[Senate Hearing 115-261]
[From the U.S. Government Publishing Office]






 
   AGRICULTURE, RURAL DEVELOPMENT, FOOD AND DRUG ADMINISTRATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2018

                              ----------                              


                         TUESDAY, JUNE 20, 2017

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met, pursuant to notice, at 10:35 a.m., in 
room SD-192, Dirksen Senate Office Building, Hon. John Hoeven 
(chairman) presiding.
    Present: Senators Hoeven, Collins, Rubio, Merkley, Leahy, 
and Tester.

                   U.S. FOOD AND DRUG ADMINISTRATION

STATEMENT OF SCOTT GOTTLIEB, M.D., COMMISSIONER, FOOD 
            AND DRUG ADMINISTRATION


                opening statement of senator john hoeven


    Senator Hoeven. The hearing will come to order. I would 
like to thank the members for being here, Ranking Member 
Merkley.
    And I certainly want to welcome FDA Commissioner Gottlieb. 
Thank you for being here this morning. We appreciate it.
    Today's hearing will focus on the Food and Drug 
Administration's fiscal year 2018 budget request. Thank you 
again for being here, Dr. Gottlieb. Obviously, this is a good 
opportunity to talk about FDA's priorities for the upcoming 
year.
    Congratulations on your confirmation. We certainly want to 
welcome you in your first appearance before the subcommittee, 
and we look forward to working with you.
    The agency you head has authority over approximately $0.20 
of every dollar spent in America. Americans expect that the 
food they eat and the drugs they take will be safe and 
effective.
    FDA's reach is vast. The agency has authority over more 
than 300,000 foreign establishments and 185,000 domestic 
establishments, ranging from food processing plants to 
facilities that manufacture lifesaving medications. In addition 
to facilities themselves, FDA is tasked with the regulatory 
responsibility of individual products.
    In delivering these regulatory responsibilities, your 
private sector partners expect transparency and certainty from 
the FDA.
    When I speak to small businesses and AG producers in North 
Dakota, their overwhelming concerns are that often overly 
burdensome regulations coming out of Washington, D.C., can 
stifle innovation and hinder their ability to create jobs. 
While we all support the FDA's mission, we must also be mindful 
of these concerns.
    I believe that FDA must avoid the trappings of one-size-
fits-all solutions, and urge you and your staff to take a 
common-sense approach.
    In regard to the budget request itself, I am concerned that 
this request relies on a significant increase in user fees that 
is not feasible and unlikely to gain congressional approval. I 
am concerned that the proposed cuts to budget authority may 
negatively impact food safety programs and slow the agency's 
important work on drugs and medical devices.
    That being said, Dr. Gottlieb, I also recognize that these 
decisions were made before you were confirmed, so I hope you 
will pledge to work with Congress to ensure that FDA has the 
resources necessary to meet its critical mission.
    We have many other issues to cover this morning, so at this 
point, I will turn to Senator Merkley for his opening comments.
    Senator Merkley.


               opening statement of senator jeff merkley


    Senator Merkley. Thank you. I am going to keep this very 
brief, because we are hoping to hear your testimony and have a 
round of questions before we go to the vote at 11.
    The department you head covers products that constitute 20 
percent of what consumers spend both in food and drugs. It 
makes that work very important, and this budget before us very 
important on everything from scientific research, support for 
State and local health organizations, blood safety work, 
medical devices, post-market surveillance, medical product 
exams, and so much more.
    And so I look forward to hearing your thoughts on the 
budget and getting to our inquiries.
    Thank you and congratulations.
    Senator Hoeven. I would suggest, at this point, we go right 
to Dr. Gottlieb's statement, so that we can come right back for 
questions and then any opening statements as well that other 
members may have.
    All right, Dr. Gottlieb.


                  summary statement dr. scott gottlieb


    Dr. Gottlieb. Thank you. Mr. Chairman, Mr. Ranking Member, 
and Members of the Subcommittee, I appreciate the opportunity 
to testify today regarding the President's budget.
    I have talked to you in the past about the steps that FDA 
is taking on the generic drug side to try to bring more low-
cost opportunities to patients when it comes to new drugs and 
improved access. I want to just briefly touch on some of the 
things we are going to be doing on the new drug side. The most 
tangible way we are going to reduce health care costs is by 
finding better treatments for a lot of costly diseases.


                           breakthrough drugs


    Toward these ends, we will be announcing soon a medical 
innovation development plan that will include a broad range of 
steps we will take to make sure that our own regulatory tools 
and policies are modern and risk-based, and designed to 
facilitate the development of potentially breakthrough new 
treatments.
    One area of focus of this new plan is going to be on 
targeted drugs, especially those that affect rare diseases or 
diseases for which there is no effective therapy. Among other 
things, FDA will be updating various guidance documents on the 
kinds of drug development techniques that help facilitate the 
discovery and development of targeted therapies. This includes 
guidance on clinical trial enrichment strategies to improve 
efficiency and adaptive trial designs so we can modernize the 
statistical tools we use to evaluate safety and effectiveness. 
We will also be taking a fresh look at policies that support 
innovation to allow drugs to be targeted only to those patients 
who are most likely to benefit from medicine. We will also be 
taking a broad range of new steps.
    Among these new actions, we will be issuing a new guidance 
document within the next 6 months on the clinical evaluation of 
targeted therapies for rare disease subsets. This new policy 
will address targeted drugs and how we can simplify the 
development of drugs targeted to rare disorders that are driven 
by genetic variations and where diseases all have a similar 
genetic fingerprint, even if they have a slightly different 
clinical expression.
    One example is a cancer, where a drug targets a particular 
molecular subset of cancer, regardless of where the tumor 
arises. We will clarify when we can give a broad approval to a 
drug in multiple different kinds of molecularly similar 
cancers, which are not particular to the tumor being in one 
specific tissue or organ. In other cases, rare subsets may be 
grouped by lab testing, so they can be studied in a single 
clinical trial.
    This sort of genetically driven medicine is more common as 
we understand the genetic basis of disease. Now, our new policy 
will describe when we will approach drug review less by how a 
disease is expressed and more by how it is driven by a common 
set of genetically driven factors.
    Many of these targeted drugs are aimed at rare and orphan 
diseases. But right now, we have a backlog of about 200 orphan 
drug designation requests where we have not responded to 
sponsors on whether the drugs will receive an orphan drug 
designation from FDA. As part of our new plan, we are 
committing today that, in 90 days, we will completely eliminate 
this backlog of requests and provide an answer back to the 
sponsors.
    To help eliminate the backlog, we have created a special 
orphan designation SWAT team. Moreover, we will never again 
develop a backlog. Going forward, we are committing today that 
every orphan drug application will receive a response from FDA 
within 90 days of the request. To enable more efficient reviews 
and timely responses to sponsors, we are also implementing a 
new streamlined orphan designation review template.
    These are just some of the things we are working on. I look 
forward to discussing with you how FDA's budget and this 
committee can support all of the agency's key priorities, 
including food safety, and enable consumers to improve their 
lives.
    Thanks a lot.
    [The statement follows:]
             Prepared Statement of Dr. Scott Gottlieb, M.D.
    Good morning Chairman Hoeven, Ranking Member Merkley, and Members 
of the Subcommittee, I am Dr. Scott Gottlieb, Commissioner of the Food 
and Drug Administration (FDA). Thank you for the opportunity to appear 
before you today to discuss the President's fiscal year 2018 Budget 
request for FDA.
    First of all, I would like to thank you all for your continued 
support of FDA. FDA has received strong bipartisan support throughout 
the appropriations process in recent years. This funding is critical to 
the agency fulfilling its mission. Without your support, we could not 
meet the critical public health challenges confronting the nation.
    I am honored to have been chosen by the President and confirmed by 
Congress to lead FDA. As a physician, an entrepreneur, a cancer 
survivor, and a father, I know personally the importance of FDA's role 
in improving and protecting the lives of all Americans. Every person in 
this country is affected in one way or another by the decisions made by 
FDA. For this reason, I am honored and humbled to serve as FDA's 
Commissioner.
    FDA's fiscal year 2018 Budget requests $5.1 billion--a nearly 10 
percent ($456 million) increase over the fiscal year 2017 Continuing 
Resolution (CR) funding level. Mindful of the larger pressures on the 
Federal budget, FDA has focused our request on the most urgent needs. 
The fiscal year 2018 Budget aims to protect the public health by wisely 
investing taxpayer dollars, requiring industries that benefit from the 
FDA's review process to pay their share, and advancing regulatory and 
administrative efficiencies.
      fda plays a critical role in america's public health system
    As a science-based regulatory agency, FDA's broad mission is to 
promote and protect the nation's public health and touches the lives of 
all Americans. Over $2.4 trillion annually, roughly 20 cents of every 
dollar, is spent by consumers on a product that FDA regulates. These 
products include human and animal drugs, medical devices, biologics, 
such as vaccines and blood, dietary supplements, and cosmetics. Tobacco 
is another product within FDA's purview--the agency protects the public 
health of future generations by reducing tobacco use by America's 
children.
    FDA's regulation of food is another critical part of FDA's mission. 
FDA works to assure that the nation's food supply is safe, sanitary, 
wholesome, and appropriately labeled. FDA has made great strides in 
promoting the safety of the foods we eat as envisioned by Congress in 
the FDA Food Safety Modernization Act (FSMA). Thanks to the support of 
this Committee and your colleagues in the House, we have been working 
closely with our state partners, to educate and assist industry during 
the implementation of FSMA's provisions. These include preventive 
controls for manufactured human and animal foods, sanitary 
transportation of our food, and as of May 30, verification that our 
high food safety standards have been met by foreign suppliers. FDA 
remains committed to working with industry to facilitate innovation to 
make safe and healthy food choices available to consumers.
 fda has a proven track record of success, but there's more work to do
    In the last year, FDA has helped bring new treatments, including 
several life- saving cures, onto the market. FDA's Center for Drug 
Evaluation and Research approved 22 novel drugs in 2016; approvals 
included the first treatment for patients with spinal muscular atrophy, 
a new drug to treat patients with a rare chronic liver disease known as 
primary biliary cirrhosis, and two new treatments for patients with 
hepatitis C. Additionally, 2016 marked the highest number of generic 
drug approvals and tentative approvals in the history of the FDA's 
generic drug program--more than 800 in total. In September 2016, FDA 
approved the first ``artificial pancreas,'' a medical device that 
automatically monitors blood sugar and provides insulin doses when 
needed. This device has the potential to improve the lives of roughly 
1.5 million Americans living with Type-1 diabetes.
    As highlighted by the above examples, FDA's collaboration with 
innovators brings products to the market that make a difference in the 
lives of all Americans. Since the creation of the first user fees in 
1992, user fees have been instrumental in allowing FDA to build 
capacity and improve the timeliness of the medical product review 
process without compromising the agency's high standards. The user fee 
programs provide FDA with the critical and stable funding we need to 
hire and train the highly-qualified reviewers needed to keep pace with 
innovation.
    However, the medical products field is ever-changing and advancing, 
and to ensure the agency has the critical resources needed to keep pace 
with this field, the Fiscal year 2018 Budget recalibrates how the 
agency finances our medical product review work. Calling for an 
increase of $1.2 billion in user fees, the fiscal year 2018 Budget 
includes a total program level of $3.2 billion for medical product 
safety investments, which is $505 million above the fiscal year 2017 CR 
level. The Budget finances the full cost of FDA pre- market review 
through user fees. These resources will dramatically increase the 
agency's capacity for pre-market review, and bring more new products to 
market faster than ever before.
                          cures implementation
    The fiscal year 2018 Budget's focus on medical products complements 
Congress' direction last December in passing the 21st Century Cures Act 
(Cures). Cures provided a dual directive to FDA-- to support innovation 
while maintaining the evidentiary standards that provide assurance to 
the American public about the safety and efficacy of medical products. 
This includes advancing patient-focused drug development and using 
real-world evidence in modern clinical trial design. As a result, Cures 
will help FDA facilitate more patient-centered, efficient, and less 
costly medical product development, ultimately leading to more timely 
patient access to important medical products. The fiscal year 2018 
Budget requests a total of $60 million to support this critical work, 
and we look forward to working with Congress, and this Committee, as 
FDA continues its work on implementing Cures.
       promoting innovation by prioritizing regulatory efficiency
    As FDA's Commissioner, part of my job is to ensure the Agency has 
the policies and processes in place needed to address the important 
public health issues of our day, as well as emerging threats of 
tomorrow. We must hold true to our consumer protection mission, while 
not hampering innovation.
    The Administration is committed to the goal of reducing barriers to 
innovation and spurring innovation on behalf of patients. At FDA, we 
understand the impact our regulations have on industry and the public--
which is why we have, and will continue to engage in robust dialogue 
with outside stakeholders to ensure our actions strike the right 
regulatory balance while maintaining our gold standard.
    The fiscal year 2018 Budget includes proposals designed to make 
sure we are taking a risk-based approach to our work and make the 
process for developing safe and effective medical products more 
efficient. By leveraging FDA's statutory mandates, including recent 
enhancements made by Cures, the agency is working to reduce review 
times by improving processes and gaining efficiencies to the greatest 
extent possible. These proposals will help reduce uncertainty in 
medical product development by increasing engagement and early 
interactions with manufacturers. Improved regulatory science and 
policies will not only lead to more efficient approvals and increased 
competition that can help reduce costs to consumers, but more 
importantly, they will improve patient- outcomes. By streamlining 
clinical trials, integrating patient voice throughout the regulatory 
process, and promoting greater preparedness for novel and emerging 
public health threats, Americans will get better products, faster.
                prioritizing administrative efficiencies
    In addition to regulatory efficiencies, FDA is taking a close look 
at all of our programs, policies, and procedures to ensure that every 
dollar dedicated to administrative costs is spent wisely. The fiscal 
year 2018 Budget proposes the establishment of a Working Capital Fund 
(WCF) to support agency-wide business services. A WCF will allow FDA to 
operate in a more efficient and transparent business environment. Over 
time, this WCF will also allow FDA to recapitalize resources to support 
IT infrastructure, reduce cost redundancy and improve service delivery 
for mission critical needs.
    Dollar for dollar, FDA remains one of the smartest investments made 
by the American taxpayer. The fiscal year 2018 Budget also identifies 
targeted reductions and program changes totaling $127 million in budget 
authority while preserving core mission activities. These reductions in 
budget authority are targeted to certain areas where better tools and 
policies will allow us to do more with less, and will be coupled with 
policy efforts to improve the efficiency of the programs that see 
reductions, to make sure that we are improving our effectiveness and 
taking a risk-based approach to our consumer protection mission.
                               conclusion
    Today, we are at an inflection point in public health. Cures for 
diseases we once believed were incurable are now within our reach. The 
fiscal year 2018 Budget will protect and advance the health and well-
being of every American, while providing American taxpayers the 
assurance that we are requiring industries that benefit from the FDA's 
review process to pay their share. I look forward to answering your 
questions today and to working with all of you going forward.

