[Senate Hearing 118-]
[From the U.S. Government Publishing Office]




 
                AGRICULTURE, RURAL DEVELOPMENT, FOOD 
                 AND  DRUG  ADMINISTRATION, AND  RE- 
                 LATED  AGENCIES APPROPRIATIONS  FOR 
                 FISCAL YEAR 2024

                              ----------                              

                       WEDNESDAY, APRIL 19, 2023

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 2:15 p.m. in Room SD-124, Dirksen 
Senate Office Building, Hon. Martin Heinrich (chairman) 
presiding.
    Present: Senators Heinrich, Murray, Tester, Manchin, 
Peters, Hoeven, Collins, and Hyde-Smith.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                      Food and Drug Administration

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

              OPENING STATEMENT OF SENATOR MARTIN HEINRICH

    Senator Heinrich. Good afternoon. This hearing of the 
Agricultural Appropriations Subcommittee is now called to 
order, and I'd like to begin by welcoming FDA Commissioner Dr. 
Robert Califf to this hearing. Thank you for being here today. 
Very much looking forward to discussing the fiscal year 2024 
Budget Request for the Food and Drug Administration.
    The responsibilities of the FDA are extensive and they 
impact every single American. Last year this committee provided 
historic funding for this agency but there is much more work 
that needs to be done and that begins with the budget request 
in front of us today.
    This request for FDA includes the discretionary increase of 
$372 million. This increase touches on a wide array of 
activities at the FDA, from enhancing food safety to advancing 
safe and effective medical products as well as continuing to 
address the ongoing Opioid crisis.
    We must ensure that the vast number of products FDA 
regulates are safe while also not slowing down important 
advancements in research and technology. These are not easy 
tasks, but this committee stands ready to work to support the 
FDA and the critical work that is done there.
    The decisions the FDA makes, whether approving a medical 
device or approving a new drug, must be guided by science and 
data, not by political pressure.
    Dr. Califf, with your long and distinguished career in 
science, I suspect you must feel the same way and that 
precisely is why a recent decision by a Federal judge in Texas 
is so disturbing to me.
    This judge has replaced his political agenda for the data-
driven process used by the FDA. He has undermined the FDA's 
safety and efficacy determination of Mifepristone and with it 
he has undermined the FDA's authority to determine the safety 
and efficacy of all medications, from insulin to cancer 
treatments.
    I know we're going to discuss this shortly and I'm 
interested to hear your thoughts, Dr. Califf, but first I look 
forward to hearing your testimony and having a robust 
discussion on this year's budget request, and I'll now turn the 
time over to Ranking Member Hoeven for any opening statements 
that he may have.
    Thank you, Member Hoeven.

                    STATEMENT OF SENATOR JOHN HOEVEN

    Senator Hoeven. Thank you, Chairman Heinrich, appreciate 
it.
    I'm also pleased that our Ranking Member for the Full 
Appropriations Committee, Senator Collins, is here. Thanks for 
joining us, appreciate it very much, and, Dr. Califf, thanks 
for being here, appreciate it very much.
    Last year when you returned to reprise your role as 
Commissioner, we were at the beginning stages of the infant 
formula crisis. During both the budget hearing and subsequent 
food safety hearing, we had frank discussions on the need for 
sustained leadership in the agency, and I expressed to you at 
that time, you know, that we had seven commissioners in the 
past decade and that we need some stability in the FDA. I'm 
pleased that you're back and I know you're working hard to try 
to provide that stability. I think it's important and I 
appreciate your efforts.
    Obviously FDA plays a critical role in the safety and 
prosperity of our nation. Your agency actually has some aspect 
of authority over approximately 20 cents of every dollar spent 
in America. You knew that, right? Pretty remarkable.
    Americans expect the food that they eat and the drugs they 
take will be safe and effective. So your reach is vast. You 
have authority over more than a 160,000 foreign establishments 
and a 135,000 domestic establishments, ranging from food 
processing plants to facilities that manufacture life-saving 
medications.
    In addition, FDA's tasked with the regulatory 
responsibility not only for the facilities but the individual 
products. So obviously that role is incredibly important, one 
that we can't take for granted, one that FDA has to get right.
    In delivering these regulatory responsibilities, it's very 
important that you have transparency and certainty and 
particularly when we look at small businesses as well as ag 
producers, like we have in my state of North Dakota, you know, 
their overwhelming concern is that the Federal Government in 
terms of that regulatory burden is reasonable, that common 
sense is applied, transparent and predictable, and so all of 
these things are vitally important to encourage the type of 
innovation and so forth that we need to continue to advance our 
economy and do it safely and well.
    So again I think as we pursue these solutions and I know 
you're involved in this and rightly so, this reorganization 
effort, we've got to avoid a one size fits all and we've got to 
use common sense. We've got to appreciate and understand the 
incredible role that small business plays in our economy, truly 
the back bone of our economy, and make sure that as you do 
these things that we don't get overly bureaucratic burdensome 
and so forth but in fact find ways to do things as effectively 
as possible and in a way that provides certainty to people 
across this country in all different aspects of the things that 
you do which are so critically important to our nation.
    Thank you for being here today with us, appreciate it.
    Senator Heinrich. Dr. Califf.

