[Senate Hearing 117-]
[From the U.S. Government Publishing Office]


 
   AGRICULTURE, RURAL DEVELOPMENT, FOOD AND DRUG ADMINISTRATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2023

                              ----------                              


                        THURSDAY, APRIL 28, 2022

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10:04 a.m. in Room SD-124, Dirksen 
Senate Office Building, Hon. Tammy Baldwin (chairwoman) 
presiding.
    Present: Senators Baldwin, Tester, Hoeven, Hyde-Smith, and 
Braun.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                      Food and Drug Administration

STATEMENT OF HON. ROBERT CALIFF, M.D., COMMISSIONER

               OPENING STATEMENT OF SENATOR TAMMY BALDWIN

    Senator Baldwin. I want to welcome everybody to our first 
budget hearing for this subcommittee of fiscal year 2023. And 
Dr. Califf, welcome back to the subcommittee. We appreciate 
your being here this morning to discuss the Food and Drug 
Administration's fiscal year 2023 budget request. In fiscal 
year 2022, this subcommittee provided historic funding for a 
wide variety of activities at the agency, and I want to 
continue that upward trajectory of the FDA, so it remains the 
world's gold standard for protecting public health.
    That starts with the budget before us, which includes 
increases for important initiatives, including a focus on food 
safety, addressing maternal and infant health, and continuing 
to address the COVID-19 pandemic.
    The fiscal year 2023 budget request for the FDA is 
ambitious and reflects the vast responsibilities of the agency. 
We need to ensure FDA has the resources they need to continue 
their mission. We must invest in safer drugs, safer medical 
devices, and a safer food supply. Dr. Califf, I am looking 
forward to hearing your vision for the FDA and how this budget 
will advance that vision and support these important 
investments. And 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, and focuses on the 
infrastructure needs of the agency. The FDA has the ability, 
and frankly the duty, to serve the public in a range of ways 
that matter deeply to people's health.
    We ask a lot of the FDA, from rigorous reviews of 
medications and medical devices, to addressing a rapidly 
changing food system. The work the FDA does impacts the lives 
of every American. Recent reports have raised serious concerns 
about the FDA's food mission and have identified many areas 
where the agency has both chronically and acutely fallen short 
of its mission to the public.
    Americans rely on the FDA to ensure that the food they are 
eating is safe and that they have the information they need to 
make informed decisions about what to feed their families. In 
many cases, it seems that the FDA has put food safety issues on 
the back burner. The FDA has to do better, and I look forward 
to hearing your response to that reporting here this morning.
    Additionally, I know from my constituents, there has been 
much frustration regarding standards of identity and FDA's lack 
of urgency when dealing with this issue. The FDA did issue a 
rule on standards of identity for yogurt, but many provisions 
were objected to by the dairy industry, and a stay was 
eventually put in place. It should not take the agency 40 years 
to update a rule.
    These are major challenges, and as chair of the 
subcommittee, I want to make sure the FDA has the resources 
they need so that Americans aren't left waiting and can trust 
the food they are eating.
    Again, I look forward to your testimony and appreciate your 
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 Chairman. Appreciate it. 
Thanks, Dr. Califf, for being here. Appreciate you being here 
to discuss FDA's funding priorities for 2023. Also appreciate 
visiting with you yesterday ahead of time so we could go 
through some things. We want to congratulate you on your return 
to the Commissioner's Office, and also thank you for your many 
years of public service.
    And I was pulling for Duke, too, as I said, mainly because 
I wanted to see Krzyzewski win it on his last year coaching. He 
has just such a remarkable, incredible record. I met Dr. Wooden 
and of course thought he was the finest basketball coach of all 
time. But I would have to say Krzyzewski is right up there with 
him.
    He is just a class act, too. Obviously, FDA plays a 
critical role in advancing the safety and prosperity of our 
Nation. You regulate more than $2.5 trillion worth of products 
on a daily basis. And so, you know, obviously, you are and have 
to be really the gold standard for food and drug safety. It is 
what the public requires.
    And really the rest of the world looks to you in terms of 
setting that standard for that safety for our citizens, and not 
just citizens of America, but obviously there is consumers 
across the world that are affected by the products that you 
oversee in your duty for safety. So in the past decade, we have 
had seven FDA Commissioners, you know, which is a lot of 
turnover in the agency, obviously. And so really, the challenge 
is of course, at the same time, pandemic, COVID-19.
    We have also had to deal with Zika, Ebola, and other, you 
know, public health issues. Opioid epidemic. So all these 
things are incredibly important and are real issues of 
obviously life and death. And so, you know, creating some 
longevity in terms of, you know, planning and long term 
planning and, you know, stability for the agency is important. 
Over the decade, we have provided almost $850 million in 
additional baseline funding. That is about an almost 35 percent 
increase over the 10 year period.
    More than $1 billion in emergency funding for public health 
emergencies. $500 million to implement 21st Century Cares Act. 
And then there is also a $1.1 billion in increased user fee 
assessments. So there is an increasing resource pool. I know 
resources are always a challenge, but we have got to deploy and 
utilize these resources wisely and as well as we can.
    You know, so I think that investment certainly represents 
our commitment of this subcommittee, and really the whole 
Appropriations committee, you know, to the safety of our food 
and drug supply. With that said, we have got to continue to 
make strategic investments, something you and I have talked 
about. We have got to modernize.
    The technology is incredibly important. It is going to play 
a huge role going forward as it is in almost every other aspect 
of what we do. But clearly, you have a challenge to get your 
technological capabilities up to where they need to be.
    And as we talked about, that is a process. I don't know 
that you ever get there, right? Because as soon as you get 
there with one part, then you have got to upgrade some other 
part. The technology develops so fast, but it is obviously 
incredibly important that we upgrade your technology..
    So again, I think that all comes as part of you trying to 
instill this, you know, longer term view, not only for your 
term as Commissioner, but for future Commissioners, getting a 
strategic plan that really you can work to deliver, and your 
successors can continue. They may modify it, you know, because 
everybody has their own ideas about things, particularly round 
here. And so but, you know, they will make changes, of course, 
but still, nailing down this plan, I think, can be a real 
legacy issue for you, particularly with your background and 
experience.
    So I think that is incredibly important. I guess those are 
the main thoughts that I have for you. And again, thanks for 
being here today and for testifying and taking our questions. 
Appreciate it.
    Senator Baldwin. Thank you. We will now hear from Dr. 
Califf, Commissioner of the Food and Drug Administration.

                 SUMMARY STATEMENT OF DR. ROBERT CALIFF

    Mr. Califf. Chair Baldwin and Ranking Member Hoeven and 
members of the subcommittee, thanks for the opportunity to 
appear before you today to discuss the 2023 budget request. 
Also, thanks for your kind comments and the delineation of the 
challenge, which I think is very real.
    As a loyal Duke fan, I am not sure Chairwoman Baldwin is 
totally on board with that wearing her Wisconsin red, but, 
well, it is good to have something like sports which comes and 
goes, and it is perfectly okay. So let me thank the 
subcommittee for your continued support, which you have just 
enumerated, particularly over the last 2 years as the agency 
has worked tirelessly to respond to the COVID-19 pandemic.
    I also want to thank the entire FDA staff. I am happy to be 
back with them and to join the effort to end this pandemic and 
ensure that we are prepared for the future. To realize our 
potential as we move forward, we need to look carefully and 
critically at the past 2 years. One of the most important 
lessons learned was the need to modernize the technology and 
scientific infrastructure that enables FDA's experts to do 
their work.
    It is also important to consider the best technology will 
be to no avail if we don't attract and retain our first rate 
workforce. The same forces that are driving the amazing 
bioscience and digital revolutions are also causing intense 
competition for the limited cadre of well-trained experts. The 
budget I present to you today will build the foundation for FDA 
to continue this good work and ultimately allow the agency to 
meet the growing needs and mandates upon which the public 
depends.
    While there are many critical priorities in our budget 
proposal, I would like to focus on three specific funding needs 
that do not get enough public attention, although you both 
mentioned them in your introductory remarks. The first is data 
and technology modernization. The second is people.
    And the third is infrastructure. I know what most people 
are thinking, with 5 minutes to present, you want to talk to us 
about data, people, and buildings? The answer is yes. Data is 
used to support every decision the FDA makes, and modern 
computation holds the key to the efficiency and effectiveness 
that I know you want. There is a reason for the saying, in God 
we trust, all others must bring data.
    The FDA houses more data than the Library of Congress and 
houses and protects trillions of dollars' worth of commercial 
and intellectual property, as well as clinical trial data that 
encompasses the health information of tens of millions of 
patients across the country and the world. But the technology 
and data systems are not of the quality we need for us to fully 
facilitate innovation in the rapidly moving industries that we 
regulate, nor to protect the public from the well-meaning, or 
from either well-meaning or intentionally harmful products.
    We must modernize to be able to keep up with burgeoning 
industries and support innovation as underscored by the 
messenger RNA vaccine effort that was so essential to our 
pandemic response. Our budget requests approximately $68 
million for data modernization to help bring the agency into 
the 21st century. Many of you have been concerned about the 
efficiency of the agency.
    Much of FDA's work involves inspections and review of 
applications and data from companies developing and refining 
products through integration of increasingly complex biology 
and digital technology. A modernized technology and data 
infrastructure at FDA will have direct benefits on these core 
functions. At the same time, we are inundated with claims from 
the real world of the post-market environment, where we often 
find major safety issues, some of those in the press as we 
speak, as these products are used by our diverse population in 
different environments.
    It would be unwise for the FDA to be hobbled by inferior 
technology to deal with food outbreaks and importation, complex 
medical products, or understanding the consequences of toxins 
in our food. FDA inspectors, even during the pandemic, traveled 
to a variety of places or used virtual technology to record 
data about the quality of products and the quality of the 
systems and processes that make the products high quality and 
safe, whether the product is a food, a complex device, or a 
sophisticated drug or vaccine.
    These inspectors currently must spend significant time 
entering data into systems that are outmoded and cannot 
integrate the information in a way that modern technology can 
support. FDA reviewers are also increasingly dealing with 
complex datasets that are generated through deep biological 
computations that involve integration of disparate sources of 
data from embedded biosensors and digital technology.
    Each Center at FDA has invested in its own technology, 
remnants of a time when interoperability was not a 
consideration and artificial intelligence seemed like science 
fiction. This balkanization wastes time, drains resources, and 
creates safety vulnerabilities. In short, we need to be able to 
do more inspections, do better and more reviews, and much more 
efficiently detect signal from noise and post-market safety.
    By embracing the full array of data science, advanced 
statistics, machine learning, and artificial intelligence, we 
can enable our inspectors and reviewers to focus their effort 
on areas where they can make a difference. This will not only 
enable our workforce to be more efficient, but also will make 
their jobs more interesting, and this is a win-win.
    Our physical infrastructure is also in desperate need of 
modernization. The agency has a $300 million backlog of 
building maintenance and repairs, which increases every year. 
Our Nation depends on these facilities to test, review, and 
evaluate the safety of the food we eat and the medical products 
we use. The budget asked for approximately $40 million to 
support these physical upgrades.
    I invite the subcommittee to visit our facilities across 
the Nation and see our work in action. I know you will agree 
our work is worth the investment. I know infrastructure doesn't 
have the same gluts as some topics, but unless we make these 
investments now, much of our ability to regulate and support 
the innovation that makes us competitive will go to waste.
    Throughout this session, I am prepared to provide specific 
examples of how data and technology modernization, support of 
our workforce, and upkeep of our facilities will lead to 
improved health and competitive advantage in global 
competition. And before I close, I want to flag an issue I know 
is a keen interest to the subcommittee.
    I am pleased to announce that this morning FDA will issue 
to propose tobacco standards, one prohibiting menthol as a 
characterizing flavor in cigarettes, and another prohibiting 
characterizing flavors other than tobacco and cigars. Through 
careful consideration of the scientific evidence and our 
authorities under the Tobacco Control Act, we have determined 
that these actions are appropriate for protection of the public 
health.
    The proposed product standards would, among other things, 
improve the health and reduce the mortality risk of current 
smokers of menthol cigarettes or flavored cigars by 
substantially decreasing their consumption and increasing the 
likelihood of cessation. This is another important move forward 
in the agency's efforts to combat youth tobacco use and promote 
health equity.
    And we look forward to working with Congress and the public 
as we seek feedback on our proposed standards. Thank you for 
inviting me, and I look forward to answering your questions.
    [The statement follows:]
            Prepared Statement of Dr. Robert M. Califf, M.D.
    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 2023 Budget Request for the Food 
and Drug Administration (FDA or the Agency).
    I would like to start by thanking the subcommittee for your 
continued support of FDA. The Agency appreciates the funding increases 
provided by the subcommittee in the fiscal Year 2022 Omnibus and your 
ongoing partnership is much appreciated as we execute our mission to 
protect and promote the public health, including our ongoing response 
work related to the COVID-19 pandemic. As we collectively work together 
as a nation to try and turn the corner of the COVID-19 pandemic, the 
Agency is using the lessons learned over the past 2 years and 
optimistically looking forward. FDA's talented and dedicated workforce 
has worked night and day for the past two-plus years to respond to the 
pandemic and this work has been deeply consequential for strengthening 
our Nation's response and protecting public health. At the same time, 
one of the biggest lessons learned from our COVID-19 response was the 
overwhelming need identified by FDA leadership to modernize the Agency, 
including through improved data processes, IT infrastructure, and 
facilities, to name just a few priorities. As a private citizen who was 
involved in the pandemic response alongside many in industry and 
academia, I can attest to the fact that this sentiment was also 
observed by many outside the Agency as well. This effort will require 
significant additional funding and we look forward to providing you 
with the rationale for our plans to meet these needs, delineating the 
benefits to the public health that will accrue, and working with you to 
make sure the FDA remains the gold standard around the world.
    FDA's fiscal year 2023 Budget Request builds upon our fiscal year 
2022 request while also acknowledging additional future needs and 
challenges. Our program level request totals $8.4 billion, which 
represents an overall increase of approximately $2.1 billion above the 
FY 2022 Enacted level. Of this total, $3.0 billion is for user fees, 
which is an increase of approximately $153 million above the fiscal 
Year 2022 Enacted level. Further, the Budget requests a total of $3.7 
billion in discretionary budget authority, which is an increase of 
approximately $356 million above the fiscal year 2022 Enacted level, 
and $1.63 billion in mandatory funding to support the Administration's 
plan to transform U.S. capabilities to prepare for and respond rapidly 
and effectively to future pandemics and other high consequence 
biological threats. These increases are organized into six critical 
areas that advance the Agency's critical activities in support of 
protecting and promoting the public health: (1) enhancing food safety 
and nutrition; (2) advancing medical product safety; (3) investing in 
core operations; (4) modernizing infrastructure, buildings and 
facilities; (5) tobacco user fees; (6) supporting Cancer Moonshot 
goals; and (7) pandemic preparedness.
                  enhancing food safety and nutrition
    FDA's Budget requests an increase of approximately $76 million 
above the fiscal year 2022 Enacted level, to support our continuing 
efforts to enhance human and animal food safety and human nutrition. 
Every American deserves access to safe and nutritious food, and our 
foods program staff at FDA work countless hours in partnership with 
federal, State, local, Tribal, and territorial partners to ensure that 
our Nation's food supply is safe. To deliver on this promise, the 
Budget requests funding to address health equity issues related to 
access to healthy and safe food. The Budget also seeks to address the 
rapid changes occurring in the way foods are produced, delivered, and 
handled. We must have modern tools and technologies to ensure the 
Agency's capabilities do not lag behind these sweeping changes. As a 
regulatory agency, if FDA cannot keep up with industry, our oversight 
will struggle to be effective. Modernization of our systems will enable 
us to prevent significant harm to the public from unsafe food.
                     new era of smarter food safety
    The Budget requests approximately $59 million, an increase of $43 
million above the fiscal year 2022 Enacted level, for our New Era of 
Smarter Food Safety initiatives. The goal of these initiatives is to 
bend the curve of foodborne illness in this country by reducing the 
number of illnesses attributed to FDA-regulated human and animal foods 
and to protect consumers from other unsafe foods. This approach builds 
on the modernized food safety regulatory framework created by the Food 
Safety Modernization Act (FSMA), including investments in animal food 
safety oversight. The requested funding would support the use of new 
technologies and data analytics to strengthen prevention activities, 
including the use of artificial intelligence, improve the ability of 
the Agency to rapidly trace food contamination back to the source and 
address the cause, and improve the efficiency and effectiveness of 
FDA's oversight activities.
                     healthy and safe food for all
    As a nation, we continue to need to improve not only the 
healthfulness of food that we put into our bodies, but also the safety 
of this food, including steps to reduce the presence of toxic metals 
and chemicals, especially in the food consumed by our most vulnerable 
and underserved citizens.
    As a cardiologist, I have seen the effect of poor nutrition on the 
human body, often beginning in childhood. Additionally, I am acutely 
concerned with the safety and availability of infant formula as a sole 
source of nutrition for many infants in our country today. To make 
progress on these issues, the Budget requests an additional $33 million 
above the fiscal year 2022 Enacted level across several initiatives 
that would seek to improve health equity through nutrition; to 
research, detect, and reduce exposure to harmful chemicals and toxins 
in food; and to complete additional nutrition work specific to infants, 
toddlers, and pregnant and lactating people.
                    advancing medical product safety
    The increasing sophistication, complexity, and digitization of 
medical products will benefit the public greatly, but these trends also 
require more sophisticated regulation to facilitate innovation and 
prevent unintended harm. In addition to our important work on food 
safety and nutrition, FDA also continues to face record levels of 
submissions for new medical products.
    Despite the pandemic, in the last few years, the Agency has 
continued to approve a record number of safe, reliable, effective, and 
innovative products that will improve the length and quality of life of 
patients and their families. In order to maintain this essential work 
and uphold the high standards upon which Americans rely when reviewing 
these products, the Budget requests an increase of approximately $95 
million above the fiscal year 2022 Enacted level. These additional 
funds will help address some of the Agency's highest priorities, 
including post-market monitoring for the continued performance, safety, 
and effectiveness of approved products and addressing public health 
issues such as the opioid epidemic. The U.S. faces significant 
challenges, including diseases and conditions, both rare and common, 
for which there are few or no therapies, current and future medical 
product shortages, and ongoing efforts to enhance patient safety. 
Investments in FDA medical product programs will assist on these fronts 
and ensure that FDA can continue to be an able, dynamic, and trusted 
partner to patients, physicians, and other health care professionals.
                            cancer moonshot
    FDA is committed to supporting efforts to deliver safe and 
effective new therapies to patients, including through working to 
advance critical disease research, including on cancer. The Budget 
requests $20 million for the Oncology Center of Excellence to support 
the Administration's goal of reducing cancer-based death and illness as 
part of the Cancer Moonshot initiative. These elements of FDA's 
contributions to the Cancer Moonshot would include the advancement of 
research, external collaborations, educational outreach programs, and 
programs that expedite the development of oncology and malignant 
hematology products using an integrated clinical evaluation approach. 
Among other activities, resources will also enable FDA to expand 
efforts that facilitate approval of important cancer treatments by 
international regulatory authorities at the time of FDA approval and 
will foster harmonization of cancer treatments in other countries with 
the U.S. standard of care.
                              supply chain
    By the time a public health emergency is declared, it is often too 
late to effectively prevent or mitigate shortages, and our goal as an 
Agency and as a nation should be to proactively intervene to assure 
patients and our health care providers on the front lines maintain 
access to the devices they need. That is why I strongly support efforts 
to fully fund the Budget's approximately $17 million request in 
additional resources for the Resilient Supply Chain and Shortages 
Prevention Program. Funding will complement foundational work supported 
with our COVID-19 supplemental dollars and will continue to build 
capabilities for a permanent program for U.S. supply chain resilience 
for medical devices. This program will help ensure that U.S. patients 
and the clinicians who care for them have access to the critical 
devices they need and help reduce U.S. dependence on devices from other 
nations, including masks, gowns, and other forms of PPE. The program 
will enhance FDA's capacity to rapidly intervene to prevent and 
mitigate device supply chain interruptions by developing and applying 
data analytics for predictive modeling, improving early signal 
detection and monitoring, and investing in preventive measures to avert 
shortages. This funding will ultimately promote enhanced resiliency in 
the medical device supply chain, and in addition to helping FDA be 
prepared for the next pandemic, it will also allow the U.S. to be 
better prepared for future events that don't rise to the level of a 
public health emergency, such as during hurricanes and other natural 
disasters, as well as during steady state operations.
    Complimentary to our initiative on devices, FDA is also seeking 
over $6 million across both the human and animal drug product areas in 
order to enhance supply chain surveillance in these industries as well. 
Investing in these key product areas at FDA will allow us to build both 
more technologically advanced supply chain surveillance systems beyond 
just devices and promote a regulatory environment that is more 
responsive to notifications from stakeholders and health care 
professionals, allowing for a nimbler and more responsive FDA.
                             cybersecurity
    Further, the Budget requests approximately $5 million above the 
fiscal year 2022 Enacted level to address medical device cybersecurity, 
along with a request for new related authorities, as we continue to see 
cybersecurity threats to medical devices increase. Cybersecurity 
exploits are one of the most substantial threats faced by this nation, 
and the impact could be particularly harmful for our health care 
system, where vulnerabilities could compromise entire hospital systems 
or disrupt manufacturing of countless devices. Funds for our device 
cybersecurity initiative will be used to help address risks associated 
with legacy devices, such as automated insulin pumps and implantable 
cardiac pacemakers, and rapidly address new medical device 
vulnerabilities.
                                opioids
    I remain deeply concerned about the devastating impact of the 
opioid crisis on families across our country. FDA's Budget includes a 
requested increase of $30 million above the fiscal year 2022 Enacted 
level to support the Administration's Advancing the Goal of Ending the 
Opioid Crisis. FDA is taking steps to address four priority areas of 
this epidemic: (1) decreasing exposure and preventing new addiction; 
(2) supporting the treatment of those with opioid use disorder; (3) 
fostering the development of novel pain treatment therapies; and (4) 
improving enforcement and assessing benefit-risk. Among other planned 
activities, these funds will address these priorities by supporting 
development of opioid overdose reversal treatments and treatments for 
opioid use disorder, assessing feasibility to integrate opioid Risk 
Evaluation and Mitigation Strategies (REMS) education into IT health 
systems/Electronic Health Records, expand current initiatives to 
interdict shipments of opioids, unapproved foreign drugs, counterfeit 
pharmaceuticals, and fraudulent products, and advance the development, 
evaluation, and marketing authorization of digital health medical 
devices that help address opioid use disorder.
                      investing in core operations
    The Budget requests an additional $158 million above the fiscal 
year 2022 Enacted level to support Agency-wide crosscutting initiatives 
that support both food safety and medical product safety and are 
complimentary to funding initiatives described earlier in this 
testimony. While the Agency has a number of critical needs in this 
area, including the ongoing need to support lab safety, address 
employee pay costs, and reduce animal testing using alternative 
methods, I would like to draw your attention to two especially critical 
topics- data and technology modernization and inspectional activities.
              data modernization and enhanced technologies
    To fulfill our ongoing and evolving public health mission, FDA 
requires the ability to continuously access, aggregate, visualize, and 
analyze multiple sources of information. Improving FDA's data processes 
and infrastructure is not only a good investment, but a necessary one 
in order to keep up with today's modern regulatory landscape. These 
investments are also important not just for FDA, but for our partners. 
FDA shares data both internally and externally and requires the ability 
to quickly and reliably extrapolate information to inform emergency 
response, as well as for standard oversight activities. FDA is 
requesting approximately $42 million above the fiscal year 2022 Enacted 
level for Agency-wide investments in centralized data modernization.
    Without additional funds to modernize our data systems, FDA will be 
forced to continue to use outmoded, legacy systems that do not 
integrate with more current systems, test reviewers will not be able to 
reliably keep up with expected growth in product submissions over the 
upcoming years, and Agency-wide efforts to leverage new data-rich 
capabilities like machine learning and artificial intelligence will be 
delayed. This translates into a slower and less effective FDA. We must 
make these investments now to ensure the Agency remains the gold 
standard for product standards and reviews.
                   optimizing inspectorial activities
    The Budget also includes a request for an increase of $24 million 
to optimize our inspections work Agency-wide. As you know, our ability 
to execute our inspections was disrupted due to the evolving COVID-19 
pandemic. The requested funding will help to bring our program back on 
track and to improve its operational readiness. As we do this, the 
requested funding would support capacity building to improve data 
analysis, increase efficiency and productivity, and ultimately 
streamline and optimize end-to-end inspections across both foods and 
medical product areas. I am aware of this subcommittee's interest in 
our inspectional work and our Budget request will help to ensure the 
Agency can modernize and execute our inspectional programs effectively.
           modernizing infrastructure, buildings & facilities
    FDA's fiscal year 2023 Budget also requests approximately $40 
million above the fiscal year 2022 Enacted level, for a total of $353 
million, to ensure that FDA's offices and labs across the country are 
optimally functioning to enable FDA to carry out its mission. This 
funding is critically needed to complete projects that will improve the 
condition of FDA's owned buildings and site infrastructure. Of the 
total $40 million request, $31 million is specifically for Buildings 
and Facilities, an increase of $18 million above the fiscal Year 2022 
Enacted level, to improve the condition of FDA's mission-critical, 
owned site infrastructure and buildings. Currently, the poor overall 
condition of FDA's owned buildings and facilities, especially its labs, 
directly affects FDA's ability to foster the scientific innovation 
necessary to improve health care, expand access to medical products, 
and advance public health goals.
                           tobacco user-fees
    Additionally, the Budget request includes $812 million in user fees 
to support FDA tobacco's program. Included within this total is an 
additional $100 million in tobacco user fees and updated authorities to 
include manufacturers and importers of all deemed products (i.e., to 
include those not already subject to user fees such as e-cigarettes) 
among the tobacco product classes for which FDA assesses user fees. FDA 
is also requesting an inflation adjustment for all tobacco user fees to 
ensure that the resources can keep up with the Agency's public health 
mandate and with the evolving marketplace of tobacco products. Without 
additional user fees, FDA will be forced to continue to spread out the 
flat budget available for tobacco regulation, which has remained 
stagnant for the past 3 years, limiting our ability to protect the over 
2 million young people who reported using e-cigarettes and other 
tobacco products in the last year.
    I must also note that in addition to presenting a heavy resource 
challenge, a lack of new tobacco user fees also represents a 
fundamental parity issue across tobacco-related industry.
    Prior to the court-ordered deadline of September 9, 2020, FDA 
received timely premarket tobacco product applications for 
approximately 6.7 million products. Thanks to the tireless efforts of 
the over 1,100 staffers at FDA's Center for Tobacco Products, together 
with the support of over 200 employees from across other parts of the 
Agency, we have met this challenge and have acted on over 99 percent of 
these applications thus far, and the remaining product reviews will be 
completed expeditiously. However, I must emphasize that this tremendous 
effort was undertaken with no additional resources--without e-cigarette 
manufacturers having to pay a single cent despite their products taking 
up a significant amount of our tobacco workload. I would strongly urge 
this subcommittee to work with authorizers in this fiscal year to 
provide the requested authority and new resources so that we may more 
expeditiously and comprehensively take the actions necessary to prevent 
new youth initiation of tobacco products, and to support those of all 
ages who are seeking to reduce smoking of tobacco products and quit 
these products.
                         pandemic preparedness
    Finally, the Budget includes a request for $1.63 billion in new 
mandatory resources over a 5-year period to implement the HHS Pandemic 
Preparedness Plan. Of this total figure, the request includes $1.1 
billion to expand and modernize FDA's regulatory capacity, IT, and 
laboratory infrastructure in order to facilitate development and 
expedite evaluation of vaccines and therapeutics that target high-
profile viral families. The request also includes $355 million to speed 
development of diagnostics, as well as $175 million to strengthen 
foreign inspections, harmonize premarket product reviews, and reduce 
zoonotic pathogen spillover.
    The funds would support biodefense preparedness, expediting overall 
vaccine design, testing, and authorization capacity by bolstering FDA's 
cadre of reviewers, increasing resources for inspections, and investing 
in electronic information exchange among stakeholders. It would 
increase the Agency's readiness to facilitate the development of new 
vaccines, including those based increasingly on mRNA technology and 
other rapidly modifiable or novel platforms, and enhance FDA's active 
and passive vaccine safety and effectiveness surveillance programs. 
This request would also support the development of a training center 
for inspection of advanced medical products.
    Along with these initiatives, the pandemic preparedness request 
would also be used to establish a cross-agency One Health Center of 
Excellence, allowing FDA to strengthen its interdisciplinary approach 
to solving multifaceted health challenges, like COVID-19, where the 
health of humans, animals, and their shared environment are 
intrinsically linked. This effort will also build internal capacity to 
address ongoing public health challenges that are exacerbated during 
pandemics like the COVID-19 public health emergency, such as human and 
animal food contamination, diabetes, heart disease, and cancer. The 
resources requested for vaccine activities, One Health, and other 
integral parts of the broader HHS Pandemic Preparedness Plan, are 
critical to ensure the United States is properly prepared for the next 
pandemic and to increasing our chances of preventing future pandemics. 
As a nation, we cannot afford to play catch up with the next threat to 
our National wellness and readiness.
                               conclusion
    I would like to close by thanking the subcommittee again for your 
continued support of the Agency, and again thank you for inviting me to 
testify today. I look forward to working with you and I am happy to 
answer your questions.