    Senator Hoeven. Thank you, Doctor. We will start with 
questions.

                       FISCAL YEAR 2018 RESOURCES

    As I noted in my opening comments, I have concerns with the 
administration's proposal to essentially double user fees. It 
does not appear that the HELP Committee will move forward with 
that proposal. Instead, Congress will likely pass the 
previously negotiated user fees.
    So my question is, based on the fiscal year 2017 
appropriation, are you confident that you are going to be able 
to meet the program needs, based on your current appropriated 
level for fiscal year 2017?
    Dr. Gottlieb. Senator, thanks for your question.
    The bottom line is, we can always do more with more when it 
comes to the resources that the agency has. I am confident that 
we have been able to be efficient in everything we do.
    I think there are still places that we can look within the 
agency to try to improve our operational efficiency. We 
recently made an announcement with respect to a realignment 
when it comes to the field activities. We are going to continue 
to look for places to improve our operational efficiency.
    We appreciate very much, though, the resources that we have 
gotten from this committee, in particular, the resources on the 
food safety side and the resources that we have gotten under 
FSMA. That that has dramatically improved the stature and the 
base of resources for food safety. It is a very different 
agency today than the one that I left 10 years ago, in that 
regard.

                             HIRING FREEZE

    Senator Hoeven. You have about 1,000 vacancies. The hiring 
freeze has been lifted for your agency. Are you moving forward? 
And where are you in that process of filling positions?
    Dr. Gottlieb. Thanks for the question. That is right. We 
negotiated the lifting of the hiring freeze about 2 weeks ago, 
I believe, and we are starting to move forward with filling 
those vacancies. I put out a notification recently to the 
Office of the Commissioner, as well as the different centers, 
in terms of the process of moving forward. But there is already 
activity with filling some of those existing open slots.

                             OPIOID CRISIS

    Senator Hoeven. What is the FDA's role in addressing the 
opioid crisis? And what are you doing?
    Dr. Gottlieb. Well, it is multifaceted. This is, in my 
view, the biggest challenge facing the agency, and I think one 
of the biggest public health crises facing this country.
    There are a lot of different components where the FDA is 
going to play a role. You look at medically assisted therapy 
where the agency plays an important role trying to address the 
current addiction problem, and trying to get better opioids on 
the market that are more tamper-resistant.
    I think where we can play a particularly important role, 
however, is on the new addiction aspects of this crisis. We 
know that most people who are going to become addicted to 
opioids are first exposed to opioid drugs in the clinical 
setting through legitimate prescription. A certain percentage 
of patients who are exposed to opioids in the clinical setting 
will go on to develop an addiction.
    So I think it is incumbent upon all of us to make sure that 
only properly indicated patients are being prescribed opioids. 
And when they are prescribed opioids, they are prescribed 
opioids for a duration that comports with the clinical 
circumstance for which the prescription was written in the 
first place.
    There are things that FDA can do to try to address these 
aspects of the problem. So that is going to be a particular 
area of focus of ours. We recently developed a steering 
committee made up of all the center leadership and senior 
clinicians within the agency to look at trying to see how we 
can think differently about this problem.
    The other place where I have tried to focus some 
policymaking attention is looking at the risk in the illicit 
setting. We traditionally have looked at the risk of illicit 
use as a component of how we evaluate the risk and benefit of 
opioids overall. But I want to make sure we have a proper 
framework in place for doing this, and we are looking not just 
at the risks associated with these drugs in their labeled 
indication but also the risks associated with how they might be 
abused and misused and diverted and used illicitly. And we have 
recently taken an action that factored into it consideration of 
how the drug was being used in the illicit setting.
    Senator Hoeven. What about approval of drugs that actually 
help wean people off some of the opioids? I know there is 
development in this area.
    Dr. Gottlieb. Right. This is the medically assisted 
therapy. We need to continue to develop good drugs in this 
area.
    One of the challenges, though, has been reimbursement. 
While it is outside my mandate, getting these drugs to patients 
is an important step as well. So we are looking at things we 
can do to help facilitate the development of clinical trials 
that move these drugs into different clinical settings to see 
how we might better study them in real-world settings. 
Hopefully, we will have more to say on that soon.

                         NUTRITION FACTS PANEL

    Senator Hoeven. Last week, the FDA announced a delay, for 
compliance to the Nutrition Facts Panel regulations. I know you 
are limited on what you can say until it is published in the 
Federal Register. But given my comment regarding one-size-fits-
all solutions, will FDA use a common-sense approach toward 
those nutrition regulations?
    Dr. Gottlieb. Thanks a lot.
    I am confident we will, Senator. We announced the delay, in 
part, to provide additional guidance to sponsors on how to 
interpret aspects of the new Nutrition Facts label.
    This is a time limited delay. This is not a suspension of 
the regulation. We are not reopening the regulation. We are 
just using this time to develop additional guidance documents 
that we will be issuing to help inform how people can comply 
with the new labeling.
    Senator Hoeven. Senator Merkley.
    Senator Merkley. Thank you, Mr. Chairman.
    And welcome, Dr. Gottlieb.

                     RESPONSE TO MINORITY REQUESTS

    The first question I have for you is, a number of news 
reports have discussed the administration's directive to 
Federal agencies not to respond to requests from minority 
Members of the Senate.
    That is completely contrary to the very long and positive 
bipartisan history both on this subcommittee and our dealings 
with the FDA under both Republicans and Democrats. I think a 
dialogue with the executive branch for all Members results in 
stronger bills more likely to have support, and it clearly 
benefits the FDA and the American public to have that dialogue.
    Can we count on you to be engaged in that dialogue and 
respond to inquiries and requests from the majority and the 
minority?
    Dr. Gottlieb. Absolutely, Senator. I responded to all the 
requests for new information that I got during my confirmation 
process from the minority. I am prioritizing timely responses 
equally from both the majority and the minority. We have 
reached out to many offices, including your own. I had the 
pleasure to meet with you twice.
    So we will not pick sides in how we provide information to 
Congress. I respect Congress, and we are going to make sure we 
are providing you the information you need.
    Senator Merkley. Thank you very much. Your outreach has 
been appreciated, and I appreciate your commitment to 
continuing on that course.

                            OPIOID ADDICTION

    During your confirmation process, you described the 
staggering human consequences of opioid addiction and 
characterized that epidemic as the biggest crisis facing the 
agency.
    Now we have a prediction that the CDC, engaged with various 
other experts, that the Trumpcare bill coming out of the House, 
we do not know what version we will see in the Senate yet, 
would cut billions of dollars from treatment for mental health 
and substance abuse disorders, and also that millions of people 
will lose their insurance, which makes it very unlikely that 
they will be seeking medical care in the first place.
    We are concerned that this budget would damage the ability 
to take on opioid addiction, with its enormous daily toll on 
lives. As someone who is leading the charge on this epidemic, 
who has presented it as a top priority, do you have concerns 
about the loss of access to health care by millions of 
Americans, if this bill is enacted?
    Dr. Gottlieb. Senator, I am very focused on what we are 
doing at FDA right now to address this crisis, as I know you 
can appreciate. And you are going to continue to see a series 
of activity out of the agency to address this crisis in 
different ways that hopefully start moving us to a posture 
where we are getting ahead of the problem, instead of always 
being one step behind.
    I have not focused a lot of attention on the various 
legislation moving through, with respect to the Affordable Care 
Act. I am very focused on what I am doing at FDA right now, 
which is more than a full-time job, as I know you can 
appreciate, and I will continue to talk to you about those 
priorities.
    Senator Merkley. There are 13 Senators who are holding a 
series of closed meetings to work to prepare a version of the 
bill that will come before the Senate, probably next week. Have 
those individuals, or as a group, brought you in to get your 
consultation and insights on the opioid epidemic?
    Dr. Gottlieb. I do not know what group you are talking 
about, but I have had conversations with individual Members 
about the opioid epidemic. I met with probably 60 Members in 
the run-up to my confirmation process. I would say that this 
issue came up in most of those meetings. Since I have been in 
this position, we have taken a lot of additional meetings with 
both Democratic and Republican Members in the House and the 
Senate, and this issue comes up a lot.
    So I have consulted widely on this issue, including with 
you, Senator, and I appreciate all the dialogue I have had with 
Congress.
    Senator Merkley. The group that I am referring to are the 
13 Republican Senators who have been delegated the authority to 
prepare a bill to be brought to the floor, one that will have 
no public input. That is the group. Has that group asked you to 
come and share your expertise on this?
    Dr. Gottlieb. I have had no dialogue with any group working 
on legislation as a group, no.
    Senator Merkley. Well, I imagine, just knowing your 
background, that you probably share my concerns that such 
issues get the insight from experts and also that the public 
has a chance to weigh in, so that we get, in this ``We the 
People'' Republic, a full opportunity to make sure we get kind 
of policy right, if you will, when it has an impact on so many 
people.
    Dr. Gottlieb. Thank you, Senator.
    Senator Merkley. Thank you.
    Senator Hoeven. Senator Collins.
    Senator Collins. Thank you, Mr. Chairman.
    Mr. Chairman, I have an opening statement that I would 
request be submitted for the record.
    Senator Hoeven. Without objection.
    [The statement follows:]
             Opening Statement of Senator Susan M. Collins
    Thank you Chairman Hoeven and Ranking Member Merkley for holding 
this important hearing to talk about the fiscal year 2018 Budget 
request for the Food and Drug Administration. And thank you, 
Commissioner Gottlieb, for testifying before the Subcommittee today.
    The volume and complexity of the FDA's work have grown considerably 
in recent years. Charged with assuring the safety and efficacy of human 
and animal drugs, biologics, and medical devices--FDA must work to 
strike the appropriate balance between encouraging innovation and 
timely access while protecting the public's health and safety. FDA also 
regulates cosmetics, tobacco, and products that emit radiation. And, it 
is responsible for ensuring the safety and security of our nation's 
food supply.
    FDA's core mission is critical to the lives of American families 
and seniors, and I will plan to touch on two issues during questions 
that are particularly top of mind--the opioids crisis and eliminating 
barriers that unduly prevent generic drug competition.
    With such an extremely broad mandate, I look forward to hearing 
from the Commissioner about the agency's priorities.