                 SUMMARY STATEMENT OF DR. ROBERT CALIFF

    Dr. Califf. Thank you, Chair Heinrich, Ranking Member 
Hoeven, and Members of the Subcommittee. Thanks for the chance 
to be here today.
    I'd like to start by thanking the Subcommittee for your 
continued support of FDA, especially over the last few years, 
as the agency has worked tirelessly to turn the corner on 
COVID-19, ensure a safe and nutritious food supply, and prepare 
for the emerging challenges of an expanding and changing 
landscape of food, medical, and tobacco products.
    This has been possible due to the vital and never-ending 
work of our dedicated FDA staff across the country and the 
world. To continue supporting their work, the budget I present 
to you today requests a total of $7.2 billion, a 7.8 percent 
increase in funding for the FDA.
    This significant increase in funding will have an immediate 
impact on optimizing the health benefits of safe and nutritious 
food, reducing harm from tobacco products, and ensuring the 
availability of safe and effective medical products.
    This funding will also enable the agency to continue to 
leverage new and emerging technologies, improve the recruitment 
and support of a highly skilled workforce, and adapt to new 
production and business models in the industries that we 
regulate.
    I want all of you to know as well as the American people 
that I, along with the leadership at FDA, will continue to make 
the long- and short-term strategic organizational changes and 
investments to ensure this agency is best positioned for future 
public health and regulatory challenges and opportunities.
    Since rejoining the agency I have consistently heard from 
industry, Congress, and other stakeholders that the Human Foods 
Program needed more attention and support. I don't have to tell 
you that the infant formula shortage highlighted many of these 
issues.
    We've begun the exciting process of implementing a 
revitalized and forward-looking FDA Human Foods Program, 
including a new model for the Office of Regulatory Affairs. 
We've announced a search for a Deputy Commissioner of Human 
Foods who will report directly to the Commissioner and will 
have clear authority over the organization's strategy and 
resource allocation of the Human Foods Program.
    As we embark on these changes, I want to be clear, our food 
is already the safest it has ever been and no other country has 
safer food, but that doesn't mean we can't improve; and while 
most public discussion has been about preventing food 
contamination, America has a critical need to improve its 
nutritional status and better understand and reduce the 
chemicals that put our food supply at risk.
    In addition to our focus on food, tobacco product 
regulation and enforcement remains one of our greatest 
opportunities to save lives.
    Although tobacco use is declining and vaping has been 
modestly declining in youth, we will lose almost 500,000 
Americans this year and millions of teenagers are already 
addicted to nicotine with many new users each day.
    That's why our budget requests an additional $100 million 
in user fees and authority to include manufacturers and 
importers of all deemed products, including electronic nicotine 
delivery systems or vaping products, among the tobacco product 
classes for which FDA assesses tobacco user fees.
    No one anticipated we'd be inundated with almost 27 million 
applications for vaping products. It's time for this industry 
to pay its fair share as we grapple with the ongoing ravages of 
tobacco and nicotine addiction.
    The U.S. continues to lead the world in medical product 
innovation but additional resources are needed to focus on key 
areas presenting new challenges. The ongoing Opioid overdose 
crisis, supply chain issues leading to a host of critical 
product shortages, increasing needs for post-market evaluation, 
and opportunities for amazing progress in battling cancer and 
neurodegenerative diseases.
    Finally, we also need to ensure continuity of the agency's 
modernization of our IT infrastructure and data processes. This 
isn't just making sure our computers are the latest model or 
that the Wi-Fi works consistently, although that is important.
    We need the ability to create systems that allow us to keep 
up with the complexities of the industries and products we 
regulate with the immense consequences for the health of all 
Americans.
    Finally, we need to be prepared for the next pandemic 
threat. We've learned a lot over the course of the COVID 
pandemic and need to assure the public that we're ready for the 
next event.
    I'd like to close by thanking the Subcommittee again for 
your continued support of the agency. As the gold standard for 
protecting health, FDA is trusted by Americans and relied upon 
around the world for our work, ensuring the safety, efficacy, 
and security of our nation's medical products and food supply.
    Once again, thanks for inviting me to testify before you 
today and I look forward to answering your questions.
    [The statement follows:]
            Prepared Statement of Dr. Robert M. Califf, M.D.
    Chairman Heinrich, 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 2024 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 greatly appreciates the funding 
increases provided by the Subcommittee in the FY 2023 omnibus, as well 
as the expanded and new regulatory authorities included in the 
legislation to address cosmetics and medical device cybersecurity. Your 
continued partnership is critical as we further our mission to protect 
and promote the public health. FDA's talented and dedicated workforce 
has worked around the clock for the past three-plus years to respond to 
the COVID-19 pandemic, confront related challenges, and ultimately 
strengthen our nation's response to future outbreaks. We appreciate 
your ongoing support on a variety of programs and initiatives, 
including the dedicated resources in several critical areas that 
support our personnel and efforts, including employee pay costs, 
infrastructure, and data-modernization to ensure continuity of our 
vital work.
    The COVID-19 pandemic has underscored the need for a swift, unified 
governmental response with collaboration across Federal agencies, 
state, local, tribal, and territorial governments, industry, and the 
private sector. As we collectively work together as a nation to turn 
the corner on COVID, the Agency is using the lessons learned to 
continue our core mission while we pursue new ways to better prepare 
for future threats and confront new challenges posed from an ever-
expanding marketplace of food, tobacco products, and medical products.
    For example, in the foods area, the Agency has remained laser-
focused on a variety of critical efforts, including stabilizing the 
supply chain for critical products such as infant formula, mitigating 
the risk of potential exposure to certain chemicals, toxic elements, 
and allergens, and facilitating consumer education regarding healthy 
foods through the development of updated and more accessible food 
labeling. Furthermore, with a Human Foods Program that regulates 
approximately 80% of foods consumed by Americans, including those 
bought in grocery stores, restaurants, and cafeterias, we are actively 
working towards a new, transformative vision for the program that is 
forward-thinking, proactive, and adaptive to an ever-changing and 
evolving landscape. FDA is taking steps, in line with the 
recommendations of the external evaluation conducted by the Reagan-
Udall Foundation, to ensure that our customers, the American public, 
can remain as fully confident in the food they eat as they are in the 
medical products they rely on to support their health; our FY 2024 
Budget places us firmly on the steps towards this path.
    The funding requested in the President's FY 2024 Budget request 
builds upon funding provided in the FY 2023 omnibus for foods and other 
product areas, while also acknowledging additional future needs and 
challenges. Our FY 2024 program level request totals $7.2 billion, 
which represents an overall increase of approximately $521.4 million in 
annual funding above the FY 2023 Enacted level. Of this total, $3.3 
billion is for user fees, which is an increase of approximately $149.5 
million above the FY 2023 Enacted level. As part of the total program 
level, the Budget also requests $3.96 billion in budget authority, 
which is an increase of approximately $372 million above the FY 2023 
Enacted level. These increases are organized into five critical areas 
that advance the Agency's activities in support of protecting and 
promoting human and animal health: (1) enhancing food safety, 
nutrition, and cosmetics oversight; (2) advancing medical product 
safety; (3) investing in core operations; (4) modernizing 
infrastructure, buildings and facilities; and (5) tobacco user fees. 
The Budget also provides $670 million of mandatory funding to advance 
the goals of HHS's Pandemic Preparedness Plan.
       enhancing food safety, nutrition, and cosmetics oversight
    FDA's Budget request provides a historic investment in FDA's Foods 
Program with $1.7 billion for food safety, nutrition, and cosmetics, an 
increase of $210.6 million above FY 2023 levels, to support our 
continual efforts and commitment to strengthening FDA's food safety and 
nutrition capacity. This funding will help to ensure our human and 
animal food supply is safe, sanitary, wholesome, and accurately 
labeled, as well as ensure that FDA can start to implement new 
authorities given by Congress to provide oversight of the safety and 
proper labeling of cosmetic products. Additionally, this Budget will 
increase FDA's inspectional capabilities, which include the risk-based 
oversight of food facilities subject to FDA's food safety regulations 
and help ensure a reliable and safe food supply chain.
New Era of Smarter Food Safety
    As a nation, our food supply is the safest it has ever been--but 
that does not mean we can't improve upon it. Specifically, as part of 
the total $1.7 billion request for FDA's Foods Program, the FY 2024 
Budget includes an increase of $37 million for our New Era of Smarter 
Food Safety initiative. This approach aims to bend the curve of 
foodborne illness by strengthening data access and analysis 
capabilities, as well as bolstering capacity and food safety 
inspectional efforts.
Healthy and Safe Food for All
    Within these requested Foods Program investments, FDA is also 
seeking resources for our ongoing efforts to provide safe food to the 
American public, with a renewed emphasis on the availability of healthy 
food options. The infant formula shortage from the last year serves as 
a stark example of the need for continued attention to the critical 
issues of food safety and security, the importance of quality 
nutrition, and the need for a safe and accessible supply of food 
products. To meet this goal, FDA is requesting an increase of $64 
million to modernize oversight of infant formula, empower consumers to 
make healthier food choices, and reduce exposure to toxic elements in 
the food supply. We are further requesting an increase of $5 million in 
order to improve FDA's ability to assess and track certain elements of 
the food supply chain and industry capacity in order to help minimize 
supply chain disruptions and enable a more resilient food system.
White House Commitment to Nutrition and Food Labeling
    Finally, I would note that as a cardiologist, I've seen firsthand 
the result of poor nutrition and diet, often stemming from childhood, 
and the long-term impacts from diet-related chronic disease that can 
occur. One of the first steps to addressing this often-neglected issue 
is to ensure consumers have adequate and necessary information on the 
food they eat. To advance these efforts, our budget also requests an 
increase of $12 million to strengthen nutrition and labeling work in 
alignment with the White House's National Strategy on Hunger, 
Nutrition, and Health.
                    advancing medical product safety
    In addition to ensuring a safe and healthy food supply, FDA's FY 
2024 Budget request includes $4.6 billion for strengthening human and 
animal health efforts across FDA's medical product centers, an increase 
of $199.9 million above the FY 2023 Enacted level.
Device Shortages and Supply Chain
    For example, as part of FDA's total medical product safety 
investments, this budget requests an increase of $11.6 million, for a 
total of $21.6 million, to continue building capabilities for FDA's 
Resilient Supply Chain and Shortages Program for medical devices, and 
for recruiting data science, supply chain, and medical device experts 
to properly staff the program. These resources support our efforts to 
help prevent and mitigate shortages of critical medical devices, 
improve our ability to work proactively with medical device 
stakeholders to assess vulnerabilities and enhance resiliency, and 
ultimately safeguard the availability of life- saving technologies that 
are most often needed by vulnerable populations.
ALS (ACT for ALS)
    In addition to maintaining access to current devices and other 
existing medical products, FDA also continues its focus on promoting 
the innovation and scientific advancement of new medical products, 
including products to address critical and rare diseases. Our medical 
products request therefore includes an increase of $2.5 million for 
staffing to implement the ACT for ALS Act and to help facilitate access 
to therapies for neurodegenerative diseases such as amyotrophic lateral 
sclerosis (ALS). Additionally, this funding will help to expand the 
related development of new scientific approaches and tools that are 
available for the development of effective new medical products to 
prevent, diagnose, mitigate, and treat rare neurodegenerative diseases.
Combating the Overdose Crisis
    Finally, in addition to the ongoing efforts at the Agency to 
promote medical product access and innovation, I also remain deeply 
involved in efforts to address an issue that has devastated countless 
families across our country, the overdose crisis. FDA's Budget request 
includes a proposed increase of $23 million, for a total of $102.5 
million, to support the continued development of overdose reversal 
treatments, as well as treatments for Opioid Use Disorder (OUD). This 
funding will also support preventative methods and tools which involve 
establishing satellite labs at International Mail Facilities with 
permanent staffing of scientists and investigators, along with 
expanding FDA's use of analytical tools for screening entries of 
potentially illicit products before they can enter our country. In 
addition, this funding will help advance the development, evaluation, 
and market authorization of digital health medical devices for further 
monitoring and addressing OUD inclusive of the patient perspective. 
Addressing this crisis is largely dependent on collaboration across the 
country, and utilizing real-time data to take effective and evidence-
based approaches on this issue remains crucial to our next steps to 
turning the corner on this epidemic.
Cancer Moonshot
    Further, FDA's Budget provides $50 million for FDA to advance the 
President's Cancer Moonshot goals. These funds will enhance Agency-wide 
efforts to improve evidence generation for underrepresented subgroups 
in oncology clinical trials, as well as to support pragmatic, 
decentralized trials and the development of sources of evidence that 
incorporate patient- generated data and real-world evidence. 
Additionally, these resources will assist in the expansion of FDA's 
efforts to facilitate the approvals of innovative and new cancer 
treatments by international regulatory authorities at the time of FDA 
approval and will foster collaboration on cancer treatments with other 
countries with standards comparable to the U.S. standard of care.
                      investing in core operations
    As highlighted in earlier portions of this testimony, our nation 
relies on FDA to provide rigorous and transparent scientific review, a 
predictable and responsive regulatory structure, a strong inspectorate, 
and expert staff to provide support for these activities. To meet these 
needs, as part of our total program level, our FY 2024 Budget requests 
$131.1 million above FY 2023 levels to continue to strengthen and 
support FDA's core operations and pursue new areas of improvement and 
innovation. In order to support further efforts, the Agency needs a 
strong framework for our programs, and for us that begins with data. 
Core operations also include initiatives such as advancing lab safety, 
information technology, and support services to help ensure FDA's 
ability to carry out its programmatic responsibilities.
Data Modernization and Enhanced Technologies
    FDA's core operations request includes an increase of $10 million 
for Data and IT Modernization to build new tools and greater capacity 
to analyze real-time information. To meet the challenges of emerging 
threats and the need for real-time evaluation, FDA relies on the 
ability to rapidly and continuously access, analyze, and aggregate 
multiple sources of information. From the COVID-19 pandemic to import 
alerts and domestic recalls, continual modernization of FDA's IT 
infrastructure has become increasingly more vital in order to keep pace 
with the evolution of outbreaks and disease. With these resources, FDA 
will continue to further build our centralized enterprise data 
modernization capabilities and strengthen the Agency's common data 
infrastructure, data exchange, and IT analytic services, talent, and 
tools. Investments in these critical areas will enable FDA to directly 
meet the challenges of our modern data-driven world, and continue to 
operate as the gold standard for product regulation and oversight.
           modernizing infrastructure, buildings & facilities
    In addition to necessary investments in our core operations, 
including digital infrastructure, the continuity of the Agency's 
critical work also requires funding to complete projects that will 
improve the condition of FDA's owned buildings and physical site 
infrastructure. As part of our overarching FY 2024 Budget, FDA's 
request provides a total of $395.9 million for infrastructure, 
buildings, and facilities. This funding will help to ensure that FDA's 
offices and labs across the country are optimally functioning. This 
funding will also directly support the Agency's priorities across the 
country by providing secure, modern, reliable, and cost-effective 
office and laboratory space that empowers FDA's workforce to protect 
and promote the safety and health of American families. By investing 
resources in FDA's facilities, the Agency will be able to continue to 
provide the high-quality infrastructure and facilities needed for FDA 
employees to work to ensure FDA can achieve its strategic priorities 
across the country and the world.
                           tobacco regulation
    As one of these strategic priorities, tobacco product regulation 
represents one of FDA's greatest opportunities to save lives. The 
Tobacco Control Act gave FDA immediate authority to regulate 
cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless 
tobacco. FDA finalized the Deeming rule in 2016, which extended FDA's 
tobacco authorities to all tobacco products, including cigars, hookah 
(waterpipe) tobacco, pipe tobacco, nicotine gels, and electronic 
nicotine delivery systems (ENDS) such as e-cigarettes. In 2022, a new 
Federal law went into effect clarifying FDA's authority to regulate 
tobacco products containing nicotine from any source, including 
synthetic or non-tobacco nicotine (NTN). FDA regulates the manufacture, 
marketing, and distribution of tobacco products. Key areas of focus 
include policy and rulemaking, compliance and enforcement, premarket 
review, research support, and public education campaigns.
    In addition to the priorities mentioned earlier across foods, 
medical products, core operations, and infrastructure, the Budget also 
requests an additional $100 million in user fees and requests authority 
to include manufacturers and importers of all deemed products--
including ENDS--among the tobacco product classes for which FDA 
assesses tobacco user fees. These products represent an increasing 
share of FDA's tobacco regulatory activities. The additional funding 
will support hiring more staff, help FDA bolster compliance and 
enforcement efforts for all tobacco products, and expand public 
education campaigns and science and research programs, as we work to 
mitigate harms and to protect consumers from the dangers of tobacco 
use. To ensure that resources keep up with new tobacco products, the 
proposal would also index future collections to inflation. This 
proposal would ensure that FDA has the resources to address all 
regulated tobacco products, including ENDS, which currently have high 
rates of youth use, as well as future novel products.
                         pandemic preparedness
    Finally, as we advance towards regular operations across our 
product centers, FDA remains aware that there is work yet to be done in 
our response to COVID-19, and it is critical that we learn from both 
our successes and the challenges we experienced to best improve our 
operations moving forward. Lessons learned from the COVID-19 pandemic 
have reiterated the need to proactively plan for the next public health 
emergency by ensuring FDA has the resources and capacity in place to 
fully respond. FDA plays a unique and central role to the whole-of- 
government response to protect and promote the public health, and in 
turn, we are requesting funding to improve FDA's core capabilities to 
help ensure there is the appropriate level of regulatory capacity to 
respond rapidly and effectively to any future pandemic or high 
consequence biological threat.
    Separate from our aforementioned requests for discretionary budget 
authority, FDA's Budget includes a request for $670 million in new 
mandatory resources available over 5 years to advance activities to 
better prepare FDA for the next pandemic. These funds would support the 
Agency's biodefense efforts, domestic and globally, by bolstering FDA's 
cadre of medical product reviewers and strengthening foundational 
processes. It would also increase FDA's capacity to leverage a One 
Health approach to respond to emerging threats. And lastly, these 
resources would help strengthen underlying technology platforms to 
improve electronic information exchange among stakeholders and bolster 
central coordinating capacity within the Office of the Commissioner. 
With these resources, FDA will have the opportunity now to build on 
lessons learned from previous responses and provide transformational 
investments to help ensure that FDA can respond quickly and effectively 
in times of a public health crisis.
                               conclusion
    This last year has presented some defining moments for the Agency 
and ample opportunities to bring the Agency into a new chapter. This 
Budget will help FDA maintain and expand on our current efforts, pursue 
new innovative strategies and methods, and provide a renewed focus on, 
and investment in, a variety of endeavors in the interest of public 
health for both humans and animals. I would like to close by thanking 
the Subcommittee again for your continued support of the Agency. I look 
forward to answering your questions today, and FDA looks forward to our 
collaboration and work together.