    Senator Baldwin. Thank you, Dr. Califf. As I mentioned in 
my opening statement, there was a recent Politico article that 
highlighted what seems to be significant dysfunction and lack 
of urgency in the food safety mission of FDA.
    Dr. Califf, I would like to give you an opportunity to 
respond to that article. And as Commissioner, I would like to 
ask you what fundamental changes are needed in order to make 
food safety more of a priority within the agency?
    Mr. Califf. Well, I do appreciate the opportunity to 
respond. And I want to assure you that any criticism like this 
is to be taken seriously, particularly since it did involve 
some former people that have worked at the FDA.
    And so I have been looking at the criticism carefully, but 
also was aware of concerns before coming back. The first order 
of business is to assure you and the public that our food is as 
safe as it has ever been. And we know much more about nutrition 
now than we did 5 years ago when I was here, thanks to the good 
work of the people who are at the FDA and at other Federal 
agencies, not to mention the States and people involved.
    And I have spent some time going to sources to verify that 
this is the case. And the people who keep the data are assuring 
me that this is the case. But that doesn't mean we can't do 
better. And in fact, a lot of what I tried to lay out in the 
opening comments was that it really is a combination of the 
people involved, with their skills and talents and the 
technology that will make a difference going forward.
    We have a plan which is on record already before I came 
back about the smarter era of food safety, which is based on 
the concept that, you know, we have a rapidly growing industry 
that has many, many facets, and the only way to really keep 
track of it and assure safety is going to be increasingly to 
use digital technologies so that we can make the best of the 
human talent that we have.
    And this is very much baked into our plan, but it is also 
very dependent on the funding that we have asked for. In 
addition to those measures, of course, we are looking at our 
internal operations and it is absolutely essential that the 
industries know who they--is accountable, who they are talking 
with. I will have more to say about that over the next few 
months, but we are intensively looking at the issue of how we 
are organized.
    Senator Hoeven already mentioned, there have been a large 
number of Commissioners in this chair, and that is very 
destabilizing for any place that you work if the bosses are 
changing at such a high frequency.
    So I don't want to rush into something and immediately 
react to suggestions that have been made. I want to do 
something that has a lasting effect so the next person in this 
chair will not be feeling like they need to start from scratch.
    Senator Baldwin. Dr. Califf, rebuilding public trust in the 
functions of the food mission area is going to take time. This 
is important for consumers and public health, but it is also 
critical for industry. Farmers, food processors, and retailers 
build their businesses to meet the process and ingredient 
claims that FDA regulates.
    These businesses need certainty so that they can focus on 
their important work of providing food that consumers can 
trust. A key way FDA has fallen short is the way it has handled 
the use of dairy terms.
    You and I have talked about this extensively before. 
Despite providing clear requirements for what products must do 
in order to use a dairy term on their label, FDA has failed to 
enforce these labels and has stood by while a wide range of 
dairy alternatives have emerged and market themselves using 
dairy terms, dairy labels.
    When we met prior to your confirmation, I appreciated the 
commitments you made to look into this and find a resolution. 
Could you share an update on where we are at?
    Mr. Califf. Glad to share an update. I mean, first, just a 
background, which you know well is that there are approximately 
280 standards of identity. The process to deal with these is 
quite cumbersome, involving rulemaking, as you know. And when 
objections are raised, then a lot of additional time goes by. 
But that doesn't mean that I am happy or anyone at FDA is happy 
with how long it has taken to get things done.
    So we do appreciate the money that has been allocated in 
this year's budget and also we have asked for more going 
forward to optimize this. Specifically, as you know, the milk 
related issues are under consideration as we speak. So I can't 
give details of exactly what is being said, but I will just 
mention two.
    One key principle and one finding, which is publicly known 
from the public meetings that we have held, I think all of us 
believe that people who buy a product should be able to 
understand what is in the product and also what the value of 
the product is, particularly when it comes to food in terms of 
nutritional value.
    And in that score, so far in the public meetings, the tenor 
has been that people generally do know the difference between 
plant and animal milk. They can tell that difference, but they 
are not very equipped to deal with what is the nutritional 
value.
    And so those are just considerations from the meeting. We 
are moving along quickly, and it is a priority to get this 
done, so I can assure you we will get done. And I know that you 
will be calling me to account for every day that it is not 
done.
    Senator Baldwin. Thank you. Senator Hoeven.
    Senator Hoeven. Thank you, Madam Chair. Going back to 
something that I mentioned in the outset and that you mentioned 
as well, and that is the turnover we have had, 7 Commissioners 
in 10 years. I want to acknowledge Dr. Woodcock for her work at 
the Center for Drugs and also for acting as Acting Commissioner 
for the past year. So I want to do that. And then, but then I 
also want to follow up with you on it, Commissioner, you know, 
with regard to your plans to modernize the agency.
    Talk a little bit about your multi-year build out plan, and 
specifically metrics and goals that you plan to use to guide 
that effort, to track results, you know, set goals and 
benchmarks for your team, also, again, with the idea that kind 
of setting it up for the next Commissioner as well, so it is 
something that continues.
    Mr. Califf. Yes, I really appreciate the question. I also 
want to publicly acknowledge Dr. Woodcock who graciously has 
agreed to stay on. And I think this is really a critical part 
of what I hope to accomplish. Neither she nor I are youngsters. 
I am 70 years old. She was actually overseeing my clinical 
trials when I was a young cardiologist.
    Senator Hoeven. Didn't you tell me you have a student at 
Duke, though? So you are a young 70 if you still got kids in 
school, man?
    Mr. Califf. No, no. My student at Duke graduated years ago. 
Got his time on ESPN for having attended the----
    Senator Hoeven. Oh, okay.
    Mr. Califf [continuing]. but he is almost 40 years old now. 
But I do have two 18 year old grandkids, so that--who are going 
to college next year. And neither at Duke, you know, I must 
say, but quite proud of them and where they are headed. Dr. 
Woodcock is going to be a great asset because she knows the FDA 
really well and she is going to be focused on the operations of 
the FDA and the kinds of improvements that I will talk about.
    I tried to get across in my opening comments, I think I 
have learned a lot both in my academic, medical, clinical 
practice and having worked at Alphabet. I have learned a lot 
about how computers can improve the efficiency of human work, 
but also make it more fun. And when we think about a job at the 
FDA, you know, it is hard work, and you get criticized every 
day and that is understood as part of it. And for us to attract 
the best people, we have got to have really first rate 
technology on that front.
    But from the point of view of our ultimate customer, the 
American public, given the expansiveness of the industries that 
we are regulating, I mean, they are really succeeding. America 
is a leader in biotechnology. We are feeding large parts of the 
world and we have the capability of doing more of it if we 
employ the technology that is in front of us.
    So how are we going to regulate this if the FDA doesn't 
have the right technology? How would you even know if it had an 
algorithm in a software that is in a tractor on a farm has a 
problem or not if you don't have people at the FDA with the 
technology that they need in order to oversee it. And the same 
would hold for the vast importation of seafood, for example, 
which has been of great interest to Congress.
    A majority of our seafood is imported, coming from faraway 
places. We can't inspect every batch of seafood, but we have a 
pilot project which we are going to expand. We are using the 
same technology that Amazon or Google would use, using 
algorithms and artificial intelligence. We can send the 
inspectors to where the highest probability of a problem is. So 
that is the kind of thing that I am talking about.
    I am talking about people at FDA that have a better job 
where they are aided by technology and can do a better job for 
the public. And one of the great things about this is that this 
will not reduce the number of people that we need because the 
industries are expanding so rapidly. It is just going to mean 
that they will be able to do a better job. It is not a loss of 
jobs. It is really making the jobs better.
    On another day, I hope we will engage in discussions about 
the job of the FDA Commissioner. There is a reason that there 
is a turnover that is so great. And, you know, I think it 
deserves careful thought by everyone involved about how to make 
this a job which maybe someone younger than age 70 would want 
to take.
    That is sort of one way of saying it. But I think it does 
deserve some consideration the conditions of this particular 
job. None of our jobs are easy. This is a particularly tough 
one. I was glad to come back because I have been through it 
already and I see the chance to do something for the next 
generations.
    But for someone in mid-career who you might want in this 
job, it is really hard to take it right now the way it is.
    Senator Hoeven. Well, I think that does merit discussion. 
And I think that is an important point you bring up and 
something we should discuss.
    Mr. Califf. I mean, it is a matter of public record that 
all of the living former FDA Commissioners have written about 
this. And, you know, we come from a variety of political 
backgrounds, having all been political appointees, but there is 
a pretty common view of it among every single living FDA 
Commissioner, and that is a fairly large number now.
    Senator Hoeven. Right. I guess one more question, we may 
have to pick it up in the next round, but advanced 
manufacturing and manufacturing here. What can we do? You know, 
we provide significant funding.
    I think it is around almost $40 million to promote domestic 
manufacturing. So there is a real concern about that now. So 
maybe start with--I am already over my time. I will save that 
one for the next round.
    Mr. Califf. Yes, I look forward to answer on the next 
round. I think is really important.
    Senator Hoeven. Yes.
    Senator Hyde-Smith. Thank you, Chairwoman Baldwin and 
Ranking Member Hoeven for having this hearing today. And I 
would also like to thank Commissioner Califf for being here to 
discuss this budget with us and appreciate your efforts and 
willingness to step up.
    Earlier this week, we had a very good conversation together 
and I really enjoyed learning about your experience in rural 
Quitman County in Mississippi and helping the folks there that 
are medically underserved, and that really hits home, since 
Mississippi is a very rural State, that you do have that 
interest.
    But I look forward to finding ways to advance rural health 
and to work on this issue together in your new role. One of the 
other issues we spoke about on our call was the FDA's decision 
to remove the in-person dispensing requirement of the chemical 
abortion drug mifepristone, and how this change would expand 
the distribution of products like this that can be delivered 
directly to someone's mailbox, effectively permitting mail 
order abortion in this country.
    And in February of this year, I sent you a bicameral letter 
requesting that you immediately rescind the removal of in-
person dispensing requirements for this drug. And your 
response, which I did get last week, said that you had 
conducted a comprehensive review of the REMS program and that 
you concluded that even without the in-person dispensing 
requirement, this drug would be safe and effective.
    And I and many others disagree with that. There is plenty 
of evidence showing this chemical abortion pill, there are 
dangers to women who take them and can be extremely dangerous 
in certain situations. It is the job of the FDA and your job as 
Commissioner to protect patients by ensuring the safety of 
drugs.
    And the stronger REMS that had been in place since 2019 
included safeguards to protect patients from unnecessary risks 
posed by this drug. And given your belief that your review was 
fully comprehensive, I will request full information on all 
literature reviewed by FDA during this process and other 
information related to that specific review. And I will be 
following up with both the letter and questions for the record 
for this hearing about the review.
    So I am just asking, can you provide full and complete 
information on this review to me in a timely manner?
    Mr. Califf. Well, Senator, first of all, thanks for noting 
the places where we will work together. And on this matter, of 
course, we will be responsive to your concerns and in a timely 
manner. I have great confidence in the FDA staff who did this 
review, and it involved a variety of materials.
    And as we also discussed, there are still a requirement for 
reporting adverse events related to this, and they will 
continue to look with due diligence.
    Senator Hyde-Smith. And do you commit to answer all the 
questions that we send you?
    Mr. Califf. I will commit to being responsive to your 
requests.
    Senator Hyde-Smith. And additionally, you said on our call 
that data showed chemical abortion numbers were going down and 
you were certainly glad about that and in favor of that. But 
however, data analyzed by the Charlotte Lozier Institute shows 
the opposite. And chemical abortions now make up more than half 
of all abortions in the United States, in this country. I did 
not realize that.
    And in 2019, chemical abortions jumped 11 percent in 
Mississippi. And this is obviously a very serious concern of 
mine from talking to OBGYN friends. And as you said, you want 
to see the number of abortions going down. What are you doing 
to reverse this trend of increasing chemical abortions and 
actually helping to lower those numbers?
    Mr. Califf. Well, just to be clear, I hope I didn't 
misspeak on our phone conversation. The total number of 
abortions is going down. The proportion of that total that are 
chemical abortions is going up, you are correct. And I think we 
all would like to see as few abortions as possible in our 
future as a general goal. So I hope you didn't take it to mean 
that I was saying that the chemical abortions were going down 
because I didn't intend to say that. It is the total number of 
abortions.
    Senator Hyde-Smith. Okay. But you--obviously you are 
correcting that of what we thought that it was going down and 
you are stating that chemical abortions are going up.
    Mr. Califf. The proportion--actually, I would have to go 
back to the record to see about the total number because of the 
total numbers coming down and the proportion that are chemical 
are going up, I actually don't have the number in front of me 
about the absolute number. I hope that makes sense to you.
    Senator Hyde-Smith. Oh, yes.
    Mr. Califf. Okay.
    Senator Hyde-Smith. Thank you very much.
    Senator Baldwin. Senator Tester.
    Senator Tester. Thank you, Madam Chair and Ranking Member. 
Appreciate you doing this hearing. It is good to see you in 
front of the committee, Doctor. I am glad that you got 
confirmed and I am glad you are here, okay.
    Mr. Califf. Thank you.
    Senator Tester. I just want to talk a little bit about FDA 
and its role in food. I could get you some statistics on what 
has been spent on medicine versus what we spend on food 30, 40, 
50 years ago. You are saying to yourself, where the hell is he 
going with this? And I can tell you right now we are spending a 
lot more money on medicine than we ever did 50 years ago. And 
quite frankly, food is a lot cheaper, which is not a bad thing.
    But in the end, I ask myself things like being a farmer, 
raising wheat, and having wheat being--so many people allergic 
to wheat, okay. Is the staff for life really the staff for life 
today? And the question is for you is not anything more than 
what does FDA, what role does FDA play, if any, in our just our 
general food supply and making determinations whether things 
like grains reduce inflammation, and whether what we are really 
eating is medicine, is going to really nourish is moving 
forward.
    Just curious, and I know this is from outer space coming in 
at you, but I am just curious to know where your vision is for 
the FDA on that, and if they want to play in that, or if they 
do play in that, or if they----
    Mr. Califf. Thanks for that question. And I want to relate 
it to a couple of things. First, Senator Hyde-Smith brought up 
rural health. And, you know, I am a cardiologist. I had a very 
busy intensive care unit practice in North Carolina for many 
years, and I have seen the consequences of having the wrong 
diet.
    My time in Quitman County, Mississippi, was dealing with 
obesity and diabetes as a problem, trying to figure out how to 
get electronic health records to interdigitate to do a better 
job of caring for it. And I would just say we are in the midst 
of it all the time. To point out one other particular thing, we 
talk a lot about vaccines and drugs and PPE for the pandemic.
    We have sort of forgotten about the food supply, which was 
a major crisis, as you remember. And the FDA had a major role 
in helping deal with the supply chain as it related to foods, 
just as one example.
    But on the science basis, and this is really critical to 
some of the discussion going on right now, Senator Baldwin 
referred to the Politico article, there is a thing at the 
National Academy of Sciences, it is called a convergence, which 
means because more of our knowledge is becoming digital, when 
we talk about chemistry, biology, physics, agriculture, and 
nutrition, it is all becoming the same underlying structure of 
knowledge.
    And so there is a real advantage to FDA dealing with the 
kind of things that you mentioned about what is safe and 
unsafe, what are the safe levels? Because across the FDA, we 
have a tremendous amount of scientific expertise. And as you 
know, we do have the responsibility for food labels.
    That is a huge part of what affects the way Americans eat. 
And then finally, you know, and a lot of this is shared with 
the Department of Agriculture, as you well know. But I think we 
are going to be looking, you know, regardless of what you think 
is causing climate change, just look at the--you know, I lived 
in San Francisco until coming back to Washington here.
    Look at what the drought is look like in California right 
now. We are going to have tremendous capability to feed the 
world if we take advantage of the technology that is before us. 
And I think the FDA is almost uniquely equipped to deal with 
that because we deal with it across human health, whether it is 
a drug or device, biologic or food.
    Senator Tester. So, we happen to have some bills, and the 
Administration has done some things on the supply chain for 
food. Senator Hyde-Smith spoke eloquently two days ago on a 
couple of bills that we have that deals with supply chain 
issues in food. And look, in my real life, I am a farmer and I 
do believe that we raise some of the safest food in the world.
    The thought does cross my mind that who is kind of watching 
to make sure what we are doing, because we tend to manipulate 
food all the time, because we know more than we have ever known 
in the history of man, that the manipulation is actually not 
making a sick, that is making us healthy?
    Mr. Califf. Well, Senator Baldwin referred to the metrics. 
I think compared to what I saw in the industry I just worked in 
Silicon Valley, the metrics and readiness of the metrics that 
we have right now related to health are just not where they 
need to be. And I was on a call yesterday with a Dr. Walensky 
at CDC, which keeps a lot of the metrics.
    We have a shared responsibility to upgrade the system 
because there is no reason with our data capabilities now that 
we shouldn't be able to sort of like the weather, you are used 
to, you know, turning on the TV and the weather report is 
saying, here is what is going to happen tomorrow, here is what 
is going to happen a month from now, or here is the next 3 
months.
    The further out you get, the less precise you are. But we 
should have that for our health, too. And in fact, I am 100 
percent sure we are capable of doing it. We just have to work 
with you to get the right funding and the right technology.
    And last thing I would mention about that, we have to work 
with the American people to build confidence that the data that 
comes up is going to be used for good purpose. And I don't want 
to make light of that other responsibility.
    Senator Tester. Well, look, I appreciate your history and 
where you have been and your knowledge, and like I said in the 
beginning, I think it is great you are in this position. I 
think you are the right person for this position. And I look 
forward to your guidance that you can help give Congress to 
make sure that we are meeting the needs of the agency, but 
ultimately the people. So, thank you. Thank you.
    Mr. Califf. Thank you.
    Senator Baldwin. Thank you. We are going to undertake a 
second round of questioning. Dr. Califf, even before the COVID-
19 pandemic, FDA did face backlogs and delays with regard to 
inspections. Last year, a Baltimore facility that was 
manufacturing the J&J vaccine was found to have contaminated 
material in their vaccines. And a recent report cited problems 
at an infant formula manufacturing site that left babies sick.
    What you are doing now to ensure more rigorous inspections 
are occurring? What are your plans for ramping those things up 
in the future? And the budget is requesting an additional $23.8 
million for increased site inspections. How will this funding 
support decreasing the backlogs that we have right now?
    Mr. Califf. Thanks for bringing up the chance to talk about 
this. And, you know, I think it is obvious to everybody in the 
midst of a pandemic, it is going to be hard to physically get 
to locations. And we even have cases, as in the infant formula 
case, which is in the press now, where a COVID outbreak in the 
facility makes it so the inspectors sometimes can't go in.
    But we are recovering now in terms of the numbers. We will 
be able to provide you with exact numbers after the meeting if 
you want to have them. But we are recovering. But we do need 
additional funding to get more inspectors out there because 
there is a backlog that is very real. What I also wanted to get 
across in my opening comments and repetitively today that we 
are dealing with an expanding industry, and a global industry, 
and Americans like homegrown food and products, but they are 
buying a lot of things that come from overseas.
    So we have got to put money into technology that allow our 
workforce to get more done, more intelligently using 
computational and artificial intelligence so that they are 
inspecting the right things at the right time.
    Senator Baldwin. Yes. On that topic, you know, aside from 
the physical plant inspections, tell me about the current 
availability of the technology and tools that you are 
describing, and how quickly those could be implemented to 
supplement the physical inspections.
    Mr. Califf. Well, I think the best way to say it is there 
is a synergy here between the plans for the people and the way 
the technology works. So just think about yourself, for better 
or worse, the way you buy things now by looking at on the 
Internet, there is three dimensional viewing you can do. You 
can test that all out and it is all done without having to 
travel and physically go to the store.
    Now, some of us will wish we more often physically went to 
stores nearby, but you can do that because of technology. So 
then imagine an FDA inspector at a mail facility and I would 
urge you to go look at this. Americans are buying all sorts of 
stuff, much of which is dangerous.
    And an inspector has to record tremendous amounts of data 
when something is picked up because every importer has a 
recourse to go to court to contest seizures and findings. 
Imagine that you are having to use the technology like you were 
buying stuff 15 years ago and then apply it to an inspector on 
the job today. A lot of things that the inspectors would 
otherwise stop are getting through because there is just not 
time to do it.
    And I think if we modernize the technology, they will be 
much more efficient. I think Dr. Hoeven got it right. You know, 
if we are synergistic, it is not linear it is more than that. 
But it is an ongoing, at least a five year effort.
    And if I might say so, the Federal Government in general is 
not ideally suited for the kind of technology outfit that is 
needed. And I think we are all going to have to work together 
at HHS on this issue. I know CDC has talked on the Hill 
extensively about the needs there.
    Senator Baldwin. Thank you. Senator Braun, have I given you 
enough time to ask your questions? Okay. Go right ahead, you 
are recognized.
    Senator Braun. It would seem like it, but I am prepared.
    Senator Baldwin. Excellent.
    Senator Braun. Thank you, Madam Chair. Good to see you 
again. I think it has probably been covered somewhat, but I 
know that your leadership at the FDA in 2016 and we have 
discussed it before to kind of weaken the risk evaluation and 
mitigation strategy protocol on the drugs used in chemical 
abortions. And studies have shown that the rate of abortion 
related emergency room visits after chemical abortions have 
risen by about almost 500 percent.
    And when we last spoke, you testified that the FDA had 
filed a court document about the evaluation of the data on the 
chemical abortion drug and that the reevaluation is imminent. 
My question is, why has the FDA allowed these weakened 
protocols for chemical abortion drugs, and are they undergoing 
FDA and court review for safety and efficacy?
    And a follow up would be, should REMS be strengthened to 
protect women from dangerous effects from chemical abortion 
drugs as well? So if you could answer those two questions, I 
would appreciate it.
    Mr. Califf. Yes. Senator Braun, we did cover this a little 
bit earlier, but I know that you are very interested in this 
and see this topic as very important. As we discussed before, 
the Commissioner doesn't make decisions about individual 
products.
    There is a team within FDA that does that. But of course, 
Commissioner gets to see the work. I have great confidence in 
the team. They have thoroughly done the job and they are going 
to continue to monitor as required by law.
    There is a requirement to submit adverse events to the FDA 
and they will continue to look. And if there is a need for a 
change, I have every confidence they will do so.
    Senator Braun. Well, I think as we transition to where that 
looks like the modality preference, I think it needs to be paid 
attention to. And it will be interesting to see if the same 
standards are adhered to with that as maybe what has been done 
in the past. Let's move to another subject on opioids.
    The National Academies report on combating the opioid 
epidemic suggested the FDA develop a new process for reviewing 
the safety of all approved opioids. I understand that you were 
confirmed not too long ago, obviously, but this information has 
been out there since 2017. Since your confirmation, have you 
reviewed the recommendations from the National Academies 
report?
    Mr. Califf. Yes. In fact, I am a member of the National 
Academies, and I asked for that report during my tenure in 
2016. So I followed it pretty carefully since I thought it was 
an important component of changing the paradigm that the FDA 
was working under.
    And there is now a draft guidance that takes into account 
one of the most important parts of that report, which is 
normally the way a decision about risk and benefit for a drug 
works is, is the risk and benefit to the individual to whom the 
product is prescribed, but that is not adequate for opioids.
    Senator Braun. So you have done a formal review of it in 
addition to reading it.
    Mr. Califf. Yes. And there is a--well, when you say formal 
review, yes. I mean I have read it and I have thought about it, 
and we have a whole team working on implementing a number of 
changes.
    Senator Braun. So then I guess to cut to the chase, when it 
comes to any rulemaking that might change vis a vis that 
report, do you anticipate that happening and when?
    Mr. Califf. I think you will see over the course of the 
next year or starting imminently, and you are probably familiar 
with the opioid summit that happens in Atlanta that Congressman 
Rogers started over a decade ago. I attended that and gave a 
very detailed speech about our plans. And it is a matter of 
public record, and we will make sure your staff gets it and you 
can look at it.
    There are a whole number of things, some of which are in 
process now and some of what you will see in the next month, 
and there are--I must say, there are a couple of areas where we 
are probably going to come back to you if there's concurrence 
within HHS and say that we need some new legal authority. Just 
to give an example of one that I am particularly concerned 
about that we have talked about a lot.
    Right now, the FDA doesn't have legal authority when it 
comes to a new drug application to require that it provide 
superiority to drugs that are already on the market. The 
comparator legal comparator standard is compared to placebo or 
nothing.
    And I think for opioids don't work like other drugs. And I 
think that is something that I would like to see happen that 
may require something from Congress to institute that. That is 
one example.
    Senator Braun. I think at the level of where the crisis 
still is relative to opioids, that additional authority and 
then subsequent rulemaking that tries to do more there, most of 
us would expect that to happen and would be warranted.
    Mr. Califf. Well, thank you. And I just want to remind you, 
as we discussed, that between my two sons, we started a not for 
profit in Dayton, Ohio, that dealt with everything from detox 
for people that were trying to withdraw from opiates all the 
way up to finding jobs and dealing with the legal system.
    So I have a pretty comprehensive list. And I know Dr. Gupta 
from West Virginia, who is now at Office of National Drug 
Control Policy (ONDCP), just released the plan from the 
Government. And we are totally in support of that, and we will 
work as hard as we possibly can. And I have seen this in real 
life in Ohio, and it is something we have got to deal with.
    Senator Braun. So on both issues, we will be watching. It 
sounds like you are willing to engage on it. And thank you for 
the time today.
    Mr. Califf. Thank you.
    Senator Baldwin. Senator Hoeven.
    Senator Hoeven. Thank you, Madam Chair. So back to the 
advanced manufacturing and drugs, biological products, and 
devices. You know, how do we do more to produce and manufacture 
those things here at home? So, clearly something we need to do, 
and people are well aware of it.
    Mr. Califf. It is so essential. And I was serving on the 
National Academies Supply Chain Committee until I was 
nominated, and I had to drop off. Their report is now out so I 
can talk about it. And I think it is useful to divide this into 
several categories. And there are other reports that you have 
in hand from various agencies.
    Resilience of the supply chain is a critical issue. And I 
think given the internationals strife right now, things that we 
didn't think were possible, we now have to also potentially 
anticipate. So we have got to have a resilient manufacturing 
base that Americans have access to. That doesn't mean that 
everything needs to be made in America because there is value 
in international trade, I think, as everyone knows.
    But if we get ourselves in a situation where another 
country could either due to a natural disaster, or intention, 
or the way markets would cut off our supply. That is a real 
problem. So FDA has been working hard on this, as you know, and 
we appreciate the funding that we have gotten. And a lot of 
energy is being spent on upgrading our own capabilities. The 
reason the FDA needs to be so involved, I see it as twofold.
    You might say, why does an industry just do this? Well, the 
markets don't necessarily work that way. And so there are areas 
where we think we can help industry quite a bit by creating 
prototypes and public, private partnerships. And the advanced 
manufacturing for our messenger RNA is one example that is 
pretty far along that you will see come to fruition fairly 
soon.
    But the other part is, as we get to the more advanced part 
of advanced manufacturing, where you can, for example, make 
drugs locally in a small little shop, which is, you know, going 
to become possible sometime in the near term, the future of 
regulating that means that we have got to be sure that we can 
tell the difference when a good job is being done and not a 
good job.
    And so the funding is much appreciated. We got more 
requests but the purpose is for exactly what you said. We think 
Americans should be secure, that the essential products that 
they need, whether it is food or drugs or devices, will be in 
hand when the time comes using all of our capabilities and 
technology.
    Senator Hoeven. I think so. And I think that is an area 
where, you know, we do have to put an emphasis and a focus on, 
because I think the public very much wants just given what is 
going on and has gone on nowadays with COVID and everything 
else. Along those lines, investment in gene therapy.
    You know, clearly we need to do more there. Talk about 
that. I didn't see a significant request in the budget for 
investment, you know, to expedite reviews for gene and cell 
therapies. Clearly, though, that is an area with incredible 
promise. So would you please address that?
    Mr. Califf. This is something that personally, as an 
intensive care unit doctor, I am very interested in and have 
spent a lot of time in the rare disease communities. In my time 
at Duke, colleagues developed the treatment for Pompe disease, 
which used to almost uniformly lead to death of young children 
and now gives some life.
    So I very much want to make this work. We did get some 
funding in this past year's budget due to some overlap issues. 
You know, people said, well, what more do you want? And we do 
appreciate the funding we have gone. But I also want to report 
that in the user fee agreements, the industry recognizes that 
this is an area where FDA needs more resources.
    So we have, I think, reached a good agreement and the user 
fees to increase the support for this area. That doesn't mean 
we are not going to come back to you later or whether areas 
where the user fees aren't going to cover.
    And again, I think a general principle, as I work with you 
all this time around, I am much more aware now of the role of 
FDA and Government in places where there is not an incentive 
for industry to develop things that society needs.
    And I think what happened with a vaccine is like the super 
example where the investment that we made early in getting all 
members, Government and private, to the table made a big 
difference. There are other areas, I might point to antibiotics 
is another area, and some areas of gene therapy and 
regenerative medicine where there is not a ready market, or no 
one is sure how it is going to be paid for.
    So we will be back in touch about that for sure.
    Senator Hoeven. Yes. And I think it really does also 
correlate into being ready to prevent the next kind of 
pandemic, so we don't have what happened with COVID-19.
    Mr. Califf. We will do everything in our power on that. And 
I do want to call your attention there to One Health, which is 
something I think this committee ought to have a particular 
interest in. I have a daughter-in-law who is a veterinarian, so 
I have heard a little bit about this personally also. But even 
going back 15 years, Duke started a medical school in 
Singapore.
    And I saw firsthand what was happening with transmission of 
viruses and bacteria from animals all over the world to humans 
and back and forth. It is due to the fact that we all travel 
these days and the international commerce. So essentially, then 
my first stint at FDA, I saw the technology evolving. Now, of 
course, we have whole genome sequencing so we can actually 
track.
    But the informatics of this and the technology involved is 
far advanced over what we currently have on hand. But so we 
have got an ask in about One Health to start something in the 
center for Veterinary Medicine. I want to put in my pitch here. 
You all are all from rural areas. So I think CBM is the most 
underappreciated part of the FDA.
    And typically, people only think about it when, you know, 
when we had the dog food problem, a lot of people wrote in and 
probably the biggest response until COVID times. But we do have 
a One Health request in which is mostly oriented to how do we 
create a data systems that allow us to track what is happening 
around the world so that we can intervene early and prevent the 
next pandemic.
    Senator Baldwin. Thank you. Senator Hyde-Smith.
    Mr. Califf. Thank you very much, Madam Chairwoman. I am 
just going to change to another issue right now on medical 
gases. More than a million patients use medical gases every day 
with like oxygen playing a critical role when we were 
responding to COVID-19.
    And the Food and Drug Administration Safety and Innovation 
Act of 2012 did an APA to issue regulations for medical gases 
by July of 2016. However, no regulations had been issued to 
date despite the requirement in place by law. And there is a 
plant in Walnut, Mississippi--I think the population of Walnut, 
Mississippi is a little over 700 people, but they produce 
medical gases.
    And the lack of regulations surrounding medical gases make 
it very difficult for my constituents in Mississippi to produce 
these lifesaving products and they have approached us with this 
issue. But where does the significantly overdue rulemaking on 
medical gases currently stand? And I know you are probably 
going to have to get back with me on this since you wouldn't 
know that immediately, I wouldn't think.
    And just asking for your commitment that the FDA will 
publish this rule--there is a deadline of May of 2022, right, 
this right now, which was set in the fall of 2021 on the 
unified agenda. And I would just like to see if you had any 
responses to that and how they should be regulated rather than 
continuing to be regulated as drug products.
    Mr. Califf. You know. Well, thank you for the question. And 
I am getting a little worried now because maybe I am so old 
that I can say I have been involved in just about everything. 
But in my younger days, I founded a company dealing with nitric 
oxide, which is in that category.
    And so I am very familiar with the issues and also an 
intensive care practice we use a lot of medical gases. And we 
will have to get back with you, but just about one thing, my 
understanding is there was a regulation. It didn't quite go 
over that well. There were other issues brought up, and we are 
taking those into account now.
    And my understanding is that we are on track. And it is 
part of the unified agenda, so it is definitely a priority, not 
just at FDA, but across the Administration. So we will get back 
with you on the details. But I think I have a pretty good 
understanding of the issues that are involved, and we will make 
sure they are taken care of.
    Senator Hyde-Smith. Great. Thank you. I appreciate that.
    Senator Baldwin. We are going to do a speed third round of 
questions. Okay. I think I have a couple more and ranking 
member does too. So we spoke earlier about the proliferation of 
synthetic nicotine products. And in the 2022 omnibus, that 
loophole was closed.
    We made it clear that FDA had the authority to go after bad 
actors in this space to protect public health. I would love a 
report on progress in this space. Dr. Califf, can you provide 
an update on the FDA's efforts to address synthetic nicotine 
products? How many companies have filed applications seeking 
authorization? And are there additional resources that need to 
be applied to this part of the mission?
    Mr. Califf. Well, thanks for bringing this up. And it gives 
me a chance to thank Congress for rapidly passing a law, 
because just for those not familiar with the issue was, we are 
regulating nicotine, but the law said tobacco and products 
derived from tobacco. And of course, if you are making nicotine 
in a synthetic laboratory, you can claim that it doesn't fall 
under the regulation.
    So that loophole was closed in a very rapid timeline, in 
about a month for people to absorb it, then a month or two to 
get applications in for those who wanted to go through regular 
pathways that are available. And we will have to get back with 
you on the exact numbers.
    But by mid-May, we should pretty well have this cleared up 
with those who shouldn't be on the market off of it, and or at 
least getting warning letters, and those who are applying, 
having their applications reviewed. I will take this moment to 
point out that all of our work at the Center for Tobacco 
Products has been done without user fees from the vaping 
industry. So, and you are aware of, you know, 6.7 million 
products.
    Actually I sort of heard the number, but when I came into 
the chair and they said, what we are trying to deal with 6.7 
million products that is a tall order. And a lot of work has 
been done, basically borrowing people's time from other funded 
areas. So we have got a request in for $100 million in user 
fees from the vaping industry because we still got a lot of 
work to do. Two million, at least two million teenagers are 
currently vaping.
    Knowing what we know about nicotine addiction, and it is 
safe to assume the majority of those are already seriously 
addicted to nicotine. And I got to say, talking to my two 18 
year old teenage grandkids, I am a little bit worried that 
there is underreporting going on among the teenage population, 
which would be understandable.
    I think this is a big problem that we want to work on and 
help with, but we have no resources dedicated to it now.
    Senator Baldwin. Not to mention, my understanding is that 
there is not an approved treatment for adolescents and youth as 
there are for adults in this space.
    Mr. Califf. Perhaps another time I would love to visit with 
you. And I think a general comment I would make is that if you 
look at people currently using tobacco products or addicted to 
nicotine with vaping, we need a care package to help them quit. 
People don't realize that the addictiveness of nicotine ranks 
right up there with opioids.
    Now, you know, nicotine doesn't make you stop breathing. So 
there is not an acute overdose issue in general. But this is 
not an easy thing to quit. And we actually, I think, could do a 
better job of putting together products, including digital 
technologies now that could help people trying to get off of 
this addiction.
    Senator Baldwin. Thank you. Senator Hoeven.
    Senator Hoeven. Thanks, Madam Chair. The public health 
emergency declaration in 2020 allows the FDA to issue emergency 
use authorizations. But when that public health emergency 
declaration expires, that doesn't mean your emergency use 
authorizations necessarily expire. So how do you plan to phase 
those out?
    Mr. Califf. Yes. So that is a great question and one that 
is sort of pressing now with the funding issue that is going 
on. We need to have these products transitioned at some point. 
The question of when is important. So on the drug side, this 
has pretty much been, I don't want to call it straightforward, 
but the same studies that were used for a EUA, as continued 
with modifications, are producing the data that you would need 
for a standard approval.
    So I think we feel on the drug side that we are in pretty 
good shape over time to phase out the EUAs and phase on the 
standard approval that a company could use. On the device, 
there is a definite plan in place that would involve 
notification and transition. We are sort of waiting on that 
time to come.
    The device side, I think, you know, has many more products 
because it includes, you know, all sorts of tests and things 
that don't usually have the same level of study that would be 
needed even for an Emergency Use Authorization (EUA), for a 
drug. And so there is work to do there, but there is definitely 
a plan, and we would be glad to get back to you with the 
details of that plan.
    Senator Hoeven. Going back to actually the question that 
the chairman started with, some of the articles that have been 
critical of the FDA recently in the food area as probably even 
more so than on the drug side with reference to the structure 
at FDA.
    So as you are doing your planning here, and as we talk 
about not only updating your technology, but the other things 
you want to do in terms of a strategic plan, goals, metrics, 
benchmarks, all those kind of things, you know, creating not 
only that stability, but strengthening the agency, whether it 
is the technology or anything else, both during your tenure, 
but for the future, are there restructuring or structural 
aspects to that that you are, you know, kind of considering in 
that strategic plan, you know, that we should be aware of, 
talking about, looking at?
    Do you think that is going to be part of what you want to 
do as you embark on this long term planning?
    Mr. Califf. Again, at my age, I have worked in every 
industry. I have been in, you know, health care, academic 
medicine, computer industry, biotech, Government. I think there 
are always are opportunities to improve structures, so I would 
say everything is on the table, but I don't think the problems 
that I have discussed today, that the primary problem is one of 
structure.
    There is some elements of structure at FDA that would be 
really hard to change, like, you know, the drug device, 
biologic food centers, and animal centers. They each have 
constituencies and industries that they interact with and 
ecosystems. And yet if you look across centers, as I have said 
before, there is a common base of science and technology that 
we need.
    That is where I think we need to work. And I don't know if 
you have looked at the latest Federal regulations on changing 
structures and Government agencies, but if you have like a good 
night when you want to take a, you know, go to sleep, you 
should try reading it. It is a challenge though.
    I don't want to wait on those structural changes to do the 
things because I think in most businesses and systems I have 
been in, having the right functions, having the right people 
doing the right functions makes the biggest difference.
    You can spend a lot of time changing a structure, and if 
you don't really figure out how to get the functionality right, 
you change your structure and you can write about it and talk 
about it but doesn't solve the problem. But the short answer 
would be everything is on the table. I don't think structural 
change is a primary issue that we need to deal with.
    Senator Hoeven. Okay. The reason I ask is because of your 
experience, your broad experience in the medical industry, both 
in the public and private sector, but also the fact that you 
had a stint at FDA before.
    So you are coming in, you are looking at these things, 
gives you some perspective, and so I am just curious as to your 
analysis of what, you know, what is going to make this agency 
as effective as it can possibly be?
    Mr. Califf. Yes, Senator. I mean, you are right to point 
out the FDA has been criticized. In fact, you are not FDA 
Commissioner if you are not waking up at 5:00 a.m. every day to 
a whole list of criticisms. That was true in 2016. It is true 
today.
    But one of the things that made me want to come back and 
that gave me great solace when I got here, is if you look at 
the center directors at the FDA, they have been there a while. 
They are very dedicated to their work. They keep coming to work 
every day despite all the criticism.
    And I know what their capabilities are. So I think there is 
continuity. It is important. And I think you pointed out a 
major issue we need to deal with, which is as the Commissioner 
is changing every year, priorities change, and every new person 
has some new things, and they don't necessarily want to be held 
to the old person's way of thinking. So more continuity there, 
I think, would make a big difference.
    Senator Hoeven. Thank you.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Baldwin. Thank you. Dr. Califf, thank you so much 
for being here today. I think we had a good interaction and 
discussion, and I look forward to working with the FDA and 
members of the committee as we start the 2023 appropriations 
process this year. Questions for the record are due by next 
Thursday, May 5th. And we would certainly appreciate the FDA's 
responses within 30 days. And with that, this hearing is 
adjourned.

