectional program. Our IT systems are
completely antiquated. Many of them are at the end of service,
or end of life. They do not talk to each other. We cannot get
them on the cloud because they are too antiquated.
And so, much of the technology and data ask that we have
here is going to, number one, be working on things like the
food establishment inventory, to get that correct and digitized
and quality controlled. To upgrade the field systems, so that
they all talk to each other or are integrated with the
commodity areas, so we have all the information at our
fingertips.
So, we will--at the same time we are recovering, we are
going to upgrade in everything we do. We are going to work on
these remote assessments where people wear cameras, and so
forth, and go around the plants. They would not substitute for
in person inspection, but they will augment the information
that we get.
So, we are committed to getting our inspectional program
back up, back and running fully by this summer to the extent we
can. Domestically, we probably can. Foreign, it is going to
depend on the state of the country and whether we can actually
get into the country. So, I cannot commit to having a full, you
know, inspection program fully operating by the fall because we
may have parts of the world where the pandemic is still raging.
But we have a plan. We published our resiliency report--
which I hope you have a copy of, and we can provide that--which
goes over how we plan to recover from this time when we were
not able to do so many inspections.
Senator Hoeven. Yeah, and so that, to me, leads to--and I
will start the question and I will have to ask you in the next
round. But the lessons learned, I mean, not just how do you
modify how you operate based on what you learned in COVID, but
how we prepare so that, A, we do not have another situation
like we have had with COVID--you know, not only trying to
prevent it, but if we do face another virus or variants, how we
make sure we deal with it without the incredible challenges,
disruptions, and problems we had this time, right? And not just
your Agency. This is something we all have to be looking at.
So, I will pick up on that next round.
Dr. Woodcock. Absolutely. And some of our ask here is for
supply chain monitoring, so that we have a better handle on
where the products are actually coming from. As Chair Baldwin
pointed out, many of them are coming from overseas and
especially for devices, we do not have, really, authorities and
we do not have a system to monitor those supply chains.
Senator Hoeven. Thank you.
Senator Baldwin. I was pleased to hear bipartisan concern
about the issues of standards of identity. I wanted to dig a
little deeper because, as I mentioned in my opening statement,
I recently reintroduced the Dairy Pride Act. That legislation
would require FDA to issue guidance for nationwide enforcement
of mislabeled, imitation dairy products within 90 days.
This is an issue that I have been working on for many years
now. And it is important to dairy farmers and the entire
Wisconsin dairy industry. I am sometimes dismayed that I even
have to offer a measure like this.
FDA does not enforce the regulations it has on the books.
So, dairy farmers follow these rules, day in and day out, in
order to honestly label their product as milk or cheese or
yogurt. Yet, a range of imitation dairy products have gotten
away with using these dairy terms, even though they do not
follow the Agency's rules. I really think it is high time that
the FDA address this violation of its own labeling
requirements.
So, please update me on what FDA is currently doing to
ensure consumers are not misled by the use of dairy terms on
non-dairy products.
Dr. Woodcock. We are working on updated guidance that would
make sure that consumers understood we are particularly
concerned about nutritional value.
Senator Baldwin. Yes.
Dr. Woodcock. For example, calcium, vitamin D, protein.
These other products are not comparable and, say if they were
fed to a young child or infant, they would not be getting what
the consumer, mother or parent thought the child was getting.
So, we really need clear labeling in those instances, to make
sure that it is not misleading. And we will try to get that as
soon as possible.
Senator Baldwin. Okay. I certainly appreciate your
assurance that you will continue to work on this, and with this
committee, to make standards of identity a priority in the
Agency.
Next, I wanted to just add my words to another inquiry that
Senator Moran made about feed additives and livestock
emissions. The Administration has set ambitious goals with
regard to climate change and reducing emissions. And the
agriculture sector really can play a key role here.
Dr. Woodcock. Mm-hmm.
Senator Baldwin. Feed additives have been shown to
dramatically reduce methane emissions from livestock. However,
the FDA's existing approach to these additives have prevented
their widespread adoption. The central issue is that FDA limits
the definition of feed additives to products that affect the
nutrition of the animal. Environmental benefits, such as
reducing methane emissions, are really not considered.
Europe has adopted a regulatory framework that considers
any environmental benefits of feed additives and New Zealand is
poised to do the same thing. That means that other countries
will be using this emissions reduction technology four or 5
years earlier than we will be able to, in the United States,
materially disadvantaging U.S. farmers and ranchers, in terms
of export markets for beef and dairy products.
So, will you take a look at this issue and identify a
solution that allows these critical products to be available
for use in the U.S. agricultural sector? And can FDA issue
guidance allowing the approval of safe feed additives, that
strictly provide environmental benefits, or does this change
need to happen legislatively?
Dr. Woodcock. I will certainly be glad to look into this
and get back to you on that issue. I am very well aware the
issue, but not further solutions.
Senator Baldwin. Okay. Senator Braun.
Senator Braun. Thank you, Madam Chair. Enjoyed our
conversation just yesterday and, of course, I am real
interested, in general, to try to get the FDA to maintain all
of its integrity and standards but pick up the pace a bit. Co-
founded the ALS Caucus here in the Senate. Know that we
recently got an Alzheimer's drug out there approved.
I still sense extreme frustration among the individuals out
there struggling with these diseases that have got clinical
trials, got stuff in motion, see good results, and especially,
willing to take the risk that, with an ALS patient, three to 4
years from day of diagnosis to when your life ends. And if you
are in one of those trials and it at least seems to be working,
how do we get more agility, maybe entrepreneurialism--look what
we did recently with the vaccine--without sacrificing the
process and the safety features?
Generally, in life, you cannot take forever and get things
done and avoid all risk. Things pass you by in the interim. So,
love to hear your thoughts on that?
Dr. Woodcock. Well, I think there are some misperceptions
about where the barriers are and the blockages. FDA does review
drugs very rapidly, due to the user fee programs. We are
probably the fastest agency in the world, in a developed
country, to get things reviewed and, if approvable, on the
market.
But for the neurodegenerative diseases, of which
Alzheimer's and ALS are a part of, the science has been slow to
develop. While we had a war on cancer--remember it started in
the '70s, now, in the last 10 years, we are seeing the fruits
of that. We are seeing new cancer drugs that are unprecedented,
that really make a difference, and are not so toxic, and the
reason is that we understand cancer and we understand the
molecular changes that lead to somebody getting a cancer. And
what is happening is, we are getting drugs that target the
specific mutations that are driving that cancer and can block
it, or that stimulate the immune system.
In neurodegeneration, we are still in a more primitive area
of science. We do not really understand why these things are
happening to people, for example, with ALS. And so then, it is
very hard. So, the problem is more in the developmental area.
We are still in, what we call, empirical development, to some
extent, which means, just try it and see if it works, rather
than we are trying to interrupt a very specific pathway and we
understand its role in bringing on the disease.
So, I believe FDA has worked very closely--I personally,
have corresponded recently with many individuals and families
of people with ALS. I totally understand the devastating
tragedies that are occurring every day to families and to
people because of this illness. And we will do everything we
can to move these therapies along and be very flexible.
However, we need good science because we need treatments that
are going to work to advance the treatment of this disease.
Senator Braun. So, I think then, it begs the question of
the main stakeholder in all of this, to me, is the patient. And
to me, it looks like the patient, often times, is not the
driver behind what might be out there to help them. So, is the
patient driving the process, at least in terms of that trade
off between the risk of having something that is not ready,
with the willingness to take it on?
So, comment a little bit about--to me, it should not be the
Agency, it should not be the drug company. Maybe it ought to be
the patient that has a little bit more say so in the speed at
which that only remedy that may be out there is going to be
available to them.
Dr. Woodcock. Well, we certainly--we have something called
patient-focused drug development we have been doing for some
time. And we do really hear the voice of the patient. We feel
the voice of the patient should be central.
A long time ago, we heard the same reasoning from people
with HIV when AIDS was common, and people were dying. And they
said, we would try anything. We do not care, just get it to us.
As soon as we got semi-effective drugs, then people wanted
drugs that were more effective. Let us live longer. Let us do
better, right? And we want the best drug for me, okay? That
will keep me alive--have fewer side effects and keep me going.
Of course, now, because of that flexibility and the effort we
put in, living with HIV is, you know, a chronic disease. And
that is where we would like to, as step one, to get some of
these neurodegenerative diseases.
So, we do listen to the patients. However, getting a lot of
effective remedies out there would not be in conformance with
the law, really, and it would not help the patients. Because if
we have all these people advocating for ineffective therapies--
we do not know if any of them work. We do not advance science.
That is not how medical science really gets to a point that
really helps people, like we have with HIV, like we are getting
there with cancer. We are improving survival rates in cancer.
So, we have to keep a balance between--I understand and we
have--you know, Congress passed, for example, Right to Try, so
people can access investigational therapies, if companies are
willing, right? And we have expanded access programs. So, if
compounds are being studied, then people can get them for
treatment if they are not going to be able to get into the
studies. So, we have those mechanisms because we understand.
We have a problem right now. People are dying. But we have
another problem. We need to build the medical science so we can
treat this disease and turn it into a chronic disease people
can live with.
Senator Braun. Thank you.
Senator Baldwin. Senator Hyde-Smith.
Senator Hyde-Smith. Thank you, Madam Chairman. One last
issue I would like to raise with you relates to the novel
medical devices, specifically for end stage renal disease
population. Four hundred thousand Medicare beneficiaries are on
dialysis and those patients have not benefited from any
meaningful advances and innovations in a long time. To address
this, I have worked for several years with a bipartisan group
of my Senate colleagues to encourage adoption of a new policy
to spur innovation in medical technology for Medicare patients
under the ESRD bundled payment system.
While we have made some progress, there still seems to be a
misalignment between how FDA evaluates novel devices for
safety, and how CMS views the same data for reimbursement
decisions. That misalignment creates a situation where a new
novel device can gain new FDA clearance, but not reach the
hands of the patients, in a meaningful way, due to differing
interpretations of the same data.
So, how can FDA and CMS work together to ensure a greater
level of coordination on how clinical data is interpreted for
novel, new technologies?
Dr. Woodcock. I will be happy to take that back and work on
it because I recognize the plight of people with ESRD and the
lack of new therapies, the lack of convenient and a really,
truly portable dialysis, and the burden that that puts on
folks. So, I am very happy to work on this. I cannot speak to
CMS policies because I do not know very much about that. But I
will definitely commit to you to work into this.
Senator Hyde-Smith. Great. I sure appreciate it. Thank you.
Senator Baldwin. Senator Hoeven.
Senator Hoeven. Madam Chair, I guess it would be your turn
again, if you wanted to go, under alternating. So, I do not
want jump in front of you.
Senator Baldwin. I am looking just at human beings in the
room. Let us keep on going and----
[Laughter]
Senator Hoeven. All right.
Very good. I just wanted to----
Senator Baldwin. Senator Moran and then I will----
Senator Hoeven. That is gracious of you, thank you.
Senator Baldwin. You can arm wrestle it out.
Senator Hoeven. Thanks, Madam Chair. So, the question I
have would be in regard to the non-prescription, safe use,
regulatory expansion final rule. Where are you and when do you
expect that to be released?
Dr. Woodcock. Yeah, well I try never commit to actually--
because it has to get through a lot of different layers before
something would come back.
Senator Hoeven. You know, you were really good in the last
round, where you told me, like, by fall you are going to catch
up on everything.
[Laughter]
I thought that was pretty good to give me that timeframe
unsolicited. So, I mean, you are on a great trend line.
Dr. Woodcock. I would tell you, I was one of the
instigators of this program, when I was head of the Center for
Drug Evaluation and Research. I am extremely interested in it.
I think it will be tremendous for consumers to have more
choices in self-care, because it is getting harder and harder
to get to the doctor's office, and all these types of things. I
believe that we can use technology to enable people, say if
they have chronic diseases, to continue to get their--some of
their medications, as appropriate, at the drug store, using
technological solutions.
So, I am very interested in moving this along and getting
it out.
Senator Hoeven. Any guesstimate?
Dr. Woodcock. I really would hate to do that and then, tell
you something wrong.
Senator Hoeven. Yeah, but you are saying it is--you are an
advocate for it, and it is a priority.
Dr. Woodcock. It is a real priority for me.
Senator Hoeven. Yeah, okay, good.
Dr. Woodcock. Absolutely.
Senator Hoeven. So, there are more plant-based protein
products coming on the marketplace and, you know, we have that
challenge between, you know, how they get labeled and is it
confusing, you know, if there is animal terminology or imagery
used. And of course, on the animal side, we want USDA driving
the labeling and, you know, we understand you have it on the
Food and Drug side--or on the Plant and Drug side.
But, you know, how do prevent misleading labeling for these
products?
Dr. Woodcock. Well, I think we have to establish clear
standards. And we work very closely with USDA on these issues
to make sure they have labeling principles, and so forth, to
make sure that those are out there, and people understand them.
So, some is education. Some is enforcement to make sure that,
if things are mislabeled, that we provide feedback to the
companies.
Senator Hoeven. Well, Senator Moran gets very, very
concerned if, like, a beef product, you know, there is a
substitute plant product for that beef product and consumers
become confused about that, and as do I. And so, you know, we
want to really emphasize that that is important, that clarity,
not only for the consumer but, you know, for our livestock
producers so they feel there is fair treatment out there.
Dr. Woodcock. Absolutely. I mean, I would say, on the plant
side, there are many people who want to make sure they are
eating a plant product, too. So, these need to be labeled very
clearly which ones they are, so that people are not misled.
Senator Hoeven. Packaging, so there is an increased desire
among, I guess, manufacturers, retail industry, State lawmakers
to advance minimum recycled content requirements. And of
course, that scenario, when there is food contact, you
regulate. So, where are you on that issue?
Dr. Woodcock. I understand that they are working on that.
We have many different food contact issues that we have to deal
with. There are, of course, many chemicals that people are more
concerned about nowadays, such as PFAS, and other types of
chemicals that we have to make sure that food contact is safe
and that nothing leeches into those. But we also cannot
establish a program that is so burdensome that it does enable
recycled products to be used.
Senator Hoeven. Yeah, and it is clearly any area there is
going to be more recycled materials used.
Dr. Woodcock. Yes. Exactly.
Senator Hoeven. Which is a good thing, right?
Dr. Woodcock. I agree.
Senator Hoeven. So, we need to have a good program there.
Dr. Woodcock. Agreed.
Senator Hoeven. With that, Madam Chairman, I yield back.
Senator Baldwin. Senator Moran.
Senator Moran. Chairman, thank you, thank you again.
Vaccines, clearly, are the primary factor in getting the
country back to normal. But COVID-19 testing will continue to
have an essential role. Direct to consumer COVID-19 testing
expedites the process in getting test kits to Americans.
The FDA appears to understand the need for DTC testing,
since the first kit was authorized in December of 2020, and
several others have been approved since the beginning of the
year. If the goal is getting as many DTC COVID-19 tests on the
market as possible, is the FDA ensuring that there is fair
consideration between both nasal swab and saliva-based tests,
assuming that all EUA requirements are met?
Dr. Woodcock. I would have to get back to you on that. I
know we have allowed 65 DTC tests of different kinds. Most of
them require you to send in your sample, but if you were
strictly at home for molecular tests, then we have done six
antigen tests that are at home tests. But saliva versus nasal
swab, that is a bridge too far for me to answer, right now. I
will have to get back to you on that.
Senator Moran. And that really is my question. Is there a
bias or a prejudice, one way or another, between those two
tests?
Dr. Woodcock. I would doubt, as long as the performance
characteristics are comfortable, then why would we have a bias?
But there may be differences in performance characteristics,
and that is what I do not know and would have to get back to
you.
Senator Moran. Okay, I welcome that. Thank you very much.
Thank you, Dr. Thank you, Chairman.
Senator Baldwin. Thank you. In 2019, Children's Hospital of
Wisconsin identified the first cases of a mystery illness
connected to vaping. FDA took way too long, in my opinion, to
crack down on companies that were clearly marketing to young
people. But I am pleased, now that e-cigarettes and other
tobacco products are now, finally required to submit pre-market
review applications. So, I have a number of questions related
to that.
I am hoping you can provide the committee with an update on
FDA's review of these applications and how you are working to
prioritize public health in this process of review. I am hoping
you can describe how the FDA's request for an additional $100
million in user fees would support this work in reviewing
product applications and prioritizing public health. And
additionally, how the FDA intends to remove new tobacco markets
from the market that do not meet the September 9th application
deadline.