    Senator Heinrich. Thank you for your testimony this 
morning, Doctor.
    As you know and I mentioned in my introduction earlier this 
month, U.S. District Judge in Texas ruled that FDA's approval 
of Mifepristone more than 20 years ago was improper and issued 
a nationwide injunction to halt it.
    This sets an incredibly dangerous precedent in terms of 
both women's reproductive rights but also the FDA's review of 
drugs.
    Doctor, I'd like to give you the opportunity to speak about 
what impact this ruling could have on other FDA-approved drugs.
    Dr. Califf. Well, as you know, Senator, that matter's 
currently pending before the Supreme Court. So, I have to be 
brief and concise, but I will say that we are concerned about 
the potential future impacts of this case as reflected in the 
extensive briefs that have been filed by the Department of 
Justice on our behalf.
    This includes a wide range of concerns ranging from the 
well-being of patients, including women who need access to this 
drug, the pharmaceutical industry, and our ability to implement 
our statutory authority. So, the considerations are extensive.
    Senator Heinrich. Switching gears just a little bit, Opioid 
and fentanyl use is having dire impacts in communities across 
the country, including my home state where two-thirds of drug 
overdose deaths involve an Opioid.
    With Naloxone approved by the FDA and now available over 
the counter, what else is the FDA doing to continue addressing 
the Opioid epidemic broadly?
    Dr. Califf. Really appreciate the chance to address this 
and we should all be concerned because the nature of the 
epidemic is changing significantly from just the prescription 
misuse to now cartels driving fentanyl being delivered by mail 
to American homes with unsuspecting parents finding teenagers 
dead, in addition to the other problems that we've seen.
    Having said that, we have a major report that's out with a 
whole host of things that we're doing, but just to name a few. 
We recently are requiring now a mail-back system to be employed 
by all the manufacturers of opioids so that when people finish 
their supplies rather than having them sit in the medicine 
cabinet, they can be mailed back to the pharmacy. We also just 
changed the labeling of long-acting opioids just last week, 
taking into account that we still don't have the data we need 
about long-term benefits. In fact, there's a hearing going--I 
mean, an advisory committee going on today to talk about that.
    We have a number of other things that we think are 
important in the future. One that I'll mention that's very 
important to us is we'd like to have the authority to require 
that any new opioid company attempting to bring an opioid to 
the market must show that the new one has superiority to the 
old ones in terms of safety.
    Right now, by law we don't have the authority to make that 
decision. It would really help us if we had that authority. 
This is a carve-out, an exception. It's not pertinent. A lot of 
times the second drug along in a class turns out to have 
advantages that were unanticipated, but this is a case where 
for opioids we really need help.
    I can go on much longer, but I know we have limited time.
    Senator Heinrich. Do you want to touch on--there's a $23 
million increase in the budget specific to this. Do you want to 
touch on your plans for that increased funding?
    Dr. Califf. Sure. A lot of it has to do with the data 
systems that we need and the testing that we need to do in 
proximity to where the opioids are coming into the market.
    If you ever want to have an interesting field trip, go to 
our International Mail Facility at JFK and see the Labrador 
retrievers. Senator Baldwin made that trip, but it's just an 
enormous amount of stuff coming in that Americans are getting 
over the Internet, I think not realizing that often they're 
getting really bad stuff.
    So, we've got to invest in the testing to intercept this 
right at the border, have the data systems and the artificial 
intelligence to screen just as we do when people come into our 
airports to sort the bad guys from the good guys, and then 
we're hoping that there's going to be development of non-
addictive pain medicines. It's a place where, in my view, the 
industry has let us down.
    I say that having been on the industry side in part of my 
career. It's a tough job, but we're not succeeding in seeing 
non-addictive pain medicines coming through the pipeline. So, 
we need to do everything we can to push the industry and work 
with the NIH to make this happen.
    Senator Heinrich. The accelerated drug approval process at 
FDA can often be a game-changer for patients with serious 
medical conditions. It's a process that's important to myself, 
many advocates actually, yet many of these drugs approved 
through that process are not then reimbursed by the Centers for 
Medicare and Medicaid Services (CMS).
    Doctor, what is the FDA doing to coordinate with CMS on 
drugs that are approved specifically through the accelerated 
process?
    Dr. Califf. Well, you may remember when I came in this 
time, you know, I likened it to a relay race where we run the 
first lap and then we hand off the baton to the payers, the 
private payers and CMS. What we're doing is try to make sure 
the information is much more seamless, that we have the 
clinical trials that are relevant to what they need, but it's 
also abundantly critical CMS does not influence our decisions 
about safety and effectiveness and we don't have any authority 
to influence CMS's decisions about the reasonable and necessary 
criteria and what we want to do is to make sure people have the 
right information so that CMS can make the best decisions it 
can, that it understands what we were looking at when we made 
our decisions.
    I think this is an area in American medicine where there's 
a lot more work to be done and we can maybe later in the 
session we can talk about.
    Senator Heinrich. Okay. Ranking Member Hoeven.
    Senator Hoeven. Mr. Chairman, I'm going to defer to our 
Appropriations Ranking Member Senator Collins for the first 
round. I always appreciate when she joins us.
    Senator Collins. Thank you very much.
    Dr. Califf, I have a series of questions that go to the 
heart of the recent court decision in Texas on Mifepristone.
    First, are FDA's regulatory decisions based on sound 
science?
    Dr. Califf. Yes, the latest available science with the best 
methods that we can find by civil servants who have no 
financial conflicts.
    Senator Collins. Second, are political or economic 
considerations weighed in your drug approval process?
    Dr. Califf. No. Of course, we're all human beings. We're 
aware of the discussions that go on, but that decisionmaking 
process is protected. Political appointees, even the 
Commissioner, me, I'm a political appointee, I think of myself 
as a doctor, but I'm politically appointed, we don't influence 
those decisions or intercede, except in very rare 
circumstances.
    Senator Collins. Third, has this abortion drug been on the 
market for more than two decades?
    Dr. Califf. Yes, 23 years, I think.
    Senator Collins. And has it been used by millions of women 
during that period?
    Dr. Califf. Many millions.
    Senator Collins. Let me read you a quote that was included 
in a filing by some physicians who were challenging the process 
by which the FDA approved this drug. These doctors say, ``For 
nearly a quarter century the FDA and the manufacturer have 
brazenly flouted the law and applicable regulations, 
disregarded holes and red flags and their own safety data, 
intentionally evaded judicial review, and continually placed 
politics above women's health.''
    Could you comment on that statement?
    Dr. Califf. Well, as I've said, we use the latest science, 
the best data to make our decisions, and these sorts of 
influences you're describing are protected within the FDA by 
the system for all drugs, not just this one.
    Senator Collins. And I appreciate those answers. I consider 
the FDA to be the gold standard globally in approving drugs and 
I find this court ruling to be more reflective of the judge's 
personal views rather than a fair and impartial analysis of the 
facts of the case.
    I do want to pick up on the issue that the Chairman raised 
because just as I question the court's decision in this case, I 
also question CMS's decision to deny Medicare patients access 
to two Alzheimer's drugs that have been approved by the FDA.
    My view is CMS should stay in its lane, the FDA should stay 
in its lane, and we've talked about that. So I'm not going to 
ask you to comment today because I want to quickly get in one 
other issue, and it has to do with cell and gene therapy 
approvals.
    Almost 5 years ago the FDA issued a forward-looking 
statement on the future of cell and gene therapy approvals and 
new policies to advance their development. The FDA stated its 
intent to maximize use of expedited programs, including 
accelerated approval to review gene therapies for serious life-
threatening diseases, and this subcommittee's bill included 
language last year to further encourage FDA to bring urgency to 
the gene therapy.
    In 2021 you stated that you are a fan of accelerated 
approval for the right conditions and as we've also talked, I 
believe that you are sincere in your belief that there's great 
promise here.
    However, what I am frequently hearing is that the FDA's 
Center on Biologics has put clinical holds without explanation 
on some promising cell therapy developments.
    Do you agree that there is a problem there?
    Dr. Califf. I want to acknowledge that I think there are 
some issues there that need to be worked out. This was 
recognized in the User Fee Agreements that were just concluded 
and you all passed just last year which are now going into 
effect.
    We're going to be hiring 150 to 200 people in this area 
under the leadership of Dr. Marks, who I think you'd agree has 
done a remarkable job with vaccines and now this is going to be 
a big focus of attention.
    I would emphasize when it comes to clinical holds, it's not 
just it's something that's going wrong with a patient. Often it 
has to do with the integration of manufacturing and a lot of 
the companies are start-ups without robust manufacturing 
facilities. So, there's a lot of work to go on, but we agree 
that this is an area we've got to move along more quickly.
    I know like everyone else you all talk about FDA approvals. 
I always feel like I need to emphasize we also don't approve a 
lot of things if they aren't safe and effective. If the risks 
outweigh the benefits, it's our job to stop those, but I do 
acknowledge that there's an issue here that we're addressing.
    Senator Collins. Thank you. Thank you, Mr. Chairman.
    Senator Heinrich. Senator Peters.
    Senator Peters. Thank you, Mr. Chairman.
    Dr. Califf, last month, as the Chair of the Senate Homeland 
Security and Government Affairs Committee, I released an 
investigative report that found that there were major blind 
spots in our ability to accurately assess vulnerabilities in 
our drug supply chain.
    From both a national and a homeland security standpoint, 
I'm particularly concerned about shortfalls in the FDA's 
ability to use data analytics to effectively assess our 
reliance on foreign sources, especially in countries with 
rising geopolitical risk, like China.
    The Defense Department, of course, relies on the same 
international market to provide drugs for our service members.
    So my question for you, sir, do you agree that the FDA does 
not have sufficient visibility to identify some of the risks 
that could lead to supply shortages and if that is the case 
what are some of your top challenges to assess this risk?
    Dr. Califf. Thanks for raising this issue. It's taking up a 
large amount of my time right now and just a couple of preface 
statements.
    We're seeing shortages in every commodity we regulate, 
including food, devices, drugs, and biologics. The only one 
we're not seeing it in is tobacco, oddly enough, the one I 
might prefer there was a shortage, it's not occurring. They 
seem to have figured it out.
    The second preface point that I would make is that I was on 
the National Academy of Medicine's Supply Chain Committee just 
before being nominated and spent a lot of time working on it 
then and the report that you put out is very consistent. I 
think there are five different reports now that make this 
point.
    If FDA is looking through a windshield, we got mud on our 
windshield because we can see some things but there's a lot 
that we can't see because we don't have requirements of the 
industry to give us the data that we need and we don't have 
funding for the data systems and analytics that we need, and, 
if you wish, I'm glad to go into any amount of detail.
    The one other point I want to make in general is that 
there's an element of this, that is clearly in FDA's lane, and 
there's an element which is more of an all of government; that 
is, when we see a problem, many of the levers that are really 
important to pull exist outside the FDA when it comes to things 
like tariffs or investments in manufacturing facilities in the 
U.S. with funding which are two of the areas I think we've got 
to look at.
    Senator Peters. Well, great. Well, I guess in further 
conversations we've had a follow-up report, two reports now, 
one we did prior to the pandemic and since then it's gotten 
worse, not better, and we've got a number of ideas how to 
address it but love to have your thoughts and meet with you at 
some point in the near future.
    Dr. Califf. I'd like to, and your point about insecure 
countries that we're dependent on is really critical right now.
    Senator Peters. Right, absolutely. Thank you.
    Sir, I'd also like to follow up with you on the FDA's work 
to restore confidence in our nation's infant formula supply.
    As you're well aware, in Michigan we witnessed the 
devastating harm that can come from bacterial contamination of 
infant formula that families rely on, and it's clear, 
absolutely clear that we have a lot more work to do. In the 
most recent Michigan case, once again contaminated formula was 
recalled only long after it was already distributed, sold, and 
consumed. This put vulnerable infants at risk and once again in 
response the FDA asked manufacturers to voluntarily notify the 
FDA of any time a product sample is found to be positive for 
Cronobacter or Salmonella, even if the affected lots have not 
yet been distributed.
    So my question is are you confident the industry will 
consistently volunteer accurate and verifiable information to 
the FDA or do you think we're going to need to be thinking of 
legislative change to require earlier industry reporting, if 
necessary?
    Dr. Califf. I am confident the majority of the industry 
will comply, but I would prefer it if the things that are 
really needed are written into law. It's a lesson I've learned 
this year.
    You know, it's like anything in America. Most people want 
to do the right thing and they do it but you have outliers. In 
the case of the infant formula situation, it's a concentrated 