    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
            Questions Submitted by Senator Dianne Feinstein
    Question. Thank you for your past leadership at FDA and continuing 
to prioritize efforts on ensuring the safety of personal care products. 
We spoke last week about the FDA still being woefully underequipped to 
ensure the safety of personal care products that we use on a daily 
basis, such as shampoo and deodorant.
    What authorities and resources does the FDA need in order to 
adequately protect Americans from harmful cosmetics?
    Answer. FDA's regulatory authority for cosmetics, which dates to 
the 1938 Food, Drug & Cosmetic (FD&C) Act, gives FDA very limited post-
market authority over cosmetic safety. In order to adequately protect 
Americans from harmful cosmetics, FDA would need explicit authority to: 
(1) require domestic and foreign cosmetic firms to register their 
establishments and list their products with FDA; (2) require domestic 
and foreign cosmetic firms to report serious and frequently occurring 
adverse events to FDA; (3) promulgate and require compliance with Good 
Manufacturing Practices regulations; (4) require domestic and foreign 
cosmetic firms to allow FDA access to records (including consumer 
complaints and safety data) during a routine or for-cause inspection; 
(5) require recalls for cosmetics that pose serious risk to the public 
health; and (6) require listing of known cosmetic allergens in the 
ingredient list on the product label for all cosmetic products. 
Additionally, FDA would need adequate funding for the increased 
resources needed to modernize FDA's Cosmetic Safety Program. Such new 
authority and additional funding would enable FDA to significantly 
strengthen its post-market surveillance systems and better protect the 
public health by helping to ensure the safety of cosmetic products and 
ingredients that are in use in the United States. A legislative 
proposal to this effect was offered in the fiscal Year2023 FDA 
Congressional Justification.
    Question. What concerns to public health has FDA documented as a 
result of lacking these authorities and resources?
    Answer. As part of FDA's work to protect consumers from unsafe 
cosmetic products on the market, the FDA routinely monitors the market 
for products and ingredients that may pose a public health risk. Over 
the past 17 years there have been numerous public health issues related 
to cosmetic safety that highlight FDA's limitations under current law 
in regulating these products, for example:

  --Asbestos Contamination of Talc-Containing Cosmetics: FDA is 
        continuing its efforts to have additional talc-containing 
        cosmetics tested for asbestos. However, the 1938 FD&C Act does 
        not require cosmetics establishments or manufacturers to 
        register their facilities or file cosmetic product ingredient 
        statements with FDA. Thus, the major source of information 
        available to FDA about cosmetics marketed in the U.S., and 
        their ingredients, is the Voluntary Cosmetic Registration 
        Program (VCRP). Because the VCRP is voluntary, it provides FDA 
        with only a limited picture of cosmetics that are being sold to 
        consumers. Furthermore, the lack of information makes it 
        difficult for the agency to efficiently target its limited 
        inspectional resources.

  --Hair products (shampoo and conditioners): During an inspection FDA 
        became aware of more than 21,000 consumer complaints of hair 
        loss, including alopecia associated with one company's hair 
        products. Because companies are not required to show their 
        consumer complaint records to FDA, the company has not provided 
        all of these consumer complaints to FDA.

  --Microbiological contamination of cosmetic products: A number of no-
        rinse cleansers, wipes, washes and mouth rinses have been 
        recalled from the market due to potential microbiological 
        contamination. For example: in early 2018, a no-rinse cleansing 
        foam contaminated with Burkholderia cepacia caused outbreaks in 
        several health care facilities in six States. In 2020, a baby 
        wash was recalled because of potential Pseudomonas aeruginosa 
        contamination. These outbreaks emphasize the importance of 
        following appropriate good manufacturing practices to reduce 
        the risk of microbial contamination of cosmetic products during 
        processing.

  --Lip products: FDA received 126 reports between August 6, 2014 and 
        June 12, 2017, of consumers developing rashes around the mouth 
        as well as blistering and cracking of the lips following the 
        use of certain lip products. FDA was not able to determine the 
        cause of the reactions because of inadequate information 
        provided by the company. The law does not require cosmetic 
        companies to list known cosmetic allergens found in fragrances 
        or flavors in the ingredient list on the product label or share 
        their safety data, or consumer complaints with FDA. In 
        addition, the complaints that came to FDA mostly from consumers 
        did not provide enough information to determine why some 
        consumers experienced reactions when they used these products.

    These examples are just a few that highlight the challenges FDA 
faces when working to protect the safety of cosmetic products in the 
marketplace. With the growth and innovation in the cosmetics industry, 
many new cosmetics products are being marketed to consumers in the U.S. 
It will be challenging to ensure the safety of these products without 
updated authorities and new resources. For example, cosmetics products 
marketed as containing probiotics (i.e., live microorganisms) are found 
increasingly in the cosmetic marketplace, with potential implications 
for skin integrity and health, and product safety, and preservation. 
Yet, there is no requirement for manufacturers to provide safety data 
to FDA for such ingredients. In light of both the pace of innovation 
and the growth of the industry, FDA has inadequate, incomplete, and 
often outdated baseline data on marketed cosmetic products and 
ingredients. FDA also has limited data on serious or frequent adverse 
events associated with cosmetic products, due to the lack of mandatory 
notification of adverse event reports. FDA appreciates your ongoing 
support for modern cosmetic authorities and adequate resources for the 
FDA Cosmetic Safety Program.
    Question. In your previous tenure at FDA, you oversaw 
implementation of many food safety regulations stemming from the ``Food 
Safety Modernization Act.'' I certainly appreciate the strides that the 
agency has made, but outbreaks of Listeria, Salmonella, and E. coli 
continue to happen regularly. What steps are you taking to implement 
all the authorities provided to FDA in the ``Food Safety Modernization 
Act,'' including for agricultural water?
    Answer. The FDA Food Safety Modernization Act (FSMA) is 
revolutionizing how we regulate our food supply. Since the law's 
passage in 2011, with the support of Congress we have been working 
diligently to implement the landmark law and modernize our food safety 
capabilities. We have published eight foundational final rules and more 
than 50 draft and final guidances to help transform our Nation's food 
safety system into a prevention-oriented framework. Currently, we have 
teams continuing the work needed to fully implement FSMA through 
additional rulemakings (such as for food traceability recordkeeping 
requirements), guidance development, training, inspections, and other 
implementation activities. As with any complex, scientific issue, FSMA 
rulemakings have involved research, analysis of data, and, in certain 
cases, engagement with the scientific community to inform decision-
making and adjustments when new science emerges. Stakeholder input also 
is essential to ensure that requirements we put into place are feasible 
to implement once enacted.
    This is true for FDA's agricultural water requirements. FDA 
originally promulgated requirements for pre-harvest, harvest, and post-
harvest agricultural water in 2015 as part of the Produce Safety Rule. 
When it became apparent that some provisions were too complex and 
difficult to implement, and as new science emerged as part of our 
investigations of produce-related outbreaks, the Agency pursued a 
rigorous and thorough process for engaging with stakeholders as FDA 
considered the practical implementation of the agricultural water 
requirements and how to best achieve related public health protections 
for covered produce other than sprouts. FDA experts participated in 
hundreds of farm visits to better understand the diversity of uses of 
agriculture water, as well as listening sessions and meetings with 
industry, consumer groups, academia, and regulatory partners. The 
Agency believes this was time well-spent to ensure that the proposed 
approach would be deeply rooted in the most current science and 
protective of public health. In late 2021, these efforts culminated in 
proposed new requirements for pre-harvest water for covered produce 
other than sprouts that we believe would be both feasible and 
effective, if finalized.
    Looking ahead, FDA is committed to building on the work of FSMA 
while taking a new approach to food safety that leverages technology 
and other tools and approaches to create a safer and more digital, 
traceable food system. This approach, which we're calling the New Era 
of Smarter Food Safety, aims to bend the curve of foodborne illness in 
this country by reducing the number of illnesses attributed to FDA-
regulated foods.
    Question. As we have discussed previously, the creation of 
appropriate regulations for the use of antibiotics in livestock must be 
a priority for the FDA. For many years, I introduced the ``Preventing 
Antibiotic Resistance Act,'' which would have required a medical need 
before administering antibiotics to food-producing animals. I 
appreciate the steps FDA has taken since 2017 to implement regulations 
in line with the provisions in my bill, but I am concerned about the 
potential for continued overuse of antibiotics in animals under the 
carve-out for preventive use. In broiler chickens, for example, the 
window FDA has allowed for administering preventive antibiotics is 
longer than the chicken's lifespan. What steps are you taking to ensure 
that antibiotics administered to food-producing animals have a 
medically-relevant need and appropriate duration?
    Answer. Establishing appropriately targeted durations of use for 
medically important antimicrobials used in the feed of food-producing 
animals is a priority and a component of FDA's overall effort to 
support antimicrobial stewardship in animals and combat antibiotic 
resistant bacteria. FDA has already initiated public comment on this 
issue and is gathering the data necessary to address the issue in a 
science-based manner, including through funding several ongoing 
studies. Our primary objective is to get product dosage regimens 
updated to better target when and for how long a medically important 
antimicrobial drug may be used in the feed of food-producing animals to 
provide effective therapy while minimizing drug exposure and resistance 
selection pressure.
    Question. Research has identified phthalates as neurotoxic 
chemicals that can do lasting harm to child brain development and 
increase children's risks for learning, attention, and behavioral 
disorders. Phthalates have also been long known to harm reproductive 
tract development in males and there is growing evidence that 
reproductive problems also occur in females. In addition, recent 
analysis of fast food restaurants found phthalates were detected in the 
vast majority of sampled foods, demonstrating that phthalates leach 
from processing equipment and packaging into food. In 2016, health and 
environmental organizations petitioned FDA to ban harmful chemicals 
called phthalates in food packaging and processing materials.
    What actions has FDA taken since then in response to this petition?
    Answer. On May 19, 2022, FDA issued a rule to amend its food 
additive regulations to no longer provide for most previously-
authorized phthalates to be used as food additives because these uses 
have been abandoned by industry. FDA revoked authorizations for the 
food contact use of 23 phthalates and two other substances used as 
plasticizers, adhesives, defoaming agents, lubricants, resins, and 
slimicides. The Agency also issued a request for information about the 
current specific food contact uses, use levels, dietary exposure, and 
safety data for the remaining phthalates still authorized as 
plasticizers for use in food contact applications.
    In addition, over the last few years, FDA has analyzed numerous 
samples of PVC and non-PVC fast food packaging and food contact 
articles (for example, gaskets, tubing, and conveyer belts) available 
on the U.S. market for the presence of phthalates. Data from these 
studies were published in 2018, 2021, and 2022, and suggest that 
manufacturers have been replacing phthalates as their primary 
plasticizer with alternative compounds. For example, no phthalates were 
detected in eight representative samples of food contact tubing that 
FDA obtained and analyzed in 2021. That evidence suggests that at this 
time the use of phthalates in food contact applications is limited and 
consumer exposures to phthalates from food contact uses is decreasing.
    Question. Does FDA have any plans to address the issue of harmful 
phthalates in food packaging and other food contact materials this 
year?
    Answer. As mentioned above, FDA issued a request for information 
about the current specific food contact uses, use levels, dietary 
exposure, and safety data for the remaining phthalates still authorized 
as plasticizers for use in food contact applications. The Agency may 
use this information to update the dietary exposure estimates and 
safety assessments for the permitted food contact uses of phthalates.
    FDA also intends to continue work investigating possible sources of 
phthalates in food contact applications. The Agency has recently 
evaluated the effectiveness of portable devices that industry and FDA 
could use to identify plasticizers, including phthalates, in PVC tubing 
as part of our continued efforts to identify phthalates in food 
packaging and processing materials.

                                 ______
                                 

            Questions Submitted by Senator Patrick J. Leahy
    Question. The COVID-19 pandemic has had a devastating effect on 
opioid usage across the Nation. The Vermont Department of Health 
recently reported that nearly 210 Vermonters died from opioid overdoses 
in 2021, the highest number of fatal opioid overdoses the State has 
ever recorded. A large contributor to the increase in overdose cases 
has been the presence of fentanyl in counterfeit opioid products. The 
FDA's budget includes a requested increase of $30 million above FY22 to 
support the Administration's goal of ending the opioid epidemic. How 
will this funding be used to combat the explosion of counterfeit 
pharmaceuticals and fraudulent products?
    Answer. The Agency is actively targeting illegal online sales of 
unapproved and misbranded opioids, including fentanyl, through 
surveillance and compliance activities. Our collaboration with the 
Department of Justice has led to successful prosecution of numerous 
defendants for illegal conduct involving the online sale of 
prescription opioids. Unfortunately, this exemplifies the availability 
of counterfeit and unapproved opioids for sale on the internet. We 
continue to send warning letters to operators of websites marketing 
potentially dangerous, unapproved and misbranded opioids, as well as 
other controlled substances such as benzodiazepines and Schedule II 
stimulants. In June 2020, FDA partnered with the National 
Telecommunications and Information Administration to launch a 120-day 
pilot with participating domain name registries to help reduce the 
availability of unapproved opioids illegally offered for sale online. 
As a result of the pilot, nearly 30 websites illegally offering opioids 
for sale became inaccessible to the public. Since 2018, FDA has hosted 
three Online Opioid Summits to look for innovative solutions to prevent 
the illegal sale of opioids through internet platforms and services, 
with the most recent held virtually in September 2021. In April 2022, 
FDA and DEA issued joint warning letters to operators of two websites 
illegally selling Schedule II stimulants, including amphetamine drugs 
products marketed as Adderall. FDA has also recently approved research 
funding for the development and deployment of new survey modules to 
collect self-reported data on awareness, experiences, etc. with 
falsified/counterfeit drugs.
    The decision to buy opioids on the internet and through other 
channels where counterfeit medications are more likely to be 
encountered reflects the significant misuse and use of opioids. Some of 
this use may be spurred by exposure to opioids for pain management. 
Inappropriate opioid prescribing and lack of proper disposal of opioid 
pain medications might contribute to the exposure. It may also reflect 
undertreatment of opioid use disorder (OUD). The tragic deaths that 
result from use of opioids and other drugs contaminated with fentanyl 
or fentanyl analogs, might be prevented by better access to opioid 
overdose reversal agents.
    In addition to continued focus on counterfeit opioid products, the 
$30 million increase in funding will go to address these underlying 
issues, by increases in staff and targeted funding into research and 
policy development in the following areas:

  --Additional research to address appropriate pain management as well 
        as opioid and polysubstance misuse, use, and overdose. These 
        activities include dynamic system modeling and analysis of 
        real-world evidence (e.g., surveys of persons using opioids 
        alone and in combination with other substances).

  --Supporting the development of novel treatments for opioid overdose 
        reversal and for OUD. These activities include modeling to 
        examine the role of naloxone administration paradigm on ability 
        to revive a person experiencing drug overdose when opioid use 
        is suspected (single substance and polysubstance use).

  --FDA's implementation of SUPPORT Act Section 3041. These activities 
        include studies on opioid packaging and disposal.

  --Expanding and promoting prescriber education to improve pain 
        management, reduce inappropriate prescribing of opioids, 
        advance development of evidence-based clinical practice 
        guidelines for acute pain, and broaden patient access to OUD 
        treatment.

    In addition, some of the funding will be invested in our Opioid 
Data Warehouse to enable FDA to use the best data and analytics in 
implementing policy and identifying emerging issues that need to be 
addressed.
    Question. 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. health care system $338 billion in 2020 
alone. Despite this, many generic drug makers still report challenges 
in bringing these more affordable drugs to market. This includes slow 
application turnarounds from the FDA and continuing anticompetitive 
actions from brand name drug companies. What does the FDA need to bring 
more generic drugs to market and bolster anticompetitive enforcement?
    Answer. FDA is committed to increasing competition for prescription 
drug and biological products to help facilitate the entry of lower-cost 
alternatives and improve patient access to affordable medicine. FDA is 
working to advance the Administration's initiatives outlined in the 
President's Executive Order on Competition in the American Economy to 
increase competition and reduce gaming of the system, including through 
FDA's Drug Competition Action Plan and Biosimilars Action Plan, and 
will continue these and other efforts this year.
    The President's fiscal year 2023 budget proposal also included a 
legislative proposal titled ``Amend the 180-Day Exclusivity Provisions 
to Encourage Timely Marketing of First Generics''. FDA is proposing to 
amend sections 505(j)(5)(B)(iv) and (D)(i)-(iii) of the FD&C Act, more 
commonly known as ``Hatch-Waxman'', that govern the 180-day patent 
challenge exclusivity provisions to specify that FDA can approve 
subsequent applications unless and until a first applicant begins 
commercial marketing of the drug, at which point approval of subsequent 
applications would be blocked for 180 days, ensuring that the 
exclusivity period actually lasts 180 days (i.e., from the date of 
first commercial marketing by a first applicant until 180 days later) 
rather than multiple years as can occur under current law. In practice, 
patent challenge exclusivity is not operating as expected to encourage 
early generic entry, because this exclusivity is often ``parked'' by 
first applicants who either receive approval but do not begin marketing 
for extended periods of time following approval, or by first applicants 
who delay in seeking final approval of their ANDAs for extended periods 
of time. FDA believes this proposal would substantially increase the 
likelihood that generic versions of patent-protected drugs will come 
into the market in a timely fashion, and that multiple versions of 
generic products will be approved quickly (leading to significant cost 
savings).
    Question. As the sale of CBD and other hemp-derived foods, 
supplements and animal feeds continues to grow in the marketplace, 
there is increasing concern and confusion about the safety of such 
products in light of the continuing absence of FDA regulation. I 
understand one of the barriers may be the FDA's earlier approval of a 
drug made with CBD, even though the CBD in that product may not even be 
derived from hemp. The FY23 Omnibus Bill directed FDA to establish a 
policy of enforcement discretion so it could properly address these 
issues?
    Can such enforcement discretion be used to enable FDA to regulate 
the introduction of hemp into food, dietary supplements and animal 
feed, such as by distinguishing the broad range of hemp CBD products 
currently in the market from the specific FDA-approved drug?
    Answer. FDA understands the significant interest in this space and 
is committed to addressing this issue, including ongoing work to 
evaluate enforcement policy options. While the Agency encourages the 
development of safe and effective therapeutics, many consumers and 
stakeholders want access to more readily available products. With 
respect to potentially relevant pathways outside of the drug approval 
context, it should be noted that even if there were no restriction on 
marketing certain drug ingredients in dietary supplements or food, 
cannabidiol (CBD) and cannabis-derived products would still be subject 
to the same safety requirements as apply to any other ingredient in the 
products FDA regulates. The Agency knows that CBD is not a risk-free 
substance, as is the case with many other compounds found in cannabis 
and must carefully consider those risks. As an additional matter, we 
note that any policies FDA adopts would only directly impact products 
subject to our jurisdiction. There may be CBD or other cannabis-derived 
products not subject to the Agency's jurisdiction.
    Question. What other approaches to enforcement discretion can 
enable FDA to address these issues, and by when can we expect such a 
policy to be instituted?
    Answer. As noted in the previous response, CBD is not a risk-free 
substance and even if FDA exercised enforcement discretion for the 
restrictions on using certain drug ingredients in food and dietary 
supplements, the CBD products would still be subject to the same safety 
standards that apply to any other ingredient in the products FDA 
regulates. FDA is prioritizing the evaluation of potential options and 
looks forward to discussing this further with Congress when there is 
additional information to share.
    Question. What additional resources, if any, does your Agency need 
in order to implement a policy of enforcement discretion to effectively 
address these issues?
    Answer. As noted in the previous responses, CBD is not a risk-free 
substance and, outside of the drug approval context, even if FDA 
exercised an enforcement discretion policy for certain cases, the CBD 
and cannabis-derived products would still be subject to the safety 
requirements that apply to any other ingredient in the products FDA 
regulates.
    However, should CBD or other cannabinoids be legally permitted in 
additional products, FDA would require additional resources to 
effectively regulate those markets.