Dr. Woodcock. Well, to, sort of, go backwards, we have sent
out many, many, many warning letters--I think 120 warning
letters to companies that are marketing that failed to submit
applications. There were 6.1 million products that we listed,
that we received in applications that need to be reviewed. We
have a deadline, I think, in mid-September to try to get
through these products.
Can you repeat some of your other questions?
Senator Baldwin. Yeah, just basically, how are you going
about review of these applications and prioritizing public
health in this process? But also, how would you put to work an
additional $100 million in user fees.
Dr. Woodcock. Okay.
Senator Baldwin. That you described in your testimony, to
support the work reviewing these products?
Dr. Woodcock. Okay, as far as prioritizing public health,
the statute that we are reviewing these products against is
very clear. We have to find a net benefit to public health for
each of these products, for them to be able to go onto the
market. And what it says, basically, is, you have to have
enough benefit in helping people to stop smoking combustible
cigarettes, that outweighs the harms, the attractiveness to
youth, and so forth, of people who may start becoming nicotine
dependent, because of these products. So, that is the bar that
we are using.
As far as the $100 million in user fees, these products do
not have to pay a user fee. And by--we have had to do a massive
diversion of staff toward this review process for these 6.1
million products and that is cutting into things like
enforcement of youth--we had--I was really appalled when I read
the numbers. The number--thousands and thousands of
establishments that had sold products--ENDS products to
underage youth. And they were given warning letters and there
were some enforcement actions, money penalties, against them.
So, that program may have to be cut back. Additional research
into tobacco may have to be cut back, and so forth.
So, the program, as it is, was not constituted to do this
massive regulatory program over the ENDS products, because that
was a more recent development with the Deeming Rule. So, that
is why we are asking for additional funds, because we need to
keep up this enforcement. If we cannot--the good news is that
youth, in the last survey, youth use of tobacco products had
decreased and that is really good news, because they had been
markedly increasing. However, we need to keep the pressure on,
and we cannot have people selling tobacco products to underage
individuals, or else, we may see this happen again.
We still have four plus million underage people who are
using tobacco products, right now.
Senator Baldwin. Yeah.
Dr. Woodcock. So, we really need to keep the pressure on
and that is why we are asking for an additional user fee.
Senator Baldwin. Thank you. One more question on this
topic. I was, like you, quite horrified to just hear about the
scale of underage use of these products. One of the challenges
is that there is not approved method of treating nicotine
addiction in children--approved by the FDA, that is. So, how
will you tackle this challenge and work with States to ensure
that, kids who are caught up--or caught using vaping products
underage, are presented with the best options to combat their
addictions.
Dr. Woodcock. Yes, so we have had a number of scientific
workshops on this issue. We work with individuals, you know,
the Nicotine Research Society, the American Academy of
Pediatrics, and so forth. It does appear that conventional
smoking cessation aides, that we have approved for adults, do
no work that well for children, for some unknown reason, right?
And so, those are not according to my folks I have talked to,
children do not have the same cues for smoking, and so forth.
So, we need to pursue more research on this and figure out
the best ways to enable--because we have a lot of children who
will becoming adults who are now addicted to nicotine. And we
need to figure out a way to stop that, as soon as possible. But
we do know, and we need to remember this, that, you know, most
committed smokers start smoking when they are underage.
Senator Baldwin. Senator Hoeven, do you have any more
questions? I have just a couple more. I guess it is our third
round, if I am doing that.
The opioid crisis continues to evolve, and it really
ravaged communities across the country. Early reports show a
recent spike in reported overdoses and deaths, as the pandemic
has increased things like socialized isolation and stress, and
reduced access to treatment and harm reduction services.
This committee provided FDA with important resources to
address the opioid crisis. And I am encouraged to see the FDA's
budget request includes an additional $38 million, as you
outlined. Can you describe how that additional funding will be
utilized to aide in the development of new treatments of opioid
use disorder? And how are you working to appropriately weigh
the need for better access to treatment with harm reduction and
protecting patients?
Dr. Woodcock. Yes, we will use the $38 million in a number
of ways. Number one, we are going to continue to step up our
efforts on interdiction at the mail facilities. Because a lot
of these fatalities are Fentanyl, and so forth, and we are
seeing a lot of different substances come through the mail. So,
we are going to step up our efforts there, have some satellite
labs.
As far as development, we need to develop better pain
medications and we need, also, to develop better treatments for
opioid use disorder--treatments that are convenient, treatments
that do not require lots of doctor's office visits, treatments
that are highly effective, and so forth. So, we are, of course,
working on that with the National Institute for Drug Abuse and
some of these dollars will go to increase our staff, okay, that
can work on these issues.
It has been very, very difficult to get new pain meds and
every single pain med we have, right now, has significant
liabilities, for example, GI bleeding, right, for the non-
steroidal anti-inflammatory agents. And of course, the opioids
have this abuse liability problem.
So, we are trying to get better pain meds. At the same
time, we are trying to encourage development of new treatments
for opioid use disorder that people can have access to because
the current ones, you know, have a lot of precautions around
them. And there is a lot of stigma associated with this and
this really decreases--there are not enough people in
treatment, compared to the number of people who suffer from
this disorder.
Senator Baldwin. That is right. Couple more questions on
pharmacy compounding. In April, the National Association of
Boards of Pharmacy and ABP wrote to the FDA requesting a delay
in enforcement of Section 503a of the Food and Drug and
Cosmetics Act. They noted in their letter that many State
boards of pharmacy have yet to sing a memorandum of
understanding under Section 503a and have expressed concerns
with the timeline, including obstacles due to the COVID-19
pandemic.
I am hopefully that all States are able, ultimately, to
sign the memorandum of understanding put forth by the FDA.
However, the October 2021 is approaching quite quickly. How is
FDA working with the National Association of Boards of Pharmacy
to resolve these concerns and ensure that all State board of
pharmacy are able to sign this MOU? And is the Agency
considering an extension of this deadline?
Dr. Woodcock. We are evaluating whether the deadline should
be extended. We have been working very closely with the
National Association of Boards of Pharmacy and, in fact, they
hold some of the databases, and so forth, that will make this
whole arrangement work. So, they are a key stakeholder in this
whole thing.
And we certainly hope--for the provisions to function
properly, we need all the States to sign on to the MOU. And as
you probably know, we have revised that. We have gone through
many different repetitions of this, and delays of
implementation to try and get it right, and make sure all the
stakeholders can agree on a path forward.
Senator Baldwin. Thank you. I want to just underscore the
importance that diversity plays in clinical trials. Health
equity is something that you mentioned in your testimony, among
underserved and minority populations is an ongoing challenge.
And I am pleased that your budget asks for an increase in $4.7
million to address this issue.
Can you talk a little bit about the work of the Office of
Minority Health and Health Equity, what they do at the FDA? And
how will FDA prioritize this additional funding?
Dr. Woodcock. Certainly. Well, first let me say that this
is a huge priority for me, personally. And I believe that we
really need to get the clinical trial infrastructure out into
communities so that wherever a person is located, they have a
chance to be in a cancer trial if they have cancer. If they
have ALS, they have a chance to be in an ALS trial, and so
forth.
As far as what we have done, as you recall, a decade ago it
was women in clinical trial and people were very concerned. We
have been publishing the Snapshots program and currently, say
for the last 5 years, women have been majority participants in
clinical trials. And that is probably how it should be because
women seek healthcare more and have various additional
conditions.
As far as minority populations, though, we are not doing
very well and much more needs to be done. The Office of
Minority Health and Health Equity is focused on this issue of
getting more diverse enrollment in clinical trials. And I have
been working with the director because it also is really an
issue that is very important to me. And so, they will be
reaching out to various healthcare institutions and providing
grants. They will be providing fellowships, because we need a
generation of people to be trained, right, so they can go out
in the community and serve those communities.
We need to shift our mindset, in my mind, from thinking,
well, we just need to encourage these folks to enroll. No, we
need to go to where they are, okay, and offer them enrollment
through the people who care from them, usually, and in the
places where they usually get their healthcare. And I think
that will be the transformation that will really enable our
clinical trial populations to reflect the people of this
country.
Senator Baldwin. Thank you. I want to thank you, Dr.
Woodcock, for being here today. I think we had a good
discussion and I look forward to working with FDA and members
of the committee, as we start the Appropriations process for
fiscal year 2022.
ADDITIONAL COMMITTEE QUESTIONS
Questions for the record are going to be due next Thursday,
June 17th. And with that, this hearing is adjourned.
Questions Submitted by Senator Jeff Merkley
Question. Over the years, I have urged FDA Commissioners to do more
to address the high rates of youth use of e-cigarettes. FDA was slow to
assert jurisdiction over e-cigarettes and has been slow to enforce
premarket requirements for them. As a result, we have an epidemic of
youth e-cigarette use--and a new generation of kids addicted to
nicotine. FDA is now reviewing applications for a large number of e-
cigarettes and has an opportunity to dramatically reduce youth use of
these products. I am concerned that FDA will again act too cautiously
and will authorize applications for products that are attractive to
kids. Do you agree that flavors are a key reason why youth use e-
cigarettes?
Answer. According to the 2020 National Youth Tobacco Survey, more
than 8 out of 10 youth e-cigarette users reported use of flavored
products. A majority of youth e-cigarette users reported using flavored
e-cigarettes in 2020, including 82.9 percent of high school e-cigarette
users and 73.9 percent of middle school e-cigarette users. Among high
school students who currently used any type of flavored e-cigarettes,
the most common flavors were fruit (73.1 percent); mint (55.8 percent);
menthol (37.0 percent); and candy, desserts, or other sweets (36.4
percent). Among middle school students, the most common flavors were
fruit (75.6 percent); candy, desserts, or other sweets (47.2 percent);
mint (46.5 percent); and menthol (23.5 percent).
Question. Do you believe that the availability of flavored e-
cigarettes over the past 10 years has had an overall harmful impact on
public health?
Answer. Flavors in tobacco products are a concern, as they can be
very appealing to youth, and are frequently listed as one of the top
three reasons youth use e-cigarettes. Additionally, kids whose first
tobacco product was flavored are more likely to become current tobacco
users than those whose first product was tobacco-flavored.
FDA began to regulate electronic nicotine delivery systems (ENDS)
products under chapter IX of the Federal Food, Drug, and Cosmetic Act,
after the issuance of the final deeming rule in 2016. FDA monitors
consumer use, including youth use, of these products. The most recent
National Youth Tobacco Survey (NYTS) continues to show youth's
preference for flavored e- cigarettes. About 8 in 10 youth e-cigarette
users are consuming products with flavors like fruit, mint, candy and
menthol. Among high school students who used flavored e-cigarettes, the
most common flavors were fruit (73 percent), mint (56 percent), menthol
(37 percent), and candy (36 percent). Among middle school students who
used flavored e-cigarettes, the most common flavors were fruit (76
percent), candy (47 percent), mint (47 percent), and menthol (23
percent). While the 2020 NYTS results show a decrease in youth use of
e-cigarettes, accounting for a large portion of the decline in overall
youth tobacco use, teen use of ENDS remains high.
FDA is working hard to ensure that illegal e-cigarette products,
especially those that attract and appeal to our children, are removed
from the market. In early 2020, FDA began prioritizingenforcement
against flavored, cartridge-based e-cigarettes, and other e-cigarettes
that appeal to youth. In line with the recent uptick in youth use of
disposable e-cigarettes, FDA notifiedseveral manufacturers of
disposable e-cigarette brands to remove their products from the U.S.
market. The September 9, 2020, premarket submission deadline, which
applied to e-cigarettes, marked a major milestone for ensuring new
tobacco products--including many already on the market--undergo a
robust scientific evaluation by FDA. FDA will also continue to enforce
the minimum age of 21 for sale of tobacco products. In addition, while
most of these FDA activities are aimed at curbing youth e-cigarette
use, FDA will continue to consider and take appropriate actions based
on the latest findings about youth use of all tobacco products.
Question. Can you envision FDA authorizing a flavored product
despite the well-established role of flavors in attracting youth to e-
cigarettes and nicotine addiction?
Answer. Ensuring new tobacco products undergo a robust premarket
evaluation by FDA is a critical part of our mission to protect the
public health, particularly youth, and to reduce tobacco-related
disease and death. As required by statute, the review process under the
Premarket Tobacco Application (PMTA) pathway makes certain that the
marketing of any new product is appropriate for the protection of the
public health, taking into account the risks and benefits to the
population as a whole. This includes how the product may impact youth
use of nicotine and tobacco, and any potential for the product to
completely move adult smokers away from use of combustible cigarettes.
As you are aware, premarket applications for many new tobacco
products currently on the market, including e-cigarettes, were due to
FDA by September 9, 2020. FDA is currently processing, reviewing, and
taking action on these applications. This work is a critical part of
how we carry out our mission to protect youth.
Question. I understand FDA is very busy reviewing the thousands of
Premarket Tobacco Project Application (PMTA) submissions from last
September. I recognize that this is a very time consuming process and
may not be complete by the 1 year mark that was given to allow these
products to stay on the market. What happens to those products which
are still under review on September 10, 2021? Will they remain on the
market?
Answer. Given the unprecedented number of applications, reviewing
all the applications by September 9, 2021, will be challenging. We are
planning and striving to review as many applications as possible during
the 1 year period described in the court order that set the September
9, 2020 application deadline.
If a product has not received a marketing authorization by the end
of the 1 year review period, the product risks FDA enforcement.
However, FDA has discretion to defer enforcement action against a
particular product, on a case-by-case basis, after September 2021.
Question. I applaud the Biden Administration's announcement in
April to ban the sale of menthol cigarettes. Are e-cigarettes part of
the ban?
Answer. Each year, more than 480,000 people in the U.S. die
prematurely from a tobacco-related disease, mainly due to smoking.
Specifically, over 40.8 million adults in the U.S. use any combusted
tobacco product (including cigarettes and cigars)--which are the
deadliest tobacco products. Of these, there are nearly 18.6 million
current smokers of menthol cigarettes. In April 2021, FDA announced our
commitment to advance two tobacco product standards to significantly
reduce disease and death from combusted tobacco products: to ban
menthol in cigarettes and ban all flavors, including menthol, in
cigars.
There is strong evidence that a menthol ban will help people quit
smoking and not take up smoking. Menthol masks unpleasant flavors and
harshness of combusted tobacco products,making them easier to start
using. This proposed product standard reiterates our commitment to
making the largest impact in reducing tobacco-related death and disease
by targeting thedeadliest tobacco products.
Non-combusted tobacco and nicotine products, such as electronic
nicotine delivery systems (ENDS), will not be part of the proposed
product standard to ban menthol in cigarettes. At the same time, our
commitment to addressing youth use of e-cigarettes and other ENDS
isunwavering. We continue to address this issue through premarket
review of tobacco product applications; compliance and enforcement
efforts; and our public education campaigns.
Question. I am concerned that the agency may approve a menthol
flavored pod or e-cigarette menthol product. The 2020 National Youth
Tobacco Survey (NYTS) showed that 40 percent of youth used menthol e-
cigarettes, which doesn't include the mentholated candy and fruit
flavors--referred to as ``iced''--which is not tracked by the NYTS. The
survey has shown that youth will migrate to whatever flavor is left on
the market. As the Administration is moving to ban menthol cigarettes,
should menthol flavored and mentholated flavors be included in the ban?
Answer. In April 2021, FDA announced it is committing to advancing
two tobacco product standards to significantly reduce disease and death
from using combusted tobacco products, the leading cause of preventable
death in the U.S. The Agency is working toward issuing proposed product
standards by April 2022 to ban menthol as a characterizing flavor in
cigarettes and ban all characterizing flavors (including menthol) in
cigars. This decision is based on clear science and evidence
establishing the addictiveness and harm of these products and builds on
important, previous actions that banned other flavored cigarettes in
2009.
Given the inherent toxicity of combusted tobacco products,
decreasing their appeal will maximize the potential public health
benefits of these regulatory actions. Each year, more than 480,000
people in the U.S. die prematurely from tobacco-related disease, mainly
due to smoking combusted tobacco products. Specifically, over 40.8
million adults in the U.S. use combusted tobacco products. By targeting
the deadliest tobacco products, we will have the largest impact in
reducing tobacco-related death and disease; these two actions combined
will save hundreds of thousands of lives.
FDA is concerned about the presence of flavors in non-combusted
products, such as e-cigarettes. However, unlike combustible products
which provide no possible benefit to public health, e-cigarettes may be
less harmful alternatives for currently addicted adult smokers who are
concerned about their health and interested in transitioning off
cigarettes. This makes the role flavors may play more complicated.