industry. So one entity not doing the right thing can create a 
problem.
    I do want to point out the recent case you talk about, we 
changed the standards and this particular entity got caught in 
the middle of it, didn't meet what we expected them to do. I 
think the whole industry is moving to the standard of 
notification and better bracketing of products, but still I 
think having the authority is so much better.
    I've been on the industry side and when the industry is 
told you must do something, it actually does it because the 
penalties are very different than in a voluntary situation.
    Senator Peters. Right. Well, thank you. Thank you, Mr. 
Chairman.
    Senator Heinrich. Thank you.
    Ranking Member Hoeven.
    Senator Hoeven. Dr. Califf, as you and I have discussed, I 
am concerned about FDA decisions to allow Mifepristone to be 
distributed by mail and without physician supervision.
    So my question to you is will you commit to following the 
decision of the courts with respect to the drug and how it's 
handled?
    Dr. Califf. I'll just say the FDA intends to comply with 
any court orders.
    Senator Hoeven. Thank you.
    And I would like to follow up on the infant formula supply. 
Talk about supply--we're still getting reports in some cases of 
supply of certain types of brands. Where are we at with the 
supply of infant formula and what else are you doing to make 
sure it's available?
    Dr. Califf. You know, I've tried to stay understated on 
this because, you know, the day of the Abbott recall was the 
day I was confirmed and I discovered all these problems inside 
the FDA that needed to be fixed. We could have a long 
discussion about how much those problems actually affected 
infant formulas specifically I don't think as much as people 
think, but that doesn't change the fact that we needed to fix 
our own house internally.
    But, I am pleased to say today we're over 90 percent in 
stock which is higher than it was before the recall. So there's 
plenty of formula out there and March 28th we put out our 
Stability Report with a whole host of things that we've done, 
but I also want to say that while we're stable at this point 
and probably a little better off than we were before the 
recall, there are four or five key things that are beyond the 
FDA that need to be fixed.
    It's a concentrated industry. We don't have enough 
variation in the suppliers. Putting up a new infant formula 
plant takes years and, in fact, Abbott has decided to put up a 
new one. It's going to take a couple years for them to do it 
and they have the most capacity in the industry already, but 
you've got to get 30 ingredients right, the quality has to be 
there. So, this is not a trivial thing for start-ups to begin 
to do.
    So, there's a lot of work to do to diversify the industry 
to assure that if there's a bad lot event like the major flood 
that occurred in Michigan, you know, one in a hundred-year 
flood, that the whole thing doesn't become short again. So, I 
don't want to appear complacent. We still have work to do. It's 
very much there in our report.
    Senator Hoeven. So I think that answer is helpful. I think 
it reassures people that supply is out there and that you're 
working on it and I think in your leadership role that's the 
kind of thing that both in terms of the information and action 
that can help address this type of situation. So I appreciate 
that.
    Dr. Califf. If I may mention, I know you're particularly 
concerned about rural areas, I'll just say in everything that 
we're currently regulating, rural areas are in need of better 
support.
    Now, you know, FDA can measure these things but we can't 
necessarily fix it, but in infant formula I know that's still a 
bit of an issue as the supply's up overall but it tends to be 
centrally distributed to start with. So, we're very much 
working on that every day. I just wanted to make sure that was 
noted.
    Senator Hoeven. Right. Particularly when you're looking for 
certain size and certain brands, certain types, you know, 
obviously it's there in the urban center and the big store but 
that's exactly right and so I appreciate that.
    In regard to the traceability rule, this goes back to my 
opening comments, and I'm concerned about the size and scope of 
the traceability rule and, you know, the workability.
    So, I mean, do you have a comprehensive list of the 
products that you're going to cover under the rule? Who's going 
to have the burden of maintaining records, the entity, the 
business, or the industry, or FDA, or both, and then are you 
going to allow exceptions again for small business, family-
owned business kind of thing?
    Dr. Califf. Sure. As we've discussed before, we've got to 
be sensitive to the needs of small organizations and we already 
have exceptions for, for example, family farms and for retail 
establishments that are small. There are exceptions, but, you 
know, there's a phrase used in the industry ``educate before 
you regulate'' and what we want to do, if we look 10 years 
ahead, we hope the entire supply chain will be digitized, 
right, so that we can distribute the right stuff to the right 
place regardless of where it is in America, but for smaller 
companies to get there, they're going to need help and support.
    We recognize that and it'll be shown in our adaptive 
approach to regulation.
    Senator Hoeven. The exception is very important and that 
rule can get away from you. So I'm glad you're watching it 
closely.
    My last question is regarding the Medicare and Medicaid 
coverage of Alzheimer's drugs. I joined with 19 of my 
colleagues, including Senator Collins, in sending a letter to 
CMS expressing our dismay for the agency's coverage termination 
on Alzheimer's drug.
    AS Commissioner and a physician, are you concerned with CMS 
choosing not to cover some of those FDA-approved Alzheimer's 
drugs?
    Dr. Califf. Senator, you know I can't comment on CMS's 
decision.
    Senator Hoeven. Sure you can.
    Dr. Califf. All I can say is we evaluated and considered it 
safe and effective.
    I'll just point this is an amazing area of biology that is 
still a problem.
    Senator Hoeven. That's the good comment for a non-comment.
    Dr. Califf. Okay.
    Senator Hoeven. You determined them to be safe and 
effective.
    Dr. Califf. But that's different than reasonable and 
necessary which is the CMS standard. I just got--you know, we 
have family involvement with this disease. It affects my family 
greatly. So, I'm very much hoping the biology works out.
    There's a whole bunch of new clinical trials about to come 
in. I think this will--I'm actually very confident having 
talked with CMS we'll get this resolved in a positive way and 
let's see the data as it comes in.
    Senator Hoeven. I appreciate that.
    Senator Heinrich. Chair Murray.
    Senator Murray. Well, thank you very much, Chair Heinrich 
and Ranking Member Hoeven.
    You know, families back home are really counting on us to 
work in this committee and across the Appropriations in a 
timely bipartisan way so we can pass our funding bills that 
keep them safe and our country strong. So I'm really glad this 
committee is continuing full steam ahead with return to regular 
order and talking about making sure that FDA has the resources 
it needs to live up to its really critical mission because make 
no mistake protecting our families is not just about how strong 
our military is, it is about how safe our food or drugs or our 
medical devices are, not to mention how smooth our supply 
chains are to ensure that families get what they need.
    We've had some tough reminders of that over the years, 
whether it's the medical supply shortages during the pandemic 
or the agency's important work to quickly, safely review COVID 
treatments and vaccines, or, as we've talked about here, the 
inexcusable baby formula shortage.
    That is really why I pressed very hard to make sure our end 
of the year package last year included some really important 
reforms to FDA, but we have more work to do, including on this 
subcommittee, to make sure we provide the resources for all 
this, as well, because there is a direct line between FDA 
having the resources it needs and the safety of American 
families.
    Every time families back in Washington State go to the 
grocery store or gather around the dinner table or fill a 
prescription or rely on a medical device, they're really 
putting their trust in FDA and their experts to uphold the gold 
standard of safety and effectiveness, and let me just say once 
again, especially in light of recent events, the determination 
about whether drugs are safe and effective needs to be left to 
the experts at FDA, not politicians and certainly not judges.
    We got a stark reminder of this in the recent weeks when 
extreme, poorly reasoned, and dangerous rulings of judges 
undermined FDA's authority to review and approve drugs by 
declaring themselves to know better than FDA's experts about 
medication abortion.
    FDA has an enormous responsibility and some hard work ahead 
to make sure it is living up to that responsibility. The last 
thing our families need at this critical moment is for 
politicians to undermine its authority or shortchange its 
efforts.
    So I'm really glad today, Dr. Califf, to have you before 
this committee to talk about what the agency is doing and what 
it requires to tackle the challenges you have ahead, and I do 
want to start out with the Mifepristone issue.
    As you know, the Supreme Court is going to decide a case 
that really threatens access to medication abortion nationwide 
and seeks to undermine the FDA's authorities to approve and 
regulate medicine.
    Let me ask the question this way. Commissioner Califf, 
would you speak to the implications of this case on the drug 
approval process and the scientific rigor with which the agency 
approaches drug applications?
    Dr. Califf. As we discussed already today, our decisions 
are based on the latest science, the best data we can find, the 
weighing of risks and benefits by our professionals who are 
full-time civil servants without financial conflict, and there 
is concern in this case about the impact on a wide variety of 
things, including patients, women in need of access to a drug 
which is approved, the pharmaceutical industry itself because 
of the threat to the separation of this decision about what's 
approval and what's not sequestered away from political 
influence. So, these are all concerns that we have.
    Senator Murray. So I take from your answer that this, of 
course, could have an implication on Mifepristone but also on 
the process that all of the drugs and tools that are going 
through the FDA?
    Dr. Califf. This is well reflected in the extensive briefs 
that the Justice Department has filed on our behalf and are 
publicly available.
    Senator Murray. Thank you very much.
    Dr. Califf, at the end of last year, as you know, I 
negotiated and passed the Modernization of Cosmetics Regulation 
Act of 2022 which Senator Collins, who just left, was a 
critical part of. It provided new authority to your agency to 
make sure that cosmetics are safe for the people who use them.
    The FDA finally, after many years, will know who is making 
and marketing what products and where and what ingredients are 
being used and when there is an adverse event, like severe 
rashes or hair falling out or worse. This is the first time and 
I'm very excited that you now have the authority to regulate 
this. I can't tell you how many people I've talked to didn't 
even know they weren't regulated before. So very important 
step. You will now have the power to take products off the 
shelves if they're not safe.
    Can you provide us with an update about how you're moving 
forward with this new authority and, importantly for this 
committee, what resources you will need to implement them?
    Dr. Califf. Sure. I'm still stunned by the average of 12 
cosmetics a day for women and six cosmetics a day for men, 
something I hadn't really considered before, but I am pleased 
to say that we're on track and I'm really excited that we've 
moved this under the auspices of Dr. Namandje' N. Bumpus, who's 
our Chief Scientist.
    If you all have not met her, I would urge you to meet with 
her. She was the Chair of a Department of Pharmacology at 
Hopkins and I tried to talk her out of coming to FDA because 
she had a good life as an endowed professor, but she's a great 
civil servant, a preeminent scientist in that role.
    We're moving along well with the registration issues that 
are part of this, developing the adverse event system. We've 
asked for $5 million for next year which is a very important 
part of the budget. Our estimate for the overall dealing with 
this $70 billion a year industry is about $40 million to get us 
where we need to be over time and we'll phase that in so that 
we can show progress.
    I know I've learned we need to show that in order to get 
people interested, but there are real safety issues that we're 
encountering. So, I'm glad we have that opportunity.
    Senator Murray. Okay. Thank you very much. Thank you, Mr. 
Chairman.
    Senator Heinrich. Senator Hyde-Smith.
    Senator Hyde-Smith. Thank you, Mr. Chairman, and thank you, 
Dr. Califf, for being here today before the committee because I 
certainly look forward to your questions.
    I just find it extremely concerning that under your watch 
the FDA allowed the dangerous life-ending, because they do kill 
the baby, chemical abortion drugs to be ordered by consumers 
through mail or purchased in retail pharmacies without ever 
seeing a doctor in person, I think that's the concern of many, 
many people. In 2016, as you know, the risk evaluation and 
mitigation strategies were changed to eliminate the 
requirements that non-fatal adverse events would even have to 
be reported to FDA.
    So that's been 7 years that if the woman almost died, it 
was not reported. It was only reported if there were fatal 
cases. The FDA that claimed this drug to be safe in part based 
on the lack of reports of non-fatal adverse events. I agree 
with the fifth circuit's description of this deeply disturbing 
this of really-not-looking-at-it or the head-in-the-sand 
approach. Because of the lackluster approach to safety, women 
seeking to use these drugs do so without the chance to be 
screened by an ultrasound for complications. My main concern is 
an ectopic pregnancy that if the baby is not positioned which 
is deadly, or if she's further along that she's saying that she 
is, I'm truly grateful that the two Federal courts have ruled 
that the FDA's most recent action failed to meet its legal 
obligation.
    So that's what the lawsuit is about, not judging if the 
drug is safe or unsafe but that the FDA failed to meet its 
legal obligation to protect the safety of women and girls and 
that it also directly violated longstanding Federal criminal 
laws that expressly prohibited the mailing and interstate 
shipping of abortion drugs.
    So the FDA, it's more of a legal issue of the procedure 
that happened than a safety issue of determining what drug is 
safe. If the Supreme Court allows the lower court rulings to go 