    Senator Collins. Thank you.

           HEALTHCARE PROVIDER EDUCATION--OPIOID PRESCRIPTION

    Doctor, we have previously discussed the need for improved 
health care provider education with regard to the prescribing 
of opioids. Medicaid beneficiaries are prescribed pain 
relievers at a higher rate than those with other sources of 
insurance. And they also, not surprisingly, given that higher 
rate, have a higher risk of overdose from prescription opioids, 
heroin, and fentanyl.
    What opportunities do you see for greater collaboration 
among the FDA, CMS, State Medicaid directors, medical 
societies, and other parties, in order to address this problem 
of appropriate prescribing of opioids?
    Dr. Gottlieb. I appreciate the question, Senator. I would 
also add the DEA (Drug Enforcement Agency) to that, because 
there might be things we can do in conjunction with our 
partners at the Justice Department.
    As part of the steering committee that we have set up, we 
are currently having discussions about what steps we can take 
to improve provider education, and maybe take a look at 
packaging as well, as a way to help make sure prescriptions are 
more appropriately matched to the clinical circumstances for 
which they are being written.
    I do not want to get too far ahead of that process, other 
than to say that this is something that is at the top of the 
list of things that we are looking at right now. This includes 
what additional steps we can do under our current authorities, 
both through the risk management plans that we currently 
promulgate in conjunction with opioids, the approval of opioids 
and other narcotics on the schedule of drugs, as well as in 
partnership potentially with the DEA. DEA obviously has 
authority to potentially look at certain requirements as part 
of the process for giving a DEA license to individual 
practitioners.
    Senator Collins. Thank you.

                              DRUG PRICES

    As you know from our numerous discussions, the Senate Aging 
Committee last year undertook a major investigation examining 
the explosion in prices of off-patent prescription drugs for 
which there is no generic equivalent. In one case, a drug was 
purchased by a company that played absolutely no role in 
developing the medicine, and then raised its price by 5,000 
percent overnight.
    One of the problems that we found is that these companies 
warded off competition from generic companies by putting their 
drugs in closed distribution systems or in specialty 
pharmacies. The intent in doing so was to delay access or even 
block access to a sufficient quantity of the brand name drug to 
do the bioequivalence studies that the FDA requires.
    These abuses are serious and contribute to the cost 
increases that we are seeing. By one estimate, in 2014, such 
abuses resulted in increased costs to consumers of $5.4 billion 
per year.
    I have had extensive conversations in hearings and 
privately with Dr. Janet Woodcock about this problem. She has 
testified that FDA has done 150 referrals to the Federal Trade 
Commission (FTC) to take a look at this anticompetitive process 
without any success. She suggested that there needs to be a law 
change in order for the Risk Evaluation and Mitigation 
Strategies (REMS) system not to be abused.
    I know that you have testified before the House 
Appropriations Subcommittee and noted your concern about this 
type of anticompetitive behavior. Should Congress revise the 
REMS law, as suggested by Dr. Woodcock, since there is only so 
much that FDA can do now about the problem?
    Dr. Gottlieb. Well, I appreciate the question, Senator.
    I know there is some legislation that Congress is currently 
contemplating in this regard. We would be happy to provide 
technical assistance on that. I think we already have. I 
believe there are things we can do within the scope of our 
current authorities through administrative action to address 
this challenge.
    There are two different challenges here. One is the REMS, 
which is sometimes misused as a way to block the ability of 
generic companies to get access to the samples they need in 
order to develop a generic drug. It takes between 1,500 to 
3,000 actual doses in order to develop a generic equivalent.
    The other issue is things are sometimes embedded in the 
contracts with the distributors or the specialty pharma 
companies that make it hard for the distributors or the 
specialty pharma companies to sell the drugs to the generic 
companies when they try to purchase them at fair market value 
in the marketplace.
    So there are two different issues. Some we can solve, or 
address within the scope of FDA, and some might require us, if 
we want to try to address it administratively, to partner with 
Medicare, where there might be opportunities to do that.
    We can identify, to your point, the situations, the 
circumstances, where we believe the generic companies are not 
able to get the access to the doses and make referrals. We 
cannot fully address some of the commercial restrictions that 
prevent them from getting access to those doses. But we could, 
in partnership with other agencies.
    Senator Collins. Thank you.
    Senator Hoeven. Senator Tester, I understand that you are 
deferring to Senator Leahy. Is that correct?
    Senator Tester. I was not going to, but go ahead.
    [Laughter.]
    Senator Leahy. There has to be some advantage of being vice 
chairman of this committee.
    Senator Hoeven. Senator Leahy.
    Senator Leahy. Thank you. I will be brief. I will put my 
full statement in the record.
    [The statement follows:]
              Prepared Statement of Senator Patrick Leahy
    Thank you, Chairman Hoeven and Ranking Member Merkley, for holding 
this hearing today to examine the President's fiscal year 2018 budget 
proposal for the Food and Drug Administration. And thank you, 
Commissioner Gottlieb [got-LEEB], for joining us here today. I thank 
the Chair and Ranking Member for giving me the opportunity to offer a 
few opening remarks.
    The Food and Drug Administration has an enormous responsibility to 
ensure the safety of all Americans. From our food supply, to 
pharmaceuticals and cosmetic products, the FDA must have the resources 
it needs to effectively review these products. That is why I was so 
disappointed and alarmed to see the woefully inadequate budget 
submission from the FDA, which, when excluding the user fee proposal 
and the mandatory funding through the 21st Century Cures Act, includes 
a 34 percent cut. The cuts include $119 million from monitoring food 
safety and a $55 million reduction in medical product safety. In my 
many years in the Senate, I have heard repeatedly that the FDA needs 
more, not less, resources to adequately fulfill the agency's mission. 
Commissioner Gottlieb, I am curious to hear from you about your 
justification for how these proposed reductions will not adversely 
impact Americans' health and safety, and help bolster consumer 
confidence in our Nation's food supply.
    The FDA also has a responsibility to approve new drugs, including 
generic alternatives. With the price of prescription drugs on the rise, 
crippling households and seniors on a fixed income, I will also want to 
discuss with you ways to help ensure more competition in the 
pharmaceutical market. Commissioner Gottlieb, as a physician and 
someone who has worked in the industry for many years, I am interested 
in hearing your thoughts.
    Finally, Dr. Gottlieb, I would be remiss if did not make one thing 
very clear: President Trump's abysmal budget assumes savings from the 
repeal of the Affordable Care Act, and deep cuts to the Medicaid 
program. As we talk today about how to increase access to safe, 
affordable--life- saving--prescription drugs, we cannot forget the 
millions of Americans that would be left without health insurance if 
the Affordable Care Act is repealed. Whatever Senate Republicans are 
crafting behind closed doors, we cannot--and should not--accept any 
proposal that strips essential and affordable healthcare from millions 
of Americans.
    As I have said in other Appropriations hearings, as Vice Chairman 
of this Committee, I will work to craft a budget that truly puts 
Americans first. I look forward to working with the other members of 
this Committee, on both sides of the aisle, who I believe also want to 
fulfill that goal.

    Senator Leahy. Commissioner, I am glad you are here today. 
I appreciate you being here.

                FDA'S FISCAL YEAR 2018 BUDGET SUBMISSION

    I was disappointed to see I think a woefully inadequate 
budget submission from the FDA. When you exclude the user fee 
proposal and mandatory funding to the 21st Century Cures Act 
that is about a 34 percent cut, $119 million is cut from 
monitoring food safety, $55 million reduction in medical 
product safety.
    I have been here for over 40 years. I have heard repeatedly 
the FDA needs more money, not less. This is the first time I 
have seen such a huge cut, especially with the price of 
prescription drugs on the rise, crippling opioids, and so 
forth.
    So I think the budget that the President has submitted is 
abysmal. It assumes deep cuts of the Medicaid program. It 
assumes repeal from the Affordable Care Act. It is kind of 
saying the check is in the mail. But I would really like to 
have a budget that puts Americans first, not political slogans 
first.

                      DRUG PRICES AND CREATES ACT

    But I want to follow up on something Senator Collins was 
saying about drug prices and the Creating and Restoring Equal 
Access to Equivalent Samples (CREATES) Act. We care, all of us, 
I do not care whether you are Republicans or Democrats, about 
the high cost of prescription drugs. I know that some of the 
pharmaceutical companies have used inappropriate delay tactics 
to limit the ability of generic competitors to enter the 
market. Some will not give the generics the samples needed for 
testing.
    I proposed a bill joined by Republicans and Democrats both 
here in the Senate and in the House, the CREATES Act, which 
would deter pharmaceutical companies from blocking cheaper 
generic alternatives.
    So can you explain again the role access to these samples 
plays in market competition?
    Dr. Gottlieb. Thanks for the question.
    The bottom line is that there is no question there are 
places where companies do take advantage of rules meant for one 
purpose as a way to gain commercial advantage. What I want to 
do is make sure we have a framework in place that makes it hard 
to do that. I think that when we put in place rules for, in 
this case, a risk management plan trying to address drug safety 
questions, we do not want to see those rules misused as a way 
to try to forestall access to generic competition that Congress 
intended under the laws that exist right now.
    So I do not want to be playing whack-a-mole with companies 
either. I want to have in place a consistent framework and a 
consistent set of rules that prevent these kinds of abuses.
    I think we can achieve that. I would be happy to work with 
Congress on the legislation that you are contemplating. But I 
also think that there are things that we can do 
administratively through our current authorities. That is where 
I am going to be focusing my attention.
    Now the REMS is not the only place where this kind of 
potentially anticompetitive behavior goes on. We are going to 
be looking across all those places. We are going to be 
announcing a public meeting very soon to solicit input from the 
public on where other people believe there are practices that 
could be forestalling access to generic competition, where 
branded companies might be taking advantage of certain rules 
that we could potentially address through our existing 
authorities.
    But this is an important focus of mine.
    Senator Leahy. You commented recently the FDA is evaluating 
whether to waive the law's existing preference for brands and 
generics for REMS. And Janet Woodcock, as mentioned already, 
testified that a statutory change might be needed.
    Which is better for you, statutory, or can you do it from 
regulatory?
    Dr. Gottlieb. Well, I have been in the job for about 6 
weeks now, and I have spent a lot of my time looking at what I 
can do, and starting to put those actions in motion. So I have 
spent far less time looking at potential statutory solutions.
    I think you just referred to the single, shared REMS, where 
branded companies and generic companies are obligated to try to 
negotiate a single REMS to try to reduce burdens on providers. 
And the question there becomes, at what point do we step in and 
say, ``You know what? The negotiations have gone on for long 
enough, and we are going to allow the generics to move forward 
with their own REMS program.''
    That is a decision we could make. We have to develop the 
administrative record to do that. That is something where we, 
through our current policy, can help address a potential stall 
tactic.
    I think if we put in place a policy signifying that we were 
willing to step in and say, ``You know what? These negotiations 
have gone on long enough. We are going to allow the generic 
company to move on their own,'' I think maybe companies might 
reach agreement quicker than they are today.
    Senator Leahy. Thank you.
    Thank you, Mr. Chairman. I think you are going to find both 
Republicans and Democrats are going to be interested in working 
with you to do that, because these prices are getting out of 
control.
    Senator Hoeven. Senator Rubio.
    Senator Rubio. Thank you.
    Thank you, Dr. Gottlieb, for being here.