Research is ongoing in this area, and as we continue tolearn more, we
will take additional and appropriate steps on flavored electronic
nicotine delivery systems (ENDS) products. In the meantime, FDA remains
committed to addressing issues related to flavors in e-cigarettes and
other ENDS products through three high priorityprogrammatic efforts:
application review, compliance and enforcement, and public education.
In the context of premarket tobacco product application review, the
burden is squarely on themanufacturer to demonstrate to FDA that the
marketing of any menthol-flavored e-cigarette meets the statutory
standard of being ``appropriate for the protection of the public
health,'' which takes into account the risks and benefits to the
population as a whole, including how the product may impact youth use
of nicotine and tobacco.
Question. Is there scientific proof that e-cigarettes actually help
smokers quit smoking?
Answer. E-cigarettes are not currently approved by the FDA as an
aid to quit smoking and may expose users to some of the same toxic
chemicals found in combustible cigarette smoke; however, there may be
potential for e-cigarettes to provide a public health benefit if adult
combusted cigarette smokers, who would otherwise not quit, are able to
exclusively transition away from combusted cigarette use or
significantly reduce their cigarette consumption. Currently, there has
been mixed evidence in the scientific literature on the role of e-
cigarettes in helping combusted cigarette smokers reduce their
cigarette consumption or quit smoking altogether.\1\ \2\
---------------------------------------------------------------------------
\1\ Wang RJ, Bhadriraju S, Glantz SA. E-Ciga rette Use and Adult
Ciga rette Smoking Cessation: A Meta-Analysis. Am J Public Health.
2021;111(2):230-246.
\2\ Hartmann-Boyce J, McRobbie H, Lindson N, et al. Electronic
cigarettes for smoking cessation. Cochrane Database Syst Rev.
2020;10:CD010216.
---------------------------------------------------------------------------
For example, some studies have reported that the likelihood of
transitioning from dual use of combusted cigarettes and e-cigarettes to
exclusive e-cigarette use is low,\3\ \4\ however, other studies have
reported that some dual users were able to reduce the number of
cigarettes smoked per day by 50 percent or more.\5\ Recent studies of
overall electronic nicotine delivery systems (ENDS) use and cessation
have also showed that adult dual use of e-cigarettes and cigarettes was
associated with a greater likelihood of cigarette cessation compared to
exclusive cigarette use.\6\ However, there are also studies that find
no association between ENDs and increase or decrease in cigarette use
in young adults. Finally, it is also important to note that given the
recent changes in the e-cigarette marketplace, including changes in
device types, nicotine delivery, nicotine content, and flavors, e-
cigarettes as a category are heterogenous.
---------------------------------------------------------------------------
\3\ Stanton CA, Sharma E, Edwards KC, et al. Longitudinal tra
nsitions of exclusive and polytobacco electronic nicotine delivery
systems (ENDS) use among youth, young adults and adults in the USA:
findings from the PATH Study Waves 1-3 (2013-2016). Tob Control.
2020;29(Suppl 3):s147-s154.
\4\ Coleman B, Rostron B, Johnson SE, et al. Transitions in
electronic cigarette use among adults in the Population Assessment of
Tobacco and Health (PATH) Study, Waves 1 and 2 (2013-2015). Tob
Control. 2019;28(1):50-59.
\5\ Pearson JL, Sharma E, Rui N, Halenar MJ, Johnson AL, Cummings
KM, et al. Association of electronic nicotine delivery system use with
cigarette smoking progression or reduction among young adults. JAMA
Network Open. 2020 Nov 2;3(11):e2015893.
\6\ Brouwer AF, Jeon J, Hirschtick JL, Jimenez-Mendoza E, Mistry R,
Bondarenko IV, et al. Transitions between cigarette, ENDS and dual use
in adults in the PATH study (waves 1-4): multistate transition
modelling accounting for complex survey design. Tobacco Control. 2020
Nov 16;16:16.
---------------------------------------------------------------------------
Research is ongoing in this area, and as we continue to learn more
and evaluate ENDS products in the context of premarket tobacco product
application review, we will take additional and appropriate steps to
ensure the protection of public health.
______
Questions Submitted by Senator Jon Tester
Question. There is widespread evidence of violations of the FDA new
tobacco policy with products being sold that do not have a pending
Premarket Tobacco Product Application. How is the FDA planning to ramp
up enforcement of this rule in addition to warning letters, since there
is still evidence of bad actors taking advantage of this situation?
Answer. Issuing warning letters to tobacco product manufacturers
and importers that violate the Federal Food, Drug & Cosmetic Act
(FDCA)'s premarket authorization requirements is an important first
step in the Agency's enforcement activities. As of May 31, 2021, FDA
has issued over 120 warning letters to firms selling or distributing
unauthorized electronic nicotine delivery systems (ENDS) that did not
submit premarket applications by the September 9, 2020 deadline.
Collectively, these companies have listed a combined total of over 1.2
million products with the FDA.
If a manufacturer or importer is in violation of the FDCA's
premarket authorizationrequirements, their product(s) will be
considered ``misbranded'' and/or ``adulterated,'' making it illegal to
sell or distribute the product(s) in interstate commerce and to import
the product(s) into the United States. If the manufacturer or importer
does not adequately address the violationdiscussed in the warning
letter, FDA may initiate regulatory action, including product seizures
and injunctions.
Question. How will you ensure that the FDA's Center for Veterinary
Medicine takes swift, decisive action to ensure antibiotics are used
judiciously in food animals while not punishing those already
practicing antimicrobial stewardship?
Answer. To advance efforts to ensure the judicious use of
antimicrobials, FDA's Center for Veterinary Medicine (CVM) developed
and began implementing a 5-year Plan for Supporting Antimicrobial
Stewardship in Veterinary Settings (5-year Plan) which established
goals for fiscal years 2019-2023. This plan has provided a clear
roadmap for engaging affected stakeholders to implement change. As part
of this plan, CVM has published multiple Guidances for Industry (GFI)
that have outlined strategies for helping to ensure the judicious use
of antimicrobial drugs in animals. Each GFI was developed with broad
stakeholder input and includes specific timelines for implementing the
recommended changes.
To support implementation of the 5-year Plan, CVM has focused on
stakeholder engagement and collaboration when developing and
implementing strategies for ensuring the judicious use of
antimicrobials. Such stakeholder engagement enables the agency to
develop strategies that are expected to be successfully implemented and
result in impactful change to antimicrobial use practices. In addition,
this collaborative approach provides greater opportunity to take into
consideration, and leverage when possible, strategies that may already
be in place by those practicing antimicrobial stewardship.
Question. How many generic drug applications are in the queue
waiting to be reviewed? How are you working to remedy this situation?
Answer. CDER provides periodic updates on key metrics related to
application review and the pre- approval process throughout the
pandemic at: https://www.fda.gov/industry/fda-user-fee-programs/cders-
work-meet-user-fee-goals-during-pandemic. In addition, we provide
information on our generic drug program monthly and quarterly
performance activities on our Enhanced Accountability and Reporting web
page at: https://www.fda.gov/industry/generic-drug-user-fee-
amendments/enhanced-accountability-reporting.
A recently performed analysis by CDER of user fee metrics across
our prescription and generic drug programs showed that FDA has been
able to take on-time actions to evaluate and close out drug
applications more than 90 percent of the time.
Additionally, we're using the funds provided to the Agency by
further streamlining and improving our review processes, including
creating a structured review platform for generic drug products and
developing a knowledge management platform for drug development.
Question. How the Biden Administration going to make sure we are
staying on top of the science as it evolves and ensuring that
genetically engineered foods are safe?
Answer. A key component of FDA's successful oversight of foods
derived from genetically engineered sources is our history of engaging
with developers early in their product development phase, prior to
marketing.
FDA evaluates the safety of foods from genetically engineered
plants and animals. With respect to plants, FDA has evaluated the
safety of food from more than 180 genetically engineered plants through
the Agency's voluntary consultation program on foods from new plant
varieties. These voluntary premarket consultations help the Agency stay
abreast of the most current scientific developments and how those
developments are being applied in products intended for market. With
respect to animals, FDA evaluates the safety of food derived from
genetically engineered animals through its mandatory approval process
of intentional genomic alterations in animals.
FDA has invested in the scientific capability necessary to stay on
top of the evolving science in this area by establishing a new division
staffed by experts in the field, including biologists, geneticists, and
bioinformaticians, along with our human food safety reviewers. FDA
staff monitor scientific and industry literature, and attend scientific
meetings where researcherspresent and discuss their findings, as well
as regularly interact with food safety counterparts in other countries
to discuss new scientific developments and what they mean for food
safety. For instance, FDA routinely participates in the Organisation
for Economic Co-operation andDevelopment's (OECD) Working Group on the
Safety of Novel Foods and Feeds, wheredelegates from OECD member and
non-member countries share developments and experience.This past April,
FDA organized a regulators virtual meeting that included regulatory
agenciesfrom North America, South America, Europe, Asia, Africa and
Australia. This meeting provided the opportunity to learn about
developments in other countries and served as an opportunity for FDA to
show leadership in the area of food produced using genetic engineering.
FDA understands that genetically engineered foods are an important part
of the United States' food supply and agricultural economy and will
continue to take steps to ensure that it is following the evolving
science regarding the use of genetic engineering to produce food.
Question. How is the Biden Administration going to pursue the
connection between the increased consumption of genetically engineered
foods and the increase in diet- related diseases?
Answer. While foods from genetically engineered plants have been
marketed since their introduction in the 1990's, FDA's safety
assessments have not revealed any evidence of a causal relationship
between their consumption and an increase in diet-related diseases. To
the contrary, the best evidence of causality between diet and chronic
disease is linked to excessive sodium, saturated fats, and sugar
consumption. The Agency's food safety evaluations have shown that foods
produced using genetic engineering do not pose unique food safety risks
and that such foods currently on the market are safe. In most cases,
foods from the genetically engineered varieties are not materially
different from foods that have historically been safely consumed. FDA
is not aware of a plausible scientific hypothesis that would connect
foods produced using genetic engineering with an increase in diet-
related diseases.
Question. How will you incorporate genetically engineered foods
safety and education into your New Era of Smarter Food Safety
Blueprint?
Answer. The New Era of Smarter Food Safety blueprint incorporates
genetically engineered foods safety and education within Core Element
3, which aims to ensure the safety of food produced or delivered using
new business models. As part of that goal, FDA will work to facilitate
safe development of new food ingredients and production technologies to
foster product innovation and market access in a safe and timely way.
For example, the Agency expects to continue offering voluntary
premarket consultations to firms that are interested in participating
in the process. Through these consultations, developers can obtain
feedback from FDA about food safety considerations associated with
their new foods and the steps that may be needed to ensure the foods
they produce are safe and lawful.
In addition, FDA will continue to collaborate with USDA and EPA on
efforts to provide science- based education and outreach on
agricultural biotechnology for foods and animal feed. The education
initiative, Feed Your Mind, features a wide range of resources designed
specifically for consumers, healthcare professionals and students.
These materials feature new web content, fact-sheets and videos using
common language, engaging graphics and stories to provide information
about genetically engineered foods, including information about the
history of genetic modifications in agriculture. This initiative is an
on-going effort, with additional materials such as a professional
learning series for dietitians and supplementary science curriculum for
high schools.
______
Questions Submitted by Senator Patrick J. Leahy
Question. Amytrophic Lateral Sclerosis (ALS) is a devastating
disease affecting too many of my constituents. Neurodegenerative
diseases like ALS are incredibly challenging for those living with the
disease and their families. Currently much is unknown about what causes
ALS and there are no prevention methods or treatments available.
Sufficient funding for research is essential for finding an effective
cure against ALS. Transparency in the FDA's process of reviewing and
approving potential therapies for ALS is also of the upmost importance.
In 2019, the FDA finalized guidance to assist in the clinical
development of treatments for ALS. The guidance included strategies to
expedite clinical trials and encouraging the use of patient input and
experience. The guidance was intended to help companies and researchers
develop new therapies, while providing the agency's view of clinical
trial designs and ways to measure effectiveness. How is the FDA helping
companies and researchers to best utilize this guidance?
Answer. The guidance is a result of collaboration of experts across
the Agency and incorporates important input from patients, researchers,
and advocates. The final guidance addresses many of the challenges
presented in ALS clinical trials and is consistent with advice that we
provide to individual sponsors developing products. Both CBER and CDER
provides advice to drug developers throughout the product development
lifecycle through both formal meetings and early-stage, informal
interactions, as well as engaging with the community more broadly. For
example, in January 2021, FDA collaborated with the Duke University
Margolis Center for Health Policy to hold a two-day workshop to discuss
the challenges impeding therapeutic development for ALS and strategies
to overcomes them.
Also in January 2021, FDA issued the draft guidance, ``Human Gene
Therapy for Neurodegenerative Diseases''.\7\ This guidance provides
proposed recommendations to sponsors developing human gene therapy
products for neurodegenerative diseases, including ALS, that are
affecting adult and pediatric patients.
---------------------------------------------------------------------------
\7\ https://www.fda.gov/media/144886/download.
---------------------------------------------------------------------------
The guidances and ongoing engagements with sponsors, academia, and
patients providerecommendations and Agency involvement on innovative
clinical trial designs and other critical considerations to help move
the field forward. However, there is consensus that
furtherunderstanding of the underlying biology for neurodegenerative
diseases is necessary to most efficiently help to advance treatments
for these diseases.
Question. Has it resulted in more treatments being brought to the
FDA for approval?
Answer. There has been increased interest in developing therapies,
including gene therapies, for the treatment of hereditary forms of ALS.
These products to treat hereditary ALS are in development, but have not
yet gathered the data necessary to support marketing applications. In
contrast, there has not been any substantial increase in the number of
products in development or submitted for approval for the treatment of
sporadic (i.e., non-hereditary) ALS. Such advancements will probably
depend on advancing science that can provide a greater understanding of
the pathophysiology of sporadic ALS.
Question. If no, how can Congress better support the FDA in its
mission to provide better patient outcomes for those living with ALS?
Answer. As noted above, there is consensus that further
understanding of the underlying biology of ALS would most efficiently
advance treatments for ALS and other neurodegenerative diseases. FDA
stands ready to work with Congress on efforts in this space.
Question. Expanded access programs, which are regulated by the FDA,
provide access to drugs in development, prior to regulatory approval
for marketing, to eligible people with life- threatening diseases, like
ALS, for which there are limited drug alternatives. How is the FDA
evaluating these patient access programs?
Answer. The vast majority of Expanded Access requests are allowed
to proceed and not put on hold. In 2019, the Government Accountability
Office made no recommendations in its report on FDA's Expanded Access
Program. The Expanded Access Program was also evaluated by an
independent consultant, and a report was published in 2018, that
included recommendations to improve the program. FDA is implementing
the 2018 recommendations, including regular updates to our website,
production of four videos explaining Expanded Access, and regularly
meeting with various stakeholders seeking additional input on the
program.
Question. Is more funding needed to improve the approval pipeline?
Answer. FDA continues to recognize the critical unmet medical need
for new, effective treatments for ALS. We are committed to working with
sponsors of novel therapies and the ALS community to facilitate
development and approval of agents to treat this devastating disease.
There is consensus that further understanding of the underlying
biology for neurodegenerative diseases, which will most efficiently
help to advance treatments for these diseases, would be best supported
by engagement between government agencies such as FDA and NIH, and
other entities such as academic institutions and industry, through a
public-private partnership (PPP). FDA stands ready to work with
Congress on efforts in this space.
Question. How can patient voices be more incorporated into the
process?
Answer. FDA is committed to incorporating the patient voice in
product development, and to facilitating access, when appropriate, to
promising investigational medical products through FDA's Expanded
Access Program for patients who are unable to access investigational
drugs through clinical trials. The Agency continually works to educate
stakeholders about clinical trials and Expanded Access, and to further
refine and streamline our Expanded Access Program. FDA has engaged and
will continue to engage in meetings with the ALS community, including
patient groups and caregivers, through listening sessions, external
engagement, patient-focused drug development meetings, and
collaboration in the pre-competitive space.
Question. I have long supported policies that would allow patients
to access safe andaffordable medications from Canada, as I believe this
is a cost-effective method to provide patients with the resources they
need to manage their healthcare needs. In 2018, Vermont became the
first state in the nation to pass legislation that would allow drug
importation fromCanada should Federal laws change. In 2020, the Trump
Administration even published a final rule to allow for states, tribes,
pharmacists, and wholesalers to submit plans to the FDA to import
medications from Canada. This final rule has faced legal challenges
from pharmaceuticalcompanies, leaving HHS unable to approve any state
submitted plans.