into effect, will the FDA fully comply with the decision 
without delay and not attempt to flout the ruling under the 
guise of some kind of enforcement discretion? Would you apply 
immediately?
    Dr. Califf. First, let me just reply to one small thing 
that you said, not such a small thing, but I do want to offer a 
different viewpoint on the adverse event reporting.
    Adverse event reporting is required of all drugs, including 
this one. The reporting of adverse events is not being ignored 
in this case. It's required just like with all drugs. What was 
done was to take away a separate form that's different from all 
the rest of the drugs.
    But with regard to your question, we're confident the law's 
on our side. We've appealed the District Court's decision to 
the Supreme Court and have sought a stay pending that appeal, 
but FDA, as I've said already, does intend to comply with any 
court orders.
    Senator Hyde-Smith. Okay. In making its decision to 
eliminate the in-person dispensing requirement, none of the 
studies the FDA cited, which were largely conducted by abortion 
activists, studied the drugs under the new no-test tele-
abortion regime.
    Despite this, the FDA concluded that it was safe, but even 
the FDA admitted that this decision would increase emergency 
room visits for pregnant women taking the drugs.
    How comfortable is the FDA in recommending practices that 
have not yet been fully tested for safety?
    Dr. Califf. Senator, since that's before the Supreme Court, 
I have to refer you to the briefs that have been filed by the 
Justice Department on our behalf. The answers to these 
questions are discussed in detail there.
    Senator Hyde-Smith. Okay. And how many studies has FDA 
considered that studied the effects of abortion drugs on young 
girls as required by law?
    Dr. Califf. Again, I'd have to refer you to the briefs that 
have been filed by the Justice Department.
    Senator Hyde-Smith. Okay. And the law also requires the FDA 
to respond to petitions within a 180 days, but the FDA waited 
roughly 14 years and nearly 3 years to respond to citizens' 
petitions challenging FDA approval and deregulation of chemical 
abortion drugs.
    Can you speak to that?
    Dr. Califf. I'll just say again this is discussed in the 
briefs that are filed by the Justice Department and it would 
take a long answer.
    Senator Hyde-Smith. Okay. My time is up.
    Senator Heinrich. Senator Tester.
    Senator Tester. Thank you, Mr. Chairman, Ranking Member, 
for having this hearing.
    I want to thank you for being here, Dr. Califf. I think you 
guys have been the gold standard. I appreciate the fact that 
you're in the position that you're in and I want to thank you 
for your work.
    I'm not going to get into the activist judges. I'm not 
going to get into any of that stuff. The fact of the matter is, 
is that the FDA has done a great job and have done it for a 
long time and it continues under your watch.
    I come from Rural America. You touched on it a little bit 
with the Ranking Member, but when we spoke last year we talked 
about the importance of ensuring good health outcomes in Rural 
America.
    Given your background as a clinical researcher, we can talk 
about the clinical trials for new and innovative medical 
treatments and how they work for Rural America.
    So clinical trials are critical, you know that, for drug 
development. Montana's rural population face many challenges in 
assessing and accessing clinical trials for innovative 
pharmaceuticals.
    So the question is this. Can you explain how the FDA's 
budget allocation supports the expansion of clinical trials to 
rural areas, including efforts to increase diversity in 
clinical research participants and ensuring safety and efficacy 
of the drugs for all Americans, regardless of geographic 
location?
    Dr. Califf. Sure. Thanks for the question.
    I think it's critically important. I can't resist making 
one comment which is that we can't ask clinical trials to fix a 
structural issue with our health care system in general, but 
having said that, we got to do everything we can for the 
clinical trials.
    We have an office essentially charged with dealing with 
diversity across the board, including clinical trials. There's 
a cross-agency task force working on this. We have several 
guidance that have come out and, of course, our increasing 
encouragement of adoption of the use of telehealth in clinical 
trials is a big part of this.
    Here, I'd also emphasize that we've got to get broadband 
out to the rural communities. The money allocated for that as I 
understand it. So we can't use that technology unless someone 
is wired up in order to be able to use it, and I can't 
emphasize enough let's say you have a significant cancer 
driving three hours to get your experimental treatment, 
something a lot of people just can't do, and so we've got to 
set up these systems that can efficiently get the clinical 
trials done.
    Finally, I'd just say the real-world evidence which has 
been a big part of my career that is using data that's all part 
of the health care system and then doing the trials more 
virtually is a rapidly growing method that we're very much in 
favor of.
    So, all these things are in play, but I'm not going to 
argue we're there yet. We've got a ways to go in this regard.
    Senator Tester. So in that regard of broadband, I can tell 
you the gentleman to my right, Senator Manchin and myself 
worked on a bill called The Bipartisan Infrastructure Package. 
It'll get these folks wired up as soon as we get that money out 
the door and get the cable in the ground.
    Dr. Califf. I had a flat tire in West Virginia and I 
couldn't even use my cell phone. It was not a pleasant night.
    Senator Tester. That's Manchin's fault.
    [Laughter.]
    Senator Tester. Let me get you his phone number.
    Dr. Califf. There was no way to call. I had to wait for a 
passerby to come by.
    Senator Tester. I want to talk a little bit not because I 
have an agenda on this, I'm just curious. You talked about 
approvals and you also talked about disapprovals.
    Can you give me a number of the drugs that you guys take a 
look at? Is it a fairly static number that you disapprove 
compared to what you approve?
    Dr. Califf. I would say it's really hard, Senator, because 
this all starts when a scientist has an idea and it's like one 
out of a thousand ideas get into human clinical trials because 
to get to human clinical trial, you got to have the money 
invested, an IRB has to be approved, the FDA has to approve it.
    Out of those that get into the first human clinical trial, 
about 90 percent don't make it to the market.
    Senator Tester. Okay.
    Dr. Califf. Now the big change that's happened is we meet 
with the companies all the time. It used to be there were a lot 
of applications submitted that had no hope. Now the only 
applications that go in are the ones that have gotten all the 
way to the end of the game. We get rid of all the others. Very 
efficient financially but also protects patients who are being 
enrolled in clinical trials for drugs that aren't going to 
work.
    Senator Tester. So you just talked about the lengths, so 
that gets into timeliness.
    As a doctor, how do you think the FDA's doing on 
timeliness, and this is being somewhat self-critical or pat 
yourself on the back?
    Dr. Califf. I think we're the fastest in the world at high 
quality. Now there's some countries that don't have much of a 
regulatory system at all. That's different. We're the fastest 
in the world, but we're also the most thorough and we're the 
only regulatory entity that does an independent analysis of the 
data.
    I'm pleased to say as of today we're meeting a hundred 
percent of our user fee agreement requirements. Remember 
industry comes in and the user fees negotiates with us and the 
primary thing that they measure is whether we're meeting our 
timeframes that are required and even in the midst of this 
recovering from the pandemic we're now meeting all of our 
requirements for timeliness.
    We just discussed earlier in the area of biologics with 
gene editing. That's an area that we're emphasizing where we've 
got to do some work.
    Senator Tester. Thank you, Dr. Califf. Keep up the good 
work.
    Senator Heinrich. Thank you, Senator Tester.
    Senator Manchin, did you want to share yourself on with the 
Doctor?
    Senator Manchin. As soon as we get that tower up, you'll be 
in good shape.
    You and I talked briefly and I want to go over some of the 
things we talked about. The FDA is holding an advisory 
committee meeting on opiates today in particular on the 
questionable clinical trial practice known as enriched 
enrollment. The agenda today has a majority of the speakers who 
attended the very questionable IMPACT Meetings that we spoke 
about and I previously expressed concerns and I think most of 
you all know about the IMPACT meetings. That was the 
questionable pay to play where they would pay to present 
themselves before the FDA advisory committees.
    The speakers today have not been disclosed, have not even, 
I don't think, disclosed their involvement with IMPACT if they 
had been partaking in those before. I find it imperative that 
this advisory committee has non-ideological presenters to avoid 
the appearance of industry influence on the agency's 
decisionmaking. As it stands, this very much appears there will 
be heavy influence on today's advisory committee.
    Let me tell you what I'm speaking about. We got more and 
more opiates coming on the market. My state is ground zero. All 
of you all have--every state has problems and you and I talked 
about this. So there shouldn't be--to put a new opiate on the 
market, some manufacturer coming to you, there has to be 
something that it's replacing, something that's not doing--and 
this is a better, more improved.
    We take nothing off. Everything stays on the market as you 
bring more on, and if you can explain that to me and what we 
can do to make sure we're passing legislation that allows you 
to remove when you find approving drug, if you can explain that 
to us, it'd be appreciated.
    Dr. Califf. Yes. So, first, we'll get back to you on the 
advisory committee meeting, but the issue that you raise, we 
discussed this earlier before you came in, but to be clear 
about it, the most important thing I think you can do is give 
us the statutory authority in the area of opioids to require 
that anything new that attempts to come on the market has to 
demonstrate clear superiority in terms of safety to the all 
drug.
    Now whatever else you want to attach to that, we talked a 
bit yesterday, it was pretty much the same conversation we had 
in 2016, as I recall. So it could really help us move more 
quickly and accomplish the common goals that we have.
    Senator Manchin. Are your staff, are they aware of the 
EFFECTIVE Act?
    Dr. Califf. Yes.
    Senator Manchin. Okay. Is there some ways that you think we 
could improve that to give you more authority?
    Dr. Califf. We'd like to work with you on that.
    Senator Manchin. Okay.
    Dr. Califf. And inviting your staff to come out to FDA and 
we'll come to you.
    Senator Manchin. We'll do that. I think she's working with 
your staff to make an appearance there and sit down and work 
with you all.
    Let me ask this. With today's meeting, what additional 
stakeholders have you invited? Did you make any adjustments so 
it'll be more of a----
    Dr. Califf. We only had that conversation last night. So 
there wasn't time to adjust the meeting, but there was an open 
session. The gentleman you brought up, Dr. Kolodney, was the 
second public speaker and I think, you know, as you pointed 
out, it wasn't two--he got five minutes but I know you'd like 
for him to get more time.
    Senator Manchin. Well, the person that I'm saying was 
basically important to the IMPACT before is the person who got 
all the time, you know, and he was definitely tied to the 
industry.
    If the pharmaceutical--I mean, you talk about the fox in 
the henhouse, that's our problem. It's just killing our state. 
It just has done irreparable damage.
    Let me ask you this. On the recommendation of external 
review of the FDA Regulations of Opiates Report that you 
ordered was to ensure the FDA be as transparent as possible 
regarding decisionmaking. Advisory committees present complex 
scientific reviews of safety and efficacy of medicines most 
patients and general public really don't have a background to 
fully understand the scientific studies discussed in these 
settings.
    Dr. Califf, you recently have been pushing to reduce voting 
in the FDA's advisory committees, even stating in a Med page 
Today interview that ``voting doesn't matter,'' but they're the 
ones that do have the expertise, the public does not, and how 
does ending voting for the advisory committee meetings improve 
the transparency and the public trust that you advocated for?
    Dr. Califf. To be clear about what I said and what I 
believe,----
    Senator Manchin. It wasn't taken out of content, was it, 
sir, because we never would do that.
    Dr. Califf. A little bit, but generally--so what I'd say, 
we're pushing to have advisory committees, not less.
    Senator Manchin. Yeah.
    Dr. Califf. The point I was making is that people focus on 
the vote, but its' the FDA that has to make the decision, not 
the advisory committee. What the FDA employees and leaders want 
out of the advisory committee is deep knowledge about the 
thinking from multiple points of view.
    What is it that is driving their thinking and because it is 
advisory, people tend to focus on like if it's an eight to five 
vote----
    Senator Manchin. Well, here is the thing. You know, you 
know the one I'm talking about. It's 11 to two.
    Dr. Califf. Yeah.
    Senator Manchin. Please don't put this drug on the market. 
They overrule and you all put it on the market. You weren't 
there. They put it on the market anyway. We begged them not to. 
Then they had the--finally the company pulled it off themselves 
but it was just horrific. I mean, I'm saying these are the 
people that have knowledge thinking it was dangerous to put it 
on the market.
    Dr. Califf. I hear you. What I want is much more public 
discussion about the issues, less focus on like a cage match of 
who's voting for what and rushing out the door.
    Senator Manchin. Just a number of states have been affected 
beyond anybody's imagination.
    Dr. Califf. Senator, as I told you yesterday, I helped 
start a not-for-profit in Dayton, Ohio, which is right there 
with West Virginia, as you know, in terms of death rates and 
other problems. I have a deep sense of what this is about and 
we're going to work on it as hard as we can. I'm not pretending 
we got everything right. So, I appreciate your concern.
    Senator Manchin. We need help on that. I was alarmed to see 
that the meeting that was going on today and how it was put 
together and the presenters and who had the time to do that. It 
just didn't seem like it was very balanced.
    Dr. Califf. I hear you.
    Senator Manchin. Thank you, sir.
    Senator Heinrich. I want to thank Commissioner Califf for 
being here today.