                                 ______
                                 

              Questions Submitted by Senator Brian Schatz
    Question. At-home over-the-counter antigen tests are an important 
public health tool to mitigate the spread of COVID-19. These tests can 
be manufactured cheaply and at-scale and should be broadly available to 
all U.S. residents and visitors. While the Biden Administration has 
invested billions of dollars to increase the production and 
accessibility of these tests, only 18 at-home, over-the-counter antigen 
tests are authorized for emergency use by the FDA, and only 5 have been 
authorized so far in 2022.
    What is the scientific rationale for FDA's performance requirement 
for over-the-counter at-home antigen tests of a minimum sensitivity of 
80 percent when it is broadly understood that there are limits to the 
technology's ability to perform at lower viral loads?
    Answer. On July 29, 2020, FDA posted a template for at-home 
diagnostic tests, including at-home antigen tests, which include 
recommendations for validating such tests, including FDA's expectation 
of 80 percent sensitivity. This is much lower than the expectation of 
95 percent sensitivity for lab-based molecular tests, most of which 
perform at over 98 percent. FDA recognized that antigen test technology 
is generally not as sensitive as PCR technology, but has several 
advantages, including lack of reliance on large lab-based instruments, 
rapid turnaround time, and potentially less expensive manufacturing 
which can facilitate greater access to testing and faster results. We 
knew that available, at-home, over the counter (OTC) tests would 
supplement laboratory testing by increasing the overall amount of 
testing performed and as a result identify more infections and help 
mitigate the spread of the virus, bolstering our pandemic response. 
Therefore, FDA accepted lower sensitivity for antigen tests to help 
increase availability of tests and provide a feasible pathway for 
authorization. 80 percent sensitivity is feasible as evidenced by the 
19 authorized OTC at-home tests to date. We recognize, however, that a 
lower bar, could result in tests missing more people, particularly 
those in early stages of infection or who are about to become 
infectious, and could lead to spread of disease from this false sense 
of security.
    FDA has also monitored evolving circumstances and growing 
scientific knowledge and made adjustments when appropriate to help 
streamline and expedite the path to market for these and other tests as 
much as possible while assuring they are supported by sound science. In 
March 2021, FDA obtained results from an NIH-sponsored study that 
supported further streamlining of FDA's at-home test recommendations. 
Based on these data, on March 16, 2021, FDA provided a supplemental EUA 
template for test developers who are interested in a streamlined path 
to authorize tests with at least 80 percent sensitivity in symptomatic 
individuals, with sensitivity falling in a range as low as 70 percent 
in certain circumstances, for developers to offer their test for OTC 
serial screening without additional data collection. Multiple tests 
were authorized under this approach within weeks.
    Question. As variants and subvariants emerge, how does FDA plan to 
use clinical data to ensure that the 18 approved at-home antigen tests 
do not become obsolete if future variants no longer have the gene that 
the test detects?
    Answer. FDA uses multiple techniques to monitor the performance of 
at-home tests with current and future viral mutations. First, all 
Emergency Use Authorization (EUA) holders, including those for at-home 
tests, are required by their letter of authorization to evaluate the 
impact of SARS-CoV-2 viral mutations on their test's performance. These 
evaluations must occur on an ongoing basis and must include any 
additional data analysis that is requested by FDA in response to any 
performance concerns the EUA holder or FDA identify during routine 
evaluation. If the EUA holder's evaluation identifies viral mutations 
that affect the stated expected performance of their device, they must 
notify FDA immediately. As the FDA's or the developer's analysis 
identifies tests whose performance could be impacted by SARS-CoV-2 
viral mutations, these tests are added to FDA's SARS-CoV-2 Viral 
Mutations: Impact on COVID-19 Tests \1\ webpage. This includes posting 
the latest information on variants and testing implications as they 
become available.
---------------------------------------------------------------------------
    \1\ https://www.fda.gov/medical-devices/coronavirus-covid-19-and-
medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests
---------------------------------------------------------------------------
    FDA is collaborating with NIH's Variant Task Force \2\ (VTF) 
program to identify and prioritize over the counter (OTC) tests for 
additional testing of clinical samples on currently circulating 
variants. VTF's activities ``currently comprise in silico genomic 
bioanalytical testing, sample collection, and clinical in vitro lab 
testing of technologies supported by the RADx program to ensure their 
detection efficacy with variants entering the population matches that 
of the original strain.'' \3\ FDA uses this clinical and analytical 
data to determine whether and how a test's performance is impacted by 
emerging variants. As part of this collaboration, the VTF and FDA use 
antibody epitope mapping, a way to identify the part of the virus that 
is recognized by the test, to predict reactivity of existing tests with 
future variants.
---------------------------------------------------------------------------
    \2\ RADx Variant Task Force Program for Assessing the Impact of 
Variants on SARS-CoV-2 Molecular and Antigen Tests--PMC (nih.gov)
    \3\ Id.
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    In addition to these pandemic specific activities, FDA leverages 
its robust medical device postmarket surveillance and signal management 
program. Monitoring adverse event reports and other safety signals has 
enabled FDA to identify problems with tests on the market and work with 
developers to correct the issue or conduct recalls as appropriate.
    Question. Although COVID-19 poses less risk to children than older 
Americans, infants and young children are vulnerable to 
hospitalization, ICU admission, and long-term health effects of COVID-
19. The CDC found these serious consequences were exacerbated when the 
Omicron variant predominated in December 2021 through February 2022. 
U.S. families are concerned about their young children's health, 
particularly as precautions, such as mask wearing requirements, are 
easing in their communities. Parents are anxiously awaiting an approved 
vaccine and there have been a series of delays to FDA's emergency use 
authorization for the Pfizer-BioNTech and Moderna vaccines for children 
under 6 years old. In December 2021, Pfizer-BioNTech announced data 
indicating a two dose 3 mg series of its vaccine generated similar 
immunogenicity for children ages 6 months to 2 years as 16- to 25-year-
olds.
    Did FDA have a role in the postponement of the Pfizer-BioNTech 
vaccine EUA amendment in December 2021? If so, what was behind that 
decision-making?
    Answer. On February 1, 2022, Pfizer announced that it had initiated 
a ``rolling'' submission for an emergency use authorization (EUA) of 
their COVID-19 vaccine in children 6 months through 4 years of age. In 
a February 11, 2022 press release, Pfizer and BioNTech announced their 
plans to extend their rolling EUA submission to FDA and to wait for 
data for the three-dose series that may provide a higher level of 
protection in this age group.\4\ Pfizer stated that their independent 
Data Monitoring Committee (DMC) for the study supported the 
continuation of the trial.
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    \4\ https://www.pfizer.com/news/press-release/press-release-detail/
pfizer-and-biontech-provide-update-rolling-submission
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    On February 11, FDA announced in a press release that it was 
notified by Pfizer of their plans to extend their rolling EUA 
submission because of the new data that had emerged in children 6 
months through 4 years of age.\5\ Based on the Agency's preliminary 
assessment of the totality of data from the ongoing trial that had been 
provided by Pfizer at that time, we believed that additional 
information regarding the ongoing evaluation of a third dose should be 
considered as part of our decision-making for potential authorization. 
As a result, FDA postponed the Vaccines and Related Biological Products 
Advisory Committee (VRBPAC) meeting originally scheduled for February 
15, 2022.
---------------------------------------------------------------------------
    \5\ https://www.fda.gov/news-events/press-announcements/
coronavirus-covid-19-update-fda-postpones-advisory-committee-meeting-
discuss-request-authorization
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    On April 29, 2022, FDA announced that it anticipates convening its 
VRBPAC to discuss the pediatric data for the Pfizer-BioNTech COVID-19 
Vaccine and Moderna COVID-19 Vaccine and the requests for emergency use 
authorization by the companies for pediatric populations. Since then, 
FDA has publicly confirmed that on June 14, 2022, the VRBPAC will meet 
in open session to discuss amending the EUA of the Moderna COVID-19 
Vaccine to include the administration of the primary series to children 
and adolescents 6 years through 17 years of age. On June 15, 2022, the 
VRBPAC will meet in open session to discuss amending the Moderna COVID-
19 Vaccine EUA to include the administration of the primary series to 
individuals 6 months through 5 years of age, and also to discuss 
amending the Pfizer-BioNTech COVID-19 Vaccine EUA to include the 
administration of the primary series to individuals 6 months through 4 
years of age.
    Having safe and effective COVID-19 vaccines available for children 
is a priority for FDA. The Agency understands the urgency to authorize 
a vaccine for age groups who are not currently eligible for vaccination 
and is working diligently to complete our evaluation of the data. 
Following a transparent public dialogue with our VRBPAC, the Agency 
will only authorize COVID-19 vaccines for children that meet our 
scientific and regulatory standards and for which the known and 
potential benefits outweigh the known and potential risks.
    Question. Why did FDA postpone its February 2022 Vaccines and 
Related Biological Products Advisory Committee meeting instead of using 
this forum to review data on Pfizer-BioNTech's two dose vaccine series 
for children ages 6 months to 2 years?
    Answer. See response above.
    Question. I am very concerned about youth use of e-cigarettes. 
According to the most recent State-level data (2019), 30 percent of 
high school students in Hawaii use e-cigarettes. Despite a court order 
setting a timeframe for FDA to complete required premarket reviews of 
e-cigarettes, an alarming variety of youth-appealing flavored e-
cigarette products are still available online and in stores. FDA should 
fully use its regulatory authority to prevent manufacturers from making 
and selling tobacco products that are enormously appealing to kids.
    When does the FDA anticipate completing its required premarket 
review process and will it use this process to remove from the market 
all e-cigarettes that are likely to attract young people, such as 
flavored e-cigarettes?
    Answer. FDA received premarket tobacco product application (PMTA) 
submissions for about 6.7 million products by the court-ordered 
September 9, 2020, deadline and we have taken action on over 99 percent 
of those total applications. There are three major phases of PMTA 
review--acceptance review, filing review, and then scientific review. 
If an application fails to satisfy regulatory and/or statutory 
requirements at any of these stages, FDA issues a negative action, such 
as a Refuse to Accept Letter, a Refuse to File Letter, or a Marketing 
Denial Order (MDO). If an application provides scientific data that 
demonstrates permitting the marketing of a product is appropriate for 
the protection of the public health, FDA issues a Marketing Granted 
Order (MGO).

    To date, FDA has made significant progress and has taken action on 
over 99 percent of the applications submitted by September 9, 2020. FDA 
has:

  --Refused to accept applications for over 200,000 products

  --Refused to file applications for over 5 million products

  --Issued MDOs for more than 1 million flavored electronic nicotine 
        delivery systems (ENDS)

  --Issued MGOs for 23 ENDS products (for devices and tobacco-flavored 
        products)

    Reviewing this volume of applications is unprecedented for the 
Agency, and we remain focused on completing our review of the remaining 
product applications. FDA allocated significant resources to review 
applications from the five companies whose brands represented over 95 
percent of the e-cigarette market because FDA believes these products 
would have the greatest chance, either positively or negatively, of 
impacting public health due to their market share- Fontem (myblu), 
JUUL, Logic, NJOY, and R.J. Reynolds (Vuse). FDA has issued decisions 
on many of these products, including:

  --JUUL Labs Inc. (JUUL device and JUULpods) on June 23, 2022

  --NJOY LLC (NJOY Daily) on June 10, 2022

  --R.J. Reynolds Vapor Company (Vuse Ciro and Vuse Vibe) on May 12, 
        2022

  --NJOY LLC (NJOY Ace) on April 26, 2022

  --Fontem, US, LLC (myblu) on April 8, 2022

  --Logic Technology Development, LLC (Logic Vapeleaf, Logic Pro, and 
        Logic Power) on March 24, 2022

  --R.J. Reynolds Vapor Company (Vuse Solo) on October 12, 2021

    Question. How many e-cigarettes remain on the market despite having 
failed to file a premarket application or having received a marketing 
order denial?
    Answer. Products for which no application is pending, including, 
for example, those for which no application was submitted, are among 
our highest enforcement priorities. From January 2021 through April 
2022, FDA issued warning letters to 240 firms that collectively have 
more than 17 million unauthorized electronic nicotine delivery system 
(ENDS) products listed with the FDA and that had not submitted 
premarket applications for these products by the September 9, 2020 
deadline.
    Additionally, any products subject to a negative decision may not 
be introduced or delivered for introduction into interstate commerce. 
Any products receiving a negative decision that are already on the 
market must be removed from the market or risk enforcement. To date, 
FDA has issued warning letters to more than 115 firms for continuing to 
unlawfully market ENDS products that are the subject of marketing 
denial orders (MDOs), Refuse to File (RTF) letters, or Refuse to Accept 
(RTA) letters.
    Many firms comply after receiving a warning letter. FDA typically 
confirms the firm's corrective action by subsequent inspection and 
surveillance. If a firm continues to violate the law, investigators 
collect evidence and depending on the facts in the case, enforcement 
action, such as an injunction or seizure, may be pursued.
    Question. Given the risk of flavored e-cigarettes to youth, why 
does the FDA allow manufacturers to continue to sell their products 
while the agency is reviewing their applications?
    Answer. All new tobacco products on the market without the 
statutorily required premarket authorization are marketed unlawfully 
and are subject to enforcement by FDA. FDA will continue to make 
enforcement decisions on a case-by-case basis according to our 
enforcement priorities and the individual circumstances.
    The Agency works closely with the Department of Justice (DOJ), 
without whose support neither injunctive actions nor seizures can be 
taken. FDA consults the DOJ regularly with respect to potential 
enforcement actions, including in relation to unauthorized tobacco 
products that are the subject of pending applications.
    Question. Is FDA evaluating menthol flavored e-cigarettes under the 
same criteria used in evaluating other flavors of e-cigarettes?
    Answer. Under Section 910(c)(4) of the Federal Food, Drug, and 
Cosmetic Act, FDA reviews all premarket tobacco product applications to 
determine if the marketing of the new product would be appropriate for 
the protection of the public health (APPH). In doing so, the statute 
requires FDA to consider the risks and benefits to the population as a 
whole, including both tobacco users and nonusers, taking into account 
the increased or decreased likelihood that existing users of tobacco 
products will stop using such products and the increased or decreased 
likelihood that those who do not use tobacco products will start using 
such products. In making the APPH assessment for an electronic nicotine 
delivery system (ENDS) product, FDA weighs, among other things, the 
negative public health impact stemming from youth initiation and use of 
the product against the potential positive public health impact 
stemming from adult cigarette smokers transitioning away from 
combustible cigarettes to the ENDS product. ENDS product flavors are an 
important consideration in ascertaining the health risks of these 
products because of a flavor's potential impact on appeal to youth and 
young adults, consumer perceptions, and product toxicity.
    Question. Menthol cigarettes and flavored cigars mask the harshness 
and soothe irritation caused by tobacco smoke, which makes it easier 
for beginners, particularly youth, to experiment and become addicted to 
these products. Menthol cigarettes are the only flavored cigarette left 
on the market and remain popular, particularly among Black communities 
targeted by the tobacco industry. I applaud the FDA's recent 
rulemakings prohibiting menthol cigarettes and flavored cigars. Is it 
still FDA's view that enforcement of the menthol cigarette and flavored 
cigar prohibitions would ``only address manufacturers, distributors, 
wholesalers, importers, and retailers'' not individual consumers who 
possess or use these products?
    Answer. Yes. If these proposed rules are finalized and implemented, 
FDA enforcement will address only manufacturers, distributors, 
wholesalers, importers, and retailers who manufacture, distribute, or 
sell such products within the U.S. that are not in compliance with 
applicable requirements. This regulation does not include a prohibition 
on individual consumer possession or use, and FDA cannot and will not 
enforce against individual consumers for possession or use of menthol 
cigarettes or flavored cigars. FDA notes that State and local law 
enforcement agencies do not independently enforce the Federal Food, 
Drug and Cosmetic Act. These entities do not and cannot enforce against 
any violation of the act or this regulation on FDA's behalf.
    Question. In recent years, interest in research on psychedelics has 
increased rapidly, including in the development of new medicines.
    What is the current status of FDA's efforts to work collaboratively 
with NIH to identify research needs that would serve all medicine 
developers in the field of psychedelic research for therapeutic 
purposes?
    Answer. The Agency has long worked with NIH and supports its 
efforts to investigate the use of psychedelic drugs to treat mental 
health conditions. Most recently, in January 2022, we worked with NIH 
to conduct a joint 2-day workshop focusing on psychedelics and 
entactogens as therapeutics for serious mental illness and substance 
use, with participation from NIH, FDA, NIDA, and NIAAA. There were 
roughly 4,500 participants from all continents (except Antarctica) and 
presenters from academia, government, and industry. The workshop was 
divided in three parts: the first part of the workshop focused on basic 
and translational research, the second part on the results of recent 
clinical trials and lessons learned, and the third part focused on 
overcoming challenges and considering the consequences of real-world 
use.
    We also note that in fiscal year 2022, FDA designated psychedelics 
as a research area of interest through our Broad Agency Announcement 
mechanism. Specifically, the Agency stated in the announcement that we 
intend to ``Improve scientific understanding of psychedelics: Develop 
methods and carry out studies to better understand the trajectory of 
psychedelics use and associated public health consequences.'' \6\
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    \6\ Food and Drug Administration Broad Agency Announcement for the 
Advanced Research and Develop//ment of Regulatory Science (Page19) 
https://sam.gov/api/prod/opps/v3/opportunities/resources/files/
47c7fd2ac6374a70acf8579beb81cbdf/download?&token=
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    Question. Please provide a list of Investigational New Drug 
applications for psychedelics on which FDA is currently engaged with 
medicine developers.
    Answer. Consistent with Federal statutes and FDA's implementing 
regulations concerning the confidentiality of commercial information, 
and to protect the integrity of the review process, FDA generally 
cannot disclose information about an unapproved application or an 
investigational new drug application, including the status of the 
Agency's review of a particular drug product \7\. Therefore, the Agency 
is unable to provide updates about specific pending applications, 
including whether a specific application has been filed. We suggest 
reaching out to the company directly for information about a specific 
development program because they can choose to disclose information 
about their product development, including any interactions with the 
FDA. Another possible source of information would be the website 
www.ClinicalTrials.gov.
---------------------------------------------------------------------------
    \7\ Relevant law includes the Trade Secrets Act (18 U.S.C. 1905), 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 33l(j)), (21 U.S.C. 
360bbb-3(h)), and FDA regulations (21 CFR 20.61(c); 21 CFR 312.130(b); 
21 CFR 314.430(c) and (d)(l)).

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                                 ______
                                 

             Questions Submitted by Senator Martin Heinrich
    Question. Colorectal cancer is the third leading cause of cancer-
related deaths in men and women in the United States. According to the 
American Cancer Society, it was expected to cause roughly 53,000 deaths 
in 2021. That's why I introduced the Colorectal Cancer Detection Act, 
which would increase access to blood-based screening tests. Can you 
share the importance of the FDA evaluating and approving blood based 
screening tests, for early cancer and disease detection especially for 
rural and Tribal communities, and even when there are other albeit more 
invasive methods of detection?
    Answer. FDA believes that marketing authorization of a well-
validated, blood-based screening test for early cancer detection will 
benefit these communities, as it will increase accessibility and 
compliance to screening, due to the less invasive nature of this type 
of testing. However, the test should be well-validated, and have 
acceptable performance characteristics, so as to minimize the number of 
individuals receiving false negative or false positive results, which 
can lead to failure to provide appropriate treatment or unnecessary 
follow-up testing, with its own attendant risks, due to the need to 
confirm the presence or absence of cancer with invasive procedures. FDA 
review and authorization of an analytically and clinically validated 
test with favorable benefit/risk assessments and transparent 
performance is very important for public health and to ensure that 
patients and their physicians are informed of the strengths and 
weaknesses of different testing options.
    An advantage of blood-based testing is the opportunity to expand 
the number of individuals who undergo colon cancer screening because 
stool-based testing procedures have limited adherence. Approximately 20 
percent of eligible individuals aged 50 to 75 years have never been 
screened for colon cancer, and half are inadequately screened.\8\ 
Blood-based cancer screening has the potential to offer a convenient 
testing option, which is expected to improve compliance with early 
detection, when treatment may be curative.
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    \8\ Richardson, Lisa et al 2022. Adults who have never been 
screened for colorectal cancer, behavioral risk factor surveillance 
System, 2012 and 2020. https://www.cdc.gov/pcd/issues/2022/22_0001.htm
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    In 2016, FDA approved the first blood-based screening test for 
colon cancer.\9\ The test (Epi proColon) relies on qualitative 
detection of DNA in the blood stream from colorectal cancer (CRC) cells 
and represents an advancement in cancer screening technologies. The 
indications for use for Epi proColon places this test as second line 
(ordered only after other CRC screening tests recommended by the U.S. 
Preventive Services Task Force (USPSTF) have been offered and rejected 
by the patient). This is because the sensitivity and specificity of the 
test is lower than stool-based methods. The benefit of the test was 
that patients may be more compliant with blood-based CRC screening 
methods compared to stool-based methods. At this time, blood-based 
testing is not recommended by the USPSTF, due to the limited evidence 
supporting its use.
---------------------------------------------------------------------------
    \9\ Food and Drug Administration Summary of Safety and 
Effectiveness Premarket Approval submission number P130001
---------------------------------------------------------------------------
    Question. Over 30 years, the FDA's accelerated approval pathway has 
had important successes, particularly with oncology treatments, which 
have approval around 3.4 years earlier than with the traditional FDA 
approval. Many patients suffering from neurological conditions and 
serious rare diseases are wondering if this success can extend to their 
own, or their loved one's condition. Can the accelerated approval 
pathway be optimized for treatments to neurological disorders and rare 
diseases?
    Answer. FDA has several programs intended to facilitate and 
expedite the development, review, and approval of products intended to 
address unmet medical need in the treatment of serious conditions, 
including: Fast Track, Breakthrough Therapy Designation, Regenerative 
Medicine Advanced Therapy Designation, Accelerated Approval, and 
Priority Review. Drugs granted accelerated approval or developed under 
any of the expedited programs must meet the same statutory standards 
for safety and effectiveness as those granted traditional approval. 
While traditional approval is based on a showing of a drug's clinical 
benefit to patients, accelerated approval is based on a different study 
endpoint: most commonly, the drug's effect on a surrogate endpoint that 
is reasonably likely to predict a clinical benefit to patients. 
Consequently, drugs approved under accelerated approval are required to 
conduct a post-approval trial to verify that the drug provides the 
expected clinical benefit.
    Accelerated approval and other expedited programs for the 
development, review, and approval of drugs and biologics are a critical 
part of addressing unmet medical needs related to neurological 
disorders and rare diseases. Through these approaches, FDA can speed 
the availability of drugs that treat serious diseases benefits patients 
and their families, while ensuring that rigorous standards for safety 
and effectiveness are met. This is especially true when the drugs are 
the first available treatment which is often the case for rare 
diseases. We are committed to ensuring the continued availability, 
transparency, and advancement of these programs to deliver drugs and 
biologics that meet FDA's gold standard to patients with rare diseases.
    Question. Over the last 2+ years, we have seen that vaccines are 
the best way to protect ourselves from COVID-19. That is why I led a 
letter to Acting Commissioner Woodcock advocating for the FDA to work 
as quickly as science allowed to authorize safe and effective COVID-19 
vaccines for children 5-11. I know the FDA is working diligently to 
evaluate vaccines for children under 5, but my constituents in New 
Mexico are eager to vaccinate their kids as soon as possible. Can you 
share an update on the FDA's timeline to evaluate and approve vaccines 
for kids under 5? Can also you share any insight about how the roll out 
of vaccines for children under 5 may differ from the rollout for ages 5 
to 11 and 12 to 17?
    Answer. Having safe and effective COVID-19 vaccines available for 
children is a priority for FDA. The Agency ensures that the data 
support a vaccine's safety and effectiveness, and a favorable benefit-
risk balance, in any pediatric population before authorizing for 
emergency use or approving a COVID-19 vaccine for use in that 
population. As with other regulatory and scientific decisions about 
COVID-19 vaccines that we have made during this pandemic, we will 
thoroughly evaluate the data on the use of COVID-19 vaccines in 
pediatric populations. Our multi-disciplinary teams of doctors, 
scientists, statisticians, and other experts will thoroughly assess the 
data when making any determination about the use of COVID-19 vaccines 
in pediatric populations.
    FDA has been working closely with vaccine manufacturers to provide 
advice as data accrue about safety and effectiveness of the vaccines. 
FDA is convening its Vaccines and Related Biological Products Advisory 
Committee (VRBPAC) meetings to discuss amending the Moderna and Pfizer-
BioNTech emergency use authorizations (EUAs) for their COVID-19 
vaccines to include younger populations. Specifically, on June 14, 
2022, the VRBPAC will meet in open session to discuss amending the EUA 
of the Moderna COVID-19 Vaccine to include the administration of the 
primary series to children and adolescents 6 years through 17 years of 
age. On June 15, 2022, the VRBPAC will meet in open session to discuss 
amending the Moderna COVID-19 Vaccine EUA to include the administration 
of the primary series to individuals 6 months through 5 years of age, 
and also to discuss amending the Pfizer-BioNTech COVID-19 Vaccine EUA 
to include the administration of the primary series to individuals 6 
months through 4 years of age.
    The agency understands the urgency to authorize a safe and 
effective vaccine for age groups who are not currently eligible for 
vaccination and is working diligently to complete our evaluation of the 
data. Following a transparent public dialogue with our VRBPAC, the 
agency will only authorize COVID-19 vaccines for children if the Agency 
finds that the evidence shows the vaccines meet our scientific and 
regulatory standards and the Agency finds that the known and potential 
benefits outweigh the known and potential risks. After a vaccine 
receives authorization, vaccine distribution and prioritization is 
coordinated by HHS and CDC.