Can you provide a timeline on when the Administration will outline
a pathway for states to import prescription drugs from Canada?
Answer. Access to more affordable drugs can be a matter of life and
death for Americans. In July 2019, the prior Administration announced
the Safe Importation Action Plan that outlined two pathways to lay the
foundation for the safe importation of certain prescription drugs
originally intended for sale in foreign countries. The pathways are set
forth in a final rule that became effective in November 2020 and a
final guidance that was issued in October 2020.
Question. Specifically, when will the FDA begin to review state
submitted plans that have already been submitted to the agency?
Answer. In an Executive Order issued July 9, 2021, the President
has directed FDA to work with States and Indian Tribes that propose to
develop Section 804 Importation Programs in accordance with the statute
and FDA's implementing regulations to reduce the cost of covered
products to the American consumer without imposing additional risk to
public health and safety.
Question. In the past, I have championed legislation to increase
competition between generic and brand name prescription drugs and to
target anticompetitive behaviors of pharmaceutical companies. Generic
alternatives saved the U.S. healthcare system $313 billion in 2019
alone. Despite this, many generic drug makers still report challenges
in bringing these more affordable drugs to market, particularly slow
application turnarounds from the FDA. How can Congress aid in FDA's
effort to bring more generic drugs to market that result in significant
cost savings to the American public?
Answer. FDA is committed to helping increase competition for
prescription drugs and biological products to facilitate the entry of
lower-cost alternatives and improve patient access to affordable
medicine. We're putting resources provided by Congress to good use to
further streamline and improve our review processes, including creating
a structured review platform for generic drug products and developing a
knowledge management platform for drug development. We stand ready to
work with Congress on efforts in this space.
______
Questions Submitted by Senator Brian Schatz
Question. I am very concerned about youth use of e-cigarettes.
According to the most recent survey data (2019), 30 percent of high
school students in Hawaii use e-cigarettes. FDA should broadly use its
regulatory authority to prevent manufacturers from introducing new
tobacco products that are enormously appealing to kids. Will FDA use
the premarket review process to remove from the market all e-cigarettes
that are likely to attract young people, such as flavored e-cigarettes?
Answer. Ensuring new tobacco products undergo a robust premarket
evaluation by FDA is a critical part of our mission to protect the
public health, particularly youth, and to reduce tobacco-related
disease and death. As you are aware, premarket applications for many
new tobacco products currently on the market, including e-cigarettes,
were due to FDA by September 9, 2020. FDA is currently processing,
reviewing, and taking action on these applications.
FDA cannot predetermine to deny marketing authorization of all
flavored e-cigarettes and other flavored tobacco products. Rather, on a
case-by-case basis, FDA will consider whether toauthorize the marketing
of a new tobacco product under the ``appropriate for the protection of
the public health'' statutory standard, and would consider doing so
only where marketing wouldlikely have at least some net benefit to
public health based upon the risks and benefits to the population as a
whole, which includes youth, young adults, and other vulnerable
populations.
Prevention of initiation and assessment of a new product's likely
impact on addiction, especially among youth, is important in
determining whether permitting the marketing of a new tobacco product
would be appropriate for the protection of the public health.
Therefore, issues related to the manufacturing and marketing of
electronic nicotine delivery systems (ENDS) products, including the use
of flavors known to be used by youth, and the manner in which the
product is marketed and sold, are all factors FDA considers as part of
our review of marketing applications for these products.
Question. What evidence would a manufacturer have to provide FDA
for the agency to authorize a flavored e-cigarette?
Answer. Ultimately, in a Premarket Tobacco Application (PMTA), the
burden of showing that the marketing of a product is appropriate for
the protection of the public health (APPH) is on the applicant. As
stated in the answer to the previous question, as required by statute,
the review process under the PMTA pathway makes certain that the
marketing of any new product is APPH, taking into account the risks and
benefits to the population as a whole. Among other criteria, FDA is
considering how the product may impact youth use of nicotine and
tobacco, and any potential for the product to completely move adult
smokers away from use of combustible cigarettes.
With respect to PMTA submissions for flavored electronic nicotine
delivery systems (ENDS) products, FDA assesses, among other things,
potential health risks to determine if permitting the marketing of a
new tobacco product would meet the APPH statutory standard for
marketing. As explained in FDA's June 2019 guidance regarding PMTAs for
ENDS products, because of the potential impact of flavors on product
toxicity and appeal to youth and young adults, scientific reviews of
flavors (e.g., toxicological analyses of flavor additives, chemistry
analyses, clinical studies, literature reviews), should be included in
a PMTA for a flavored e-liquid or ENDS product.
Under section 910(b)(1)(A) of the Federal Food, Drug, and Cosmetic
Act, FDA considers the health risks of a new tobacco product and
whether the new tobacco product presents less risk than other tobacco
products. FDA considers the appeal and use of ENDS product flavors
important in ascertaining the health risks of these products. In this
regard, FDA recommends that PMTA applicants describe research on flavor
development including, but not limited to, market segmentation analysis
or sensory testing. Applicants should describe consumerperceptions of
product appeal and use intentions among current ENDS users, other
tobacco product users and nonusers, based on labeling and actual use of
flavors, as well as productdesign. Information on consumer perception
is especially important given the attractiveness of flavors to youth
and young adults. Additionally, to provide a better understanding of
the appeal of flavors to adults, FDA recommends that PMTA applicants
provide information examiningadult appeal of such flavors in their
decisions to initiate use, cease use of more harmful products, or
engage in dual use.
Question. Cigarette smoking and other consumption of tobacco
continues to be a leading contributing cause of cancer and heart
disease in America. In the previous administration, the FDA gave
priority to using its existing statutory authority to issue regulations
that would reduce the nicotine content in tobacco products to non-
additive levels, but unfortunately never issued final regulations. Does
FDA under President Biden plan to make reduction of nicotine in tobacco
products to non-addictive levels a priority?
Answer. Each year, 480,000 people die prematurely from a smoking-
attributable disease, making tobacco use the leading cause of
preventable disease and death in the United States. The vast majority
of the adverse health effects of tobacco use are ultimately the result
of addiction to the nicotine in combustible tobacco products, leading
to repeated exposure to toxicants from those products.
As part of FDA's ongoing public dialogue about nicotine, the Agency
issued an Advance Notice of Proposed Rulemaking (ANPRM) to obtain
information for consideration in developing a potential tobacco product
standard to lower nicotine in cigarettes to minimally addictive or
nonaddictive levels. The ANPRM sought comments, data, research results,
and other new information on topics including, but not limited to, the
maximum nicotine level that would be appropriate for the protection of
the public health, the best approach for implementation of the product
standard, and any unintended consequences that might occur as a result
of the product standard. FDA continues to closely examine this issue.
FDA is committed to implementing a science-based, comprehensive
approach to tobacco and nicotine regulation. As part of this effort, on
April 29, 2021, FDA announced that it is committing to advancing two
tobacco product standards to significantly reduce disease and death
from using combusted tobacco products. The Agency is working toward
issuing proposed product standards by April 2022 to ban menthol as a
characterizing flavor in cigarettes and ban all characterizing flavors
(including menthol) in cigars. This decision is based on clear science
and evidence establishing the addictiveness and harm of these products
and builds on important, previous actions that banned other flavored
cigarettes in 2009. FDA will continue to gather evidence and data
regarding the public health impact of all categories of tobacco
products and the potential need for additional product standards.
Question. A recent letter to the editor of the New England Journal
of Medicine highlights the alarming rapid increase in youth usage of
flavored so-called ``disposable'' e-cigarettes. While the authors
include several concerned scientists at the FDA and the CDC, it does
not seem that the FDA is doing enough to keep pace with rapid market
changes that occurred after the Trump Administration in early 2020
carved these products out of the ban on flavored e-cigarettes. While
FDA has acted on some disposable products, the manufacturer of the most
popular disposable e- cigarette--``Puff Bar''--changed its product
formulation to use synthetically-derived nicotine to get around FDA's
tobacco authorities. What is the FDA's plan to ensure that e-cigarette
manufacturers are not able to circumvent FDA regulations and continue
to market and sell youth-appealing flavors?
Answer. While the 2020 National Youth Tobacco Survey (NYTS) data
showed that 1.8 million fewer U.S. youth were currently using e-
cigarettes compared to 2019, FDA remains concerned that the data also
showed an alarming increase in the number of youth who used disposable
e-cigarettes. FDA considers new data to continue to inform FDA's
enforcement and other actions. As a result of the disturbing increase
in use of flavored disposable products reported in the 2020 NYTS
survey, FDA made those products an enforcement priority. As part of the
Youth Tobacco Prevention Plan and consistent with FDA's policy to
prioritize enforcement against e-cigarettes and other deemed products
on the market, the Agency has taken compliance and enforcement actions
to stop youth use of, and access to, ENDS products. For example, FDA
issued a warning letter to XL Vape LLC (doing business as Stig Inc.), a
popular disposable e-cigarette brand among youth, for the unauthorized
sale of their ENDS products. FDA also issued warning letters to
companies, including Puff Bar, for the unauthorized sale of flavored
disposable e-cigarettes and e-liquids, as well as for the unauthorized
sale of ENDS products that imitate packaging for products such as
Cinnamon Toast Crunch cereal, Twinkies, and Cherry Coke.
The possible use of synthetic nicotine by Puff Bar and,
increasingly by others, is a deeplytroubling trend by companies who
appear to be trying to take advantage of what they perceive to be a
loophole in the law to evade FDA jurisdiction. It is clear marketing of
these products israpidly increasing and that questions about FDA's
authority under current law need to be resolved.
We are testing ENDS claiming to contain only synthetic nicotine. If
we find that such a product actually contains any tobacco-derived
nicotine, we have jurisdiction under our tobaccoauthorities and can
pursue enforcement if the product is in violation of those authorities.
If we find that a disposable ENDS product contains only synthetic
nicotine, enforcement becomes more complicated because such a product
likely does not meet the current statutory language in the Federal
Food, Drug, and Cosmetic Act (FD&C Act) defining tobacco products as
products ``made or derived from tobacco.''
We are exploring how to best address the growing number of products
where the jurisdiction is under review due to the source of nicotine.
The Agency is reviewing all of our options to determine whether these
products can be regulated under our existing authorities.
We take this issue very seriously, and we are working to find the
appropriate solution. We are exploring all potential options and are
discussing this topic internally to pursue a sustainable, effective
solution.
______
Questions Submitted by Senator John Hoeven
Question. The FDA Center for Veterinary Medicine was investigating
dilated cardiomyopathy (DCM) and a potential connection to certain pet
foods. The FDA released statements about this investigation in 2018 and
2019 that impacted the pet food industry and its supply chain,
including many farmers in my state, although it wasn't clear that a
definitive connection between diet and DCM had been established at the
time of those statements.
Is the FDA continuing this investigation, and if so, what is its
current status? Does the FDA plan any further statements on the issue
or plan to release any relevant details pertaining to the investigation
at this time?
Answer. In 2018, FDA's Center for Veterinary Medicine started
exploring a spike in the number of veterinary medical reports of a
heart condition in dogs known as dilated cardiomyopathy (DCM). Between
July 2018 and November 2020, FDA issued four updates regarding the
investigation into the potential link between DCM and certain limited-
ingredient diets. The June 2019 update included a spreadsheet of all
DCM case reports submitted to FDA through the end of April 2019. FDA
issued these updates to shed light on this emerging animal health
signal to the veterinarians treating dogs with DCM and the scientific
community. Following these updates, FDA received many additional
reports of DCM associated with limited-ingredient diets with a high
proportion of pulses. FDA has not taken regulatory action against any
firm or product and has not determined that any specific pet food
products are unsafe or definitively linked to non-hereditary DCM.
The Agency sees this issue as an ongoing, collaborative scientific
exploration. The scientific community continues to assess the available
information and fill data gaps to determine what factors may contribute
to the development of this non-hereditary DCM.
FDA continues to encourage pet food manufacturers, academic
researchers, and the veterinary nutrition and cardiology community to
share information to better understand the apparent link between
limited-ingredient diets and non-hereditary DCM and to identify any
potential causal pathways. At this time, FDA does not plan to post any
additional updates on a routine basis.
Question. Page 73 of the Budget Justification notes that ``the
Foods Program statutory responsibility for the following premarket
review activities that help to foster competition and innovation and
fall within the FDA goal of improving and safeguarding access: Review
and approval of all new food contact substances, food contact
materials, packaging, antimicrobials, and other indirect food
additives.'' Is the FDA keeping track of new State-based food packaging
content laws and communicating about the important role FDA plays in
food contact safety?
Answer. FDA is aware of numerous activities at the State level
pertaining to the recycled content of packaging products and maintains
communication with State agencies. For example, FDA has responded to
multiple requests from State environmental/public safety departments
pertaining to the dietary exposure aspects to be considered when
formulating or reviewing such initiatives. In addition, FDA has
published guidance which details the aspects considered by the Agency
when reviewing submissions pertaining to the safety of use of recycled
material in food packaging. This guidance can be found on the Agency's
website at https://www.fda.gov/regulatory- information/search-fda-
guidance-documents/guidance-industry-use-recycled-plastics-food-
packaging-chemistry-considerations.
Question. Considering consumer health and safety, what risk does
FDA consider as food packaging is manufactured with post-consumer
recycled content? How is FDA addressing that risk?
Answer. The Federal Food, Drug, and Cosmetic Act requires premarket
review and authorization of all food additives, including substances
used in food packaging. To fulfill this mandate, FDA operates the food
contact notification program, through which industry provides
information to establish safe conditions of use for the food contact
substance. If post-consumer recycled material is used as feedstock in
the manufacture of food packaging, there is the potential for the
inclusion of unauthorized food contact substances and for incidental
contamination by the consumer or during collection. The majority of
recycling processes can only remove incidental contamination from
incoming material (i.e., dirt, contamination from secondary use of the
original product by the consumer) and cannot remove intentionally added
substances (i.e., substances added to plastic during manufacture for an
original, non-food contact use).
To address the above risks, FDA administers a voluntary review
program to assesses the ability of a specific recycling process to
achieve a purity suitable for use in food packaging. Thisreview
considers any controls put in place to ensure that the incoming
feedstock does not include material from non-food contact uses, and the
ability of the process to clean the incomingfeedstock in a manner that
ensures that incidental contamination is removed. If, upon review, the
data is sufficient to demonstrate that the recycled material is of a
purity suitable for the intended use, FDA will issue a no-objection
letter for the specific recycling process. FDA has issued more than 240
letters of no objection for industrial recycling processes expected to
produce recycled plastics of suitable purity for food contact
applications. A list of submissions for which FDA has issued a
favorable opinion on the suitability of a specific process for
producing post- consumer recycled plastics to be used in manufacturing
food contact articles is available at https://
www.cfsanappsexternal.fda.gov/scripts/fdcc/?set=RecycledPlastics.
Question. Do you believe that FDA can keep pace with rapidly
changing packaging content mandates? How long does a review by FDA
take?
Answer. Recently, FDA has noted a large increase in voluntary
submissions to the Agency requesting review of recycling processes to
produce material for use in food contact applications. FDA expects this
trend will continue due to increasing demands for recycled materials.
Due to the limited supply of recycled feedstock from approved food
contact uses, market incentives are driving toward inclusion of
recycled material from non-food contact uses. As a result, the
complexity of the recycling processes submitted to the Agency has
increased as manufacturers attempt to use advanced recycling
technologies to produce recycled material of a purity suitable for use
in food packaging from non- food contact sources. Many of these
advanced recycling technologies are novel and have not been verified or
reviewed by FDA.
In general, the average length of time for FDA to review a
submission of recycling processes is two to 3 months, and a complex
submission may take 4 months or longer to complete.
However, the Agency is concerned that the increase in both the
number of submissions to the Agency requesting review of recycling
processes and the complexity of those submissions are expected to
increase FDA's review time for these submissions. This could decrease
industry'sreliance on this voluntary recycling program as a
verification that recycled material is safe before using such material
in food packaging.