                             PREMIUM CIGARS

    As you know, as we discussed for your confirmation, there 
are a number of small businesses in Florida that have been 
making premium hand-rolled cigars for generations. The industry 
is at stake.
    Last year, under the previous administration, they 
finalized a rule that would require premium cigars, not the 
stuff you get from behind the counter, but the premium ones, to 
regulate the manufacture, import, packaging, labeling, 
advertising, promotion, sale, and distribution, at the premium 
cigar level.
    So it is already illegal to sell tobacco products to anyone 
under the age of 18, which I think addresses the underage 
smoking issue. Plus, the premium cigar market really is not 
marketed toward that. It is a different market altogether.
    Are there any plans to reevaluate the inclusion of premium 
hand-rolled cigars from this rule, as was proposed under the 
preliminary rule?
    Dr. Gottlieb. Thanks for the question.
    We are currently looking at aspects of the rule. As you 
know, there was a 3-month delay in implementation of certain 
compliance dates announced before I arrived at FDA. We are 
coming up on the end of that delay.
    Whatever we do in this regard is going to need to be 
science-based, of course. But we are cognizant of the 
challenges faced by small businesses. I also understand that 
there are a number of legislative measures to exempt premium 
cigars. If Congress were to act, we would be happy to work with 
legislators to mitigate any unintended consequences of these 
measures.
    I do not want to comment too specifically, given that there 
is pending litigation right now around this issue, other than 
to say that I understand the concerns. You and I have had the 
opportunity to talk about them on a few occasions now. I do 
understand the concerns of the small businesses that make 
premium cigars, Senator.
    Senator Rubio. Yes. And just for those who might be 
watching, we are talking about the premium cigars, or what the 
name implies, a premium cigar.
    Dr. Gottlieb. That is right.
    Senator Rubio. I mean, it is an expensive product marketed 
toward a very specific audience. If it is science-based, I 
think it will show, as we have seen repeatedly, that it is 
really not a product that it is marketed to people under age, 
or the like.

                      PEDIATRIC CANCER TREATMENTS

    Real quick, I really appreciate the assistance FDA has 
provided to me and to Senator Bennet on our legislation, RACE 
for Children, to close the gap on cancer treatments that exist 
between adults and children. I was just wondering if you could 
provide some background as to why the FDA initially requested 
legislation to close this loophole after years of trying to 
encourage development of pediatric cancer treatments only 
through the Best Pharmaceuticals for Children Act?
    Dr. Gottlieb. Well, I know the legislation, Senator. I 
assure you, we want to do everything we can to try to make 
products available to pediatric patients, particularly 
pediatric patients who have rare diseases where current 
available therapy might not fully address their clinical needs. 
I know that we have provided technical assistance with respect 
to this legislation and have worked with your office and will 
continue to do that.
    Senator Rubio. Just again, as an aside, what Senator Bennet 
and I are aiming at is, right now it is basically on an 
incentive system, where we are trying to incentivize companies, 
in every one of their trials, to have a pediatric component. 
Unfortunately, it is not working.
    They are not doing that enough because sometimes the target 
audience is not big enough for them, or the target potential 
patient mix is not large enough for them to be encouraged to do 
that.
    So our hope is to be able to drive more of that. I think 
everyone has been impacted in their own families by pediatric 
cancer, and it is critically important that we develop new 
treatment options at that level, because when it strikes a 
family, it is devastating.
    So again, we thank you for your cooperation and look 
forward to continuing to interact with you.
    Thank you, Mr. Chairman.
    Senator Hoeven. Senator Tester.

                            TOBACCO PRODUCTS

    Senator Tester. Thank you, Mr. Chairman. I am glad I stuck 
around for Marco's questions, because the fact is, I think he 
is absolutely right on the premium cigars. I would tell you, on 
the other side, there are companies that are marketing their 
tobacco products to kids, and, hopefully, you can do something 
about that, too, because it is ridiculous. It smells bad.
    You do not need to comment on that. I just hope you would 
pursue that.

                             GENERIC DRUGS

    Would you agree that expediting the review of high-need 
generic drugs should be a priority for the FDA?
    Dr. Gottlieb. We currently do expedite various categories 
of what I think you and I might agree are high-need generic 
drugs. In fact, we just announced we are going to be 
prioritizing the review of drugs that do not face any 
competition. There are 180 generic drugs right now, or drugs 
that are off-patent.

                        FISCAL YEAR 2018 BUDGET

    Senator Tester. And the chairman talked about 1,000 
vacancies. CBO has estimated that, if we are going to do this, 
it could be as many as 500 additional employees over the next 5 
years. At $60,000 a year a pop, that is a fair amount of money.
    I think it is the right thing to do. I think it is an 
important thing to do. But how, under this budget, are you 
going to be able to accomplish that?
    Dr. Gottlieb. Well, look, as the chairman noted, I was not 
involved in the formulation of the budget.
    Senator Tester. I got it.
    Dr. Gottlieb. I would have to, obviously, make it work, if 
the budget were to pass as it was proposed.
    These are challenging budgetary times. We are going to have 
to figure out ways to do more with less. We have tried to 
target the cuts that this budget does distribute. This budget 
is an overall increase, but there will be certain cuts 
distributed under the budget, because of the way the money is 
allocated with the emphasis towards the user fees.
    We will have to try to, and we have tried to allocate the 
reductions to places of lower priority. But in an agency where 
there is an important mission, and a lot of what we do is 
important, sometimes it is challenging to find those areas. We 
have tried to do the best we can to identify them.
    Senator Tester. I think this is really important. I think, 
as many of the people on this committee have talked about, 
prescription drugs is a huge driver in health care costs. They 
are huge. We need to make sure they are safe. But the backlog, 
whether it is with generics or orphan drugs, as you talked 
about in your opening statement, is critically important.
    I love to do more with less, but we have to do a lot more 
with a third less, and I just do not see how that works. You do 
not have to justify this, because I have heard the ``more with 
less'' from a lot of different folks.
    But the truth is, in the end, if we are going to be able to 
hold you accountable and you come back in and say, ``You know 
what? I just did not have the manpower to do it,'' that is our 
job here, to make sure you have the manpower to do it. And your 
recommendations are really important when it comes to manpower.
    And I get it. There is fat in every agency. And there are 
priorities in every agency. So I would hope that you would be 
honest with us and say, ``You know what? This is a big issue.'' 
Because I think the generic drug thing is a huge issue. And to 
get these high-need generics out I think is something we should 
all try to achieve. But you also need to be realistic on the 
manpower and the budget that it takes, because it is important.
    Dr. Gottlieb. Well, Senator, as you are trying to think 
through what you think are the appropriate allocations to help 
support the agency's mission, you can rest assured I would be 
happy to work with you to provide you any advice you need.
    Senator Tester. Not only me but this entire subcommittee on 
your budget. I would love to get your recommendations. Because, 
like I said, I think this is an incredible driver in health 
care, and we need to figure out ways to do reduce costs.

                             GENERIC DRUGS

    I think generics have been one of the bright lights over 
the last 15, 20 years, however long they have been around. And 
so when we see hedge fund folks buying up prescription drug 
companies, doing the kinds of things Senator Collins talked 
about, we have to figure out ways to block that, whether it is 
through your agency or some other agency.
    Dr. Gottlieb. Right. We are also going to contemplate this 
very issue in the GDUFA reauthorization that is before Congress 
right now.
    Senator Tester. All right. Thank you.

                   IMPORTATION OF PRESCRIPTION DRUGS

    Now I want to talk about importation of prescription drugs. 
There have been all sorts of efforts over the last 20 years 
that I know of, from Montana hauling busloads of folks up into 
Canada to buy prescription drugs. There have been bills put 
forth here for reimportation, some of them good, some of them 
not so good.
    Do you think Americans should be allowed to import drugs 
from other countries?
    Dr. Gottlieb. Well, this question has been put to FDA 
Commissioners across both Republican and Democratic 
administrations, and there is a certification. It is currently 
legal to have drug reimportation, as long as the Secretary of 
Health and Human Services can certify the safety of the drugs 
that are coming in. That legislation has existed through both 
Republican and Democratic administrations.
    I have not taken a fresh look at this question. I have not 
been asked to. I am happy to look at it. But I would remind the 
committee that FDA Commissioners dating back to when I was last 
at the agency about 15 years ago have not been able to make 
that certification.
    Senator Tester. Have not been able to make the 
certification of safety, of it being a safe product reimported?
    Dr. Gottlieb. Of the ability to put in place the proper 
regulatory architecture that, if you have reimportation of 
drugs, to make sure that the chain of custody can be 
guaranteed, that you are actually getting a drug that was 
manufactured by legitimate----
    Senator Tester. Right. I think that is a legitimate 
concern. I think there is also a legitimate concern of 
Americans being gouged for their prescription drugs. I am 
almost to the point where I think we may be subsidizing other 
countries for their cheaper prescription drugs.
    I do not know that to be a fact. But the truth is that when 
I go into Montana, and I think the same can be said for North 
Dakota or Oregon, we hear about this issue a lot.
    Dr. Gottlieb. And I am trying to take steps to address it, 
Senator, as you know, through what we are doing to try to bring 
more competition onto the market.
    I think you are absolutely right. I do not think it is a 
debatable proposition. We are subsidizing drugs for other 
countries through the high prices we pay here to support the 
research and development, and we need to address that, too. I 
am not the trade representative, obviously, but I am trying to 
do all I can through within the context of my agency.
    Senator Tester. Thank you for your answers.
    Thank you, Mr. Chairman, for allowing me to go over time.
    Senator Hoeven. Absolutely, Senator.