                     ADDITIONAL COMMITTEE QUESTIONS

    Questions for the record are due by next Wednesday, April 
26th and we'd certainly appreciate responses back from FDA 
within 30 days.
             Questions Submitted by Senator Martin Heinrich
    Question. Last December, the Reagan-dall Foundation released its 
evaluation of the FDA's human foods program and highlighted serious 
organizational challenges within the agency.
    Since that report was issued, several senior staff within FDA 
announced their departure from the agency. How will FDA continue to 
move forward and address the challenges identified within the 
Foundation report with such a significant change in senior leadership?
    Answer. Following the release of Reagan-Udall Foundation's 
Operational Evaluation of FDA's Human Foods Program, Commissioner 
Califf announced a proposal for a unified Human Foods Program (HFP) and 
a new model for the Office of Regulatory Affairs (ORA). Since the 
announcement, the Agency has made significant progress to implement the 
vision, including initiating a competitive national search for a new 
Deputy Commissioner for Human Foods who will report directly to the 
Commissioner and provide leadership and expertise for FDA's entire 
nutrition and food safety programs. The Commissioner has identified 
competent and capable FDA senior leaders to fill the leadership roles 
in ORA, the Center for Food Safety and Applied Nutrition (CFSAN), and 
the Office of Food Policy and Response (OFPR) during the transition, 
while the Agency is also working to address the challenges identified 
in the Reagan-Udall report through an Agency-wide approach. FDA has 
created an internal Implementation and Change Management Group--
comprising current and future leaders from all components of the Human 
Foods Program and from other Centers--to develop a detailed plan to 
ensure the successful execution of a unified Human Foods Program and to 
restructure ORA into an enterprise-wide organization supporting the 
priorities of the Human Foods Program and the Centers, while focusing 
on the core functions of inspections, import operations, sampling, 
laboratory analysis, and investigations.
    Question. Where is the agency on hiring a Deputy Commissioner for 
Human Foods?
    Answer. The Agency's search for a Deputy Commissioner for Human 
Foods commenced in late February through a vacancy announcement under 
our Title 21 hiring authority (granted to us by the 21st Century Cures 
Act). FDA is currently in the process of interviewing several qualified 
candidates and hopes to make a selection for this important position as 
soon as possible. This is a critical role and the Agency is moving as 
quickly as possible, although we need to follow the necessary legal 
processes. The Agency looks forward to keeping you apprised of our 
progress.
    Question. Your budget requests an additional $11.6 million to 
continue building capabilities for FDA's Resilient Supply Chain and 
Shortages Program for medical devices. With supplemental funding ending 
in 2025, how does the FDA plan to manage this program for the long 
term?
    Answer. FDA appreciates the funds Congress has provided thus far--
the $10 million total provided across FY 2022 and FY 2023 were the 
first funds provided to FDA's base for medical device supply chain 
efforts, and we have been able to transition some staff and 
capabilities funded by the COVID-19 supplementals to start building a 
permanent, serviceable program. The Agency is still in a building 
stage, however--having essentially started building from scratch during 
the pandemic, FDA has had to develop infrastructure where it did not 
exist, recruit expertise it did not have, and start building 
capabilities and a program where none had existed.
    What FDA has today remains a largely reactive program. It is making 
a huge difference for the domestic supply chain, but major 
vulnerabilities continue to put the nation's supply chain and the
    U.S. healthcare system as a whole, at risk. Medical device 
shortages most often impact vulnerable and underserved populations, 
such as children, rural communities, and veterans. The Agency is also 
aware that China accounts for approximately 45% of finished medical 
devices imported into the U.S., and that the U.S. remains heavily 
dependent on China for raw materials and components that are used to 
make medical devices. Patient safety and national security depend on 
having preventative capabilities. FDA seeks to get out of ``response 
mode'' by focusing on what is needed for a serviceable, sustainable 
program where the Agency can intervene and help prevent shortages from 
happening in the first place.
    The request for an additional $11.6 million is the difference 
between a such a reactive program and transitioning to a proactive 
program that is preventive--so regardless of the situation, whether it 
is a massive pandemic or a spot shortage in one part of the country, 
FDA is not left scrambling and playing catch up. Without these 
additional funds in FY 2024, FDA will need to start scaling back the 
existing program capabilities as COVID supplemental funding runs out.
    Question. How does FDA view shortages in medical devices from a 
national security perspective?
    Answer. Medical product supply chains are critical to U.S. national 
security, and preventing shortages and interruptions depend, in part, 
on FDA having the resources and the authorities to establish a 
proactive supply chain program to prevent these problems from happening 
before they occur, particularly in the face of global threats and 
cybersecurity attacks. Simply stated, health security is national 
security.
    The nation's continued dependence on China for critical devices and 
the raw materials and components used to manufacture them is one of the 
largest threats to health security and infrastructure. This was evident 
during the early phases of the pandemic, China held products hostage 
and did not allow the U.S. to get them out of that country. There also 
continue to be cybersecurity threats that could force manufacturers to 
go offline.
    In order to build a strong healthcare structure that is resilient 
to these national security challenges, FDA needs the resources to have 
visibility into the supply chain and get information as early as 
possible. The Agency also needs critical authorities, including the 
removal of the temporal limitation of ``during, or in advance of'' a 
public health emergency for notifications of manufacturing disruptions 
to the FDA. Additionally, FDA needs the authority to require 
manufacturers to maintain and share Risk Management Plans.
    Having a proactive system and information to help better understand 
vulnerabilities and risks, and to work with manufacturers to prevent 
potential supply chain shortages before harm comes to patients and 
healthcare providers strengthens national security.
    Question. The infant formula crisis the country experienced 
highlighted the importance of moving away from a few large 
manufacturers to allowing smaller facilities more capacity. How is FDA 
working with smaller infant formula companies to expand their capacity?
    Answer. Recognizing the importance of a resilient and diversified 
supply chain, FDA has taken numerous steps to help all producers, 
regardless of size, have the ability to access and support the U.S. 
market for infant formula. In May 2022, to help address the infant 
formula shortage, FDA issued the ``Guidance for Industry: Infant 
Formula Enforcement Discretion Policy''\1\ to describe considerations 
for firms and formulas entering the market temporarily under FDA's 
exercise of enforcement discretion. During the initial period of 
enforcement discretion, when supply chain concerns were at their peak, 
FDA developed webpages about the new formulas that were entering the 
market under FDA's exercise of enforcement discretion, with information 
about how to safely switch to those formulas, if needed. Subsequently, 
in September 2022, FDA issued the ``Guidance for Industry: Infant 
Formula Transition Plan for Exercise of Enforcement Discretion''\2\ to 
outline a path for interested firms marketing products in the U.S. 
under the exercise of enforcement discretion to bring those products 
into compliance with all U.S. requirements to facilitate longer-term 
availability of those products in the market.
---------------------------------------------------------------------------
    \1\ https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/guidance-industry-infant-formula- enforcement-discretion-
policy
    \2\ https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/guidance-industry-infant-formula- transition-plan-exercise-
enforcement-discretion
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    Additionally, FDA hosted multiple webinars in autumn 2022 to 
support infant formula firms interested in marketing their products in 
the U.S., including those marketing as part of the transition plan and 
new market entrants more generally. Topics of the webinars included: 
the Infant Formula Transition Plan guidance, FDA's requirements and 
recommendations for new infant formula submissions, protein efficiency 
ratio (PER) studies, and growth monitoring studies (GMS). Following 
these webinars, in February 2023, FDA issued ``Draft Guidance for 
Industry: Protein Efficiency Ratio (PER) Rat Bioassay Studies to 
Demonstrate that a New Infant Formula Supports the Quality Factor of 
Sufficient Biological Quality of Protein,'' \3\ with more information 
relating to a key component of a new infant formula submission. Most 
recently, FDA has announced two additional webinars to be held on 
Wednesday, May 24, 2023, and Wednesday, June 7, 2023, to provide 
stakeholders with information on regulatory requirements and 
considerations for infant formula ingredients and packaging.
---------------------------------------------------------------------------
    \3\ https://www.fa.gov/regulatory-information/search-fda-guidance-
documents/draft-guidance-industry-protein- efficiency-ratio-rat-
bioassay-studies-demonstrate-new-infant-formula
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    More broadly, on March 28, 2023, FDA published the Immediate 
National Strategy to Increase the Resiliency of the U.S. Infant Formula 
Market.
---------------------------------------------------------------------------
    *ERR14*\3\  The strategy describes immediate actions FDA took to 
address the shortage and details the Agency's plans for improving the 
resiliency of the infant formula market, while noting multiple issues 
that are beyond the purview of FDA. The immediate strategy represents a 
first step toward issuing, with input from the National Academy of 
Science, Engineering and Medicine, a long-term national strategy in 
2024 to improve preparedness against infant formula shortages by 
outlining methods to improve information-sharing, recommending measures 
for protecting the integrity of the infant formula supply chain, and 
preventing contamination. The longer-term strategy will explore new 
approaches to help facilitate entry of new infant formula manufacturers 
to increase supply and mitigate future shortages and assess whether 
additional regulatory authorities are needed to gain insight into the 
supply chain and risks for shortages.
    \4\ https://www.fda.gov/food/infant-formula-guidance-documents-
regulatory-information/immediate-national- strategy-increase-
resiliency-us-infant-formula-market
---------------------------------------------------------------------------
    *ERR14*Question. Can you update the Committee on FDA's efforts 
ensure such a crisis never happens again?
    Answer. FDA has taken a great number of measures to reduce the 
potential of a similar incident occurring in the future. However, it 
should be noted that it is not possible to completely prevent all 
outbreaks, and the infant formula industry remains concentrated in the 
U.S. Further, the industry ultimately has the primary responsibility to 
produce safe, nutritious, and high-quality infant formula.
    Since February 2022, the Agency has had ongoing and extensive 
engagement with the infant formula industry to identify and implement 
opportunities to strengthen preventive control practices and engage on 
the development and refinement of the FDA's Strategy to Help Prevent 
Cronobacter sakazakii Illnesses Associated with Consumption of Powdered 
Infant Formula (released November 15, 2022). FDA food safety experts 
have engaged with industry, state, international, and other partners 
to: explore environmental factors that may contribute to contamination 
in facilities; review issues related to specific foodborne hazards to 
identify potential mitigation measures or knowledge gaps; review 
regulations to identify provisions that may be strengthened; identify 
prevention measures that can be taken to reduce future incidences of 
foodborne illness; and identify knowledge gaps to expand our 
understanding of food safety issues and limit recurrences of underlying 
root causes responsible for contamination.
    Already, the Agency is seeing actions advanced through the 
prevention strategy that will help to prevent recurrence of 
contamination. FDA food safety experts have advanced a charge through 
the National Advisory Committee on Microbiological Criteria for Foods 
(NACMCF) to gain scientific insight on possible industry and public 
health interventions to address Cronobacter infections associated with 
powdered infant formula. In addition, the Agency has engaged with the 
National Academy of Science, Engineering and Medicine (NASEM) to 
examine and report on challenges in the supply, market competition, and 
regulation of infant formula in the U.S.
    Furthermore, on March 28, 2023, FDA published an immediate national 
strategy\5\ to increase the resiliency of the U.S. infant formula 
supply chain, protect against future contamination and other potential 
causes of shortages, and ensure parents and caregivers have access to 
infant formula and the information they need. The strategy describes 
immediate actions FDA took to address the shortage and details the 
Agency's plans for improving the resiliency of the infant formula 
market, while noting multiple issues that are beyond the purview of 
FDA. It also traces the events that led up to and followed the 
voluntary recall of infant formula by Abbott Nutrition in February 
2022, the temporary pause in production at the Abbott Nutrition 
facility in Sturgis, Michigan, as well as numerous other factors that 
contributed to and exacerbated the shortage. The immediate strategy 
represents a first step toward issuing, with input from NASEM, a long- 
term national strategy in 2024 to improve preparedness and explore new 
approaches to help facilitate entry of new manufacturers to increase 
supply and mitigate future potential shortages.
---------------------------------------------------------------------------
    \5\ https://www.fda.gov/food/infant-formula-guidance-documents-
regulatory-information/immediate-national- strategy-increase-
resiliency-us-infant-formula-market
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    To specifically ensure the issues encountered at Abbott Nutrition's 
Sturgis, MI, facility will not be repeated, FDA negotiated a consent 
decree with Abbott Nutrition, which was entered by the U.S. District 
Court for the Western District of Michigan on May 16, 2022. This 
consent decree requires Abbott to take steps necessary to safely 
produce infant formula in close coordination with FDA and under our 
oversight of its manufacturing and food safety processes. More broadly, 
FDA is committed to conducting surveillance food safety inspections of 
all infant formula manufacturers at least annually and to use remote 
regulatory assessments, as needed. Work is also underway to 
significantly expand and improve infant formula training for 
investigators and other appropriate staff to ensure every infant 
formula inspection is robust, thorough, and focused on the most 
critical aspects of the infant formula manufacturing process.
    FDA is also working to monitor the infant formula supply and supply 
chain to assess general market health and current and future demand, 
and identify potential signs of production and supply chain challenges 
by analyzing industry production data, in-stock rates, sales data, and 
information on key supply chain characteristics. Much of the work on 
infant formula will be coordinated through the creation of a new Office 
of Critical Foods responsible for oversight, coordination, and other 
activities related to critical foods, which is defined to include 
infant formula and medical foods. FDA will continue to build on these 
efforts throughout FY 2023 as a result of $7.5 million in additional 
funding provided by Congress for infant formula-related activities. 
This is enabling the Agency to hire 16 new full-time equivalents (FTE) 
in the Center for Food Safety and Applied Nutrition. FDA's FY 2024 
request contains an additional $21 million to further expand its work 
in this area.
    However, the infant formula industry needs to take its 
responsibility to produce safe food more seriously. FDA has reviewed 
conditions during recent inspections of powdered infant formula 
manufacturers and has identified numerous areas for improvement across 
the infant formula industry. The Agency outlined these areas for 
improvement in a March 8, 2023, letter, which was a call to action for 
all members of the infant formula industry to help protect our most 
vulnerable population by, among other things, evaluating established 
systems of production and in-process controls and ensuring that 
appropriate controls are implemented at any point, step, or stage in 
the production process where control is necessary to prevent 
adulteration of infant formula. In addition, the infant formula 
industry is now required to establish and implement risk redundancy 
plans to minimize the impact of any future disruptions in production. 
Industry must ensure they are producing formula consistent with high 
U.S. food safety standards and maintaining their facilities so recalls 
and shutdowns are minimized.
    Question. The recent White House National Strategy on Hunger, 
Nutrition, and Health highlighted the need to empower consumers to make 
healthier food choices. The budget is requesting an additional $12 
million to strengthen the FDA's work on nutrition and labeling. Can you 
detail how this additional funding will be used?
    Answer. The additional requested funding of $12 million, which 
includes 19 FTE, will be used to enhance and strengthen the nutrition 
and labeling work performed by FDA. This includes the development of a 
standardized, science-based, front-of-package labeling scheme that 
would help consumers, particularly those with lower nutrition literacy, 
quickly and easily identify foods that can help them build a healthy 
dietary pattern. Front-of-package labeling would complement the 
Nutrition Facts label by displaying simplified, at-a-glance nutrition 
information and giving consumers additional context to help them 
quickly make more informed food selections.
    FDA will also continue to examine the use of the nutrient content 
claim, ``healthy,'' in food labeling to ensure that it aligns with 
current nutrition science and the Dietary Guidelines for Americans. FDA 
will continue its rulemaking effort to update the nutrition criteria 
for when the ``healthy'' nutrient content claim can be put on a 
product, which will help to provide consumers with information to make 
more informed dietary choices. FDA will also continue its work to 
develop a symbol companies can use on food packages to depict the 
nutrient content claim, ``healthy.'' In addition, FDA will work to 
finalize a guidance on using Dietary Guidance Statements on food 
labeling in order to help consumers understand how a particular food 
can contribute to a healthy eating pattern. Additional funding will 
also go towards advances in e- commerce, such as gathering additional 
public input to inform a possible guidance for the food industry on 
nutrition, ingredient, and allergen information that should be 
available for groceries sold online.
    FDA will also assess progress in reducing sodium in processed 
packaged and prepared foods and begin the process to develop revised, 
voluntary sodium reduction targets as part of the Agency's broad and 
continued approach to facilitating the reduction of sodium intake, as 
outlined in the White House National Strategy. In October 2021, the 
Agency issued voluntary, short-term (2.5 year) sodium reduction 
targets. The request will support FDA in finalizing a regulation that 
will provide companies with additional flexibility in the use of safe 
and suitable salt substitutes in standardized foods, for which salt is 
an optional or required ingredient, giving industry additional tools to 
produce foods lower in sodium content.
    Question. The Drug Supply Chain Security Act (DSCSA) of 2013 
established a uniform, interoperable framework for tracing 
pharmaceutical products throughout the supply chain. On the DSCSA's 
final implementation deadline of November 27, 2023, supply chain 
trading partners will be required to provide and receive serialized 
transaction data along with serialized product upon a change of 
ownership. The supply chain is at a critical point and it appears that 
industry may not be fully ready which could lead to supply chain 
challenges.
    The pandemic brought to light many issues in the drug supply chain. 
To this day we still struggle with shortages of drugs including 
Adderall and Albuterol, among others. If the DSCSA is not properly 
implemented, it could cause more shortages. Is the FDA concerned about 
drug shortages if product is not able to move through the supply chain?
    Answer. The DSCSA program is critical to improve the detection and 
removal of potentially dangerous drugs from the supply chain and help 
protect patients from receiving a drug that may be counterfeit, stolen, 
contaminated, or otherwise harmful. The Agency has heard from trading 
partners and other stakeholders about implementation challenges, 
particularly related to data and data exchange issues, and concerns 
that not everyone in the supply chain will have their systems and 
processes in place to meet the November 2023 requirements. FDA 
considers all stakeholder concerns and examines all available 
regulatory options to minimize the chance of supply chain disruptions.
    Question. If manufacturers aren't ready, how will that affect 
pharmacies and patients?
    Answer. FDA has heard that while there has been industry progress 
towards enhanced drug distribution security requirements, stakeholders 
are concerned about the current status of readiness of trading partners 
in the supply chain and implementation challenges. Stakeholders 
indicated that some of these challenges may lead to supply chain 
issues, potentially affecting the distribution and availability of 
certain prescription drugs. The Agency is actively continuing 
stakeholder outreach and engagement on these issues. In addition, FDA 
will be conducting a small dispenser assessment that will examine 
necessary software and hardware accessibility, and the cost to obtain, 
install, maintain, and integrate them into business practices. The 
assessment will help FDA identify and consider compliance challenges 
faced by small dispensers (i.e. small pharmacies).