Question. Page 324 of the Budget Justification notes that the
``Intergovernmental Affairs (IGA) staff works to facilitate the
agency's communication and collaboration with state, local, and
territorial officials and regulatory partners. In addition, per the
agency's Tribal Consultation Policy, the IGA staff has been designated
as the agency's primary liaison with tribal governments. In addition to
proactively providing timely information on the important activities of
the agency, the IGA staff serves as a primary entry point for these
important stakeholders on issues of significant concern to states,
localities, territories and tribes, and works to ensure that questions
from these stakeholders related the agency's policies and programs are
addressed in as timely a manner as possible. In fiscal year 2021,
significant engagement by the IGA team with state, local, territorial
and tribal stakeholders related to issues such as the regulation of
cannabis and cannabis-derived products, tobacco products, device
sterilization, opioids and other controlled substances, food safety,
and compounded drugs. In addition, IGA has been an active participant
in the agency's response to the COVID-19 pandemic by supplying
information proactively to state, local, territorial and tribal
officials, as well as responding to COVID-19 inquiries from these
stakeholders.'' Do you expect that the findings from IGA's work in the
states on cannabis policy will help speed up development on a national
regulatory framework for CBD products?
Answer. As it now stands, 40 states and territories, as well as the
District of Columbia, have medical cannabis programs, and 20 states and
territories, as well as the District of Columbia, permit adult-use of
cannabis. It is estimated that nearly 1 in 3 Americans now lives in a
state where adult-use is legal under state law. However, each state
legislates, regulates, and operates its cannabis programs differently.
FDA has fielded inquiries related to cannabis regulation from
nearly every state and territory, and a number of tribal governments.
In addition, the Agency engages with these important stakeholders in
many ways including:
--speaking with several states' cannabis regulatory agencies and
departments of health to learn more about their regulatory
cannabis programs and adverse event reporting systems;
--encouraging states to submit adverse event reports to FDA through
the MedWatch Program;
--holding discussions and panels with state cannabis regulators and
state associations;
--encouraging stakeholder feedback to our draft guidances regarding
drug products containing cannabis or cannabis-derived
compounds;
--talking with states and encouraging them to share information so
FDA can learn more about their approaches and requirements, as
well as any challenges they may be facing, related to quality
considerations for cannabis and cannabis-derived compounds
within their systems; and
--interacting with states' Attorneys General.
Each of these engagements is important, and FDA continues to
further the dialogue withstakeholders who share the Agency's mission to
promote and protect the public health. These engagements will help to
inform any efforts FDA may make to regulate cannabis products, and also
to provide FDA's regulatory partners in states, localities,
territories, and tribes with an important mechanism for collaboration
in this space.
Question. Considering the growing patchwork of State regulations on
hemp-derived products, if Congress considers legislation related to CBD
in supplements and food, do you believe that the inclusion of an
express preemption provision is an important consideration?
Answer. FDA stands ready to engage in continued dialogue with
Congressional offices and provide technical assistance on this topic,
but is unable to comment without specific language for legislative
proposals.
Question. Page 212 of the Budget Justification notes that the
``National Center for Toxicological Research (NCTR) in collaboration
with FDA's Office of the Chief Scientist, researchers in NCTR's
Division of Neurotoxicology continue to examine the effects of CBD
exposure during development. Effects from this early exposure will be
evaluated throughout adulthood and include neurocognitive effects. This
will create valuable information that currently does not exist or is
unavailable publicly. NCTR expects the data from this study to aid FDA
in regulatory decisionmaking and to help the public make healthier
decisions regarding the use of CBD-containing products. This research
is projected to be completed in fiscal year 2023.'' What resources are
necessary to ensure that this work can be completed by 2023?
Answer. Utilizing funding provided to FDA for CBD in fiscal year
2020 and fiscal year 2021, NCTR began a collaborative research project
to bridge existing data gaps and provide critical information for FDA
decisionmaking. With these resources, FDA has been able to make
significant progress on this project, and NCTR will complete the lab
work on this study in mid-fiscal year 2022. However, NCTR still needs
to finish the analysis to be used for decisionmaking. FDA expects to
complete this analysis and issue publication by late fiscal year 2023.
Question. What data gaps have been identified by FDA as necessary
to fill in order to establish a regulatory framework for CBD, and how
is FDA working to address such gaps?
Answer. Before enactment of the Agriculture Improvement Act of
2018, which removed hemp from the definition of marijuana in the
Controlled Substances Act, it was very difficult for anyone to conduct
research into CBD. It is known that There are public health risks
associated with products containing CBD, as well as unanswered
questions relating to the safety of CBD in products other than the one
FDA-approved CBD-containing drug, Epidiolex.
FDA continues its work to obtain data to better understand the
safety profile of CBD and its effects on human health and will continue
to update Congress and the public on progress andfindings. This
includes a large-scale market sampling study covering thousands of
products to better understand how CBD is marketed and consumed, as well
as the prevalence ofcontaminants in products and whether product labels
are accurate. Other research occurring within FDA aims to better
understand the potential toxicity mechanisms and concerns for safety,
including examining the effects of long-term CBD exposure, during in-
utero development, potential effects on the male reproductive systems,
and concerns for drug-drug interactions. In addition, FDA has a
partnership with the University of Mississippi to better understand
more about CBD that has been added to cosmetics. FDA is also aware that
other efforts into research have been underway and encourage
stakeholders to provide the Agency with their data.
Question. Will additional research be necessary for other hemp-
derivatives?
Answer. Prior to enactment of the Agriculture Improvement Act of
2018, which removed hemp from the definition of marijuana in the
Controlled Substances Act, but preserved FDA authorities over hemp
products, it was very difficult to conduct research because hemp was a
schedule I substance. As a result, there has been very little research
conducted on the over 80 known cannabinoids contained within hemp and,
at the moment, even less is known about most of these constituents than
is known about CBD (e.g., toxicity (neurological, liver, reproductive),
drug interactions, cumulative exposure, and chronic use).
Given more recent significant public interest in a range of
cannabis-derived products and constituents beyond just CBD, this year
FDA broadened the scope of the cross-Agency CBD Policy Working Group
and reestablished it as the Cannabis Product Committee.
Question. Is FDA concerned with the proliferation of CBD products
on the market prior to this work being completed, and how is FDA
addressing CBD products already on the market?
Answer. FDA recognizes that there is significant public interest in
CBD. It is not a risk-free constituent and there are public health
risks associated with products containing CBD, and unanswered questions
relating to the safety of CBD in products other than the one FDA-
approved CBD-containing drug, Epidiolex. In addition, there remain
questions regarding how CBD is marketed and consumed, as well as the
prevalence of contaminants in products and whether product labels are
accurate.
FDA has been addressing CBD products which have raised particularly
significant concerns. In 2019, the Agency issued 22 warning letters to
firms selling violative products and has issued an additional 25 since
the beginning of 2020. In addition, several firms voluntarily recalled
their CBD-containing products as a result of heavy metal contamination.
Over the past year, much of FDA's focus on compliance has included
unapproved products claiming to prevent or cure COVID-19 and other
serious diseases in humans or animals, products in higher risk dosage
forms, such as injectable, ophthalmic, and inhalation products, and
products marketed as conventional foods, especially those marketed for
use by children and other vulnerable populations. Additionally, FDA has
tested the chemical content of cannabinoidcompounds in some of these
products, and many were found to not contain the levels of CBD claimed.
In addition, FDA is currently reviewing risk-based enforcement
priorities in light of thechanging landscape for CBD products. Also,
FDA continues to pursue testing of approximately 2,000 products as part
of the Congressionally mandated marketplace sampling study, which aims
to compare analytical results to the product label and help inform how
products are generally being marketed.
Question. The 2020 National Youth Tobacco Survey found an estimated
1.73 million fewer current youth tobacco product users than in 2019.
Further, the survey found 1.8 million fewer youth using e-cigarettes
compared to 2019. While this is meaningful progress, more can and
should be done to continue this trend. What type of evidence-based
interventions is the agency considering to restrict access at retail?
Would this include new technologies thatwould improve age verification
compliance with Tobacco 21? Does the agency provide any assistance to
small ``mom & pop'' retail stores with compliance?
Answer. As part of FDA's overall efforts to address the sales and
distribution of electronic nicotine delivery systems (ENDS), we
consistently investigate how youth gain access to tobacco products,
including youth access to tobacco products through social sources,
brick and mortar retailers, and online establishments. We proactively
seek information regarding new technology and access controls. For
example, while the Agency cannot endorse a specific vendor, we may hold
listening sessions to obtain knowledge about a specific ID scanning
technology. FDA also reviews a manufacturer's use of age verification
technology for new products that go through the premarket tobacco
application (PMTA) pathway to market. A PMTA authorization will include
post-market restrictions to help ensure kids do not have access to the
product; for example our recent IQOS market authorization required
youth access controls including the use of age-gating for their
websites where IQOS products are advertised and can be purchased.
Additionally, FDA has made resources available to retailers to help
reduce underage sales. For example, FDA has developed webinars, such as
``FDA Tobacco Compliance Webinars Tips for Retailers: Prevention Sales
to Minors'' and Q&A documents available on our public website that
address age verification for both brick and mortar and online
retailers. We offer free resources to assist retailers in calculating
the age of customers, such as the digital age verification calendar
that is available as part of the ``This is Our Watch'' voluntary
retailer education program and the FDA Age Calculator App that can be
downloaded to mobile devices. As new information becomes available, FDA
will continue to examine this important issue and will continue to
develop educational materials for retailers and interested
stakeholders.
Question. In light of the agency's fiscal year 2022 budget request
and its proposal to increase the tobacco user fee, how is the agency
currently utilizing its funding to ensure efficient review of pending
product applications and address illegally marketed products, including
flavored disposables?
Answer. FDA has used its funding to make investments in hiring
additional staff, enhance IT systems, and develop process improvements
to ensure efficient processing and review of premarket applications.
Prior to, and after, the September 9, 2020 application deadline, FDA
developed and is implementing processes that maximize the number of
products reviewed while ensuring the protection of public health.
We have greatly increased the number of staff that we have
conducting premarket reviews. FDA's Center for Tobacco Product's
(CTP's) staff in the Office of Science has increased more than ten-fold
since 2011, from around 40 to over 500 full-time employees. The
majority of these staff spend most of their time on product review.
The Center is utilizing an approach to prioritize and work through
acceptance, filing, and scientific review of complete applications as
quickly as possible while ensuring that decisions are based on science
and grounded in the considerations Congress laid out in the
FamilySmoking Prevention and Tobacco Control Act. For example, FDA
developed a process todetermine the review order of applications, using
a combination of randomization, as well as dedicating a portion of our
reviewing resources to the products that account for the largestmarket
share. Another efficiency put in place is the option for applicants to
group or bundle their products that are similar or related, such as of
the same category and subcategory (e.g., ENDS e-liquids or filtered
cigars), into a single submission. FDA provided a proposed worksheet to
use to create bundled/grouped information with directions for
applicants' ease of use. Building these and other efficiencies into the
submission and review process help industry with application submission
as well as FDA in our review.
FDA is also using its funding to take compliance and enforcement
actions against products that are illegally marketed, including
disposable products. In January 2021, FDA issued the first set of
warning letters to firms that had not submitted premarket applications
to FDA by September 9, 2020 and are continuing to market unauthorized
electronic nicotine delivery systems (ENDS) after that deadline. As of
May 31, 2021, FDA had issued more than 120 warning letters to firms
selling or distributing unauthorized ENDS and that did not submit
premarket applications by the September 9, 2020 deadline. Collectively
these companies have listed a combined total of over 1.2 million
products with FDA.
In order to ensure efficient review of pending product applications
and address illegallymarketed products, including flavored disposables,
FDA has either reallocated or reprioritized currently available funds
to regulate ENDS. FDA currently does not have the authority to collect
user fees for e-cigarettes and other ENDS, and certain other deemed
products. As part of the fiscal year 2022 budget, FDA requests an
additional $100 million and requests authority to include manufacturers
and importers of all deemed products among the tobacco product classes
for which FDA assesses tobacco user fees. To ensure that resources keep
up with new tobaccoproducts, the proposal would also index future
collections to inflation. Without the additional$100 million as
requested in the fiscal year 2022 budget, CTP will have to continually
shift funding from current objectives to cover these new classes of
products.
Question. The media has covered a number of stories about synthetic
nicotine products and uncertainty in regulatory status of these
products, as well as whether Tobacco 21 applies to these products.
Moreover, it is not clear whether FDA is currently regulating these
products to review ingredients, manufacturing processes, flavors and
marketing. Is FDA currently regulating synthetic nicotine products? If
not, does the agency plan to assert jurisdiction, and if so, when?
Should FDA assert jurisdiction, will the agency require removal of
these products from the market until they have been authorized?
Answer. We share your concerns regarding electronic nicotine
delivery systems (ENDS) claiming to contain only synthetic nicotine
(not nicotine sourced from tobacco). We are testing ENDS claiming to
contain only synthetic nicotine. If we find that such a product
actually contains any tobacco-derived nicotine, we have jurisdiction
under our tobacco authorities and can pursue enforcement if the product
is in violation of those authorities. If we find that a disposable ENDS
product contains only synthetic nicotine, enforcement becomes more
complicated because such a product likely does not meet the current
statutory language in the Federal Food, Drug, and Cosmetic Act (FD&C
Act) defining tobacco products as products ``made or derived from
tobacco.'' It is clear marketing of these products is rapidly
increasing and that questions about FDA's authority under current law
need to be resolved.
We are exploring how to best address the growing number of products
where the jurisdiction is under review due to the source of nicotine.
The Agency is reviewing all of our options to determine whether these
products can be regulated under our existing authorities.
We take this issue very seriously, and we are working to find the
appropriate solution. We are exploring all potential options and are
discussing this topic internally to pursue a sustainable, effective
solution.
Question. In its recently released a roadmap for improving
inspectional oversight, FDA highlighted the challenges brought by the
pandemic and the ensuing backlog of inspections for food and medical
product facilities. Page 20 of the Budget Justification requests an
increase of $18.8 million for ORA to address inspections delayed by the
pandemic and the anticipated growth in the medical product industry.
Can you describe how FDA will use these funds, and discuss whether
other approaches beyond increased funding--such as technology-enabled
remote inspections (not remote interactive evaluations) or expanded use
of mutualrecognition agreements with trusted and capable health
authorities--should also be leveraged during and outside of a Public
Health Emergency to ensure efficient use of limited resources while
still maintaining the overall integrity of the inspection process?
Answer. The budget requests $18.8 million for ORA to increase
inspections and the number of unannounced inspections of regulated
facilities, including those manufacturing essential medicines, medical
countermeasures, and critical inputs. The additional resources will
help address the FDA facility inspections that were postponed due to
COVID-19 and allow ORA to add 65 FTEs to our inspections program. In
addition, the request will enable improvements to the systems
supporting the data information exchange elements with our state
partners and of our International and Domestic Mutual Reliance
Recognition Agreements (MRA), and add capabilities to systems that
support data exchanges with our state partners. These enhancements will
increase the efficiency of Agency operations.
Outside of additional funding, FDA has identified and leveraged new
approaches to our operations. FDA has tested the use of wearable
technology as part of mission-criticalinvestigations during the
pandemic. This one-time limited trial provided significant insights
into the potential that exists with this type of technology,
particularly in how it can help onsite investigators remotely tap the
expertise of subject matter experts. The Agency is furtherevaluating
how best to leverage this technology moving forward.
FDA is also collaborating with international partners who have
leveraged remote interactive tools like livestream technologies to gain
insights into the experiences they have and lessonslearned. We continue
to develop best practices through our work with international groups
such as the Pharmaceutical Inspection Convention Scheme.
FDA also expanded the scope of information gathered from our
existing MRA partner inspectorates to address pandemic travel
restrictions. Now, FDA's pharmaceutical qualityoversight program
acquires and evaluates MRA-partner, third-country inspection
information, which has allowed FDA to assess CGMP conformance in lieu
of an FDA inspection in certain cases.
FDA supports the continued evaluation and exploration of a variety
of technology advancements and expanded reliance on oversight
activities conducted by trusted authorities, which may be leveraged to
aid FDA inspectional activities and the Agency's oversight of regulated
facilities and operations.
Question. Page 222 of the Budget Justification notes a $7.5 million
increase for the National Center for Toxicological Research (NCTR) ``to
address important questions of validation and regulatory trust building
for the new alternative paradigms, which are key to enable the
implementation of the strategies articulated in the FDA Predictive
Toxicology Roadmap. Working in close collaboration with the product
centers on study selection and design, NCTR will conduct studies aimed
at appraising side-by-side the value of guideline and alternative
testing paradigms.'' Can you explain how this funding will help inform
updated non-clinical regulatory requirements that encourage the use of
non-animal methodologies in drug development?
Answer. The FDA has long relied on guideline animal-based assays to
guide and support its regulatory decisions because medical product
sponsors have lacked scientifically validated alternatives. However, as
articulated in its Predictive Toxicology Roadmap, the FDA envisions a
future regulatory framework more reliant on alternative testing
paradigms (e.g. in vitro and in silico models).