                     ADDITIONAL COMMITEE QUESTIONS

    We have votes that have been called, so at this point, we 
are going to adjourn the hearing.
    I do want to thank you, Dr. Gottlieb, for being here today. 
I appreciate you not only being here but your good work.
    For members of the committee, any questions that you want 
to submit for the hearing record should be turned into 
subcommittee staff within 1 week, which is Tuesday, June 27th. 
We would appreciate if we could have a response back from you, 
Doctor, within 4 weeks from that point.
               Questions Submitted by Senator John Hoeven
                              alzheimer's
    Question. Alzheimer's disease is a major public health threat to 
our country. Patients and providers currently have few impactful 
therapeutic options when fighting Alzheimer's disease. Costs associate 
with Alzheimer's disease have been estimated to be $236 billion, per 
year. And unless we get new medicines to slow the progression of the 
disease, cure it, and even one day prevent its onset, those annual 
costs are projected to top $1 trillion by 2050. In no uncertain terms, 
we urgently need new FDA-approved drugs for Alzheimer's disease. To 
achieve this important goal, FDA must ensure that the right regulatory 
policies and processes are in place to encourage and facilitate 
innovation. The status quo with regard to Alzheimer's disease must 
change.
    What is the FDA's policy of requiring clinical trials for new 
Alzheimer's medicines to meet two endpoints, or co-primary endpoints--
one related to cognition and one related to function?
    Answer. As stated in FDA's 2013 draft guidance on Alzheimer's 
disease (AD), clinical trials in the dementia stage of AD should use a 
co-primary outcome measure approach in which a drug demonstrates 
efficacy on both a cognitive and a functional or global assessment 
scale. The measures of neuropsychological performance are sensitive, 
and on their own, these measures may not be clinically meaningful. 
Thus, co-primary endpoints are intended to ensure that the drug's 
observed effect on cognition is clinically meaningful. Before the onset 
of overt dementia, however, milder functional and/or global impairments 
are more challenging to assess accurately, especially for patients 
early in the spectrum of the illness. Accordingly, as expressed, in 
FDA's 2013 draft guidance on AD, openness to the use of a single 
primary endpoint, such as the Clinical Dementia Rating--Sum of Boxes 
score, that integrates both cognition and function in a single 
assessment. Additional assessments may also be appropriate for use in 
clinical trials, and FDA is open to considering other assessments that 
integrate both cognition and function.
    Question. From your new position as FDA Commissioner, do you 
believe the co-primary endpoint standard is appropriate? Have you 
asked, or will you ask your staff to look into this issue?
    Answer. As noted in response to Question #1, and as stated in FDA's 
2013 draft guidance on Alzheimer's disease, clinical trials in the 
dementia stage of AD should use a co-primary outcome measure approach 
in which a drug demonstrates efficacy on both a cognitive and a 
functional or global assessment scale. The measures of 
neuropsychological performance are sensitive, and on their own, these 
measures may not be clinically meaningful. Thus, co-primary endpoints 
are intended to ensure that the drug's observed effect on cognition is 
clinically meaningful. Before the onset of overt dementia, however, 
milder functional and/or global impairments are more challenging to 
assess accurately, especially for patients early in the spectrum of the 
illness.
    Accordingly, as expressed, in FDA's 2013 draft guidance on 
Alzheimer's disease, openness to the use of a single primary endpoint, 
such as the Clinical Dementia Rating--Sum of Boxes score, that 
integrates both cognition and function in a single assessment. 
Additional assessments may also be appropriate for use in clinical 
trials, and FDA is open to considering other assessments that integrate 
both cognition and function. The Agency is prepared to approve new 
treatments for Alzheimer's disease that are supported by substantial 
evidence of effectiveness on clinically meaningful outcomes. FDA works 
closely with drug sponsors to help them develop this evidence.
                                opioids
    Question. The opioid epidemic continues to plague this country. 
Both the CDC and World Health Organization recommend treatment for pain 
starting with non-opioids prescription medication before using opioids. 
What is FDA doing to ensure non-opioid prescriptions receive a 
prioritized and timely review?
    Answer. FDA's prescription drug efforts are part of a larger, 
coordinated Departmental strategy around addressing the opioid crisis. 
HHS strategy includes five priority areas:
  --Improving access to prevention, treatment, and recovery services, 
        including the full range of medication-assisted treatments;
  --Targeting availability and distribution of overdose-reversing 
        drugs;
  --Strengthening our understanding of the crisis through better public 
        health data and reporting;
  --Providing support for cutting edge research on pain and addiction; 
        and
  --Advancing better practices for pain management.
    The FDA continues to support efforts to better understand the 
treatment of pain, especially as it relates to balancing the need to 
effectively treat pain with the public health crisis related to opioid 
use disorder and overdose. Currently, there are FDA-approved drug 
treatment options, opioids and non-opioids, available for the 
management of pain.
    FDA has a number of programs, such as Fast Track and Breakthrough 
Designation, which are intended to facilitate the development and 
expedite the review of products that, for example, meet unmet medical 
needs. Novel non-opioid medications with the potential to provide pain 
relief in situations in which opioids often are used could be 
appropriate candidates for such programs. FDA is also working with the 
National Institute on Drug Abuse to encourage the development of non-
addictive pain medication.
    Question. How many non-opioid treatments are currently under review 
by FDA and are scheduled for review in the next 12-24 months?
    Answer. Although FDA is unable to discuss the substance of any 
matters that may be pending before the Agency, FDA can assure you that 
the Agency understands the value in and supports the development of new 
treatment options for pain. In fact, there are a number of novel non-
opioid products under development.
    Question. What if anything can be done by FDA to ensure more 
prescription non-opioid medications are available to treat pain?
    Answer. Currently, both opioid and non-opioid FDA-approved drugs 
are available for the management of pain. There are also medical 
devices indicated to treat specific types of pain. FDA understands the 
value in new treatment options for pain, and continues to work with the 
medical device and drug industries to explore new options for patients 
in pain, especially options that have improved safety profiles and are 
less likely to result in addiction or abuse. FDA has a number of 
programs, such as Fast Track and Breakthrough Designation, which are 
intended to facilitate the development and expedite the review of 
products that, for example, meet unmet medical needs. Novel non-opioid 
medications with the potential to provide effective pain relief in 
situations in which opioids often are used could be appropriate 
candidates for such programs.
    FDA is also working with the National Institutes of Health's (NIH) 
National Institute on Drug Abuse to encourage the development of non-
opioid pain medications, and has been involved in discussions with NIH 
in a series of meetings to facilitate development of non-addictive pain 
treatment. In addition, FDA looks forward to a future in which 
substantially all opioid medications are less susceptible to abuse than 
the conventional formulations that dominate the market today.
                         antibiotic resistance
    Question. I'm concerned about superbugs--the reports coming out of 
Asia and other countries is that much of their food-producing livestock 
is ridden with multi-drug resistant bacteria. FDA and our farmers have 
eliminated high-value antibiotics from our farm systems, but others 
haven't done much at all. There's a lot we can do to deter the 
development of antibacterial resistance, but it seems the cat is out of 
the bag and we really need a strong and ongoing pipeline of new drugs.
    What can we do to develop the next generation of antibiotics?
    Answer. Antimicrobial resistance (AMR) is one of the most serious 
threats to global health in this century. FDA has taken a leading role 
in addressing this critical threat by working with key stakeholders to 
identify new approaches to stimulate antibacterial research and 
development, including by streamlining clinical trial designs; 
enhancing surveillance through systems such as the National 
Antimicrobial Resistance Monitoring System; and actively participating 
in global efforts to reduce resistance.
    Recent FDA efforts include administering the incentives available 
to sponsors under the Generating Antibiotic Incentives Now (GAIN) Act. 
FDA has granted 136 Qualified Infectious Disease Product (QIDP) 
designations, including approximately 71 designations for novel drugs. 
FDA has approved ten drug products with QIDP designation. Moreover, FDA 
has written, reviewed and revised a number of guidance documents to 
provide clarity and predictability on recommended trial designs and 
development pathways. The Agency has also engaged the scientific 
community through public meetings, partnerships, and regulatory science 
research.
    Efforts to strengthen the antibacterial drug pipeline must also 
address significant economic and scientific challenges. The President's 
Advisory Council on Combatting Antibiotic-Resistant Bacteria (PACCARB) 
recently finalized their report with recommendations addressed to 
Secretary Price for incentivizing the development of vaccines, 
diagnostics, and therapeutics/anti-infectives for both human and animal 
health to address the issues surrounding antibiotic resistance. HHS' 
Biomedical Advanced Research and Development Authority (BARDA) and the 
National Institute of Allergy and Infectious Diseases (NIAID) have 
helped to launch important, new efforts in this space, such as the 
Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator 
(CARB-X), a public-private partnership that provides funding to 
accelerate the preclinical discovery and development of antibacterial 
drugs.
    As you noted, FDA has been actively working with various 
stakeholders, in the animal drug context, to implement judicious use 
policies to promote antimicrobial stewardship. Such efforts include 
working with animal drug sponsors to transition medically important 
antimicrobials used in the feed or water of food-producing animals to a 
marketing status requiring veterinary oversight, and eliminating the 
use of these products for production (such as growth promotion) 
purposes. Implementation of this transition process was completed in 
January 2017 marking an important step forward in promoting 
antimicrobial stewardship in animal agriculture.
    In addition, strengthening the pipeline for antimicrobials or 
alternatives to antimicrobials intended for use in food-producing 
animals by developing appropriate incentives (including public-private 
partnerships) to spur drug and vaccine development is also important to 
ensure antimicrobial therapy is available to meet the current and 
future needs of these animals and to provide a safe, wholesome food 
supply.
                     foreign high risk inspections
    Question. Over the past several years the Committee has provided 
FDA with additional resources to develop a targeted, risk-based, and 
efficient inspection model for high-risk establishments for onsite 
verifications.
    Given the challenges of expanded geography, constantly expanding 
inventory of foreign exporters, and finite budgetary resources, how 
will FDA leverage third party site verification services to complement 
FDA foreign site planning and inspection activities?
    Answer. In fiscal year 2016, FDA spent the bulk of the money 
provided to Office of Global Regulatory Operations and Policy (GO) on 
commercial foreign onsite verification reviews in support of expanding 
global coverage. FDA contracted with Dun & Bradstreet (D&B) to provide 
site verification information on specific facilities. D&B performed 
site verifications across all of the regulated commodities. With 
respect to medical products, the remaining funds were used in support 
of the pharmaceutical GMP mutual recognition initiative and enhancing 
the Center for Drug Evaluation and Research (CDER) site selection 
model. Regarding foods, the remaining funds were used to enhance the 
process and consolidate the responsibilities of foreign food inspection 
planning in the Office of Regulatory Affairs.
    In fiscal year 2017, Office of Global Regulatory Operations and 
Policy, (GO) expanded the number of foreign onsite verifications and 
facility data delivered through D&B for foreign medical device and food 
establishments. These specific commodities were chosen due to the value 
and impact that commercial onsite verifications provide these programs. 
For the pharmaceutical program, GO has worked with CDER to issue grants 
for analysis that will support the development of quality scorecards 
for pharmaceutical facilities and products. A quantitative 
characterization of the state of quality can enhance oversight by 
improving the site selection model's identification of high-risk 
foreign facilities.
    As part of the reauthorization of the Generic Drug User Fee 
Amendments (GDUFA) in the FDA Reauthorization Act (FDARA), FDA 
committed to working on a guidance explaining the risk-based site 
selection model as well as outreach activities to better inform foreign 
regulatory counterparts about our model.
                                 ______
                                 