                                 ______
                                 

              Questions Submitted by Senator Tammy Baldwin
    Question. How is the agency considering the widespread concern from 
consumers, farmers and producers over FDA not enforcing dairy standards 
of identity?
    Answer. FDA establishes food standards of identity to promote 
honesty and fair dealing in the interest of consumers, and this remains 
an Agency priority. The Agency recognizes that there has been 
significant development and commercial activity in the area of plant-
based alternatives to traditional food products, including plant-based 
beverages labeled with names that include the terms of dairy standards 
of identity, such as ``milk.'' In February 2023, FDA issued a draft 
guidance\6\ entitled ``Labeling of Plant-Based Milk Alternatives and 
Voluntary Nutrient Statements.'' This draft guidance explains that, 
while plant-based milk alternatives are not permitted to be offered for 
sale as ``milk,'' the use of the term ``milk'' as part of the name of 
plant- based milk alternatives does not mean that such products are 
represented as ``milk'' as defined in FDA regulations. The draft 
guidance also provides recommendations for labeling plant-based 
beverages with additional nutrition information to help consumers 
compare these products to milk and make informed dietary choices. 
Empowering consumers with nutrition information they can use to 
identify healthier choices more easily is a priority under FDA's 
Nutrition Initiatives. FDA is interested in hearing from stakeholders 
and encourages all interested persons to submit comments to the draft 
guidance docket by July 31, 2023.
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    \6\ https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/draft-guidance-industry-labeling- plant-based-milk-
alternatives-and-voluntary-nutrient-statements
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    Question. How will these concerns be implemented into the final 
Guidance for Industry: Labeling of Plant-Based Milk Alternatives and 
Voluntary Nutrient Statements?
    Answer. On May 1, 2023, FDA reopened the public comment period for 
90 more days to allow additional time for interested persons to develop 
and submit comments to the draft guidance. The deadline for comments is 
July 31, 2023. The Agency welcomes comments on any aspect of the draft 
guidance. This topic is of great interest to a variety of stakeholders 
with differing perspectives and FDA anticipates receiving useful 
information from comments. All comments, data, and research timely 
submitted to the docket will be reviewed and considered before 
beginning work on a final guidance.
    Question. How does the FDA plan to evaluate animal feed additives 
with environmental claims, such as those intended to target enteric 
methane emissions, in a safe and timely manner?
    Answer. FDA understands Congress's and stakeholders' interest in a 
robust and timely pathway for environmentally beneficial products to 
enter the market for use in animal food.
    The Federal Food, Drug, and Cosmetic Act sets the regulatory 
paradigm to which products used in animal food are subject. Articles 
(other than food) intended to affect the structure or function of the 
body of an animal are drugs under the Act. Some products with 
environmental claims, such as those non-nutritive substances that 
affect an animal's function to reduce methane emissions, meet the 
definition of a drug.
    FDA remains engaged with Congress and stakeholders to consider 
potential solutions. The Agency is also considering alternative 
approaches for the regulation of these products in the absence of 
legislation. In the interim, FDA is working with sponsors to identify 
alternative pathways to market, where appropriate, on a case-by-case 
basis.
    Question. The FDA is now 19 months past a court ordered deadline to 
finish its review of e- cigarette applications, and 8 months past a 
deadline set by Congress to review applications of synthetic nicotine 
products. Unauthorized vaping products remain on the market. Why have 
these products been allowed to stay on the market, and what is the 
current backlog of applications?
    Answer. FDA continues to make significant progress on reviewing 
applications despite their sheer volume and the rapidly evolving 
tobacco product landscape. To date, FDA has received premarket tobacco 
product applications for 26 million products, the vast majority of 
which are for e- cigarettes, and has successfully completed its review 
of 99 percent of them. This includes one million applications for non-
tobacco nicotine products, including synthetic nicotine--for which FDA 
has successfully completed review of 99.5% of applications. FDA has 
been working diligently to ensure we are processing applications as 
quickly as possible while also ensuring the decisions are 
scientifically accurate, legally defensible, and aligned with the 
authorities granted by Congress.
    FDA has been clear that all new tobacco products on the market 
without the statutorily required premarket authorization are marketed 
unlawfully and are subject to enforcement by FDA. We will continue to 
closely monitor the marketplace and take compliance and enforcement 
actions on a case-by-case basis according to our enforcement priorities 
and the individual circumstances. Compliance and enforcement actions 
include: warning letters, civil money penalties, seizures, and 
injunctions, among others. Importantly, FDA does not have independent 
litigation authority. Therefore, we work with the U.S. Department of 
Justice (DOJ) to inform our enforcement actions. The DOJ must evaluate 
the legal risks of pursuing particular actions and decide whether to 
litigate cases on our behalf.
    Question. On April 26, 2022, the Director of the Center of Drug 
Evaluation and Research testified under oath at a Senate HELP Committee 
hearing that ``The Center for Drugs currently does not have a contract 
with McKinsey and across FDA. [W]e anticipate that further contracts 
will not be issued pending the outcome of the investigations.'' This 
followed a 2022 congressional investigation that found that at least 22 
McKinsey consultants worked for both FDA and opioid manufacturers on 
related topics, including at the same time. Can you confirm that over 
the last year, McKinsey has not been hired by the FDA and will not be 
hired in the future?
    Answer. FDA does not have any active contracts with McKinsey. Due 
to rules governing competition, it would be inappropriate to comment on 
future plans absent an explicit prohibition or debarment of McKinsey. 
The Federal Acquisition Regulation (FAR), particularly Part 6, 
prescribes policies and procedures to promote full and open competition 
in the acquisition process.

                                 ______
                                 

               Questions Submitted by Senator Joe Manchin
    Question. The enriched enrollment or EERW process has made it 
significantly easier for the FDA to approve opioids and allow for broad 
marketing to the public. The process removes patients with pre-existing 
opioid sensitives from clinical trials, instead of sticking with 
traditional double-blind studies. This has skewed results and seriously 
underestimates risks associated with the proposed drug involved in the 
clinical trial.
    The External Report of FDA Regulations of Opioid Analgesics notes 
that ``there are several limitations of EERW design that warrant 
additional consideration for opioid[s]''.

  --Will the FDA commit to following the recommendations of the report 
        and hold another Advisory Committee meeting focused on FDA's 
        use of enriched enrollment for opioid approvals?
    Answer. The Agency understands your concern with enriched 
enrollment randomized withdrawal (EERW) trials. As you know, the Agency 
recently held an Advisory Committee meeting with the Drug Safety and 
Risk Management Advisory Committee to review EERW trial design.\14\
---------------------------------------------------------------------------
    \14\ April 19, 2023: Meeting of the Anesthetic and Analgesic Drug 
Products Advisory Committee Meeting Announcement and Materials
---------------------------------------------------------------------------
    The Agency is reviewing the discussion from the Advisory Committee 
and if there is further need to obtain independent expert advice on 
scientific, technical, and policy matters related to EERW design FDA 
will at that time consider the need for an additional Advisory 
Committee meeting regarding EERW design.
    Question. The Fiscal Year 2022 Consolidated Appropriations report 
included language directing the FDA to ``conduct a study to review EERW 
study designs used in the approval of new prescription opioids for 
chronic pain.'' This study is intended to specifically look at the use 
of EERWs use to approve new opioids. Will the FDA commit to completing 
this study?
    Answer. As noted in Question 1, the Agency is conducting an ongoing 
review of the use of EERW trial design. An element of the review was 
the Advisory Committee held on April 19th, 2023.\15\
---------------------------------------------------------------------------
    \15\ April 19, 2023: Meeting of the Anesthetic and Analgesic Drug 
Products Advisory Committee Meeting Announcement and Materials
---------------------------------------------------------------------------
    Question. I introduced the FDA Accountability for Public Safety Act 
to ensure Advisory Committees are properly used. Specifically, if a 
Committee votes against approval and you decide to go against this 
vote, you must submit a report to Congress that includes the medical 
and scientific evidence to justify its approval. How will the FDA 
ensure Advisory Committee discussions are clear and transparent?
    Answer. FDA's advisory committee meetings are conducted in 
accordance with the Federal Advisory Committee Act, which requires that 
timely notice of advisory committee meetings be published in the 
Federal Register, that the meetings generally be open to the public, 
and that records of all meetings be maintained and available to the 
public, subject to limited exceptions. To that end, and to be as 
transparent as possible, FDA maintains a public website for each of its 
advisory committees that includes agendas, presentation materials, 
minutes, and transcripts of all meetings of the committee. FDA's 
advisory committee meetings can also be viewed live via webcast and 
when meetings are held on FDA's campus or at other locations, members 
of the public and press are able to attend in person. Advisory 
committees make non-binding recommendations to the FDA, which generally 
follows the recommendations, but is not legally bound to do so. The 
available science and data guide the Agency's decisionmaking.
    Question. Between November 2021 and November 2022, the CDC reported 
that over 78,000 people died of an opioid related overdose. While we 
know opioids can be prescribed with legitimate prescriptions to treat 
pain, we also know that even with prescriptions, opioids can kill. 
These pills kill via respiratory depression, essentially, they make you 
go to sleep and forget to breathe. However, we do know of several non-
opioid treatments to treat pain that don't result in respiratory 
depression. What is the FDA doing to speed up approval of non-opioid 
treatments for pain?
    Answer. Addressing the overdose crisis continues to be one of FDA's 
top public health priorities, and the Agency agrees that there is still 
much work to do as deaths from drug overdoses remain at historically 
high levels. One of FDA's four Overdose Prevention Priorities under our 
Overdose Prevention Framework \16\ is supporting primary prevention by 
eliminating unnecessary initial prescription drug exposure and 
inappropriate prolonged prescribing. A key activity under this priority 
is the development of novel, non-opioid pain therapies, which the 
Agency believes will ultimately help prevent new cases of overdose and 
reduce deaths. FDA is committed to doing its part to help spur this 
development. To support such developments, the Agency recently 
published draft guidances titled ``Development of Non-Opioid Analgesics 
for Acute Pain''\17\ (February 2022) and ``Development of Local 
Anesthetic Drug Products With Prolonged Duration of Effect'' (March 
2023). These guidances are intended to assist sponsors in the 
development of alternatives to opioids for the management of pain. 
Additionally, FDA is developing a guidance for industry on the 
development of non-addictive medical products for the management of 
chronic pain, as stated on the 2023 CDER guidance agenda.
---------------------------------------------------------------------------
    \16\ https://www.fda.gov/drugs/drug-safety-and-availability/food-
and-drug-administration-overdose-prevention- framework
    \17\ Development of Non-Opioid Analgesics for Acute Pain
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               Questions Submitted by Senator John Hoeven
    Question. In fiscal year (FY) 2023, Congress provided $5 million in 
new funding to implement an FDA-wide New Alternative Methods (NAMs) 
Program with the goal of advancing the development, qualification, and 
implementation of NAMs for product testing. It is important that the 
funds are used to provide regulatory clarity to sponsors and the 
community as to what constitutes a ``regulatory-grade'' NAM. Please 
provide an update on the implementation plan for the NAMs program.
    Answer. FDA appreciates that Congress provided $5 million in new 
funding in FY 2023 to implement an FDA-wide New Alternative Methods 
(NAMs) Program. With dedicated resources for alternative methods, FDA 
is beginning to implement a program to evaluate the suitability and 
validity of these methods to best inform the Agency's regulatory 
decisionmaking process. Centrally coordinated and managed by FDA's 
Office of the Chief Scientist, this core program focuses on 
establishing cohesive and comprehensive strategies to advance the 
development, qualification, and implementation of NAMs for regulatory 
use. The program broadens and complements longstanding work led by FDA 
Centers and Offices, including specific programmatic objectives such as 
expanding capacity to qualify alternative methods and filling 
information gaps with applied research to support new policy and 
guidance development.
    The FY 2024 President's Budget builds on the FY 2023 Budget by 
requesting an additional $1.5 million in funding within the Office of 
the Chief Scientist to further support the NAMs Program by providing 
strategic coordination, implementation, and oversight, as well as to 
develop a qualification process to assess NAMs for regulatory use.
    As follow up to a presentation for the Science Board to FDA at its 
June 2022 meeting,\7\ the Agency is working to establish a Science 
Board subcommittee that will be charged with continued discussion on 
the topic of NAMs and will look to consider the board's recommendations 
as part of the overarching efforts for continued progress. The Agency 
is also assessing its current activities to identify capabilities, 
critical gaps, and potential actions that could be taken to continue 
and enhance ongoing efforts to advance development and adoption of 
alternative methods.
---------------------------------------------------------------------------
    \7\ https://www.fda.gov/advisory-committees/committees-and-meeting-
materials/2022-meeting-announcement- science-board-fda-06142022
---------------------------------------------------------------------------
    Question. It is my understanding that Canada just updated their 
Listeria monocytogenes (Lm) policy and continue to base their policy on 
whether foods support or do not support growth of the pathogen. Will 
FDA also incorporate a risk-based approach that is reflective of the 
current scientific evidence?
    Answer. FDA is developing three guidance documents on the following 
topics:

  --The Agency's enforcement policy for Listeria monocytogenes (Lm) in 
        foods.

  --Classifying food as ready to eat (RTE) or not ready to eat (NRTE).

  --Control of Listeria monocytogenes in RTE foods.

    In the development of these documents, FDA is considering updated 
scientific information, including current thinking regarding the 
enforcement policy for foods based on whether foods support the growth 
of Lm. All three documents are a priority for FDA, and the CPG and 
guidance on classifying food as RTE or NRTE are on FDA's 2023 ``Foods 
Program Guidance Documents Under Development.''8 The Agency's goal is 
to issue Listeria policies that are grounded in the best available 
science, protective of public health, and practical for industry to 
implement.
    8 https://www.fda.gov/food/guidance-documents-regulatory-
information-topic-food-and-dietary-supplements/foods- program-guidance-
under-development
    Question. The Reagan-Udall Foundation evaluation on the tobacco 
program raised significant questions about the lack of a cohesive plan 
at the Center for Tobacco Products (CTP), finding, ``the lack of 
clarity about CTP's direction, its priorities and its near-term and 
longer-term goals and objectives, hinders CTP's ability to effectively 
carry out its mission establish efficient programs to accomplish its 
goals and objectives, and set appropriate metrics to assess outcomes.''
    For fiscal year (FY) 2024, the President's budget requests a $100 
million increase for tobacco user-fees. How would this additional 
funding be employed, and does the agency have a plan to address the 
issues raised in the Reagan-Udall Foundation's Evaluation Report?
    Answer. FDA welcomed the opportunity for the independent external 
review by the Reagan-Udall Foundation and is committed to addressing 
all the recommendations outlined in its evaluation report as 
expeditiously as possible. In February 2023, FDA announced the Center 
for Tobacco Products' (CTP's) plans for addressing the 
recommendations.\9\ FDA also developed a new webpage\10\ describing 
CTP's activities to address the recommendations, by topic area, that 
will be updated routinely to reflect progress.
---------------------------------------------------------------------------
    \9\ https://www.fda.gov/tobacco-products/ctp-newsroom/all-center-
approach-ctps-response-reagan-udall-foundation- evaluation-report
    \10\ https://www.fda.gov/tobacco-products/about-center-tobacco-
products-ctp/actions-address-recommendations- reagan-udall-evaluation-
ctp
---------------------------------------------------------------------------
    A key recommendation of the report was that CTP create and 
implement a new strategic plan that identifies the Center's strategic 
objectives and plots an operational roadmap of the steps CTP will take 
over the next 5 years to achieve those objectives. Development of the 
strategic plan commenced in February 2023, and will build upon prior 
strategic plans the Center has created and implemented since its 
inception. For the new strategic plan, CTP will engage with both 
internal and external stakeholders during development. We anticipate 
release of the plan no later than December 2023.
    The Reagan-Udall Foundation report also specifically recommended 
that ``additional resources should be sought, particularly to provide 
some parity among the tobacco sectors assessed under user fees for the 
Center's work.'' Currently, FDA is only authorized to assess user fees 
on tobacco products that fall within six product classes.\11\ The 
authorized collection amount is fixed and is not indexed to 
inflation.\12\ FDA believes that an additional $100 million in user 
fees, indexed to inflation, represents an appropriate increase in 
resources to ensure comprehensive regulation of the changing tobacco 
product marketplace. An additional $100 million will enable FDA to 
expand much-needed activities for the newly regulated products, with 
three-quarters of the additional resources being dedicated to 
compliance and enforcement and product review; the remaining resources 
would be allocated to scientific research, regulation and guidance 
development, and public education.
---------------------------------------------------------------------------
    \11\ Per section 919 of the Federal Food, Drug, and Cosmetic Act, 
these six classes are: cigars, pipe tobacco, cigarettes, snuff, chewing 
tobacco, and roll-your-own tobacco. FDA does not currently have 
authority to assess and collect user fees for ENDS products.
    \12\ Section 919 authorizes the total amount of user fees FDA must 
assess and collect each year. For the first 10 years of the FDA tobacco 
program, the total amount of user fee collections increased each year. 
Beginning in FY2019, the authorized amount is fixed at $712 million.
---------------------------------------------------------------------------
    Question. The issue of access to compounded hormones remains a 
concern for millions of patients who rely on access to compounded 
therapies. In response to a question for the record I posed last year, 
the agency cited the National Academies of Sciences, Engineering, and 
Medicine's (NASEM) report stating, ``FDA intends to consider the 
information in the NASEM report.'' The FDA did not mention any other 
scientific studies on this topic in its response.
    Will FDA review all relevant stakeholder comments and consider 
additional peer-reviewed scientific studies as part of the agency's 
review of the NASEM report and its recommendations?
    Answer. When developing Agency policies, FDA intends to consider 
all relevant information, including the NASEM report and stakeholder 
comments and submissions, while taking into account patient access 
concerns. Moreover, before implementing a new policy, the Agency 
generally provides an opportunity for public comment, whether the 
policy is announced through a draft guidance, Federal Register Notice, 
or proposed rulemaking.
    As background, compounded ``bioidentical hormone replacement 
therapy'' (cBHRT) products are not FDA-approved, which means these 
products have not undergone an FDA assessment of safety, effectiveness, 
or quality prior to marketing.
    To help inform the public and the FDA's policies regarding 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.