To ensure the Agency relies on the best data to inform its pre-
clinical regulatory decisions, this transition needs to be predicated
by a process of trust-building in and maturity of the newparadigms.
While there is increasing data in the literature reporting the outcome
of toxicology studies based on alternative testing methodologies, very
rarely do these studies directly compare the value and challenges of
new methodologies with the current animal-based testingmethodologies
that have been scientifically validated.
With this funding, NCTR would implement a new research program in
collaboration with other FDA product centers to enable a side-by-side
comparison of current guideline and new testing approaches. Drug
development is a prime example of the value of this program. While the
industry has moved towards the use of novel non-animal-based testing to
screen potential drug candidates as part of their business model,
technology has generally not been developed in a way that allows these
new testing methodologies to be utilized in the context of generating
pre- clinical data that is then used to support the safety of new drugs
submitted to the FDA. It isexpected that this new research program
would support efforts to adopt new testing processes that are less
reliant on animal experimentation to support the pre-clinical safety
assessment of the products FDA regulates.
Question. We have seen the success of regulatory innovation on the
part of FDA, not only in the swift development of vaccines and
therapeutics to address the COVID-19 crisis, but also with two approved
gene therapies for rare disease, including for Type 1 SMA, which robs
the lives of babies when left unchecked. And the field of gene therapy,
a novel treatment approach that has the potential to transform the
lives of people with rare diseases through a single administration with
a lasting benefit, is burgeoning--your staff have noted the 1,000 plus
gene therapy applications on file. Many of these gene therapies are
being developed to treat diseases that are serious or fatal, with no
other treatment options. It seems there is a tremendous opportunity to
leverage the successes of developing and delivering COVID-19
countermeasures to addressing these unmet needs of people with rare
disease who are desperately waiting for treatments, including gene
therapies. What steps can FDA take to apply best practices from the
COVID- 19 response so that we can act with the same urgency to bring
these novel treatments to people with rare disease?
Answer. CBER is using every tool available to advance the
development of promising biological products while facilitating applied
scientific research to evaluate their safety, effectiveness and
manufacturing. For example, FDA meets with prospective innovators and
developers of advanced manufacturing technologies and innovative
investigational products at early stages to provide informal
consultation. Early interaction with sponsors was critical to the rapid
development and authorization of COVID-19 vaccines. Mechanisms for
these interactions beyond the COVID-19 context include the CBER Initial
Targeted Engagement for Regulatory Advice on CBER products (INTERACT)
program and the CBER Advanced Technologies Team (CATT) meeting program.
Other best practices from the COVID-19 response include how to
streamline and be more efficient in guidance development. That is very
important for gene therapy and cell therapy, because guidance documents
for such a rapidly evolving field tend to only be good for three, four,
or 5 years. Therefore, being able to either revise the guidances or
draft new guidances more efficiently is key as new science will result
in the Agency updating its regulatory and scientific recommendations.
FDA also uses existing programs such as the Regenerative Medicine
Advanced Therapy (RMAT) Designation, Breakthrough Therapy Designation,
and Accelerated Approval to expedite the development of innovative
biological products, including gene therapies and other products
intended to treat rare diseases.
Question. FDA is recognized as the gold standard and fastest
regulatory agency in the world, and Congress has charged FDA to keep
pace with rapidly advancing science and be an innovation facilitator,
most recently through the 21st Century Cures Act. FDA has led the world
by approving the first two gene therapies. However, a pattern of recent
decisions by FDA has begun to halt or delay development of gene
therapies. At the same time, we are seeing progress overseas in
advancing the field through regulatory modernization and collaboration.
One consequence of delays is the exodus of clinical trials to other
countries, which further delays access to potential cures for U.S.
patients. Not to mention the loss of innovation rooted in theU.S. and
the associated manufacturing investments that we have all agreed must
be a priorityafter this pandemic experience. To fulfill its role as a
gatekeeper of scientific progress, what steps is FDA taking to ensure
development and trials in the cutting edge field of gene therapy are
allowed to proceed, providing opportunities for American patients,
physicians, and innovators and making gene therapy a reality for the
many patients with unmet medical needs?
Answer. Cellular and gene therapy-related research and development
in the U.S. continue to grow at a fast rate, with a number of products
advancing in clinical development. In addition to regulatory oversight
of clinical studies, CBER provides proactive scientific and regulatory
advice to medical researchers and manufacturers.
Scientific development in this area is fast-paced, complex, and
poses many unique questions during a product review. One of the most
important steps the FDA can take to support safe innovation in this
field is to create policies that provide product developers with
meaningful guidance to answer critical questions as they research and
design their gene therapy products.
CBER issued six final guidances in fiscal year 2020 to help support
development of novel gene therapies. The guidances provide
recommendations on manufacturing issues and on gene therapy products
for specific disease areas.
In addition, CBER continues to work to support advanced
manufacturing of gene therapy products. This includes intramural
regulatory science projects undertaken by our cadre ofscientific
experts, extramural awards that can catalyze innovation, and continuing
dialogue with sponsors, manufacturers, and academics in the space.
CBER also uses existing FDA programs, when appropriate, to expedite
the development of innovative biological products including gene
therapies. These include the Regenerative Medicine Advanced Therapy
(RMAT) Designation, Breakthrough Therapy Designation, and Accelerated
Approval.
Question. The field of genetic and cellular therapies holds great
promise to address and potentially cure genetic and other serious
diseases, and is moving at an incredible pace. Over the last year,
several drug developers with advanced programs have encountered issues
with the FDA related to potency assays, resulting in delayed product
development and delay in innovative new products reaching patients with
life-threatening conditions. Does the President's budget provide
adequate resources for the FDA to address to address these challenges
and help find solutions to ensure patients are able to realize the
benefit of these innovative treatments?
Answer. The fiscal year 2022 Budget allows the Biologics Program to
advance public health through innovative regulation that promotes the
safety, purity, potency, effectiveness, and timely delivery of
biological products including cell, tissues, and gene therapies to the
American public.
Question. Efforts to ensure that adulterated, counterfeit, and
unapproved products are not being distributed and marketed to
physicians and patients play a key role in fulfilling the FDA's mission
of safety and efficacy. I understand that there are entities that are
marketing unapproved products in the U.S. for the treatment of
keratoconus, and that physicians are using these products under the
guise of clinical trials with parameters that, in terms of size,
duration, and design may run counter to the FDA's own guidance and
regulations for evaluating a product for safety and efficacy. Can you
explain the how the agency discovers and takes action against companies
illegally marketing unapproved products in the U.S., and identify any
areas where the agency feels its authorities are inadequate?
Answer. FDA takes reports of problems with medical devices very
seriously and follows up on reports to protect patients and assure they
can continue to depend on medical devices to improve and extend their
lives. The Agency becomes aware of the illegal marketing of unapproved
products within the U.S. through a variety of sources, including but
not limited to, market and Internet surveillance, the Office of
Regulatory Affairs (ORA's) Consumer Complaints and inspectional
findings, import surveillance, and medical device reports (MDR), with a
majority received through allegations of regulatory and research
misconduct. An allegation of regulatory misconduct is a claim that a
medical device manufacturer or individuals marketing medical devices
may be doing so in a manner that violates the law. An allegation of
research misconduct (ARM) is any written, electronic, or oral
communication that alleges or claims misconduct in a clinical
investigation.
FDA performs an investigation of these products to ensure they are
under FDA's jurisdiction, assesses whether there are violations, and
then uses a risk-based approach to prioritize regulatory and
enforcement actions against those responsible for any violations.
Current authorities enable FDA to take action against companies
manufacturing, distributing, and selling illegal unapproved products,
but pose certain procedural challenges. For example, authorities
requiring certain electronic allegation submission, with designated
data fields, such as the device identifier portion of Unique Device
Identifier (UDI-DI) or indicating lack of UDI, would streamline the
allegation submission process and potential risk assessment, all
facilitating the Agency's prompt understanding of an allegation,
thorough investigation, and appropriate regulatory action.
Also, FDA receives numerous claims of companies offering for sale
illegal unapproved products in the online marketplace, such as on
Amazon, eBay, Facebook, or via independent sellers. Internet laws
generally provide such third-party platforms with a civil liability
shield for violative products sold and distributed by sellers on these
platforms; such laws restrict FDA's ability to take civil enforcement
action against these online marketplaces.
Finally, FDA would note that field alert reports, for example, help
to quickly identify qualitydefects in distributed drug products that
may present a potential safety threat. However, current field alert
report requirements do not apply to drugs that are not marketed under
approvedapplications, including marketed unapproved drugs. There have
been a number of situations where a recall has been conducted where, if
a field alert report had been required, the Agency could have
encouraged manufacturers to investigate complaints more thoroughly and
recall the product sooner. Consideration could be given to the
expansion of these field alert report requirements to drugs that are
not marketed under approved applications.
Question. What can the FDA do in instances like this where it
appears that the IND/IDE process is being misused in order to provide
access to unapproved products?
Answer. FDA is committed to working with sponsors to facilitate the
development and approval of new medical products and to protect the
rights and safety of individuals participating in clinical
investigations. Clinical investigation design and conduct concerns may
be addressed through administrative or other actions, which vary
depending on whether the investigation is subject to the
Investigational New Drug (IND) or Investigational Device Exemption
(IDE) requirements. First, FDA may disapprove or withdraw approval of
an IDE or place an IND on clinical hold, for example, if the plan or
protocol for a Phase 2 or Phase 3 investigation of a drug is clearly
deficient in design to meet its stated objectives, or there is reason
to believe that the investigational medical device as used is
ineffective. However, as outlined in Section 520(g)(4) of the Federal
Food, Drug, and Cosmetic Act (FD&C Act), FDA cannot disapprove an IDE
because the investigation may not support approval or clearance of a
device. Neither section 505(i) of the FD&C Act nor FDA's regulations
specifically prohibit the conduct of a clinical investigation under an
IND solely because the investigation is not an adequate and well-
controlled study designed to support marketing approval.
Second, FDA's Bioresearch Monitoring (BIMO) program is a
comprehensive program of on-site inspections and data audits designed
to monitor all aspects of the conduct and reporting of FDA- regulated
research to ensure compliance with FDA's regulations. The IDE and IND
regulations prohibit, for example, test marketing an investigational
product, commercializing aninvestigational product, unduly prolonging
an investigation, or representing that an investigational medical
product is safe and effective for the purpose for which it is being
investigated. Advisory, administrative, and judicial actions may be
pursued based on the inspectional observations and in accordance with
applicable regulations.
Question. Page 55 of the Budget Justification for the FDA includes
a proposal to extend the provisions that currently apply to counterfeit
drugs in sections 301 (prohibited acts), 303 (penalties), and 304
(seizure) of the FD&C Act and Title 18 of the U.S. Code to also
covercounterfeit devices as a way to give the agency more tools against
device products that find their way into interstate commerce. Can you
provide more details on this proposal, and explain if these authorities
could also impact the agency's ability to seek enforcement actions
against unapproved products that make their way into interstate
commerce?
Answer. FDA believes it is important that counterfeit medical
devices be treated akin to counterfeit drugs and that the government
have comparable authorities regarding enforcement against their
manufacture, distribution, and sale. The Safeguarding Therapeutics Act
of 2021 (Public Law 116-304) gave FDA important new authorities to
destroy, rather than return, certain counterfeit devices interdicted
during entry to the United States. However, the law does not make it a
crime to manufacture, hold for sale, or distribute a ``counterfeit
device,'' as newly defined by the Act. FDA's proposal would complement
the authorities of the new law by extending protections for the
American public with regard to counterfeit devices that have entered
U.S. commerce, or are being manufactured domestically.
Specifically, FDA's proposal would make it a prohibited act to
manufacture, sell, or distribute counterfeit medical devices, authorize
the seizure of such counterfeit devices, regardless of where they are
discovered in the supply chain, and strengthen criminal penalties
formanufacturing, selling, or distributing counterfeit devices so they
are comparable to the penalties for the same conduct for counterfeit
drugs. Although counterfeit devices may already be subject to
prohibitions on adulterating or misbranding a medical device, the
penalty provisions associated with the corresponding prohibited acts
are significantly lower (and thus, much less of a deterrent) than the
penalty associated with the counterfeit drug prohibited act. Further,
because counterfeit drugs are per se contraband under the Federal Food,
Drug, and Cosmetic Act, aligning the statutory provisions for
counterfeit devices to those for counterfeit drugs would make it more
straightforward to prosecute counterfeit devices cases, without having
to establish additional elements, such as entering the product into
interstate commerce.
These provisions would strengthen the government's ability to
address the public health (as well as economic) threats posed by these
counterfeit devices, particularly for those products that have already
entered the domestic supply chain.
______
Questions Submitted by Senator Mitch McConnell
Question. Developing a regulatory pathway to provide certainty for
CBD as a food additive and a dietary supplement is important to
consumers and producers across the country. How will FDA provide
certainty to this growing industry given that CBD in dietary
supplements and foods are available in stores across the country and
easy for the entire population to consume today?
Answer. FDA notes that the Agency has already established a clear
regulatory pathway for CBD through the drug approval process, and there
is also a clear pathway for certain human hemp-derived food products
that do not contain CBD. Additionally, FDA has released guidance to
help with the development of additional drug products from botanicals,
including cannabis, by providing information about manufacturing
standards.FDA recognizes the need for policies to bring greater clarity
to the marketplace, as well as allowing the Agency to more effectively
protect the public against products which may cause harm. There are
known public health risks associated with products containing CBD, and
there are unanswered questions relating to the safety of CBD in
products other than the one FDA-approved CBD-containing drug,
Epidiolex. Given the significant public interest in a range ofcannabis-
derived products and substances beyond just CBD, this year FDA
broadened the scope of its high-level working group and reestablished
it as the Cannabis Product Committee.
FDA continues its work to obtain data to better understand the
safety profile of CBD and will continue to update Congress and the
public on progress and findings. This includes a large-scale market
sampling study covering thousands of products, as well as a partnership
with theUniversity of Mississippi to better understand more about CBD
that has been added to cosmetics. FDA is also aware that other efforts
into research have been underway and encourages stakeholders to provide
the Agency with their data.
In addition, FDA is currently reviewing risk-based enforcement
priorities in light of the changing landscape for CBD products. As FDA
considers pathways outside of the drug approval context, the Agency
must apply the same statutory requirements to CBD as the Agency would
any other ingredient in the products we regulate. Even if the Agency
were to create an exception to the prohibition of CBD in food and
dietary supplements, all of the safety and processing standards would
still apply, such as those for food additives or new dietary
ingredients. FDA has been examining the available data to see whether
CBD can meet those existing statutory and regulatory standards.
In addition, FDA also notes that if an exemption for CBD were made
to allow its addition to foods or dietary supplements at any
established level, the Agency does not currently have the authorities
or resources necessary to effectively regulate that market.
Particularly if CBDproducts were legally permissible as dietary
supplements, this lack of appropriate authorities and resources could
jeopardize public health.
Question. In 2019, FDA stated three to 5 years is the Agency's best
estimate of a timeframe for completing notice-and-comment rulemaking
from start to final rule. Two years later, we still don't have any
additional clarity or certainty from FDA on the regulatory pathway for
products that contain CBD. Why has FDA not moved forward to propose
regulation on this topic?
Answer. The timeline for notice-and-comment rulemaking is generally
3-5 years once FDA has enough scientific evidence to inform, support,
and legally defend the potential regulatory policy proposal. The Agency
continues to underscore the need for additional data to inform the
safety profile of cannabis products that contain CBD and has expressed
concerns regarding the safety risks associated with these products.
Examples of ongoing research being undertaken by the Agency to help
develop such data include a large-scale market sampling study covering
thousands of products, a partnership with the University of Mississippi
to better understand more about CBD that has been added to cosmetics,
NCTR studies looking at male reproductive toxicity of CBD,
pharmacokinetics, and developmental neurotoxicity, consumer use
patterns, healthcare provider perceptions, application of advanced data
science analytical methods to data mining of online information (e.g.
social media, product reviews). In the meantime, FDA is currently
reviewing its enforcement priorities with the objective of updating the
draft guidance that was under development last year.
Question. What is the timeline for issuing guidance the FDA may
offer about using hemp grain as an additive for livestock feed? Do you
anticipate that guidance coming at the same time as the regulatory
pathway for CBD as a food additive or dietary supplement?