             Questions Submitted by Senator Mitch McConnell
                                opioids
    Question. Given your public statements, it seems that the FDA and 
Congress agree that combating the opioid epidemic remains a top 
priority. How do you plan to coordinate FDA's prescription drug abuse 
efforts with other agencies? Specifically, how will the FDA work with 
the NIH to accelerate innovative cures and non-opioid pain therapies to 
the market faster?
    Answer. FDA understands the value in and supports the development 
of new treatment options for pain, and is committed to continue working 
with our colleagues at the National Institutes of Health, including the 
National Institute on Drug Abuse, and other government agencies to 
explore new options for patients in pain, especially options that are 
not addictive. Since June 2017, FDA has collaborated with NIH via a 
series of three meetings to facilitate development of non-addictive 
pain treatment and treatment for opioid addiction and overdose 
prevention/reversal. Also, in May 2017, FDA hosted a public meeting on 
pain management with participation from many Federal agencies to 
discuss, among other things, non-addictive pain treatment options. FDA 
notes that the Agency's prescription drug efforts are part of a larger, 
coordinated Departmental strategy around addressing the opioid crisis.
    Question. The FDA Opioid Action plan issued in February 2016 
included a commitment to collaborate with advisory committees. FDA 
stated that after considering advisory committee recommendations and 
reviewing existing requirements, the agency was inviting affected 
opioid manufacturers to a meeting to inform them of the agency's 
intention to require a Risk Evaluation and Mitigation Strategy (REMS) 
for immediate-release (IR) opioids. This meeting was held on January 
25, 2017. Where is the agency in the process of expanding REMS to 
include IR opioids? What steps has the agency been taking to consult 
and work with stakeholders on the expansion of the REMS?
    Answer. On July 10, 2017, FDA announced that it intends to update 
and modify the existing Risk Evaluation and Mitigation Strategy (REMS) 
for extended-release/long-acting (ER/LA) opioid analgesics, and for the 
first time, to include immediate-release (IR) opioid analgesic products 
in the modified REMS program. FDA expects this action to take place in 
the coming weeks. The modified REMS is expected to include revisions to 
the existing FDA Blueprint for prescriber education which describes the 
content that must be covered in an educational program for it to be 
considered REMS-compliant.
    FDA sought input from relevant stakeholders in a variety of 
settings on a number of issues related to the ER/LA Opioid Analgesic 
REMS, including at an Advisory Committee meeting in May 2016, during a 
public workshop in May 2017, and through establishment of a docket 
announced in a Federal Register notice in May 2017.
    On May 3 and 4, 2016, FDA convened a joint meeting of the Drug 
Safety and Risk Management (DSaRM) Advisory Committee and the 
Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) to 
discuss whether the ER/LA Opioid Analgesics REMS assures safe use, 
whether it is unduly burdensome to patient access to the drugs, and 
whether it (to the extent practicable) minimizes the burden to the 
healthcare delivery system. FDA also sought input on possible 
modifications to the ER/LA Opioid Analgesic REMS, including expansion 
of the scope and content of prescriber training and expansion of the 
REMS program to include immediate-release (IR) opioid analgesics.
    On May 9 and 10, 2017, FDA held a public workshop to seek input on 
how to best support prescriber and other healthcare provider education 
on appropriate pain management and opioid analgesic prescribing. This 
meeting convened government experts and representatives from state 
licensing boards, professional associations, healthcare systems, 
patient groups, and other stakeholder groups involved in the challenges 
of improving pain management while addressing the opioid epidemic.
    In addition to the panel discussions at the meeting, FDA is also 
considering comments submitted to two public dockets which closed on 
July 10, 2017. The first docket asked for public comment on how to best 
support prescriber and other Health Care Provider education on 
appropriate pain management and opioid analgesic prescribing. FDA has 
received more than 250 comments to the docket. The second docket under 
review considers modifications to the existing FDA Blueprint for 
Prescriber Education for Extended-Release and Long-Acting Opioid 
Analgesics in light of recommendations from the May 2016 Advisory 
Committee meeting. The draft revisions to the Blueprint would broaden 
the Blueprint to incorporate information on pain management, including 
the principles of acute and chronic pain management, non-pharmacologic 
treatments for pain, and pharmacologic treatments for pain (both non-
opioid analgesic and opioid analgesic). More than 680 comments were 
submitted to this docket.
    Question. Also included in the action plan was the commitment to 
expand access to abuse deterrent formulations (ADF) to discourage 
abuse. Beyond the FDA's guidance issued in April 2015 related to the 
types of studies to assess abuse deterrence efficacy and suggested 
labeling, what other actions has the FDA taken to expand access to ADF 
or assist manufactures in the development and subsequent approval 
process for bringing these formulations to market?
    Answer. FDA's support of opioid products with abuse-deterrent 
formulations (ADF) is one of a number of steps to which FDA has 
committed which is focused on policies aimed at reversing the opioid 
epidemic while still providing patients in pain access to effective 
relief. To date, the Agency has approved ten opioids with labeling 
describing properties expected to deter (though not completely prevent) 
one or more routes of abuse. The 2015 final guidance for industry, 
Abuse-Deterrent Opioids--Evaluation and Labeling, provides information 
on abuse-deterrent formulations for applicants seeking such approval.
    Given the lower cost, on average, of generic products, the 
availability of generic ADFs is an important step toward balancing the 
need to reduce opioid abuse with helping to ensure access to 
appropriate treatment for patients in pain. To that end, in March 2016, 
FDA issued draft guidance entitled General Principles for Evaluating 
the Abuse Deterrence of Generic Solid Oral Opioid Drug Products. The 
draft guidance, when finalized, will provide recommendations regarding 
studies that should be conducted to show that a generic opioid is no 
less abuse-deterrent than a brand name opioid with abuse-deterrent 
labeling with respect to all potential routes of abuse.
    FDA continues to engage advisory committees, as appropriate, to 
provide advice on novel or challenging issues that arise in connection 
with the development and evaluation of abuse-deterrent opioids. In July 
2017, FDA held a public workshop with expert panel members and 
interested stakeholders about the challenges in using currently 
available data and methods for assessing the impact of opioid 
formulations with properties designed to deter abuse on opioid misuse, 
abuse, addiction, overdose, and death in the post-market setting.
    FDA remains committed to working with sponsors and other 
stakeholders to support the development of and access to opioid 
formulations with properties that could lead to a meaningful reduction 
in prescription opioids misuse and abuse compared to the conventional 
formulations.
    Question. FDA requires manufacturers of extended release (ER/LA) 
opioids to make available REMS-compliant training for prescribers of 
ER/LA opioid analgesics, yet physician participation in these training 
programs is voluntary. At the same time, FDA is holding manufacturers 
of ER/LA opioids accountable to industry-negotiated performance goals 
that manufacturers are struggling to meet. As part of the REMS, the ER/
LA opioid manufacturers agreed to specific performance goals amounting 
to 160,000 active prescriber participants in the voluntary REMS-
compliant training programs by March 2016. However, the most recent 
report showed that only 66,000 prescribers completed training, meaning 
the participation rate amounted to 41 percent of their goal. Beyond 
updating the ER/LA opioid analgesics REMS, how will the FDA encourage 
prescribers of these drugs to participate in the training?
    Answer. Under the current ER/LA REMS, companies are required to 
make training available to healthcare providers that prescribe 
extended-release/long-acting (ER/LA) opioid analgesics. The companies 
may meet this requirement by working with accredited continuing 
education providers who offer training to prescribers; however, 
prescribers are not currently required to complete this training in 
order to prescribe ER/LA opioid analgesics.
    The Agency has been carefully evaluating existing requirements and 
assessments of the ER/LA Opioid Analgesic REMS, specifically how 
prescribers are trained on the use of opioids and management of pain. 
To make sure providers are properly informed about suitable prescribing 
and the risks and benefits associated with opioid drugs, FDA intends to 
update the existing REMS on ER/LA opioid analgesics, and for the first 
time, extend these same regulatory requirements to the manufacturers of 
immediate release (IR) opioid analgesic products. The new training will 
be aimed at making sure providers who write prescriptions for the IR 
opioids are doing so for properly indicated patients, and under 
appropriate clinical circumstances. In addition to expanding the 
training to include more healthcare providers, the training will also 
include expanded information on pain, broad principles of acute and 
chronic pain management, pharmacologic treatments other than opioids, 
and the use of other therapies for pain that do not involve medication.
    FDA agrees that all healthcare providers involved in the management 
of pain should be educated about the safe use of opioids. Based on the 
feedback the Agency has received from two public meetings over the past 
year, FDA is actively exploring the question of whether, in the future, 
there should be mandatory provider education and how to operationalize 
such a requirement. As part of the Opioid Policy Steering Committee's 
responsibilities, FDA will be reviewing the data necessary to 
understand the most effective way to move forward.
    Question. In 2011, FDA issued an Advisory to Drug Manufacturers 
regarding glass contamination of injectable drugs and recommended 
specific actions the industry could voluntarily take to address the 
problem. Does the current administration have plans to update the 
Advisory?
    Answer. FDA has met with manufacturers who are working to develop 
glass medical products to address quality issues with respect to glass 
product design and manufacturing for glass products intended for 
injectable drugs. The Agency has also initiated a study comparing 
various types of glass products intended for use in injectable drug 
products and expects to begin analyzing the results of that study by 
the end of the year. Additionally, industry experts have initiated 
studies of new types of glass products to determine superiority to 
current products and suitability with actual drug product formulations. 
FDA will use the analysis of its own study, as well as discussions with 
industry and any other appropriate available data, when considering 
whether to update the 2011 advisory.
           electronic distribution of prescribing information
    Question. Congress has prevented the implementation of the 2014 
Obama administration proposed rule titled the ``Electronic Distribution 
of Prescribing Information for Human Prescription Drugs Including 
Biological Products.'' Given Congress's explicit concerns, does the 
current administration have plans to revise or withdraw this rule?
    Answer. FDA is continuing to review its options with regard to the 
above rulemaking in light of Sec. 734 of Division A, Title VII, of the 
Consolidated Appropriations Act, 2017, which states:

        SEC. 734. None of the funds made available by this Act may be 
        used to propose, promulgate, or implement any rule, or take any 
        other action with respect to, allowing or requiring information 
        intended for a prescribing healthcare professional, in the case 
        of a drug or biological product subject to section 503(b)(1) of 
        the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353(b)(1)), 
        to be distributed to such professional electronically (in lieu 
        of in paper form) unless and until a Federal law is enacted to 
        allow or require such distribution.
                                 ______
                                 
                Questions Submitted by Senator Roy Blunt
                            drug review time

    Question. It has come to my attention that the FDA median new drug 
application (NDA) review times vary widely--from 175 days for oncology 
and anti-viral drugs to 375 and 400 days for neurology and psychiatry 
drugs. In fact, most NDAs have a median review time of more than 300 
days. Patient needs are not being met with such long review times. 
Could you please provide me the following:
    Compare each division's interpretation and implementation of 
authority under the Food and Drug Administration Safety and Innovation 
Act to exercise flexibility in meeting the approval standard regarding 
unmet medical need, including under the accelerated approval pathway.
    Answer. CDER has a longstanding commitment to regulatory 
flexibility regarding the evidence required to demonstrate that the 
approval standard has been met for products that are intended to treat 
serious or life-threatening diseases, especially where no satisfactory 
alternative therapy exists. This regulatory flexibility extends 
throughout the Center and is stated in FDA's regulations at 21 CFR 
312.80--Subpart E.
    FDA instituted its Accelerated Approval Program--one of the 
Agency's expedited programs--to allow for earlier approval of drugs 
that treat serious conditions and that would provide a meaningful 
advantage over available therapies. Provisions of the Food and Drug 
Administration Safety and Innovation Act of 2012 facilitate somewhat 
broader use of accelerated approval to expedite patients' access to 
important treatments for serious conditions.
    Divisions across CDER exercise flexibility in determining whether 
drugs meet approval standards (full or accelerated) based on whether 
available data indicate that a drug's benefits outweigh the risks for 
its intended use(s). Medical need, available alternatives, nature of 
the disease, and patient input are among the factors considered in 
assessing benefit and risk. Average review times depend on multiple 
factors such as the amount and quality of data provided by the 
applicant to CDER, available data (including from natural history 
studies, if applicable) about the disease or condition to be treated, 
and the number of applications under review at the time. Depending on 
the drug under consideration, review teams may work across divisions, 
leveraging CDER resources to promote collaboration and innovation in 
the regulatory process.
    Question. Identify policies, practices and procedures, staffing and 
resource issues, division culture and precedents, and other factors 
which cause or contribute to the differences in review times among 
divisions for both priority review and standard review New Drug 
Applications.
    Answer. Differences in review and approval times between CDER 
divisions can be the result of many factors such as the quality of 
available data (which depends in part on the rigor of study design) 
provided to support an application, complexity of the disease, whether 
other effective therapies are available, and the amount and quality of 
epidemiologic and natural history data about the disease. All divisions 
within CDER are fully focused on our mission of protecting and 
promoting public health by helping to ensure that human drugs are safe 
and effective, meet established quality standards, and are available to 
patients. As such, division culture places these goals as paramount 
when reviewing applications, including those being considered under the 
Agency's expedited review programs.
    Question. Make recommendations for actions that could be taken to 
materially reduce differences in New Drug Application review times 
among Food and Drug Administration divisions for both priority reviews 
and standard reviews and shall include recommendations concerning New 
Drug Applications reviewed under the accelerated approval pathway.
    Answer. By leveraging FDA's statutory mandates, the Agency is 
working to reduce review times by improving processes and gaining 
efficiencies to the greatest extent possible. This includes helping to 
reduce uncertainty in drug development by encouraging sponsors to 
contact the Agency early and often, especially for those products being 
developed under expedited review programs. Streamlining clinical 
trials, integrating patient voice throughout the regulatory process 
based on successful models of participation, and promoting greater 
preparedness by establishing nimble approaches to address novel and 
emerging public health threats will help Americans get better products, 
faster.
    FDA is embarking on PDUFA VI, which provides resources for the 
highly successful, and resource-intensive, breakthrough therapy program 
and streamlines the review of drug/device or biologic/device 
combination products. As a result, the Agency suggests that applicants 
with products designated as ``breakthrough therapies'' engage in early, 
frequent, and meaningful communications with the Agency to better 
enable promising safe and effective products to reach patients faster. 
Further, PDUFA VI emphasizes patient-focused drug development efforts 
through a more systematic, science-based approach to collecting 
meaningful patient input. Review times across CDER divisions are likely 
to be enhanced by advancing drug development tools, including biomarker 
qualification, and increaseing understanding of how ``real-world 
evidence'' can be generated and used in regulatory decisionmaking. 
Pilot programs to explore novel approaches to the design of complex 
clinical trials and the application of advanced modeling techniques to 
preclinical and clinical data are also important options to consider 
for reducing review times.
                            fda review time
    Question. I am concerned about the cost to the healthcare system 
and confusion to consumers and physicians due to Polyethylene Glycol 
(Rx PEG) 3350 Abbreviated New Drug Applications remaining on the market 
when there is a proven over-the-counter drug available. My 
understanding is that the FDA has been looking into this issue for more 
than 10 years to confirm that this is a contravention of the Durham 
Humphrey Amendments to the Food, Drug, and Cosmetic Act.
    Can you explain to me why this review has taken so long and appears 
to be ongoing without resolution?
    Answer. The distinction between prescription and OTC drugs was 
codified by the Durham-Humphrey Amendments, which were enacted in order 
to address the marketplace confusion that arose from the simultaneous 
marketing of identical or nearly identical drugs on a prescription and 
OTC basis for identical or equivalent uses (Public Law 82-215, 65 Stat. 
648 (1951). See, e.g., H.R. Rep. No. 82-700, at 5 (1951). The Agency's 
detailed rationale for this action is set forth in the Notice of 
Opportunity for Hearing published at 73 F.R. 63491 (Oct 24, 2008).
    The sponsors of the abbreviated new drug applications (ANDAs) for 
prescription PEG 3350 products refused the FDA's request that they 
withdraw these products voluntarily. As a result, the Notice of 
Opportunity for Hearing was issued, which was followed in May of 2014 
by a Draft Proposed Order. Following issuance of the Draft Proposed 
Order, several ANDA holders for prescription PEG 3350 drugs submitted 
responses asserting that there is a genuine and substantial issue of 
material fact that necessitates a hearing.
    Consistent with 21 CFR Part 12 and 314.200, the Office of the 
Commissioner must review the requests for hearing, the Draft Proposed 
Order, and the ANDA holder's objections to the proposed order, and must 
determine whether to grant a hearing or enter a final order withdrawing 
approval of the ANDAs. The timeframe will depend in part on whether a 
hearing is granted or denied. The Office of the Commissioner is 
actively considering the matter at this time. The docket for this 
matter is available at regulations.gov, Docket No. FDA-2008-N-0549.
    Question. How much time is needed until FDA can come to a 
conclusion on this issue?
    Answer. The sponsors of the abbreviated new drug applications 
(ANDAs) for prescription PEG 3350 products refused the FDA's request 
that they withdraw these products voluntarily. As a result, a Notice of 
Opportunity for Hearing was issued, which was followed in May of 2014 
by a Draft Proposed Order. Following issuance of the Draft Proposed 
Order, several ANDA holders for prescription PEG 3350 drugs submitted 
responses asserting that there is a genuine and substantial issue of 
material fact that necessitates a hearing.
    Consistent with 21 CFR Part 12 and 314.200, the Office of the 
Commissioner must review the requests for hearing, the Draft Proposed 
Order, and the ANDA holder's objections to the proposed order, and must 
determine whether to grant a hearing or enter a final order withdrawing 
approval of the ANDAs. The timeframe will depend in part on whether a 
hearing is granted or denied. The Office of the Commissioner is 
actively considering the matter at this time. The docket for this 
matter is available at regulations.gov, Docket No. FDA-2008-N-0549.
                                 ______
                                 