                                 ______
                                 

               Questions Submitted by Senator John Hoeven
    Question. Breakthrough and expedited approval pathways allow FDA 
efficient development opportunities for treatments of diseases and 
conditions that have few or no therapeutic options. Drug repurposing 
could be a viable option to meet unmet medical needs, if approval 
pathway qualifying criteria specifically included drug repurposing use 
cases. An example of this could be allowing preliminary clinical 
evidence from real-world data sources such as off-label use in clinical 
settings. Another could be creating pathways for accelerated or 
priority review of labeling supplements of previously approved FDA 
products that have demonstrated a clinical benefit for rare/infectious 
disease populations. Does FDA plan to use existing funding under your 
current operating budget or the requested funding for FY 23 to specify, 
update, or create expedited or accelerate approval pathway(s) such as 
drug repurposing to maximize the value of FDA regulated products for 
all populations, especially those with rare conditions or special 
populations?
    Answer. The Agency agrees that data on how approved drugs are being 
repurposed may inform the development of new clinical uses for these 
drugs as potential treatments for diseases and conditions that have few 
or no therapeutic options. FDA has and will continue to consider fit-
for-purpose real-world data in regulatory decisions relating to the use 
of repurposed drugs, including utilizing such data when appropriate 
under our expedited programs for drugs and biologics to treat serious 
conditions. These programs have been and will continue to be utilized 
to advance consideration of repurposed drugs.
    The agency has also devoted significant resources to exploring the 
use of repurposed drugs for diseases or conditions with unmet medical 
needs. In December 2019 the agency launched the CURE ID repository (a 
website and mobile application) globally, and rapidly expanded it in 
June of 2020 to respond to the COVID-19 pandemic.\10\ The repository 
captures clinical outcomes from the clinical community when drugs are 
used for new conditions, in new populations, in new doses or in new 
combinations. Health care professionals generally may choose to 
prescribe or use a legally marketed human drug or medical device for an 
unapproved or uncleared use when they judge that the unapproved use is 
medically appropriate for an individual patient. The systematic 
collection of real-world experience in the CURE ID platform can help 
identify drug candidates for additional study, encourage further drug 
development and serve as a resource for physicians to share information 
where no FDA-approved product proven to be safe and effective exists 
for the new use. Repurposing approved drugs for new clinical uses can 
potentially offer an efficient drug-development pathway for treatments 
of diseases and conditions that have few or no therapeutic options.
---------------------------------------------------------------------------
    \10\ https://www.fda.gov/drugs/science-and-research-drugs/cure-id-
app-lets-clinicians-report-novel-uses-existing-drugs
---------------------------------------------------------------------------
    In June of 2020, the agency also announced the creation of a 
public-private partnership (PPP), convened by the Critical Path 
Institute, called the CURE Drug Repurposing Collaboratory (CDRC) and 
provided funding to initiate this effort. The Agency plans to continue 
our work with the CDRC, which has since received additional support 
from HHS. Additionally, the Agency has continued to work with National 
Institutes of Health (NIH), the Reagan Udall Foundation,\11\ and the 
Critical Path (C-Path) Institute \12\ to explore avenues to advance 
research and policy regarding existing therapeutics.
---------------------------------------------------------------------------
    \11\ https://www.fda.gov/drugs/news-events-human-drugs/repurposing-
patent-drugs-research-regulatory-challenges-12052019-12062019
    \12\ https://c-path.org/programs/cdrc/
---------------------------------------------------------------------------
    The agency believes that the existing expedited programs for drug 
development and the agency's ability to leverage these programs when 
approved drugs show promise with rare diseases are sufficiently 
flexible and robust to address public health needs, including with 
respect to repurposing, or expanding the approved uses of, approved 
drugs. The agency is committed to utilizing these programs when 
appropriate to expedite development of repurposed drugs, including 
drugs repurposed for rare diseases. The Agency will also continue 
working with sponsors pursuing repurposing opportunities for areas of 
unmet medical need. The FDA instituted its Accelerated Approval Program 
to allow for earlier approval of drugs that treat serious conditions, 
and that fill an unmet medical need, based on a surrogate endpoint 
reasonably likely to predict benefit. Validated surrogate endpoints can 
be used for traditional approvals. A surrogate endpoint is a marker, 
such as a laboratory measurement, radiographic image, physical sign or 
other measure that is thought to predict clinical benefit, but is not 
itself a measure of clinical benefit. The use of a surrogate endpoint 
can considerably shorten the time required prior to receiving FDA 
approval.
    While the agency believes the current accelerated approval pathway, 
enhanced by the agency's other expedited programs, provide an 
appropriate means for expanding the approved uses of approved drugs, 
the President's budget includes a legislative proposal titled 
``Ensuring Feasibility and Timeliness of Confirmatory Studies and 
Enhancing Withdrawal Procedures for Prescription Drugs Approved through 
Accelerated Approval''. This proposal seeks to amend the accelerated 
approval provisions of the FD&C Act to (1) revise section 506(c)(2)(A) 
of the FD&C Act such that FDA may require, as a condition of a drug 
product application's acceptance for filing, or as a condition of a 
drug product's receipt of accelerated approval, that a drug sponsor 
must first demonstrate that a proposed post-approval (i.e., 
confirmatory) study is adequately designed to verify and describe 
clinical benefit and can be completed in a timely manner; (2) revise 
section 506(c)(3) so that FDA can follow its dispute resolution 
procedures for drug applications when withdrawing a drug product's 
accelerated approval; and (3) revise the withdrawal standard at FD&C 
Act 506(c)(3)(C) so that it mirrors the analogous withdrawal standard 
set forth in section 505(e) for drugs with traditional approvals. The 
FD&C Act does not provide FDA with easily implementable legal 
authorities to help target the problem of studies that progress too 
slowly. FDA believes that such a provision would help provide greater 
assurance at the time of a drug product's accelerated approval that the 
confirmatory study can progress in a timely manner, and reap high-
quality, interpretable results. Enhancing the timeliness and quality of 
confirmatory studies will help support FDA's regulatory decision-making 
for drugs approved through the accelerated approval pathway and 
minimize the time that a product is marketed based on accelerated 
approval before its clinical benefit can be confirmed.
    Question. It is important to ensure that those who require 
compounded hormone therapies are able to access them in a safe manner. 
As FDA reviews recommendations from the National Academies of Sciences, 
Engineering, and Medicine's report on the Clinical Utility of 
Compounded Hormones, will you commit to work with, and be responsive 
to, all relevant stakeholders as part of FDA's review of the report and 
its recommendations?
    Answer. This is an issue the Agency takes seriously. As you know, 
to help inform the public and FDA's policies regarding compounded 
bioidentical hormone replacement therapy (cBHRT), the Agency entered 
into an agreement with the National Academies of Sciences, Engineering, 
and Medicine (NASEM) to convene an ad hoc committee to conduct a study 
on the clinical utility of cBHRT drug products. The committee also 
reviewed which populations may benefit from the use of these 
preparations and considered whether the available evidence supports 
their use to treat patients. The committee issued its report, ``The 
Clinical Utility of Compounded Bioidentical Hormone Therapy,'' on July 
1, 2020.\13\
---------------------------------------------------------------------------
    \13\ https://www.nationalacademies.org/our-work/clinical-utility-
of-treating-patients-with-compounded-bioidentical-hormone-replacement-
therapy
---------------------------------------------------------------------------
    Reports published by NASEM aim to provide independent, objective 
expert advice. With regard to cBHRT, NASEM held six open session 
meetings for the Committee on Clinical Utility of Treating Patients 
with Compounded Bioidentical Hormone Replacement Therapy. According to 
NASEM, these meetings provided an opportunity for the committee to 
gather data and contextual information from relevant BHRT compounders 
and BHRT medical professionals.
    The NASEM report discusses some of the uncertainties of the 
potential benefits and safety risks associated with the use of these 
compounded products. FDA believes the results of NASEM's research 
provide important information that will increase public understanding 
regarding cBHRT products. When developing Agency policies, FDA intends 
to consider the information in the NASEM report, along with information 
and comments received from members of the public, while taking into 
account patient access concerns.
    Question. We understand that FDA expects to issue revised long-term 
sodium reduction targets in the next few years. How will FDA ensure 
these targets are scientifically-based and achievable, while at the 
same time taking into account the need to preserve consumer choice?
    Answer. FDA is committed to voluntary sodium reduction efforts, and 
providing consumers with the education and resources needed to choose 
lower-sodium foods will be important to reducing risk for negative 
health outcomes like hypertension and cardiovascular disease. Reducing 
sodium intake has the potential to prevent hundreds of thousands of 
premature deaths and illnesses in the coming years. FDA is focusing its 
work with industry on meeting the short-term goals. Any longer-term 
voluntary sodium reduction targets would be science-based and 
achievable, and would provide an opportunity for public input and 
stakeholder engagement, in keeping with the Agency's mission and 
established procedures.
    Question. At the urging of Congress, FDA published final guidance 
on mitigation of bacteria in blood platelets, which took effect in 
October of 2021. This guidance suggested multiple options to address 
the problem of bacterial contamination in platelets, which due to their 
nature must be stored at room temperature. In December, FDA issued a 
notice stating that one bacterial mitigation method in particular has 
been implicated in recent cases of sepsis and two patient deaths. The 
FDA also said it is investigating more cases. Can you provide me with a 
status update of the investigation?
    Answer. FDA shares the goal of enhancing the safety of the blood 
supply through controlling the risk of bacterial contamination of 
platelets. With respect to the cases of septic transfusion reactions, 
as explained in our April 2019 and December 2021 safety communications, 
FDA continues to investigate cases of septic reactions and bacterial 
contamination where additional genetic testing indicated a potential 
common source, and which involved various bacterial risk mitigation 
approaches. To facilitate further investigation, FDA encourages blood 
establishments and transfusion services to contact FDA when they 
identify suspected contamination of platelets with the implicated 
organisms, or suspected septic transfusion reactions involving 
pathogen-reduced platelet components.
    Regarding cases of septic transfusion reactions which involved 
certain bacterial species, further genetic testing by CDC indicates a 
high probability that the organisms are related. Although genetic 
testing conducted by the CDC indicated these organisms may have a 
common source, no such source has been identified to date. As part of 
our ongoing investigation, CDC and FDA maintain regular communication 
and coordination. This also includes interactions with blood collectors 
and device manufacturers. We continue to monitor and investigate any 
reports where the implicated organisms are identified either by 
bacterial testing or during investigation of clinical reactions.
    Question. Is FDA seeing instances of health care systems limiting 
consumer choice by providing patients with only one bacterial 
mitigation methodology? If so, do you believe this is concerning?
    Answer. Hospitals generally make the decisions on what blood 
components they would prefer to use for their patients, and these 
decisions may depend on what their blood collector can provide. FDA has 
been contacted by a few health care providers regarding the bacterial 
mitigation strategies implemented by their blood suppliers. However, 
patients are not usually offered choices of different types of blood 
components, and we are not aware that recipients of platelets have 
expressed concern. FDA is aware of the unique operational and inventory 
challenges in various hospital settings; consequently, our 
recommendations present blood collection establishments and transfusion 
services multiple options for complying with FDA's regulations that 
require blood establishments to reduce the risk of bacterial 
contamination of platelets.
    FDA works with blood establishments and transfusion services 
equally to implement FDA's requirements, based on the options they 
choose. While we recognize that blood suppliers make business decisions 
that may affect their hospital customers, such negotiations or 
contractual relationships fall outside the statutory provisions and 
regulations that we enforce.
    Question. The FDA determines whether drugs are safe and effective, 
and is the gold standard in science-based, rigorous drug review. Are 
you familiar with a National Coverage Determination (NCD) recently 
finalized by the Centers for Medicare and Medicaid Services related to 
an Alzheimer's disease drug approved by FDA under the accelerated 
approval process? Are you concerned that this NCD appears to establish 
new requirements for FDA-approved drugs, and if so, could this 
undermine FDA's gold standard? Do you believe this could cause 
companies who are seeking accelerated approval to reconsider moving 
forward with their applications?
    Answer. The agency is committed to using expedited programs to 
bring medicines to underserved populations with serious conditions and 
unmet medical need when the science supports the decision within the 
statutory authorities given to FDA by Congress. Our decision regarding 
Aduhelm exemplifies that commitment. It is important to distinguish 
between FDA's and CMS' role. The standard for Medicare coverage is not 
the same as the standards for FDA approval of a drug. Our role is to 
determine if drug is safe and effective for its intended use. The 
agency cannot speak for CMS. We continue to see sponsors pursue 
accelerated approval.

                                 ______
                                 

             Questions Submitted by Senator Mitch McConnell
    Question. In 2021, FDA stated to my office that FDA was continuing 
to accept ingredients listed in the Office Publication (OP) of the 
Association of American Feed Control Officials (AAFCO) for use in 
animal food, as long as no safety issue arises. FDA stated that ``at 
this time no approved animal food additive petitions, or ingredients 
definitions listed in the AAFCO OP, for any substances derived from 
hemp, and FDA is unaware of any generally recognized as safe (GRAS) 
conclusions regarding the use of any substances derived from hemp in 
animal food.'' FDA stated the Agency is continuing to encourage 
stakeholders to develop the necessary data and submit GRAS notices, 
food additive petitions, or AAFCO ingredient definitions for hemp-
derived animal food ingredients that do not contain CBD. FDA stated the 
Agency has no plans to issue guidance on this topic at the time (2021), 
but that FDA has been actively engaged with the industry and researches 
on the data needed to access the correct safety measures for hemp-
derived animal feed. As FDA continues to study the safety measures, 
what is the timeline for issuing guidance the FDA may offer about using 
hemp grain as an additive for livestock feed?
    Answer. At this time, FDA does not have plans to issue guidance 
about hemp grain in particular, but has referred interested parties to 
other available guidance on the animal food review process (GFI 221: 
Recommendations for Preparation and Submission of Animal Food Additive 
Petitions and GFI 262: Pre-Submission Consultation Process for Animal 
Food Additive Petitions or Generally Recognized as Safe (GRAS) 
Notices). FDA continues to actively engage with the hemp industry 
regarding data needed to demonstrate the safety of these ingredients 
for animal food. As announced publicly by the submitter, the Agency is 
currently reviewing the first submission for hemp-derived ingredients 
for use in animal food.
    Question. In 2020 and 2021, Congress provided FDA with increases 
totaling $7 million for additional research and work on CBD. FDA's 
March 2020 report to Congress on potential regulatory pathways included 
a number of key questions FDA wanted to address including the effects 
of daily use, comparing different methods of exposure, effects on 
children and others.
    Despite this Congressional priority, there is no further clarity 
for the CBD market today than there was in 2018. It has been more than 
3 years since passage of the Farm Bill that legalized hemp. President 
Biden's 2023 FDA budget notes that the agency is continuing to research 
CBD, but provides no details on movement and no additional funding is 
requested.
    How has FDA allocated the appropriations funding from Congress, and 
how have these steps advanced FDA's plans to regulate CBD?
    Answer. FDA appreciates the funding Congress has provided since 
fiscal Year2020 to support the Agency's efforts on cannabis and 
cannabis derivatives. Of the $7 million appropriated for these efforts, 
FDA has allocated funding to the Center for Food Safety and Applied 
Nutrition ($3 million), the Office of Regulatory Affairs ($2 million), 
the Center for Veterinary Medicine ($1 million), and FDA headquarters 
($1 million). These resources are being used for a variety of purposes, 
including to support additional FTE in several programs to support the 
work in this quickly expanding area.

    Funds have also supported efforts including:

  --Several ongoing toxicology studies with CBD, including an in vitro 
        evaluation of male reproductive toxicity of CBD and its main 
        metabolites, developmental neurotoxicity of CBD in rats, immune 
        modulating effects of perinatal exposure to CBD in rats, and 
        multiple studies on CBD pharmacokinetics

  --A large-scale product sampling and testing study targeting 
        approximately 1400 samples to test for toxic elements, 
        pesticides, residual solvents, microbes, and 11 cannabinoids

  --Monitoring and analyzing adverse event data from multiple sources

  --Partnering with external groups to obtain market, consumer, and 
        safety data

  --Ongoing monitoring of scientific literature

  --Issuance of warning letters to firms marketing products that pose 
        particular public health concerns, including products with 
        unsubstantiated claims for treating serious diseases, including 
        cancer, ALS, and COVID-19; products marketed towards children; 
        products marketed for use in food producing animals; and 
        products with concerning routes of administration (e.g. 
        ophthalmic).

    Question. FDA's March 2020 report to Congress identified six 
additional next steps FDA would undertake while evaluating potential 
pathways to market CBD. These included establishing Enforcement policy, 
gathering additional safety information, further engagement with 
Federal, State, Local, Territorial, Tribal, and International Partners, 
further evaluation of ``Full Spectrum'' and ``Broad Spectrum'' hemp 
extracts, additional research, and product sampling. What actions has 
FDA taken to implement these six steps? What does FDA plan to continue 
doing in each of these six areas?
    Answer. FDA has undertaken a number of actions to implement the 
steps outlined in the report issued in response to the Further 
Consolidated Appropriations Act of 2020. Specifically, the Agency has 
initiated the following:

  --Gathering additional research and safety information, including the 
        evaluation of ``Full Spectrum'' and ``Broad Spectrum'' hemp 
        extracts and product sampling: FDA participated in a Health 
        Canada study to establish a consistent, validated, analytical 
        method for the quantitation of hemp and cannabinoids broadly in 
        a variety of products. Additionally, the Agency has four 
        ongoing method development and chemical profiling projects and 
        seven in vitro testing projects, all working with hemp extracts 
        provided by the FDA Center of Excellence, National Center for 
        Natural Product Research. FDA is also finalizing the results of 
        a long-term sampling study, which collected and tested nearly 
        1,400 products (including tinctures/oils, capsules, gummies, 
        drinks, food, pet products, and cosmetics) from both internet 
        purchases and brick and mortar locations. FDA anticipates this 
        report being finalized in Fall 2022. A second year of the study 
        is being initiated and will focus on further sampling of pet 
        products and an additional evaluation of variability within and 
        between products.

  --Engagement with Federal, State, Local, Territorial, Tribal, and 
        International Partners: According to the National Conference of 
        State Legislatures, as of February 3, 2022, 37 States, four 
        territories and the District of Columbia allow the medical use 
        of cannabis products; and as of May 27, 2022, 19 States, two 
        territories and the District of Columbia have enacted measures 
        to regulate cannabis for adult non-medical use. It is estimated 
        that nearly 1 in 3 Americans now lives in a State where adult-
        use is legal. However, each State legislates, regulates, and 
        operates its cannabis programs differently. FDA has fielded 
        inquiries from nearly every State and territory, and from a 
        number of Tribal governments. In addition, we engage 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.

  --Enforcement Policy: The Agency understands the significant interest 
        in this space and is prioritizing the evaluation of potential 
        enforcement policy options. FDA looks forward to discussing 
        this further when there is additional information to share.
    Question. Can you provide an update on the activities laid out in 
the FDA Fall 2021 Data Acceleration Plan?
    Answer. FDA has undertaken a number of activities to meet the goals 
laid out in the Data Acceleration Plan. Some safety vigilance 
activities include performing comprehensive evaluations of existing FDA 
safety surveillance and epidemiologic databases, such as the FDA 
Adverse Event Reporting System and the American Association of Poison 
Control Centers National Poison Data System; funding a pilot project to 
explore the utility of media reports and social media (i.e., Reddit) 
for the identification of new safety signals with cannabis-derived 
products (CDPs); developing custom based surveys to obtain data related 
to CDP utilization and associated adverse events; and exploring the 
capabilities of different electronic health record (EHR) data sources 
to capture exposure information and for safety signal detection. As a 
result of data obtained through some of these activities, FDA has taken 
a number of actions related to safety of CDPs, such as issuing a 
consumer update for delta-8 THC \14\ and issuing a safety alert for 
edible products containing THC and the potential for accidental 
pediatric exposures.\15\
---------------------------------------------------------------------------
    \14\ https://www.fda.gov/consumers/consumer-updates/5-things-know-
about-delta-8-tetrahydrocannabinol-delta-8-thc
    \15\ https://www.fda.gov/food/alerts-advisories-safety-information/
fda-warns-consumers-about-accidental-ingestion-children-food-products-
containing-thc
---------------------------------------------------------------------------
    Question. Please provide a review of what information has been 
collected by FDA to determine the parameters for safety.
    Answer. During review of the marketing application for the CBD-
based drug Epidiolex, FDA identified certain safety risks, including 
the potential for liver injury and for adverse reactions caused by the 
interaction between Epidiolex and other medications. FDA has reviewed 
published literature to assess the safety of the use of CBD in human 
food. FDA identified potential for liver injury from CBD and 
potentially harmful interactions with certain drugs, and studies in 
animals have shown that CBD can interfere with the development and 
function of testes and sperm, decrease testosterone levels, and impair 
sexual behavior in males.
    In order to better understand potential effects of CBD, as stated 
above, FDA is investigating potential CBD interference with 
testosterone production and underlying mechanisms of toxicity. The 
results of this study align with other studies indicating that CBD 
might have negative effects on the male reproductive system. The first 
results from this study have been published. Other ongoing FDA studies 
include investigation of developmental neurotoxicity of CBD in rats, a 
study of immune modulating effects of perinatal exposure to CBD in 
rats, and multiple studies on CBD pharmacokinetics.
    Other data collection efforts are ongoing including a large-scale 
product sampling and testing study targeting approximately 1400 samples 
to test for toxic elements, pesticides, residual solvents, microbes, 
and 11 cannabinoids, monitoring and analyzing adverse event data from 
multiple sources, and partnering with external groups to obtain market, 
consumer, and safety data.
    Question. Does FDA ever expect to issue a proposed rule? If not, 
why not and what barriers continue to exist?
    Answer. Over the past several years, the Agency has worked to 
collect data about the effects of CBD in animals and humans, including 
potential adverse effects. Based on the information FDA currently has 
obtained, the appropriate regulatory pathway is still uncertain. FDA is 
prioritizing the evaluation of potential options and looks forward to 
discussing this further with Congress when there is additional 
information to share.