Answer. FDA is considering this issue independently from
consideration of a potential additional regulatory pathway for
cannabis-derived products containing CBD for humans. There are
established pathways that companies can follow if seeking to market
hemp-derived animal food products that do not contain CBD. Animal food
ingredients must be the subject of an approved animal food additive
petition or generally recognized as safe (GRAS) for its intended use in
food for the intended species.
In coordination with state feed control officials, FDA also intends
to continue accepting ingredients listed in the Official Publication
(OP) of the Association of American Feed Control Officials (AAFCO) for
use in animal food, as long as no safety issue arises. At this time,
there are no approved animal food additive petitions, or ingredient
definitions listed in the AAFCO OP, for any substances derived from
hemp, and FDA is unaware of any GRAS conclusions regarding the use of
any substances derived from hemp in animal food. However, the Agency
has continued to encourage stakeholders to develop the necessary data
and submit GRASnotices, food additive petitions, or AAFCO ingredient
definitions for hemp-derived animal food ingredients that do not
contain CBD. Although FDA has no plans to issue guidance on this topic
at this time, the Agency has been actively engaged with the hemp
industry and researchers on the data needed to assess the safety of
hemp-derived ingredients in animal food for the animals themselves and,
when applicable, the safety of the resulting human food products (e.g.,
meat, milk, and eggs) for people.
Question. It is my understanding that to date, Congress has
appropriated $7 million to FDA for cannabis and CBD related activities.
Within these funds, please provide a breakdown on how much has been
allocated for research. What data was found in this research, and what
additional data, if any, does FDA believe it still needs to collect
before a regulatory pathway for CBD can be offered?
Answer. To date, approximately $5.2M ($1.2M fiscal year 2020; $4
million fiscal year 2021) has been spent on research which included a
large-scale market sampling study covering thousands of products, a
partnership with the University of Mississippi to better understand
more about CBD that has been added to cosmetics, NCTR studies looking
at male reproductive toxicity of CBD, pharmacokinetics, and
developmental neurotoxicity, consumer use patterns, healthcare provider
perceptions, application of advanced data science analytical methods to
data mining of online information (e.g. social media, product reviews).
This research is ongoing, and the Agency anticipates some analytical
results in fiscal year 2022 and fiscal year 2023.
______
Questions Submitted by Senator Roy Blunt
Question. Dr. Woodcock, in light of the Alzheimer's drug approval
news this week, it is even more imperative that the agency work on
approving easy-to-use, low cost diagnostic tests for Alzheimer's, such
as a blood test. A St. Louis company, C2N Diagnostics, has been working
on a blood test that can be used as a diagnostic tools for those having
symptoms of Alzheimer's. However, the test is still at the FDA awaiting
clearance from the agency. Can you share how the agency is prioritizing
reviews of Alzheimer's diagnostic tests?
Answer. The diagnosis of Alzheimer's disease is based on clinical
criteria and supported by diagnostic tests, including MRI, PET, and
cerebrospinal fluid (CSF) measures of Alzheimer's disease biomarkers.
We agree that diagnostic tools used to support the diagnosis of
Alzheimer's disease, including blood tests, can be of great value to
public health. FDA has cleared two Direct-to-Consumer (DTC) saliva-
based tests for Alzheimer's disease. These tests have been geared
toward the detection of genetic variations that predispose a person to
Alzheimer's disease, and this approach may hold promise for an earlier
diagnosis of Alzheimer's disease in some patients. However,
predisposition tests that provide information about an individual's
risk of getting Alzheimer's disease are different from tests that
diagnose Alzheimer's disease.
CDRH is open to engaging with sponsors who want to bring beta-
amyloid based tests to market, using blood or other specimens such as
CSF.
In addition to blood-based tests, multiple sponsors have engaged
with FDA about developing diagnostic imaging products, including
imaging agents and analysis software, to aid in the diagnosis and
monitoring of Alzheimer's disease. CDER has approved GE Healthcare's
Vizamyl (NDA 203137) to estimate beta amyloid neuritic plaque density
in adult patients with cognitive impairment who are being evaluated for
Alzheimer's disease or other causes of cognitive decline. CDER also
approved TAUVID from Avid Radiopharmaceuticals, a radioactive
diagnostic agent indicated for PET imaging of the brain to estimate the
density and distribution of aggregated tau neurofibrillary tangles in
adult patients with cognitive impairment who are being evaluated for
Alzheimer's disease. CDRH is open to engaging with sponsors who want to
develop software to aid in the diagnosis and monitoring of Alzheimer's
disease.
Programs such as the voluntary Breakthrough Device Designation
Program enable FDA to offer approaches to making certain tests and
other devices that provide for more effective treatment or diagnosis of
life-threatening or irreversibly debilitating diseases or conditions
available as rapidly as possible. When sponsors of devices have
breakthrough device designation, they can expect prioritized review of
their submission.
Question. How far behind is FDA on these reviews as a result of
COVID-19?
Answer. Review of most Premarket Approval Applications were not
paused during the COVID-19 pandemic. However, responses to some Q-
submissions, which are mechanisms available to sponsors through which
they can request FDA feedback, were delayed or are currently delayed
due to resource limitations resulting from FDA's COVID-19 response.
Since January 2020, FDA has received almost 7,000 Emergency Use
Authorization (EUA) requests and pre-EUA submissions for devices, and
has granted EUAs or full marketing authorization to over 1400 devices,
including almost 400 tests. We have issued 10-fold more EUAs for
devices during COVID-19 than all other previous public health
emergencies combined. As a result, there have been some delays in other
work areas. We continue to receive 100+ EUA requests and pre-EUA
submissions for tests per month, in addition to working on other COVID-
19 device EUAs, and our ``traditional'' work.
Question. Does FDA take into account the impact of an approval as
it is prioritizing work? For example, a blood test for Alzheimer's
would not only impact a person diagnosed, especially now with a new
drug approved to treat a possible cause, butalso make it much easier to
screen patients for Alzheimer's clinical trials to develop other
treatments. Typically screening and enrollment represents close to 50
percent of the close of clinical trials in Alzheimer's disease.
Answer. We agree that diagnostic tools used to support the
diagnosis of Alzheimer's disease, including blood tests, can be of
great value to public health, and we encourage the developers of such
tests and others to engage with us.
Question. Dr. Woodcock, several of the COVID-19 vaccine developers
have indicated we may need a vaccine booster. However, more recently,
other public health experts indicate there is growing evidence that a
first round of global vaccinations may offer enduring protection.
According to Pfizer's own data, their shot remains 91 percent effective
for at least 6 months after the vaccination. I think it could be very
dangerous if vaccine companies, rather than public health experts, are
setting the public's expectations around COVID-19 boosters. As Cornell
professor John Moore said, ``you've got to look at whether there's a
corporate agenda behind this.'' What is your opinion on whether we will
need a COVID-19 booster?
Answer. All three FDA-authorized vaccines prevent COVID-19 and
related serious outcomes, including hospitalization and death.
Currently, FDA, vaccine manufacturers, and other scientists are working
to try to understand how long the authorized vaccines will provide
protection for the prevention of COVID-19.
Currently available information suggests that the three COVID-19
vaccines that FDA has authorized for emergency use protect the American
public against COVID-19 caused bycurrently circulating strains of SARS-
CoV-2, the virus that causes COVID-19. However, if there is an
emergence of other SARS-CoV-2 variants in the U.S. that are moderately
or fully resistant to the antibody response elicited by the current
COVID-19 vaccines, it may be necessary to tailor the vaccines to those
variant strains.
The need for and timing of COVID-19 booster doses have not been
established; however, scientific efforts are ongoing to determine if,
and when, such a booster dose would be needed. FDA will continue to
monitor the COVID-19 vaccines and will provide updates to the public as
data becomes available.
Question. If a booster is necessary, how will it be determined? For
example, is it when efficacy reaches a certain level? And what level is
that?
Answer. COVID-19 is still considered a new disease in the United
States and the world. FDA scientists and other scientists in Federal
agencies, academia, and the global community are collaborating to
expand knowledge of the disease and ways to treat it and prevent it.
Scientific efforts are ongoing to determine if, and when, a booster
dose of a COVID-19 vaccine would be needed. An immune marker that
reliably predicts protection against infection or disease (e.g., a
specific level of antibody response) has not yet been established for
COVID-19. The need for boosters will depend on several factors,
including whether immunity wanes over time and the ability of currently
authorized vaccines to protect against emerging and/or circulating
variants of concern. FDA will continue to monitor the COVID-19 vaccines
and will provide updates to the public as data becomes available.
Question. Along those same lines, there have been several news
reports on how the COVID-19 vaccine is not delivering a high level of
antibodies for those people that areimmunocompromised, who are often
the same people most vulnerable to COVID-19. There was a Wall Street
Journal article recently on how the standard regiment for COVID-19
vaccines is not working for transplant patients, and some anecdotal
reports that a booster shot is effective for these patients in boosting
their antibodies.
Is FDA working with the COVID-19 vaccine manufacturers and other
agencies, such as the CDC, on guidance for booster shots for those who
are immunocompromised?
Answer. FDA scientists and other scientists in Federal agencies
including the CDC, and academia, are collaborating to expand knowledge
of the disease and ways to treat it and prevent it. The Fact Sheets for
the authorized COVID-19 vaccines include information to convey that
immunocompromised persons, including individuals receiving
immunosuppressant therapy, may have a diminished immune response. A
modification to the dosage regimen set out in the letter of
authorization and described in the fact sheets, in order to provide
additional doses for immunocompromised individuals, would require data
to support a new dosing regimen. After submission of these data and
evaluation by FDA, and if supported by the data, the letter of
authorization and fact sheets could be changed to provide a revised
dosing regimen.
It is important to recognize that the immunocompromised population
is not homogeneous with respect to the degree of immunocompromise and
the nature of the immunocompromise.However, based on the totality of
available data, FDA considers the benefits of COVID-19 vaccines
currently available under EUA to outweigh their risks in
immunocompromisedpopulations. In addition, to help those who are
immunocompromised be protected from COVID-19 and related serious
outcomes, including hospitalization and death, it is important for the
general population to get vaccinated, to strive toward herd immunity.
CDC, after receiving advice and guidance from its Advisory
Committee on Immunization Practice (ACIP) releases publicly available
recommendations on immunization practices for COVID-19. The need for
and timing of COVID-19 booster doses, including forimmunocompromised
populations, have not been established. FDA will work with other
Federal agencies to provide appropriate public updates as new
information becomes available.
Question. When can we expect any information on the FDA on guidance
for this specific population regarding COVID-19 vaccine boosters?
Answer. Any revisions to the letter of authorizations and fact
sheets for authorized COVID-19 vaccines to provide additional
information related to immunocompromised individuals, such as
modifications to the dosage regimen, would first require data to
support a new dosing regimen.
After submission of these data and evaluation by FDA, if supported
by the data, the letter of authorization and fact sheets could be
changed to provide a revised dosing regimen.
______
Questions Submitted by Senator Jerry Moran
Question. Animal biotechnology has enormous potential to address
numerous agricultural, environmental, humanitarian, and public health
challenges. Since the mid-1990s, U.S. Food and Drug Administration
(FDA) has applied its ``new animal drug'' regulatory paradigm to these
products. Just two biotech animals for intended for food use have been
approved in the United States under that system.
FDA's one-size-fits-all system has been slow to get these
technologies to producers and undermines U.S. competitiveness by
steering innovators away from the US to more friendly foreign markets
who are establishing more efficient regulatory systems for this
technology to entice researchers and product developers.
A modern U.S. regulatory system for animal biotech is needed to
pave the way for breakthroughs that can help prevent and respond to
zoonotic diseases, improve animal well-being, make our farming and food
systems more sustainable, protect our environment, and bolster our
resilience to climate change.
In December, U.S. Department of Agriculture (USDA) issued an
Advanced Notice of Proposed Rulemaking (ANPR) aimed at restructuring
the U.S. regulatory system for animal biotechnology. Will the FDA
commit to working with USDA and other counterparts within the
Coordinated Framework to develop science-based policies that foster
innovation?
Answer. Yes, FDA meets regularly with its Coordinated Framework
counterparts at USDA and EPA on issues concerning biotechnology
products and will continue to do so.
FDA recognizes that innovations in animal biotechnology offer
tremendous opportunities for advancing public and animal health. The
Agency is committed to fostering advances in this field while ensuring
the safety of animal biotechnology products. FDA uses a flexible, risk-
basedapproach to its oversight of these products. The Agency is engaged
in a continuing effort to gather feedback from animal biotechnology
stakeholders in order to enhance the predictability, transparency, and
efficiency of its oversight of intentional genomic alterations in
animals. As part of this process, FDA established the Veterinary
Innovation Program, which is available to most developers of
intentional genetic alterations in animals and is aimed at
facilitatingadvancements in the development of innovative animal
products by providing greater certainty in the regulatory process,
encouraging development and research, and supporting an efficient and
predictable pathway to approval.
Question. Will the FDA to put forward a streamlined regulatory
approach to animal biotech that is science based and risk appropriate;
ensures human, environmental, and animal safety; and provides a
transparent, predictable, and efficient pathway to market?
Answer. FDA is engaged in a continuing effort to gather feedback
from animal biotechnology stakeholders in order to enhance the
predictability, transparency, and efficiency of FDA's oversight of
intentional genomic alterations in animals. As part of this effort, the
Agency created the Veterinary Innovation program, which is available to
most developers of IGAs in animals and is aimed at facilitating
advancements in the development of innovative animal products by
providing greater certainty in the regulatory process, encouraging
development and research, and supporting an efficient and predictable
pathway to approval. FDA's approach is science- and risk-based, with
regulatory expectations that are appropriate to a product's risk.
______
Questions Submitted by Senator Cindy Hyde-Smith
Question. Understandably, in light of COVID-19, FDA had to pause
pharmaceutical manufacturing inspections in 2020. While the Agency
continued to report meeting goal dates and approving new drugs
throughout the year, we are now more than a year into this situation
and overall, in 2020, FDA was unable to conduct only about 60 percent
of its planned inspections. What is FDA's plan to resume in-person
foreign and domestic inspections and how does the Agency plan to deploy
the $500 million that was appropriated to FDA in the American Rescue
Plan Act of 2021?
Answer. FDA has begun making strides towards resuming normal
inspectional activities. However, due to current travel restrictions
and other complicating factors it is not possible to anticipate when we
will be back at pre-pandemic levels of foreign inspections. FDA has
been conducting mission- critical inspections throughout the pandemic.
Although routine surveillance inspections were initially postponed,
prioritized domestic inspections resumed in July 2020. The Agency has
established prioritization plans for inspectional operations for all
regulated commodities to help construct a systematic method for
tackling postponed oversight activities. There is more detailed
information about this plan in the recently published ``Resiliency
Roadmap for FDA Inspectional Oversight,'' which details our plan for
the future of FDA inspectional activities.
In October 2020 FDA resumed in-country inspections from the China
Office. In January 2021, FDA temporarily resumed inspections from the
India office and will resume inspections again once it's safe for FDA
and industry personnel. FDA's Office of Regulatory Affairs
receivedfunding for recovery activities, including inspections
modernization and hiring staff to conduct postponed inspections, as
well as $38.3 million to support CDER-related inspections.
Question. Rising costs of prescription drugs remains one of the top
concerns for the American people. While biologics account for a small
number of prescriptions each year, they make up more than 40 percent of
prescription drug spending. As you know, biosimilars have the potential
to save patients and the healthcare system billions over the next
decade, but to fully achieve this promise FDA needs to increase
biosimilar approvals. A recent article cited that goal dates for
biosimilar products have dropped even further from 75 percent to 67
percent. Can you share why FDA is increasingly missing goal dates for
these important medicines? Is this related to delayed foreign
inspections and if so, how does FDA plan to improve on these numbers
and get more biosimilars to market?
Answer. As of March 2021, an estimated 68 applications across all
commodity areas have been delayed due to the inability to conduct pre-
approval, pre-market, or pre-license inspections.\8\ Due to the small
numbers of actions in a given quarter for BsUFA, a missed goal has a
large percentage impact on performance and can drop the BsUFA
percentage below the 90 percent on-time action performance goal. FDA
has released its plan to address postponed inspectional work using a
risk-based approach and is committed to doing so as quickly as
possible.