                                 ______
                                 

            Questions Submitted by Senator Susan M. Collins
    Question. Clinical Holds. I wanted to follow up on the issue of 
clinical holds, which I raised during the hearing. Clinical holds can 
be an important and appropriate tool for the Agency to utilize when a 
potential concern with an application has surfaced, but they are not a 
substitute for timely, constructive, and clear communication to 
sponsors. Further, when clinical holds are imposed for an ongoing 
development program, there should be urgency brought to resolving it.
    The anecdotal evidence suggests that the review process for cell 
and gene therapy is becoming more protracted, and I am concerned that 
the lack of face-to-face meetings may be negatively affecting the FDA's 
ability to keep pace and retain its scientific and regulatory stature 
as the gold standard.
    How many clinical holds have been issued in the past year? What 
percentage of cell and gene therapy applications have been subject to a 
clinical hold? Please include whether the Agency either sought or 
granted live meetings to discuss and potentially resolve the Agency's 
questions that led to the clinical hold.
    Answer. Of the 262 cell and gene therapy Investigational New Drug 
applications (INDs) received in calendar year 2022, 54 (20.6%) were 
placed on clinical hold in the initial 30 days after receiving the 
application. The Center for Biologics Evaluation and Research (CBER) 
and the Center for Drug Evaluation and Research (CDER) began accepting 
requests for in-person, face-to-face industry meetings on February 13, 
2023, for certain meeting types. As such, no in-person, face- to-face 
meetings were held for INDs put on clinical hold within CY 2022. 
However, throughout that time, FDA has continued to hold ``live'' 
meetings (e.g., via teleconference) when appropriate.
    It is important to note that the likelihood an IND application will 
be allowed to proceed is related to the quality and completeness of 
each IND section (Chemistry, Manufacturing and Controls (CMC), 
Pharmacology and Toxicology (P/T), and Clinical), whether all the 
identified safety risks are adequately addressed, and whether the 
sponsor provides timely responses to Agency information requests. There 
may be additional challenges encountered by the review team during the 
review of an original IND, which may include:

  --Grossly inadequate or missing sections of the IND for CMC, P/T or 
        Clinical review.

  --Inadequate donor eligibility information.

  --Inclusion of a device (e.g., delivery device, companion 
        diagnostic), human factors study, or combination product 
        classification that requires a consultative review(s) from 
        another Center. Based on our experience, oftentimes such 
        inclusions are inadequately or poorly addressed in submissions.

  --Requirement for clinical subspecialty review from another Center.

  --Cross reference of a Master File or IND in another product Office 
        within the Center or another Center, requiring a consultative 
        review.

    FDA remains committed to working with all sponsors to resolve 
issues and help speed development of new products, while maintaining 
high, scientifically based safety and efficacy standards.
    Question. Written Responses. I remain interested in the Agency's 
progress towards restoring face-to-face (FTF) meetings with sponsors 
and relying less on Written Response Only (WRO) communications. While I 
am pleased that FDA announced on January 30, 2023, that is was 
restoring some FTF meetings, the Agency has not expanded the FTF option 
for all types of meetings. The opportunity for critical discussion and 
meaningful scientific exchange are diminished under a WRO. FDA needs to 
preserve WRO as a tool for routine exchanges and clarifying responses 
to sponsors, but should otherwise be working to restore live options 
for most types of meetings and requests.
    What is the current timeline for full restoration of FTF 
interactions across each meeting type?
    Answer. The Agency understands the desire to conduct face-to-face 
(FTF) meetings. There are three formats for formal meetings with FDA, 
namely FTF (can be either in-person or virtual), Teleconference, and 
Written Response Only (WRO). As noted, WROs are one of these meeting 
formats and are an important and efficient tool under the appropriate 
circumstances. For each meeting request, the Agency carefully considers 
the specific questions posed by the drug developer, as well as the 
context (e.g., stage of development, product complexity, clinical 
indication and unmet need). When the Agency expects that our responses 
will be straightforward (e.g., referral to content of a specific 
guidance document) or will reiterate points made in previous 
discussions with the sponsor, then FDA has commonly provided written 
responses. When the questions are complex, for example with a product 
that raises new scientific questions, or an innovative trial design, 
the Agency has been more likely to offer a FTF meeting via 
videoconference or in-person.
    While WROs have been and will continue to be an important tool, FDA 
has continued to hold ``live'' meetings (e.g., discussion via 
teleconference or virtual face-to-face) with sponsors and applicants 
over the past 3 years for any meeting type when appropriate. The 
announcement on January 30 provided new information about the 
reintroduction of in-person FTF meetings, which were precluded during 
the pandemic. The reintroduced in-person FTF meetings (which will 
include a hybrid component to allow broader participation) will 
continue to expand until all meeting types are included.

                                 ______
                                 

            Questions Submitted by Senator Cindy Hyde-Smith
    Question. Over a million patients a day use medical gases under the 
supervision of healthcare professionals across the country. We 
congratulate the FDA for releasing a notice of proposed rulemaking for 
medical gases on May 23, 2022. However, the FY 2017 Consolidated 
Appropriations Act required a final rule to be issued by July 15, 
2017--nearly 6 years ago. The public comment period ended on August 23, 
2022 and FDA received a total of 4 public comments on the proposed 
rule. I was dismayed to see in the Fall 2022 Unified Agenda that FDA 
had put the rulemaking on the backburner, listing it as a long-term 
action with a projected publication date of October 2024. That means 
FDA is projecting it needs 29 months to respond to four public comments 
to finalize the medical gas rulemaking.
    It is deeply frustrating that the subcommittee is being told--six 
years after a statutory deadline--that it will be another year before 
FDA issues a final rule on medical gases. The FY 2023 Joint Explanatory 
Statement requires the FDA to produce quarterly reports on progress 
until the final rule is published. We would rather have the final rule 
rather than make you produce more reports. Can you commit to this 
Committee that you will accelerate the final rule and publish it in 
2023?
    Answer. FDA is working in earnest to finalize and publish the 
medical gas final rule by the projected publication date, but we cannot 
guarantee publication on a given timeline because certain aspects of 
the rulemaking and clearance process are outside of FDA's control. This 
rulemaking is large and complex because it is intended to address a 
wide range of topics and is anticipated to include changes to existing 
regulations as well as the addition of entirely new regulations. 
Developing this rule has also required coordination across numerous 
Agency components, given the range of subjects involved, including 
labeling, current good manufacturing practice, certification, and 
safety reporting. In making changes based on the comments we received 
to the proposed rule, we must also ensure that any revisions do not 
create issues for other regulatory areas. We would be happy to provide 
updates, as appropriate.

                                 ______
                                 

               Questions Submitted by Senator Deb Fischer
    Question. Feed additives can include enzymes, vitamins, and 
minerals that help livestock to increase feed efficiencies and reduce 
environmental impact. However, slow approvals prevent advancements in 
these additives and their benefits. Can you discuss how additional 
resources in the past few years have helped the Center for Veterinary 
Medicine speed up the review process?
    Answer. FDA received an additional $5 million in FY 2020 and an 
additional $1 million in FY 2022 for animal food ingredient reviews, 
which allowed the Center for Veterinary Medicine (CVM) to successfully 
hire more staff and improve timeliness for pre-market review of 
multifaceted and innovative new animal food ingredients. The animal 
food ingredient industry is rapidly evolving and submissions of 
innovative new animal food ingredients have become more complex and 
contain more scientific data for CVM to analyze. Since receiving these 
increased resources, FDA has increased its on-time rate from 44% of 
reviews to 73% of reviews this past year, all while moving over twice 
as many reviews through the system. Additionally, CVM's Office of 
Surveillance and Compliance underwent a reorganization in 2022 to more 
fully align its resources and work, which included establishing the 
Division of Animal Food Ingredients (DAFI). All 36 FTEs in DAFI are 
focused on work related to the pre-market review of new animal food 
ingredients, which includes reviewing new submissions, developing 
policy, evaluating science, and administering functions associated with 
the pre-market animal food ingredient processes.
    Question. I also understand the Center for Veterinary Medicine is 
working to update their policy manual to better address innovative new 
products in the feed industry. How is that going and are there other 
items that the Center for Veterinary Medicine is doing to improve the 
animal food ingredient review process?
    Answer. CVM is reviewing its Policy and Procedures Manual (PPM) 
Guide 1240.3605, Regulating Animal Foods with Drug Claims, in part to 
keep pace with innovative uses of substances in food for animals. In 
October 2022, the Center held a public listening session to gain 
stakeholder input on potential changes resulting from this review. 
Substances that benefit animal production, the environment, human food 
safety, or the animal's microbiome, and positively impact animal 
agriculture are a part of the discussions as to the best way to 
regulate them to ensure safety, effectiveness, and provide innovative 
products to animal producers.
    At this point in FDA's evaluation, the Agency believes it will 
issue an updated Guidance for Industry. However, it should be noted 
that evaluating claims about the effects of food ingredients will 
increase the workload for the ingredient review staff and new claims 
will also present the need for new expertise for their evaluation. To 
prepare for the anticipated additional workload, CVM continues to 
update and streamline operating processes and procedures. CVM is also 
engaging and training the animal food industry on effective ways to 
submit data to expedite the review process.
    Question. In the FY24 Budget Request, you noted that FDA will 
develop a standardized system to help consumers quickly and easily 
identify foods that are part of a healthy eating pattern. FDA will also 
make sure ``healthy'' labeling aligns with current nutrition science 
and the Dietary Guidelines for Americans with a proposal to update the 
nutrition standards for when ``healthy'' claims can be put on products, 
and will also develop a symbol to be used to depict and easily 
communicate a food as ``healthy.'' Can you discuss what coordination 
has been done with USDA in regards to the healthy label? Specifically, 
how would meat products under USDA labeling jurisdiction be treated by 
FDA's proposed rule?
    Answer. The proposed rule developed by FDA was shared with USDA, 
which reviewed it and engaged with FDA throughout the clearance 
process. FDA carefully considered USDA's input before publishing the 
proposed rule. The proposed rule only applies to foods subject to FDA's 
labeling regulations. This includes the meat products that are 
regulated by FDA, specifically game meat and seafood. Meat and poultry 
products under USDA jurisdiction are subject to the regulations set 
forth by USDA. However, the definitions for nutrient content claims for 
FDA and USDA are typically identical or very similar due to our inter-
departmental collaborative efforts.
    Question. What assurances has the agency provided to food 
manufacturers to avoid potential lawsuits for being out of compliance 
with the updated ``healthy'' definition during the proposed compliance 
period after a new definition is updated?
    Answer. Even after any new requirements for the definition of the 
nutrient content claim ``healthy'' are in effect, manufacturers may 
begin to comply with the new requirements or they may continue to use 
the old definition of ``healthy'' until the compliance date arrives. 
FDA notes that manufacturers would not be required to comply with 
requirements of the final rule until the compliance date. The Agency 
has proposed an effective date 60 days after the date of publication of 
the final rule in the Federal Register, with a proposed compliance date 
3 years after the effective date. This timeframe would provide industry 
time to revise labeling to come into compliance with the new 
requirements.

                          SUBCOMMITTEE RECESS

    Senator Heinrich. With that, this hearing is adjourned.
    Dr. Califf. Thank you.
    Senator Heinrich. [Whereupon, at 3:14 p.m., Wednesday, 
April 19, the subcommittee was recessed, to reconvene subject 
to the call of the Chair.]