[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.
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    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.
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    \8\ https://www.fda.gov/media/148197/download
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    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.
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    \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
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    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]