                                 ______
                                 

                Questions Submitted by Senator Roy Blunt
    Question. The accelerated approval pathway has been successful in 
ensuring patient access to new medications, and has been especially 
effective for patients with cancer. Previously, you have recognized the 
benefits of the pathway, while also looking for additional ways to 
confirm clinical benefit for the drugs approved under accelerated 
approval. As part your approval process, you noted that you would 
reform the agency's accelerated approval pathway? What reforms do you 
see implementing? Are you committed to continuing the accelerated 
approval pathway?
    Answer. The President's budget includes a legislative proposal 
titled ``Ensuring Feasibility and Timeliness of Confirmatory Studies 
and Enhancing Withdrawal Procedures for Prescription Drugs Approved 
through Accelerated Approval''. This proposal seeks to amend the 
accelerated approval provisions of the FD&C Act to (1) revise section 
506(c)(2)(A) of the FD&C Act such that FDA may require, as a condition 
of a drug product application's acceptance for filing, or as a 
condition of a drug product's receipt of accelerated approval, that a 
drug sponsor must first demonstrate that a proposed post-approval 
(i.e., confirmatory) study is adequately designed to verify and 
describe clinical benefit and can be completed in a timely manner; (2) 
revise section 506(c)(3) so that FDA can follow its dispute resolution 
procedures for drug applications when withdrawing a drug product's 
accelerated approval; and (3) revise the withdrawal standard at FD&C 
Act 506(c)(3)(C) so that it mirrors the analogous withdrawal standard 
set forth in section 505(e) for drugs with traditional approvals. The 
FD&C Act does not provide FDA with easily implementable legal 
authorities to help target the problem of studies that progress too 
slowly. FDA believes that such a provision would help provide greater 
assurance at the time of a drug product's accelerated approval that the 
confirmatory study can progress in a timely manner, and reap high-
quality, interpretable results. Enhancing the timeliness and quality of 
confirmatory studies will help support FDA's regulatory decision-making 
for drugs approved through the accelerated approval pathway and 
minimize the time that a product is marketed based on accelerated 
approval before its clinical benefit can be confirmed.
    Question. Dr. Califf, there has been concern from several different 
companies about FDA review, and how long the process to get clearance 
from the agency. We have heard from constituent companies, including 
Avadel Therapeutics, with concern how long the timeline has stretched.
    Can you share how the agency is prioritizing review of drugs?
    Answer. Earlier this year the Agency released our PDUFA \16\, BsUFA 
\17\ and GDUFA \18\ annual performance reports. In these reports the 
agency delineates the previous year's performance on various user fee 
goals, including review timelines, within the three programs. Despite 
an increased workload, FDA has maintained a high level of performance 
in meeting PDUFA, BsUFA, and GDUFA goals and initiatives.
---------------------------------------------------------------------------
    \16\ https://www.fda.gov/media/156077/download
    \17\ https://www.fda.gov/media/155870/download
    \18\ https://www.fda.gov/media/155760/download
---------------------------------------------------------------------------
    In PDUFA, FDA agreed to specific goals for improving the drug 
review time and created a two-tiered system of review times--Standard 
Review and Priority Review. A Priority Review designation means FDA's 
goal is to take action on an application within 6 months (compared to 
10 months under standard review).
    A Priority Review designation will direct overall attention and 
resources to the evaluation of applications for drugs that, if 
approved, would be significant improvements in the safety or 
effectiveness of the treatment, diagnosis, or prevention of serious 
conditions when compared to standard applications.

    Significant improvement may be demonstrated by the following 
examples:

  --evidence of increased effectiveness in treatment, prevention, or 
        diagnosis of condition;

  --elimination or substantial reduction of a treatment-limiting drug 
        reaction;

  --documented enhancement of patient compliance that is expected to 
        lead to an improvement in serious outcomes; or

  --evidence of safety and effectiveness in a new subpopulation.

    While the agency cannot speak to any specific product due to 
commercially confidential information, we encourage the company to 
reach out to the relevant review division for more information on their 
specific product.
    Question. How has COVID-19 contributed to this issue, and would you 
agree that there is a backlog of drugs that have not been reviewed?
    Answer. The continuing COVID-19 epidemic has certainly made for 
unique circumstances in the agency. For PDUFA in fiscal Year 2021, 
despite the sustained high workload, the increased use of expedited 
programs, and the development and review of new therapeutics and 
vaccines to address the public health emergency, FDA rose to the 
challenge and maintained its high level of performance in meeting PDUFA 
goals and initiatives. As noted in the PDUFA Performance Report for 
fiscal Year 2021, FDA completed 2,055 actions as of September 30, 2021. 
FDA is currently meeting or exceeding 9 of the 12 review performance 
goals for fiscal Year2021. With 1,466 submissions under review and 
still within the PDUFA goal date, FDA has the potential to meet or 
exceed 10 of the 12 review performance goals for fiscal Year 2021.
    Question. Does this issue extend to other product reviews, such as 
devices?
    Answer. Review times for tests and other device Emergency Use 
Authorization (EUA) requests have increased over time as the number of 
EUA and Pre-EUA submissions quickly surged to unprecedented levels 
during the COVID-19 pandemic. Since January 2020, FDA has received over 
8,000 EUA requests and Pre-EUA submissions for devices (including over 
1,000 so far in Fiscal Year 2022). The Agency continues to receive 
nearly 120 device EUA requests and pre-EUA submissions each month, the 
majority for tests, and has begun receiving conventional submissions 
from firms intending to transition their products beyond emergency use.

    In order to address high submission levels of device EUA requests, 
FDA has implemented important measures to reduce review times. These 
steps include:

  --Temporarily reassigning staff to increase review capacity;

  --Leveraging contractors from outside organizations to provide 
        technical expertise to supplement our review staff (personnel 
        authorized to work alongside full-time employees, integrated 
        into our internal review teams);

  --Using supplemental funds from Congress to hire 30 new, temporary 
        staff to support review of EUAs;

  --Implementing a triage process for new EUA requests; and

  --Working to efficiently use resources for low-impact and poor-
        quality submissions, including expanding the use of holds when 
        important data is missing, and instituting a process to 
        prioritize submissions where our resources should be focused 
        (namely, on those submissions that would have the greatest 
        impact on public health).

    Additionally, as a result of the unprecedented number of EUA 
requests and pre-EUA submissions that FDA received for COVID-19 tests 
and collection kits, we have not been able to review some non-COVID in 
vitro diagnostic (IVD) pre-submissions. To address this issue, FDA's 
IVD office has focused on increasing staffing to address the increased 
volume of work, allowing us to provide more resources to our 
conventional premarket workload. We are pleased to announce that, as of 
June 1, 2022, FDA plans to accept all non-COVID IVD pre-submissions. 
Due to the continued elevated workload related to COVID-19, it is 
likely that these IVD pre-submissions will initially be reviewed under 
an extended timeline.
    FDA looks forward to our continued interactions with device 
submission sponsors and appreciates their patience and understanding as 
we work to return to normal operations while continuing to respond to 
the public health emergency. The commitment that FDA and the medical 
device industry share to prioritize innovation and increase patient 
access is central to our mission to protect and promote the public 
health. This commitment is exemplified by the recommendations for the 
reauthorization of Medical Device User Fee Amendments for Fiscal Years 
2023-2027 (MDUFA V) in the commitment letter, which has been submitted 
to Congress. The recommendations in the MDUFA V commitment letter are 
intended to increase efficiency of regulatory processes and reduce the 
time it takes to bring safe and effective medical devices to the U.S. 
market.

                                 ______
                                 

               Questions Submitted by Senator Jerry Moran
    Question. The Drug Quality and Security Act of 2013 (DQSA) includes 
strong protections intended to promote patient safety and to strengthen 
the integrity of the FDA drug approval process. The Agency has said it 
will clarify its position on DQSA's prohibition on compounding drugs 
that are ``essentially a copy of an approved drug'' when using FDA-
approved drugs as the starting material. When will the Agency provide 
this clarity? Does the Agency intend to ensure that the use of FDA-
approved drugs as a starting point, and that a change in a container 
closure system (eg, a transition from vial to a syringe), would not 
fall within the meaning of the essentially a copy prohibition? This 
lack of regulatory clarity has led to numerous, very costly lawsuits 
that are driving up the price of compounded medications and resulting 
in a shortage of ready-to-administer drugs. As a result, patients are 
encountering increased barriers inhibiting their access to essential 
medications.
    Answer. Since the enactment of the Drug Quality and Security Act, 
FDA has made significant progress on clarifying the Agency's policies 
on compounding drugs that are ``essentially a copy of an approved 
drug,'' taking into consideration real world implications as well as 
comments and concerns expressed by the public. The questions and 
comments regarding compounding raise complex issues requiring extensive 
review by Agency officials, and efforts have been made to provide the 
Agency's thinking. Most recently, on January 1, 2018, FDA issued a 
final guidance for industry, ``Compounded Drug Products That Are 
Essentially Copies of Approved Drug Products Under Section 503B of the 
Federal Food, Drug, and Cosmetic Act,'' that aimed to provide further 
clarity on the Agency's policies. The Agency has since received further 
questions and comments related to its policies for applying the 
``essentially a copy'' provision, including questions regarding when 
outsourcing facilities compound drugs starting with an approved drug 
rather than a bulk drug substance. While we cannot provide a specific 
timeline, FDA understands that these questions are important to 
stakeholders and is currently working diligently to address them, 
including addressing these issues in an updated guidance.
    Question. The Agency announced earlier this year that it will 
undertake notice-and-comment rulemaking related to the Memorandum of 
Understanding (MOU) between the FDA and States that regulates the 
number of compounded therapies distributed across state lines. As the 
Agency drafts this proposal, it's important to ensure that patients 
have unfettered access to the compounded medications they need to live. 
A recent version of the MOU issued by the FDA included dispensed 
(patient specific prescriptions) within the definition of distribution 
which would limit the distribution of compounded preparations shipped 
across state lines to 50 percent of all prescriptions each month for 
States signing the MOU. Although many compounding pharmacies do not 
exceed this threshold, low-volume pharmacies located near state borders 
who will be disproportionately and adversely impacted. This means 
patients who receive their compounded therapies from out of state may 
have to find a new pharmacy to provide their medicines at the end of 
each month. This is unacceptable. One way to fix this patient access 
problem is to exclude the number of drugs dispensed to specific 
patients, pursuant to a prescription, from the total number of drugs 
pharmacies distribute across state lines. Will the revised MOU proposal 
do this?
    Answer. As you noted, in February 2022, the Agency publicly stated 
that FDA intends to undertake notice-and-comment rulemaking related to 
statutory provisions regarding certain distributions of compounded 
human drug products and a standard memorandum of understanding (MOU) 
between FDA and States. The standard MOU is an agreement that is 
intended to address interstate distribution of inordinate amounts of 
compounded drugs and complaint investigation by a State regulator 
relating to compounded drugs distributed outside the state. Federal law 
limits distribution of compounded drugs outside the state by a 
pharmacist, pharmacy, or physician located in a State that has not 
entered into the MOU to 5 percent of total prescription orders 
dispensed or distributed. An essential element of FDA's rulemaking 
process is a public comment period, which provides an important 
opportunity for stakeholder engagement. We wish to also note that under 
the most recently published MOU (which is now suspended) States signing 
the MOU would have agreed to report, among other things, information 
about compounders who have distributed interstate more than the 50 
percent threshold described. We would like to emphasize that this 
reporting threshold would not have placed any limit on the distribution 
of compounded drugs interstate by a pharmacy located in a State that 
entered into the MOU.
    Question. I have been outspoken about shortages in our Nation's 
blood supply, which is of great concern to patients and hospitals in 
Kansas. I recently became aware of some actions by blood centers which 
may restrict hospital choice when it comes to blood platelets intended 
for transfusion and further exacerbate shortages of this particular 
blood product. I am specifically referring to FDA's guidance addressing 
the mitigation of bacterial contamination in blood platelets, which 
became effective in October of 2021. This guidance to industry suggests 
up to three clinically equivalent mitigation strategies for blood 
platelets. Yet some major blood centers are forcing hospitals to 
purchase blood platelets prepared with only one of the options which I 
understand is not only the most expensive option, but is also 
associated with a shorter product shelf-life than the other options 
resulting in more wastage. Importantly, this option has been linked to 
multiple cases of sepsis and fatalities per an FDA bulletin in December 
of 2021. FDA stated in this bulletin that it is investigating even more 
cases. This is of concern to me, from a hospital choice, cost, and 
patient safety perspective--what steps will FDA take to ensure that 
hospital choice is preserved and blood shortages are minimized?
    Answer. FDA guidance addressing the mitigation of bacterial 
contamination in platelets presents blood collection establishments and 
transfusion services multiple options for complying with FDA's 
regulations to reduce the risk of bacterial contamination of platelets. 
FDA will continue to monitor the safety and availability of the blood 
supply and the effectiveness of the strategies recommended for 
controlling the risk of bacterial contamination of platelets, included 
in the December 2020 guidance. While we recognize that blood suppliers 
make business decisions that may affect their hospital customers, such 
negotiations or contractual relationships fall outside the statutory 
provisions and regulations that we enforce.
    With respect to the cases of septic transfusion reactions, as 
explained in April 2019 and December 2021 safety communications, FDA 
continues to investigate cases of septic reactions and bacterial 
contamination where additional genetic testing indicated a potential 
common source, and which involved various bacterial risk mitigation 
approaches. To facilitate further investigation, FDA encourages blood 
establishments and transfusion services to contact FDA when they 
identify suspected contamination of platelets with the implicated 
organisms, or suspected septic transfusion reactions involving 
pathogen-reduced platelet components.
    Question. As you know, the law Congress approved is clear that OTC 
hearing devices are intended only for those over the age of 18 with 
``perceived mild-to-moderate hearing loss.'' However, the proposed rule 
allows OTC devices to be amplified up to 120 decibels (dB) without 
imposing any hearing gain limit. This threshold allows those with 
hearing loss greater than the intended mild-to-moderate level to access 
OTC hearing devices. This hurts consumers and patients in two ways. 
First, it means individuals suffering from greater levels of hearing 
loss could put off a needed visit with a licensed hearing professional. 
Doing so could lead to worsening their existing symptoms, delaying an 
accurate diagnosis and treatment, and even creating irreparable damage 
to their hearing. Secondly, it means those with perceived mild-to-
moderate hearing loss would be exposed to harmful levels of noise that 
could result in further damage to their long-term hearing. In order to 
avoid these concerns, FDA should impose a gain limit of 25 dB and an 
overall output limit of 110 dB.
    Ninety-one stakeholders ranging from patient advocacy organizations 
to trusted hearing providers submitted formal comments to the FDA 
expressing concern that the proposed 120 dB maximum output limit and 
omission of a gain requirement will put patient safety at risk. These 
stakeholders include University of Kansas Medical Center, the American 
Academy of Otolaryngology--Head and Neck Surgery, American Society on 
Aging, the American Speech-Language-Hearing Association, the American 
Academy of Audiology, and more.

    The Kansas Board of Hearing Aid Examiners expressed the following 
concerns with the proposed rule:

        ``We concede that a lower output limit of 110 dB SPL may be 
        suboptimal for enjoyment of some live music, but we feel that 
        this is a worthy trade-off to mitigate the risk of noise-
        induced auditory damage from the hearing aid. The FDA proposed 
        rule suggests that consumers can remove a hearing aid within 30 
        to 60 seconds following onset of loud acoustic events. This may 
        be true for many but we are concerned that vulnerable 
        populations, such as those with cognitive and/or physical 
        limitations, may be unable to remove the hearing aids quickly 
        enough to avoid acoustic trauma.''

    Dr. Califf, I think you would agree it is important to protect 
consumers. Can you tell me what is being done to ensure OTC hearing 
aids will not cause greater hearing loss for individuals?
    Answer. FDA appreciates the feedback you have provided with respect 
to the proposed rule, Medical Devices; Ear, Nose, and Throat Devices; 
Establishing Over-the-Counter Hearing Aids, and for sharing your 
concerns about the output limits proposed for over-the-counter hearing 
aids, as well as the views of stakeholders who express similar concerns 
based upon their professional judgment. As you know, section 709(b)(2) 
of the FDA Reauthorization Act of 2017 (Public Law 115-52) directs FDA 
to establish or adopt output limits appropriate for over-the-counter 
hearing aids as well as other requirements that provide reasonable 
assurance of the safety and effectiveness of the devices.
    FDA is currently reviewing and considering the comments submitted 
to the docket. Many of them cited quantitative methods to develop an 
output limit they believe is appropriate to over-the-counter hearing 
aids. Further, as you noted, many such comments suggested that FDA 
establish a limit on gain, separate from and additional to the 
appropriate output limit. Conversely, several current hearing aid users 
provided comments describing the benefits they personally receive at 
specific (quantified) amplification levels. People with expertise in 
electronics and sound amplification similarly added to our knowledge of 
real-world performance. In sum, while many professionals back a lower 
output limit, many other professionals-some of them hearing aid users 
themselves-voiced support for FDA's proposed output limit.
    All of these perspectives addressed a nexus of complex medical and 
scientific issues, the real-world effects for hearing aid users, and 
protecting and promoting the public health. To determine appropriate 
output and, potentially, a gain limit, FDA continues to engage with the 
comments addressing the scientific literature, patient perspectives, 
institutional knowledge (e.g., adverse event reports), and expertise of 
other agencies, including the National Institutes of Health. Our 
scientific deliberations are ongoing.
    As we finalize the requirements, we are keeping in mind concerns 
about users who might delay a productive visit with a hearing health 
care provider and users who might be exposed to harmful amplification 
levels from over-the-counter hearing aids. These concerns are some of 
the most important considerations for the safety and effectiveness of 
over-the-counter hearing aids and carry over into additional 
requirements (e.g., labeling, electroacoustic performance, design 
features, and conditions for sale).
    FDA remains committed to establishing a science-based regulatory 
category for over-the-counter hearing aids that provides reasonable 
assurance of safety and effectiveness while promoting access to devices 
that will help address a significant public health need.
    Question. New innovations in plant breeding techniques, such as 
genome editing, will be crucial to sustainably increase agricultural 
production and enhance food and nutritional security. Clear FDA policy 
for food derived from genome editing improved varieties is critical if 
we are to expand the diversity and availability of food.
    FDA's biotechnology consultative process for food derived from 
biotech plant variety is over 25 years old. In the last several years, 
there has been observable decline in the predictability and timeliness 
of the process. The ability of our farmers to remain competitive 
globally depends on timely access to the newest and best varieties.
    How do you plan to expediate modernization of the FDA process so it 
doesn't become an unnecessary hurdle to innovation, especially from 
small and medium sized public and private enterprises?
    Answer. FDA agrees that innovation in plant breeding techniques is 
important for the future of agriculture and that the voluntary 
consultation process can take longer than it has in the past. Some of 
this is due to the complexity of products entering FDA's program. For 
example, the Agency recently completed voluntary consultations on two 
separate products that contained 8 and 13 new genes. There are also 
many new, smaller companies engaging with the Agency, and it requires 
greater staff time to walk them through the voluntary consultation 
process.
    FDA is taking steps to help address the timeliness concern. For 
example, the Agency is beginning to strengthen the Center for Food 
Safety and Applied Nutrition's Biotechnology Team to help address the 
new, complex and innovative products coming through the door, and has 
improved the process work-flow for the consultation process. FDA also 
intends to update its guidance on voluntary consultation procedures, 
last updated in 1997, to reflect what it has learned over the past 25 
years.
    FDA is also in the process of developing draft guidance for 
industry regarding foods from genome edited plant varieties. Issuing 
this draft guidance is a priority. FDA has already taken several steps 
to help inform our drafting process, including issuing a request for 
information in January 2017. The Agency has reviewed the comments and 
has been following (and participating in) the international 
conversation around these techniques while developing the draft 
guidance. While this draft guidance is under development, FDA is 
actively working with developers of genome edited plants. Many of these 
firms are small and medium sized entities that benefit from FDA's 
iterative voluntary consultation process to help them understand their 
legal responsibilities as they bring safe and innovative products to 
market.
    Question. FDA, CVM holds the regulatory authority for gene-edited 
(GE) farm animals and is currently exercising their regulatory 
authority using the proposed GFI #187 that seeks to treat the genetic 
application like a new animal drug. Does FDA intend to publish their 
finalized version of GFI #187 within the next year to give increased 
clarity to their future regulatory process for GE animals and is the 
agency considering how their final guidance could support the MOU 
signed with USDA, APHIS in January 2021 for shared regulatory authority 
for GE farm animals?
    Answer. FDA's regulation of intentional genomic alterations (IGAs) 
in animals is focused on ensuring that the IGAs are safe to animals, 
safe to consumers, and accomplish what their developer claims they will 
accomplish. FDA regulates them under the Federal Food, Drug, and 
Cosmetic Act and FDA's existing regulations. GFI #187, as with all FDA 
guidance documents, represented the FDA's current thinking on a 
particular subject. While guidance documents are not binding on the 
public or FDA, they are an important way to communicate FDA's 
recommendations to developers of FDA-regulated products.
    FDA first issued GFI #187 in 2009 and issued a draft revised 
version in 2017. In response to stakeholder concerns, FDA has now 
significantly revised GFI #187 including splitting it into two parts. 
The resulting guidances are currently under OMB review. The need to 
publish GFI #187 to provide greater clarity to stakeholders and the 
public is independent of the HHS-signed MOU, which is currently not in 
effect.
    FDA is making continuous improvements to its regulatory oversight 
to ensure a transparent, flexible and science-based approach to 
efficiently get safe products to market. One such improvement is FDA's 
implementation of additional risk-based flexibilities as demonstrated 
by FDA's recent low risk determination for the marketing of food and 
other products from genome edited SLICK cattle.
    FDA supports both FDA and USDA utilization of their respective 
expertise under existing authorities to help provide regulatory 
certainty to the animal biotechnology industry. It is critical to 
continue progress in this field so that developers of innovative 
biotechnology products have the information they need to bring 
beneficial products to market without further delay.
    Question. FDA, CVM has recently engaged in stakeholder meetings, 
facilitated by the Reagan-Udall Foundation, to discuss public-private 
partnerships for antimicrobial use data collection for food-producing 
animals. Will the agency pursue any antimicrobial use data collection 
process purely on a voluntary basis or are there plans by the agency 
for mandatory antimicrobial use data collection and reporting for food-
producing animals in the near future?
    Answer. Section 105 of the Animal Drug User Fee Amendments of 2008 
(ADUFA) amended section 512 of the Federal Food, Drug, and Cosmetic Act 
(FFDCA) to require antimicrobial drug sponsors to annually report to 
FDA the amount of antimicrobial active ingredient in their drugs that 
have been sold or distributed for use in food-producing animals. There 
is no parallel statutory requirement for producer and veterinary 
practitioner reporting of antimicrobial use data. Although sales and 
distribution data are useful, antimicrobial use data would better 
inform FDA and other interested stakeholders about how antimicrobial 
drugs are being used, enhance understanding about the drivers of 
antimicrobial resistance, and help to identify use practices 
opportunities that reflect good stewardship of antimicrobials.
    Given the importance of this information, FDA has pursued 
strategies for collecting antimicrobial use data, including funding 
several cooperative agreements with researchers to develop pilot data 
collection methodologies. The initial findings from these pilot 
projects were published in a series of papers in Zoonoses and Public 
Health \19\ in November 2020. The agency hopes to gain additional 
insight into the feasibility of establishing a voluntary data 
collection system from a report drafted by the Reagan-Udall Foundation 
(the Foundation) for the Food and Drug Administration. The report, 
entitled Exploring the Potential for a Public-Private Partnership to 
Support the Tracking and Monitoring of Antimicrobial Use in Food-
Producing Animals \20\, summarizes key findings from a series of 
targeted conversations with stakeholders from animal agriculture, 
veterinary, and public health organizations, along with other key 
representatives. The objective is to determine the feasibility of 
establishing a voluntary public-private partnership to collect and 
analyze data on antimicrobial use in food-producing animals. FDA has 
opened a docket through August 21, 2022 to receive public comment on 
the report and the Foundation plans to host a public meeting on June 
14, 2022, to share insights from the report and to allow for questions 
from the public.
---------------------------------------------------------------------------
    \19\ https://onlinelibrary.wiley.com/toc/18632378/2020/67/S1
    \20\ https://reaganudall.org/sites/default/files/2022-05/
Tracking%20and %20Monitoring%20of%20Antimicrobial%20Use%20in%20Food-
Producing%20Animals%20Preliminary%20Summary%20Report.pdf
---------------------------------------------------------------------------
    Question. What steps does FDA intend to take to improve the 
standards of identity review process going forward?
    Answer. FDA recognizes the importance of updating standards of 
identity in an efficient and transparent manner and appreciates the 
$1.5 million in new funding for standards of identity (SOIs) work in 
fiscal Year 2022. FDA is working to support innovation, especially when 
it can increase the availability of healthier foods in the food 
marketplace, by continuing its work to modernize food SOIs. This is 
part of our daily work and we are taking several steps to facilitate 
the process, including:

  --Developing principles to more transparently communicate what we 
        consider when we establish, revise, or eliminate a food 
        standard. FDA started this process in 2005 when it published a 
        joint proposed rule with USDA to provide each agency a set of 
        general principles. After re-opening the comment period on the 
        2005 proposed rule, FDA is working with USDA to re-issue a 
        proposed rule for stakeholders to provide input on.

  --Prioritizing SOI work that supports FDA's nutrition initiatives.

  --Using new strategies to more efficiently work on SOIs, such as 
        making amendments across multiple SOIs--allowing FDA to update 
        more than one in a single rulemaking when applicable.

  --Updating individual standards of identity that focus on (1) 
        improving public health and (2) to allow the use of modern 
        technologies. Many standards are outdated and, as a matter of 
        good government, need to be updated to better serve our 
        stakeholders.

  --Continuing to review citizen petitions that request FDA to 
        establish, revise, or eliminate a standard of identity. Citizen 
        petitions for standards of identity that do not promote honesty 
        and fair dealing in the interest in consumers or do not contain 
        sufficient data will be denied.

  --Continuing to transparently communicate about FDA's recent actions 
        and current activities on the Agency's recently developed SOIs 
        webpage (see https://www.fda.gov/food/food-labeling-nutrition/
        standards-identity-food).
  --In November 2021, FDA published guidance for industry to clarify 
        aspects of the temporary marketing permit (TMP) process and to 
        describe changes that streamline and simplify the TMP 
        application process. TMPs allow a company to test the market 
        acceptance of products that deviate from an SOI, in order to 
        obtain data necessary for reasonable grounds in support of 
        their citizen petition to amend an SOI and ensure the interests 
        of consumers are adequately safeguarded.

    Modernizing SOIs will enhance industry's ability to innovate and 
produce healthier food while maintaining the basic nature, essential 
characteristics, and nutritional integrity of the food.
    Question. Will FDA commit to establishing a transparent standards 
review process that includes reasonable deadlines for agency action and 
greater accountability to consumers, industry and Congress in the 
future?
    Answer. Yes, FDA is committed to establishing a transparent 
standards review process and, as part of this commitment, launched an 
SOI webpage in April 2022 that includes a general overview of what an 
SOI is and its purpose, priorities for updating SOIs, a list of current 
SOIs that are being reviewed, and updates and current statuses (https:/
/www.fda.gov/food/food-labeling-nutrition/standards-identity-food).
    Question. What actions is FDA taking to address stakeholders' 
objections and requests for hearings regarding the recently updated 
standard of identity for yogurt?
    Answer. On March 22, 2022, FDA published a notice to clarify that 
the effectiveness of certain provisions of the yogurt standard of 
identity have been stayed. Dairy standards of identity are subject to 
formal rulemaking procedures, which provide a 30-day period for any 
person adversely affected to file an objection and request a hearing. 
If objections are properly filed, then the provisions to which 
objections were made do not go into effect (i.e., they are ``stayed''). 
FDA received properly filed objections to certain provisions of the 
final rule within this timeframe; those provisions are stayed pending 
final FDA action on the objections. FDA is actively evaluating the 
objections. Publishing a response to the objections received is a CFSAN 
priority.

                                 ______
                                 

            Questions Submitted by Senator Cindy Hyde-Smith
    Question. Dr. Califf, 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 by this month (May 2022)'s deadline 
set in the Fall 2021 Unified Agenda?
    Answer. On May 20th, FDA announced a notice of proposed rulemaking 
\21\,\22\ that proposes to establish regulations regarding 
certification of designated medical gases and that proposes to amend 
the current good manufacturing practice (CGMP), postmarketing safety 
reporting, and labeling regulations that apply to certain medical 
gases.
---------------------------------------------------------------------------
    \21\ https://www.federalregister.gov/public-inspection/2022-10458/
current-good-manufacturing-practice-certification-postmarketing-safety-
reporting-and-labeling
    \22\ https://public-inspection.federalregister.gov/2022-10458.pdf
---------------------------------------------------------------------------
    FDA has engaged with stakeholders and Congress for several years to 
gather input and evaluate the need for changes to regulatory 
requirements for medical gases. If finalized, this proposed rule would 
clarify the regulatory obligations of entities that manufacture, 
process, pack, label, or distribute medical gases.

    Examples of proposed key provisions include:

  --Proposed labeling requirements to clarify the statement of 
        ingredients and quantity of contents for designated medical 
        gases, revise warning statements for certain designated medical 
        gases, and establish more limited labeling requirements for 
        bulk or transport containers.

  --Proposed CGMP requirements that recognize important differences in 
        how medical gases are manufactured, processed, packed, and held 
        compared to other types of drugs, including the reuse of 
        containers and labeling; mixing and commingling of gases; that 
        gases are generally manufactured in a closed, pressurized 
        system; and that many medical gases are generally not expected 
        to expire or degrade.

  --Proposed regulations to codify the certification process for 
        designated medical gases, including provisions regarding 
        supplements to granted certifications, annual reporting, and 
        withdrawal or revocation of approval of an application.

  --Proposed safety reporting requirements under which certain events 
        related to designated medical gases would not need to be 
        reported to the Agency.

    Question. Dr. Califf, I received your April 21, 2022, letter 
responding to a bicameral letter I sent you on February 18, 2022. Our 
letter had requested that you immediately rescind the removal of in-
person dispensing requirements for the chemical abortion drug 
mifepristone (Mifeprex). Your recent response said that you had 
conducted ``a comprehensive review of the Mifepristone REMS Program,'' 
and that you concluded that without the in-person dispensing 
requirement, the drug would remain ``safe and effective.'' However, as 
I noted at the hearing, I disagree, as do many others.
    I have reviewed quite a lot of evidence showing that this drug is 
actually quite dangerous to the women and girls who take them. Given 
your unequivocal statement that your review was comprehensive, then, I 
have a list of questions for you. Thank you for your commitment at the 
hearing to be responsive to all of my questions about this.
    Did your ``comprehensive'' review include the following relevant 
studies? If so, please indicate how FDA considered them, referencing 
all correspondence, analysis or conclusions FDA reached related to 
them. If not, please explain why you excluded them from the review and 
how your review can be considered ``comprehensive'' without them.

  --https://doi.org/10.1177 percent2F23333928211053965 James Studnicki, 
        et al., A Longitudinal Cohort Study of Emergency Room 
        Utilization Following Mifepristone Chemical and Surgical 
        Abortions, 1999-2015, Health Services Research and Managerial 
        Epidemiology. Vol. 8 1-11 (2021).

  --https://doi.org/10.1093/humrep/der016 Mentula MJ, Niinimaki M, 
        Suhonen S, et al., Immediate Adverse Events After Second 
        Trimester Medical Termination of Pregnancy: Results of a 
        nationwide registry study, Human Reproduction. 2011;26(4):927-
        932;

  --https://doi.org/10.1097/aog.0000000000000897 Chen MJ, Creinin MD, 
        Mifepristone with Buccal Misoprostol for Medical Abortion, 
        Obstet. Gynecol 126 (1) July 2015 12-21

  --https://doi.org/10.1186/s12905-018-0645-6 Carlsson I, Breding K, 
        Larsson PG, 2018, Complications Related to Induced Abortion: A 
        Combined Retrospective and Longitudinal Follow-up Study, BMC 
        Women's Health 18:158.

    Answer. With the exception of the Studnicki study, which was 
published in November 2021, after the completion of our literature 
review, the Agency considered these studies, as well as other studies, 
as part of its review of the Mifepristone REMS Program. A discussion of 
these studies can be found in the citizen petition response we 
reference in the April 15, 2022 letter.
    Question. In reviewing the data to determine safety, the FDA would 
necessarily have had to make calculations to determine rate of 
complications or incidents. What was the rate of complications as 
determined by the FDA? Please describe the calculations, including the 
numerator and denominators used and how those numbers were determined 
adequate for statistical purposes. What rate did FDA determine would 
exceed safety and therefore require the REMS for mifepristone to have 
remained unchanged?
    Answer. FDA's determination as to whether a REMS is necessary to 
ensure that the benefits of a drug outweigh its risks is a complex, 
drug-specific inquiry, reflecting an analysis of multiple, interrelated 
factors (such as the seriousness of any known or potential adverse 
events that may be related to the drug and the background incidence of 
such events in the population likely to use the drug; and the expected 
or actual duration of treatment with the drug) and of how those factors 
apply in a particular case. In conducting this analysis, FDA considers 
(based on premarketing or postmarketing risk assessments) whether there 
is a particular risk or risks associated with the use of the drug that, 
on balance, outweigh its benefits and whether additional interventions 
beyond FDA-approved labeling are necessary to ensure that the drug's 
benefits outweigh its risks.
    Question. In the course of this review, did FDA consult with non-
government employees during this process, and if so, whom? Please 
provide names, titles and organizations for all outside individuals 
consulted in the review.
    Answer. The Agency did not consult with any non-government 
employees during the course of its review of the Mifepristone REMS 
Program.

                                 ______
                                 

               Questions Submitted by Senator Mike Braun
    Question. Since Congress legalized hemp in 2018, the FDA has failed 
to provide a pathway for the industry to bring their products to 
market. Congress has provided funding increases to support research on 
CBD products. This data is to help FDA provide regulatory clarity. In 
2020, FDA put out two reports requested by this Committee on CBD, 
including one on mislabeled or adulterated CBD products and the other 
on potential regulatory pathways and data gathering efforts on CBD. 
What steps has FDA taken with this funding to evaluate a potential 
pathway to market CBD that preserves the spirit of free market 
competition and transparency?
    Answer. FDA appreciates the funding Congress has provided since 
fiscal Year 2020 to support the Agency's efforts on cannabis and 
cannabis derivatives. Unfortunately, prior to passage of the 
Agriculture Improvement Act of 2018, there was very little research 
into this area, so this funding has been critical in helping the Agency 
begin to fill knowledge gaps.
    These resources are being used for a variety of purposes, in 
particular to study and collect data on cannabidiol (CBD) and other 
cannabinoids to better understand their effect on humans and animals. 
In addition, FDA is using funds to better understand the marketplace 
for cannabis-derived products (CDPs), for policy development, and to 
hire additional FTE in several of our programs to support the work in 
this quickly expanding area. These are necessary steps as FDA 
prioritizes the evaluation of potential regulatory options. The Agency 
looks forward to discussing this further with Congress when there is 
additional information to share.
    Question. In recent years, the animal nutrition industry has made 
significant strides with respect to developing technologies that can 
help reduce on-farm emissions. Yet FDA's regulatory process 
administered by the Agency's Center for Veterinary Medicine (CVM) does 
not facilitate the deployment of these innovations.
    For environmental claims and performance claims for animal feed 
additives, the CVM still reviews these claims as if they were animal 
drug claims. In my view, these regulations are overdue for an update. 
For example, the CVM Program Policy and Procedures Manual Guide 
1240.3605 was last updated on September 18, 1998.
    Can you detail for the committee what steps you intend to take and 
are currently taking to ensure the FDA regulatory review of these 
claims is updated expeditiously to reflect the important environmental 
benefits of modern animal nutrition technologies?
    Answer. CVM has established a workgroup and is currently evaluating 
the possibility of environmental and performance claims for foods under 
existing authorities. We are looking at all the options under our 
current authority to address this issue and exploring ways in which our 
historic approach could change to reflect the evolving scientific 
knowledge while still maintaining safety standards and consistency with 
current laws. This evaluation will inform CVM's plans to update 
policies in the Program Policy and Procedures Manual Guide 1240.3605. 
If new animal food additive review policies are developed, additional 
resources would be needed to support review of the anticipated increase 
in submissions and to ensure timely safety review of any new claims on 
currently marketed products.
    Question. I'm concerned that over the past few years, while FDAs 
Center for Drug Evaluation and Research (CDER) has announced a draft 
guidance titled ``Innovative Approaches for Nonprescription Drug 
Products,'' no further action has been taken to date. Potential changes 
were first described in 2012 and while some progress has been made, we 
are, years later, still waiting for a rule. The pandemic has 
illustrated the importance of consumers having ready access to a range 
of over-the-counter (OTC) self-care products. This lengthy delay is 
standing in the way of a potential pathway that could allow for more 
complex switches of OTC products, increasing access, affordability, 
equity, and convenience for consumers.
    Without this rule, consumers will further be denied the cost 
savings from prescription to OTC switches and the convenience of the 
availability of these medicines over-the-counter. I am concerned that 
while we have heard this administration discuss the importance of OTC 
medicines, we've seen little action on this rule. What can you tell me 
about the FDAs delayed action on prescription-to-OTC Switch?
    Answer. Currently, nonprescription drug products are limited to 
drugs that, among other things, can be labeled with sufficient 
information for consumers to appropriately self-select and use the drug 
product without the supervision of a health care practitioner. For 
certain drug products, limitations of labeling present challenges for 
adequate communication of such information needed for consumers.
    On June 27, 2022, FDA announced the issuance of a proposed rule 
which, if finalized, would establish requirements for certain 
nonprescription drug products that would need an additional condition 
that an applicant must implement to ensure appropriate self-selection 
and/or appropriate actual use, by consumers without the supervision of 
a health care practitioner.\23\ The proposed rule is be intended to 
address situations when labeling alone is not sufficient to ensure that 
the consumer can appropriately self-select or use a drug product 
correctly in a nonprescription setting, and would allow an applicant to 
submit an application proposing an additional condition that a consumer 
must successfully fulfill before accessing the drug product. The 
proposed rule is intended to increase the availability of safe and 
effective nonprescription drug products.
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    \23\ https://www.fda.gov/news-events/press-announcements/fda-
introduces-innovative-proposal-advance-consumeraccess-nonprescription-
drugs
---------------------------------------------------------------------------
    Question. Breakthrough and expedited approval pathways allow FDA an 
expanded universe of flexibility to unlock efficient development 
pathways for treatments of diseases and conditions that have few or no 
therapeutic options. Drug repurposing could be a viable option to close 
unmet medical needs if approval pathway qualifying criteria 
specifically included drug repurposing use cases.
    Does FDA envision using a portion of existing funding under their 
current operating budget or the requested funding for FY23 to specify, 
update, or create expedited or accelerate approval pathways to maximize 
the value of FDA regulated products for all populations, especially 
those with rare conditions?
    Answer. The Agency agrees that data on how approved drugs are being 
repurposed may inform the development of new clinical uses for these 
drugs as potential treatments for diseases and conditions that have few 
or no therapeutic options. FDA has and will continue to consider fit-
for-purpose real-world data in regulatory decisions relating to the use 
of repurposed drugs, including utilizing such data when appropriate to 
support the criteria for our expedited programs for drugs and biologics 
to treat serious conditions. These programs have been and will continue 
to be utilized to advance consideration of repurposed drugs.
    The agency has also devoted significant resources to exploring the 
use of repurposed drugs for diseases or conditions with unmet medical 
needs. In December 2019 the agency launched the CURE ID repository (a 
website and mobile application) globally, and rapidly expanded it in 
June of 2020 to respond to the COVID-19 pandemic.\24\ The repository 
captures clinical outcomes from the clinical community when drugs are 
used for new conditions, in new populations, in new doses or in new 
combinations. Health care professionals generally may choose to 
prescribe or use a legally marketed human drug or medical device for an 
unapproved or uncleared use when they judge that the unapproved use is 
medically appropriate for an individual patient. The systematic 
collection of real-world experience in the CURE ID platform can help 
identify drug candidates for additional study, encourage further drug 
development and serve as a resource for physicians to share information 
where no FDA-approved product proven to be safe and effective exists 
for the new use. Repurposing approved drugs for new clinical uses can 
potentially offer an efficient drug-development pathway for treatments 
of diseases and conditions that have few or no therapeutic options.
---------------------------------------------------------------------------
    \24\ https://www.fda.gov/drugs/science-and-research-drugs/cure-id-
app-lets-clinicians-report-novel-uses-existing-drugs
---------------------------------------------------------------------------
    In June of 2020, the agency also announced the creation of a 
public-private partnership (PPP), convened by the Critical Path 
Institute, called the CURE Drug Repurposing Collaboratory (CDRC) and 
provided funding to initiate this effort. The Agency plans to continue 
our work with the CDRC, which has since received additional support 
from HHS. Additionally, the Agency has continued to work with National 
Institutes of Health (NIH), the Reagan Udall Foundation,\25\ and the 
Critical Path (C-Path) Institute \26\ to explore avenues to advance 
research and policy regarding existing therapeutics.
---------------------------------------------------------------------------
    \25\ https://www.fda.gov/drugs/news-events-human-drugs/repurposing-
patent-drugs-research-regulatory-challenges-12052019-12062019
    \26\ https://c-path.org/programs/cdrc/
---------------------------------------------------------------------------
    The agency believes that the existing expedited programs for drug 
development and the agency's ability to leverage these programs when 
approved drugs show promise with rare diseases are sufficiently 
flexible and robust to address public health needs, including with 
respect to repurposing, or expanding the approved uses of, approved 
drugs. The agency is committed to utilizing these programs when 
appropriate to expedite development of repurposed drugs, including 
repurposed drugs for rare diseases. The Agency will also continue 
working with sponsors pursuing repurposing opportunities for areas of 
unmet medical need. The FDA instituted its Accelerated Approval Program 
to allow for earlier approval of drugs that treat serious conditions, 
and that fill an unmet medical need, based on a surrogate endpoint 
reasonably likely to predict clinical benefit. Validated surrogate 
endpoints can be used for traditional approvals. A surrogate endpoint 
is a marker, such as a laboratory measurement, radiographic image, 
physical sign or other measure that is thought to predict clinical 
benefit, but is not itself a measure of clinical benefit. The use of a 
surrogate endpoint can considerably shorten the time required prior to 
receiving FDA approval.
    While the agency believes the current expedited approval pathway, 
enhanced by the agency's other expedited programs, provides an 
appropriate pathway for expanding the approved uses of approved drugs, 
the President's budget includes a legislative proposal titled 
``Ensuring Feasibility and Timeliness of Confirmatory Studies and 
Enhancing Withdrawal Procedures for Prescription Drugs Approved through 
Accelerated Approval''. This proposal seeks to amend the accelerated 
approval provisions of the FD&C Act to (1) revise section 506(c)(2)(A) 
of the FD&C Act such that FDA may require, as a condition of a drug 
product application's acceptance for filing, or as a condition of a 
drug product's receipt of accelerated approval, that a drug sponsor 
must first demonstrate that a proposed post-approval (i.e., 
confirmatory) study is adequately designed to verify and describe 
clinical benefit and can be completed in a timely manner; (2) revise 
section 506(c)(3) so that FDA can follow its dispute resolution 
procedures for drug applications when withdrawing a drug product's 
accelerated approval; and (3) revise the withdrawal standard at FD&C 
Act 506(c)(3)(C) so that it mirrors the analogous withdrawal standard 
set forth in section 505(e) for drugs with traditional approvals. The 
FD&C Act does not provide FDA with easily implementable legal 
authorities to help target the problem of studies that progress too 
slowly. FDA believes that such a provision would help provide greater 
assurance at the time of a drug product's accelerated approval that the 
confirmatory study can progress in a timely manner, and reap high-
quality, interpretable results. Enhancing the timeliness and quality of 
confirmatory studies will help support FDA's regulatory decision-making 
for drugs approved through the accelerated approval pathway and 
minimize the time that a product is marketed based on accelerated 
approval before its clinical benefit can be confirmed.

                          SUBCOMMITTEE RECESS

    Senator Baldwin. The hearing was adjourned.
    [Whereupon, at 11:21 a.m., Thursday April 28, the 
subommittee was recessed, to reconvene subject to the call of 
the chair.]