---------------------------------------------------------------------------
\8\ https://www.fda.gov/media/148197/download
---------------------------------------------------------------------------
We also continue to implement our Biosimilars Action Plan (BAP),
first announced in July 2018, encouraging innovation and competition
among biologics and the development of biosimilars. The BAP applies
many of the lessons learned from our experience with generic drugs to
accelerate biosimilar competition with four key strategies: (1)
improving the efficiency of the biosimilar and interchangeable product
development and review process; (2) maximizing scientific and
regulatory clarity for the biosimilar product development community;
(3)developing effective communications to improve understanding of
biosimilars among interested parties (patients, clinicians, and
payors); and (4) supporting market competition by reducing gaming of
FDA requirements or other attempts to unfairly delay market
competition.
Question. Lupus is a chronic and complex autoimmune disease that
primarily targets young women. FDA has engaged with outside
stakeholders to hear about the unmet needs of lupus patients and the
need for diversity in lupus clinical trials. Yet, while there is some
progress, significant barriers continue to impede the development of
therapeutics for lupus. I understand that public-private partnerships
are a tool that FDA has employed with patient organizations and other
key stakeholders for other diseases and conditions, including kidney
disease, diabetes, Huntington's disease, and multiple sclerosis. Do you
believe such an approach would add value for advancing lupus
treatments?
Answer. Systemic lupus erythematosus (SLE) is a serious disease,
affecting a variety of organ systems, that can result in significant
morbidity and mortality.
Public-Private Partnerships (PPP) are one of several valuable tools
available to FDA. These collaborations are convened by external
organizations in which FDA and multiple stakeholder organizations,
including non-profit and for-profit organizations, work together to
achieve ashared goal by building knowledge or developing a common
understanding of issues and potential solutions.
In the case of SLE, much of the work that could be done through a
PPP is already happening through other efforts including the Lupus
Federal Working Group \9\ (LFWG). As directed by Congress, in 2003 NIH
established the LFWG, which includes representatives from FDA, OWH,
HRSA, AHRQ, CDC, 11 NIH Institutes and Centers, patient organizations,
and the private sector. The LFWG met most recently on May 13, 2021. In
addition to active participation in the LFWG, FDA has recognized the
challenges with studying SLE and its manifestations and has been
collaborating with all stakeholders to expedite drug development in
this space. This includes participation in and speaking at events,
including the Lupus Foundation of America meetings in 2015 and 2018,
the externally-led Patient Focused Drug Development meeting in 2017,
the Lupus Policy Summit in 2017, and the Lupus 21st Century Conference
in 2020. In addition, in March and April of this year, the FDA Office
of Minority Health and Health Equity held three Patient Listening
Sessions \10\ to better understand the lupus patient community's
perceptions about participating in clinical trials and to advance
diversity in SLE clinical trials through the development of multi-media
health education tools and resources.
---------------------------------------------------------------------------
\9\ https://www.niams.nih.gov/about/working-groups/lupus-Federal
\10\ https://www.fda.gov/patients/learn-about-fda-patient-
engagement/fda-patient-listening-sessions
---------------------------------------------------------------------------
As a result of FDA engaging with stakeholders, several successful
drug development programs resulted in recent approvals of products for
lupus nephritis (belimumab and voclosporin) and pediatric SLE
(belimumab). FDA continues to encourage drug development in this space
to address the remaining unmet medical needs.
Question. Dr. Woodcock, as you know medical oxygen is an essential
and indispensable front line treatment for COVID-19 that has been
saving lives across America. We have seen tragic news from India about
what can happen when there is a shortage of medical oxygen. In 2012,
Congress enacted historic and bipartisan reforms for medical gases--
which include medical oxygen--included in the Food and Drug
Administration Safety and Innovation Act (FDASIA Section 1112) that
required the Food and Drug Administration (FDA) to promulgate new
regulations for medical gases by July 9, 2016. When FDA failed to meet
the FDASIA statutory deadline, in a further effort to get FDA to
comply, language was enacted in the fiscal year 2017 Consolidated
Appropriations Act which required FDA to publish final medical gas
regulations by July 15, 2017. Separate regulations for medical gases
will ensure that these products are regulated in a way that takes into
account the unique safety considerations of medical gases and will
ensure they are available to the health systems that need them,
especially as the nation continues to treat individuals for COVID-19. I
am concerned that the FDA has failed to follow through on its statutory
obligations from 2012 and 2017 to establish separate regulations for
medical gases especially in light of their significant use in treating
COVID-19. Where does this significantly overdue rulemaking on medical
gases currently stand and will you commit to me that the FDA will
publish this rule prior to the August 2021 deadline set in the Spring
2021 Unified Agenda?
Answer. The Agency is working in earnest to revise Federal drug
regulations with respect to medical gases. FDA has held three
comprehensive public workshops that have covered several areas of FDA's
regulation of medical gases, including labeling, current good
manufacturing practice, postmarket safety reporting, certification of
designated medical gases, and drug registration and listing. The Agency
has carefully considered proposed regulatory changes submitted to the
public docket by stakeholders. The Agency understands the need for our
drug regulations to be better tailored to medical gases and is working
quickly to do so.
This rulemaking is large and complex because it is intended to
address a variety of subjects. Proposed changes to the regulations are
anticipated to include changes to current good manufacturing practice
(cGMP), labeling, and postmarket reporting regulations applicable to
medical gases, generally aiming for less stringent regulation where
appropriate, and is alsoanticipated to address the certification
process for designated medical gases established in FDASIA.
Developing this proposed rule has required close scrutiny of
existing regulations to identify the major areas for revision to more
specifically address medical gases, review feedback fromnumerous
sources on the key differences between medical gases and other drug
products, and ensure there are no unintended consequences associated
with any of the new proposedrequirements. This is a very technically
complex area of regulation.
We note that FDA addressed the rulemaking requirements in FDASIA
with FDA's 2015 report to Congress assessing the need for changes to
the regulations for medical gases and the 2016 container closure rule.
The rulemaking currently in development is in response to section 756
of the fiscal year 2017 Consolidated Appropriations Act.
We want to assure you that issuance of this proposed rule remains a
high priority. This is a particularly complex rulemaking effort,
continuing to demand significant internal deliberations that are
ongoing. Additionally, we continue to carefully balance this rulemaking
with otherpriority work.
We note that, while this rulemaking has been underway, industry has
demonstrated its ability to continue to provide critical medical gases,
including at increased demand, throughout the pandemic.
Question. In the context of countering youth use of tobacco, FDA
undertook some efforts recently. 2020 guidance led to changes in the
availability of various products, though flavored disposable products
were notably left out of such guidance. Another thrust of that guidance
was FDA's suggestion that it would prioritize enforcement against
manufacturers of products who have not taken sufficient action to
prevent minors' access. One avenue certain businesses have taken that
might pose a challenge to the agency's goal of preventing youth use is
developing and selling synthetic nicotine products. It is my
understanding that some such products are marketed, sometimes implying
that their absence of tobacco could pose a benefit. Further, I have
heard reports that some manufacturers are producing products that
otherwise would be unavailable if the nicotine they contained were
isolated from tobacco. If these reports are true, then these
manufacturers are flaunting regulations from FDA and CTP. We
understand, via his public comments, that CTP Director Mitch Zeller has
indicated that the FDA is addressing these issues on a case-by-case
basis. Can you speak to efforts that the FDA is taking or has taken to
address these types of products and associated marketing? Does the FDA
have a recommendation for Congress on how to address this issue, be it
legislative, regulatory, or other? How does the FDA currently fund
enforcement or other activities directed at synthetic nicotine
products?
Answer. We share your concerns regarding electronic nicotine
delivery systems (ENDS) claiming to contain only synthetic nicotine
(not nicotine sourced from tobacco). We are testing ENDS claiming to
contain only synthetic nicotine. If we find that such a product
actually contains any tobacco-derived nicotine, we have jurisdiction
under our tobacco authorities and can pursue enforcement if the product
is in violation of those authorities. If we find that a disposable ENDS
product contains only synthetic nicotine, enforcement becomes more
complicated because such a product likely does not meet the statutory
language in the Federal Food, Drug, and Cosmetic Act (FD&C Act)
defining tobacco products as products ``made or derived from tobacco.''
It is clear marketing of these products is rapidly increasing and that
questions about FDA's authority under current law need to be resolved.
We are exploring how to best address the growing number of products
where the jurisdiction is under review due to the source of nicotine.
The Agency is reviewing all of our options to determine whether these
products can be regulated under our existing authorities.
We take this issue very seriously, and we are working to find the
appropriate solution. We are exploring all potential options and are
discussing this topic internally to pursue a sustainable, effective
solution.
______
Questions Submitted by Senator Senator Mike Braun
Question. In the 2018 Farm Bill, Congress de-scheduled hemp with
less than 3 percent THC from the controlled substances list. Since that
time, many Hoosier farmers have begun growing Hemp, a crop that yields
many environmental and financial benefits for American farmers. At the
same time, there has been an exponential increase in consumer demand
for hemp-derived cannabinoid (CBD) products. Yet the agency has stalled
on any action to address CBD in the marketplace, despite the fact that
without regulation, the market has developed without any oversight and
now hundreds--if not thousands--of products exist with no consumer
protection for illicit products. What is the status of FDA's plan for
CBD?
Answer. FDA notes that the Agency has already established a clear
regulatory pathway for CBD through the drug approval process, and there
is also a clear pathway for certain human hemp-derived food products
that do not contain CBD. Additionally, FDA has released guidance to
help with the development of additional drug products from botanicals,
including cannabis, by providing information about manufacturing
standards.
FDA recognizes the need for policies to bring greater clarity to
the marketplace, as well as allowing the Agency to more effectively
protect the public against products which may cause harm. Before
enactment of the Agriculture Improvement Act of 2018, which removed
hemp from the definition of marijuana in the Controlled Substances Act,
it was very difficult foranyone to conduct research into CBD. There are
public health risks associated with productscontaining CBD, as well as
unanswered questions relating to the safety of CBD in products other
than the one FDA-approved CBD-containing drug, Epidiolex. Given more
recent significant public interest in a range of cannabis-derived
products and substances beyond just CBD, this year FDA broadened the
scope of its Agency-wide working group which has been facilitating work
on CBD and reestablished it as the Cannabis Product Committee.
FDA continues its work to obtain safety data and will continue to
update Congress and the public on progress and findings. This includes
a large-scale market sampling study covering thousands of products, as
well as a partnership with the University of Mississippi to better
understand more about CBD that has been added to cosmetics. FDA is also
aware that other efforts into research have been underway and encourage
stakeholders to provide the Agency with their data.
In addition, last year, FDA developed a risk-based draft
enforcement priorities guidance, though it did not get published. FDA
is currently reviewing these enforcement priorities in light of the
changing landscape for CBD products.
Question. Do you agree that there needs to be regulatory certainty
for the largely unregulated CBD marketplace?
Answer. As noted in the previous response, FDA recognizes the need
for policies to bring greater clarity to the marketplace, as well as
allowing the Agency to more effectively protect the public against
products which may cause harm. To support this effort, FDA continues
its work to obtain safety data and will continue to update Congress and
the public on progress and findings. FDA is currently reviewing risk-
based enforcement priorities in light of the changing landscape for CBD
products. Also, FDA continues to pursue testing of approximately 2,000
products as part of the Congressionally mandated marketplace sampling
study which aims to compare analytical results to the product's label
and help inform how products are generally being marketed.
Question. Is there an estimated timeline by which you think FDA
will be providing further guidance to Congress and other interested
stakeholders with regard to food and beverage products in the
marketplace that contain CBD?''
Answer. As noted in previous responses, FDA is currently reviewing
risk-based enforcement priorities in light of the changing landscape
for CBD products. In addition, in November 2019, FDA issued 15 warning
letters for companies illegally selling products that contain CBD in
ways that violate the FD&C Act, including products promoted as
conventional human foods. In those letters, FDA stated that, based on
the lack of scientific information supporting the safety of CBD in
food, the Agency cannot conclude that CBD is generally recognized as
safe (GRAS) among qualified experts for its use in human or animal
food, and that foods containing CBD are adulterated. FDA has also
stated on the Agency's website that it is a prohibited act to introduce
or deliver for introduction into interstate commerce any food to which
CBD has been added.
Question. In December, U.S. Department of Agriculture (USDA) issued
an Advanced Notice of Proposed Rulemaking (ANPR) aimed at restructuring
the U.S. regulatory system for animal biotechnology. In January, USDA
and the Assistant Secretary for Health and Head of the Public Health
Service at the U.S. Department of Health and Human Services signed a
Memorandum of Understanding (MOU) establishing a regulatory pathway at
the Department of Agriculture for agricultural animal biotechnology
innovation.
The MOU helps American livestock producers compete globally, as
these pathways are approved in key trading partner markets like Canada.
Further, this technology can make livestock more efficient,
environmentally sustainable, and resilient.
Unfortunately, this MOU has not gone into effect, since it has yet
to be published on U.S. Food and Drug Administration (FDA) websites.
What is the status FDA publishing the MOU on its website?
Answer. FDA recognizes that innovations in animal biotechnology
offer tremendous opportunities for advancing public and animal health.
The Agency is committed to fostering advances in this field while
ensuring the safety of animal biotechnology products. FDA uses a
science, risk-based approach to these products.
On January 19, 2021, USDA and HHS signed a Memorandum of
Understanding regarding the transfer of oversight of intentional
genomic alterations (IGAs) in animals of amenable species for
agricultural use from FDA to USDA. The MOU seeks to bind FDA to
exercise its enforcement discretion over these IGAs. The current
administration continues to study this issue.
Question. Will FDA commit to working cooperatively with USDA in
developing a streamlined regulatory approach to animal biotech to
provide an efficient and viable path to market?
Answer. FDA maintains an ongoing working relationship with USDA and
remains committed to cooperation. One example of our cooperation was
the recent approval for both food and biomedical use of an intentional
genomic alteration in a line of pigs known as GalSafe that have no
detectable alpha-gal sugar on the surface of the pigs' cells. Alpha-gal
can trigger allergic reactions in certain individuals and is believed
to be a cause of rejection of transplanted tissues and organs. FDA met
and shared updates with USDA during its review process. USDAapproved
the label for food derived from GalSafe pigs and regulates slaughter of
these animals for human food.
Question. The 2020 Medical Device User Fee Amendments (MDUFA)
Financial Report to Congress and 2020 MDUFA Annual Performance report
were due to Congress in January 2021. When does FDA plan to transmit
the MDUFA reports to Congress?
Answer. The FDA user fee financial reports were delivered to
Congress on June 22, 2021, including the MDUFA financial report for
2020. The report is linked here: fiscal year 20 MDUFA Financial Report.
FDA is working on the 2020 performance reports for MDUFA, PDUFA, GDUFA,
and BsUFA, and will transmit them to Congress as soon as possible. We
will notify your office when the report is transmitted and available
online.
Question. Since March of 2020, Congress has provided FDA with $716
million insupplemental appropriated funds to assist with COVID,
including supporting the review ofdevices and diagnostics associated
with Covid-19. How much of this funding has the Center for Devices and
Radiological Health (CDRH) received to date and how much of this
funding will CDRH receive in the coming years?
Answer. We appreciate Congress' support for our Agency's critical
COVID-19 response efforts, including to support the review of devices,
and the flexibility in spending these dollars over several years. CDRH
will receive a total of approximately $144.3 million in COVID-19
supplemental appropriated funds. CDRH spent approximately $7.4 million
of these funds in fiscal year 2020, received approximately $53.8
million in fiscal year 2021, and will receive the remaining $83.1
million in approximate funds in fiscal year 2022 through fiscal year
2025.
______
Question Submitted by Senator Richard Shelby
Question. The enforcement date for the FDA's Memorandum of
Understanding Addressing Certain Distributions of Compound Drug
Products (MOU) is October 26, 2021. Given the COVID-19 pandemic, State
Boards for Pharmacy have had challenges to meet in the last 16 months
that limited availability to incorporate new Federal regulations and
determine long-term planning. Will you delay the enforcement date of
the MOU 1 year to October 26, 2022?
Answer. We have received a request from the National Association of
Boards of Pharmacy, among others, to extend the period of time before
we intend to enforce a provision of the law that limits distribution of
compounded human drug products out of the state in which they are
compounded by compounders in states that do not sign the MOU. We are
currently providing 1 year--from publication of the final standard MOU
last October to October 27, 2021--for states to consider and sign the
MOU before we intend to enforce the limit. We are actively considering
the requests for further extension. States may sign the MOU at any
time, including after we begin enforcement of the limit. We continue
active, direct engagement with state entities considering signing the
MOU to address their questions and concerns.
SUBCOMMITTEE RECESS
Senator Baldwin. The hearing was adjourned.
[Whereupon, at 11:26 a.m., Thursday, June 10, the
subcommitee was recessed, to reconvene subject to the call of
the Chair.]
[all]