            Questions Submitted by Senator Dianne Feinstein
                              antibiotics
    Question. I was encouraged that the FDA recently announced the full 
implementation of Guidance for Industry #213. This is an important step 
in maintaining the effectiveness of antibiotics by ensuring the 
judicious use of antibiotics in food-producing animals and limiting the 
use of antibiotics to situations that are necessary to protect animal 
health.
    However, I remain concerned by the significant number of antibiotic 
labels that lack defined durations of use, defined dosages, or that 
could allow usage under the previous label of ``growth promotion''.
    I understand the FDA has collected comments through the Federal 
Register on this issue, but what is the timeline as well as the 
specific policy actions the FDA plans on taking regarding these 
problematic labels?
    Answer. FDA agrees that the full implementation of Guidance for 
Industry #213 in January 2017 is a critical and important step forward 
to foster the judicious use of antimicrobial drugs and curb 
antimicrobial resistance. FDA has and continues to express its 
appreciation for the cooperation of the animal pharmaceutical industry 
for meeting its commitment to fully align all affected products with 
the GFI #213 recommendations. FDA recognizes that additional work is 
needed to ensure that the labeled use conditions of all medically 
important antimicrobial drug products are aligned with the principles 
of judicious use. As you noted, one issue of concern is the fact that 
some medically important antimicrobial drug products approved for use 
in animal feed or water have at least one therapeutic indication 
without a defined duration of use.
    While this remains a concern, it is important to note that as of 
January 2017 it is no longer legal to use such feed or water 
antimicrobial products for production (such as growth promotion) 
purposes and their use must be under the authorization of a licensed 
veterinarian. FDA believes that veterinarian oversight plays a critical 
role in ensuring that medically important antimicrobials are used 
judiciously.
    In September 2016, FDA published a Federal Register notice 
requesting comment from the public on this duration of use issue. A key 
objective in seeking public comment is to optimize the use of medically 
important antimicrobials by using a dosage strategy that maximizes drug 
effectiveness, minimizes target animal toxicity, and has an 
appropriately targeted duration of use. FDA received numerous 
substantive comments on this issue and is still in the process of 
analyzing these comments. Once FDA has finished analyzing the comments, 
the Agency will develop a timeline with proposed actions for addressing 
this issue. It remains an Agency priority to foster stewardship of 
medically important antimicrobial drugs in food-producing animals and 
help preserve the effectiveness of these antimicrobials in animal and 
human medicine.
    Question. How will the FDA continue to improve its collection of 
data related to antibiotic use on farms and large production 
facilities?
    Answer. Having access to better data on antimicrobial use and 
resistance is critical for assessing the impact of actions already 
implemented and for guiding additional steps for fostering judicious 
antimicrobial use in veterinary settings. FDA is currently working 
closely with the U.S. Department of Agriculture (USDA) to coordinate 
data-collection activities across agencies. FDA experts are working 
with experts at the USDA/Animal and Plant Health Inspection Service 
(APHIS) Center for Epidemiology and Animal Health on strategies for 
collecting, analyzing, and reporting data on antimicrobial use. FDA has 
taken a number of additional actions to enhance data on antimicrobial 
use and resistance. For example, in September 2015, FDA, in 
collaboration with the USDA and the Centers for Disease Control and 
Prevention (CDC), held a public meeting to obtain input on strategies 
for enhancing the collection of antimicrobial drug use and resistance 
data. Moreover, in May 2016, FDA issued a final rule revising the 
annual reporting requirements for antimicrobials sold or distributed 
for use in food-producing animals to require species-specific estimates 
of antimicrobial sales or distribution data for major food animal 
species.
    In August 2016, FDA funded two cooperative agreements with 
university researchers to develop and pilot methodologies to collect 
detailed information on antibiotic use practices in cattle, swine, 
chickens, and turkeys. These ongoing projects are expected to provide 
important information on data collection methodologies and will help 
support ongoing efforts at USDA to optimize long-term strategies for 
collecting and reporting such data. In August 2017, FDA published a 
proposed approach for using a biomass denominator to adjust annual data 
on the amount of antimicrobials sold or distributed for use in food-
producing animals in the U.S. to take into account the size of animal 
populations. This adjusted estimate will provide insight into broad 
shifts in the amount of antimicrobials sold for use in food-producing 
animals. FDA is inviting comment on the methodology and utility of this 
type of data analysis.
    Question. Will the FDA continue to enhance coordination with the 
Department of Agriculture for on-farm data collection?
    Answer. Given the many challenges associated with collecting 
nationally representative on-farm data on antimicrobial use across the 
various food animal production sectors, FDA believes it is essential to 
continue to work in close collaboration with USDA on this issue. FDA is 
currently working closely with USDA to coordinate data collection 
activities across agencies. FDA experts are working with experts at the 
USDA/APHIS Center for Epidemiology and Animal Health on strategies for 
collecting, analyzing, and reporting data on antimicrobial use. 
Specifically, USDA/APHIS's National Animal Health Monitoring System 
provides essential data collection infrastructure for antibiotic-use 
practices in livestock and poultry operations and zoonotic pathogen 
infection in U.S. food-producing animals via its established survey 
cycle and in-plant biological survey capability. Having access to 
better data on antimicrobial use and resistance is critical for 
assessing the impact of actions already implemented and for guiding 
additional steps for fostering judicious antimicrobial use in 
veterinary settings. In support of FDA's ongoing work with USDA on this 
issue, FDA has taken a number of additional actions to enhance data on 
antimicrobial use and resistance. For example, in September 2015, FDA, 
in collaboration with the USDA and CDC, held a public meeting to obtain 
input on strategies for enhancing the collection of antimicrobial drug 
use and resistance data.
    In August 2016, FDA funded two cooperative agreements with 
university researchers to develop and pilot methodologies to collect 
detailed information on antibiotic drug use in cattle, swine, chickens, 
and turkeys. These ongoing projects are expected to provide important 
information on data collection methodologies and will help support 
ongoing efforts at USDA to optimize long-term strategies for collecting 
and reporting such data. Moreover, in August 2017, FDA published a 
proposed approach for using a biomass denominator to adjust annual data 
on the amount of antimicrobials sold or distributed for use in food-
producing animals in the U.S. to take into account the size of animal 
populations. FDA's methodology relies on USDA data to estimate the 
number of animals in a particular U.S. livestock population, including 
annual totals of animals slaughtered and annual totals of livestock 
imported into or exported from the U.S. This adjusted estimate will 
provide insight into broad shifts in the amount of antimicrobials sold 
for use in food-producing animals. FDA is inviting comment on the 
methodology and utility of this type of data analysis.
    Question. Please provide an update on the progress of collecting 
species-specific data for the end-of-year use summary.
    Answer. In May 2016, FDA issued a final rule revising the annual 
reporting requirements for drug sponsors of antimicrobials sold or 
distributed for use in food-producing animals to obtain estimates of 
sales by major food-producing species (cattle, swine, chickens, and 
turkeys). The additional data will improve our understanding of how 
antimicrobials are sold or distributed for use in major food-producing 
species and help further target efforts to ensure judicious use of 
medically important antimicrobials.
    Section 105 of the Animal Drug User Fee Amendments of 2008 (ADUFA 
105) requires antimicrobial drug sponsors to annually report to FDA the 
amount of all antimicrobial drugs they sell and distribute for use in 
food-producing animals. ADUFA 105 also requires that FDA issue annual 
summary reports of these sales and distribution data collected from 
sponsors. The law further requires that these data be reported out by 
antimicrobial drug class. To report summary data in a manner protective 
of both national security and confidential business information, only 
those antimicrobial drug classes and other categories with three or 
more distinct sponsors of approved and actively marketed animal drug 
products are independently reported.
    FDA is currently reviewing the sales and distribution data 
submitted for the 2016 reporting year. The first annual summary report 
containing estimated species information is expected to publish by 
December 31, 2017.
    Question. Please provide an update on the National Action Plan for 
Combating Antibiotic-Resistant Bacteria.
    Answer. Along with their Federal partners, FDA continues to 
implement the National Action Plan for Combating Antibiotic-Resistant 
Bacteria and to support the ongoing work of the Presidential Advisory 
Council on Combating Antibiotic-Resistant Bacteria (PACCARB). An 
assessment of progress being made under the National Action Plan was 
published by the PACCARB in March 2016. The full report is available at 
https://www.hhs.gov/sites/default/files/paccarb-final-report-
03312016.pdf. More recently, FDA, along with partner agencies, provided 
an update to their Year 2 milestones and accomplishments in the 
National Action Plan to the council members at the PACCARB's September 
13-14 public meeting.
    FDA is committed to advancing efforts to foster the judicious use 
of antimicrobial drugs in animals. The Agency has issued a number of 
important guidance documents and regulations to support its judicious 
use strategy and has actively engaged in outreach efforts to support 
effective implementation.
                      diversity in clinical trials
    Question. Section 907 of the 2012 Food and Drug Administration 
Safety and Innovation Act directed FDA to take a closer look at the 
inclusion and analysis of demographic subgroups in applications for 
drugs, biologics, and devices--including by sex, race and ethnicity, 
and age--and issue a report on findings.
    The report that was issued was followed by an ``Action Plan to 
Enhance the Collection and Availability of Subgroup Data'', which 
included 27 responsive and pragmatic actions, which fall under three 
overarching priorities: improving the completeness and quality of 
demographic subgroup data collection, reporting and analysis; 
identifying barriers to subgroup enrollment in clinical trials and 
employing strategies to encourage greater participation; and making 
demographic subgroup data more available and transparent.
    Please provide an update on the implementation of this Action Plan.
    Answer. In February 2016, FDA hosted the public meeting ``Enhancing 
the Collection, Analysis, and Availability on Demographic Subgroup 
Data,'' to provide a public update on implementation of the Action Plan 
(AP). FDA has completed implementation on 26 of 27 action items in the 
AP. Highlights are as follows:
    To address priority I, data quality, FDA authored two guidance 
documents: ``Collection of Race and Ethnicity Data in Clinical Trials'' 
and ``Evaluation and Reporting of Age, Race, and Ethnicity Data in 
Medical Device Clinical Studies.'' Both provide clear and detailed 
guidance for regulated industry on clinical trial inclusion data 
matters. FDA has updated its MedWatch forms for adverse events 
reporting to include fields for race and ethnicity. FDA released its 
``Women's Health Research Roadmap'' to better coordinate women's health 
research across the Agency.
    To address priority II, participation, FDA declared 2016 the ``Year 
of Diversity in Clinical Trials'' to make a strong push to promote 
representation of diverse groups in clinical trials. Activities like 
the Minorities in Clinical Trials Campaign and the Diverse Women in 
Clinical Trials Initiative included public service announcements, 
educational materials, webinars, and print/digital outreach. Two public 
stakeholder meetings were held:
    In April 2015, the Institute of Medicine and FDA hosted a joint 
meeting titled ``Strategies for Ensuring Diversity, Inclusion, and 
Meaningful Participation in Clinical Trials: A Workshop.'' 100+ 
participants attended and a publication detailing the proceedings was 
released in April 2016. In December 2015, FDA and Johns Hopkins held a 
joint workshop titled ``Assessing Safety and Efficacy for a Diverse 
Population'' to advance understanding of the importance of clinical 
trial diversity.
    To address priority III, data transparency, FDA launched Drug 
Trials Snapshots (DTS). DTS publishes in clear, consumer-friendly plain 
language demographic data from clinical trials that supported FDA 
approval of new molecular entities and original biologics. 100+ DTSs 
have been published.
                        safety of imported food
    Question. The United States imports food products from more than 
200 countries and territories through over 300 U.S. ports. Food imports 
have more than doubled in the past decade. As the volume of imports 
grows, so does the potential for foodborne illness resulting from 
imported food.
    FDA has bilateral and multilateral food safety-related arrangements 
and agreements with numerous countries to ensure the safety of imported 
food, and I understand that FDA is also exploring other ways to 
leverage the work of the food safety authorities in other countries, in 
accordance with section 305 of the 2011 FDA Food Safety Modernization 
Act (FSMA). One approach that FDA has been testing as part of this 
effort is referred to as ``systems recognition,'' under which FDA would 
review certain other countries' food safety systems to ensure that 
those systems are comparable to that of the United States.
    How do FDA's agreements with other countries ensure that those 
countries will effectively address U.S. food safety requirements and 
respond in a timely manner to problems that are identified?
    Answer. FDA recognizes that food safety issues and outbreaks can 
arise in all countries and Systems Recognition accounts for this 
reality. Systems Recognition focuses not only on the ability of food 
safety systems to help ensure safe food, but also on the ability of 
food safety authorities in foreign countries to identify, address, and 
contain food safety issues and outbreaks that may arise, learn from 
past events, and strengthen their system over time.
    Systems Recognition describes whether: (1) a country's food safety 
system provides a similar, though not necessarily identical, system of 
protections as the U.S. food safety system, and (2) the country's food 
safety authority or authorities provide similar oversight and 
monitoring activities for food produced under its jurisdiction. Systems 
Recognition is based on the premise that food safety systems with 
similar elements and similar levels of oversight lead to similar food 
safety outcomes.
    FDA conducts assessments of foreign food safety systems through the 
application of ten standards, outlined in the International 
Comparability Assessment Tool (ICAT). These core elements of a food 
safety system are important to ensure effective food safety outcomes. 
For example, FDA evaluates a system's capacity for responding to 
identified problems through surveillance, investigation, response, and 
subsequent review of alleged food-related incidents and emergencies 
that can reduce the incidence of illness, injury, and outbreaks. FDA 
also examines the food safety authority's strategies, procedures, and 
actions to enforce and achieve compliance with food safety laws and 
regulations and to evaluate the effectiveness of its compliance and 
enforcement program. If FDA determines that a country's food safety 
system meets the ICAT criteria, FDA implements a Systems Recognition 
Arrangement with monitoring and periodic reevaluation by FDA through 
the duration of the arrangement.
    Question. To what extent has FDA evaluated the effectiveness of 
these agreements in keeping the U.S. food supply safe?
    Answer. FDA is continuing with efforts to assess potential Systems 
Recognition partners to determine whether additional partnerships can 
be achieved. At the same time, the Agency is engaged in a program of 
monitoring and evaluation for currently recognized partners. To date, 
Systems Recognition arrangements have been put into place with New 
Zealand, Canada, and Australia. The latter two arrangements were 
completed within the past 15 months.
    Food safety outcomes typically are judged by microbiological or 
chemical levels, incidence of foodborne disease, or some other 
quantitative food safety performance measure. Beyond these case-level 
measures, FDA is currently exploring additional correlations between 
food safety performance measures and the elements making up food safety 
systems as a way to measure a food safety system's overall regulatory 
performance, in keeping with FSMA's mandate to approach food safety 
from a systems perspective.
    Before determining whether to enter into a Systems Recognition 
Arrangement with another country, FDA uses a tool called the 
International Comparability Assessment Tool (ICAT) to assess the 
country's food safety system, including the laws, regulations, 
programs, and policies upon which a foreign food safety authority 
relies to help ensure the safety of food. Based on FDA's experience 
with the oversight of domestic state programs and the Manufactured Food 
Regulatory Program Standards (MFRPS), from which the ICAT was derived, 
FDA believes that the standards reviewed through the ICAT assessments 
correspond to comparable food safety outcomes associated with the food 
safety system.
    To ensure that Systems Recognition Arrangements remain relevant and 
effective, each arrangement and corresponding foreign competent 
authority undergoes a periodic review and will be reassessed every 5 
years. This schedule allows the parties to monitor and modify terms of 
the arrangement as needed to account for developments in either party's 
food safety regulatory system.
    Question. Please provide an update on the results of the systems 
recognition pilots with New Zealand and Canada.
    Answer. After establishing Systems Recognition Arrangements with 
New Zealand in 2012 and Canada in 2016, the countries moved to the 
implementation phases for both countries.
    Under the arrangements, FDA and each systems-recognized country are 
engaged in regular discussions to promote consumer protection 
throughout implementation. FDA and the foreign competent authority 
continue, through ongoing bilateral communication and periodic reviews, 
to examine the performance of each country's regulatory system to help 
ensure that the arrangements continue to provide the appropriate level 
of public health protection. In addition, the bilateral arrangements 
are reviewed periodically, including when the level of food safety 
assurance required under domestic law or achieved by one of the parties 
significantly changes. For example, FDA has updated its assessment tool 
to incorporate new FDA Food Safety Modernization Act standards, and 
Canada's Safe Foods for Canadians Act will prompt a re-review of the 
bilateral terms next year. In addition, all Systems Recognition 
Arrangements include full reassessment at five-year intervals.
    Ongoing monitoring of the New Zealand and Canada system-recognized 
countries has proved useful in assuring FDA that appropriate public 
health outcomes have been achieved under these Systems Recognition 
Arrangements.
    Question. How, if at all, does FDA plan to use the ``systems 
recognition'' approach and integrate it with its broader efforts to 
ensure the safety of imported?
    Answer. The FDA Food Safety Modernization Act (FSMA) provides FDA 
with a variety of new authorities to help ensure the safety of imported 
foods and takes into account the capability of the regulatory system of 
the exporting country to assure compliance with U.S. food safety 
standards for a given food. FSMA also directs FDA to consider bilateral 
and multilateral arrangements and agreements to leverage the work done 
by foreign competent authorities to help ensure the safety of imported 
foods. Both Systems Recognition and commodity-specific arrangements 
achieve this directive.
    FDA uses Systems Recognition when the Agency determines it can rely 
on another food safety authority's implementation of a science-based 
food safety system. This level of regulatory partnership and leveraging 
requires a rigorous assessment process to support a determination that 
FDA is justified in recognizing a foreign food safety system and using 
the work of a foreign government to inform FDA's regulatory 
decisionmaking process.
    Because Systems Recognition takes into account the role of the food 
safety system of an exporting country, it informs FDA's risk-based 
decisionmaking and resource allocation regarding inspections, 
monitoring, admissibility, and follow-up when food safety incidents 
occur. Leveraging the regulatory oversight of comparable food safety 
systems allows FDA to enhance its risk-based targeting of resources 
with respect to import controls, foreign facility inspections, and 
foodborne outbreaks. These arrangements with foreign competent 
authorities complement FDA's upcoming implementation of the FSMA import 
tools, such as the Foreign Supplier Verification Program (FSVP) 
regulation, Third-Party Certification, and the Voluntary Qualified 
Importer Program. The FSVP regulation incorporates Systems Recognition 
by establishing modified requirements for importers of certain types of 
food imported from foreign suppliers in good compliance standing with 
the food safety authority for a country whose food safety system FDA 
has determined to be comparable to the U.S. system under the Systems 
Recognition initiative.
                     food safety modernization act
    Question. In September 2016, FDA extended the compliance dates for 
many regulated facilities under the Food Safety Modernization Act 
(FSMA), especially small and very small businesses that fell under the 
main core regulations including Preventive Controls for Human and 
Animal Food, Produce Safety Standards, and the Foreign Supplier 
Verification Program (FSVP) for food imports. Please provide an update 
on the implementation of these regulations.
    Answer. In 2016, FDA finalized the last of seven foundational rules 
to implement FSMA and is now focusing on implementation of the 
regulations. FDA extended certain compliance dates in August 2016 for 
very specific activities required in four of the FSMA rules, but these 
extensions did not affect the majority of the provisions contained in 
the seven rules. FDA is working to address the issues for which the 
Agency extended the compliance dates as we proceed with implementation 
of the rules. FDA's implementation activities include industry 
education, training, outreach, and technical assistance; developing 
inspection protocols and strategies to achieve compliance; training for 
FDA and state regulators; establishing necessary information technology 
systems to support industry, FDA, and states; and coordinating with our 
partner organizations.
            key highlights of fda's implementation efforts:
    Question. FDA initiated inspections to evaluate compliance with two 
of the regulations--Preventive Controls for Human Food, and Foreign 
Supplier Verification Programs. Rollout of additional inspection 
programs are planned for this year.
    FDA established a Technical Assistance Network to provide technical 
assistance to stakeholders for interpretation of the regulations.
    FDA is in the third year of a five-year cooperative agreement with 
the National Association of State Departments of Agriculture, NASDA, to 
bring together a range of state partners to collaboratively plan 
implementation of the Produce Safety regulation and Preventive Controls 
for Animal Food regulation, including facilitating outreach and 
education and delivery of training to state regulators.
    Recently, FDA announced the second round of funding to 43 states 
for nearly $31 million to develop produce safety regulatory programs. 
In 2016, FDA awarded nearly $22 million to 42 states. The cooperative 
agreement is renewable for 5 years, provided availability of funds and 
successful performance by states. Given the states' local presence, 
knowledge, and relationships with the farm community, FDA believes the 
states are very important in helping to provide oversight and direct 
technical assistance.
    In June 2017, FDA began accepting applications from accreditation 
bodies in support of the accredited third-party certification program. 
FDA posted the Strategy for FSMA training, which outlines the work FDA 
is doing to prepare its staff, state partners, and industry to 
implement the regulations. As part of the training strategy, FDA 
engaged with the Food Safety Preventive Controls Alliance, the Sprout 
Safety Alliance, and the Produce Safety Alliance to develop industry 
training on the regulations.
    Since October 2016, FDA has released 13 FSMA-related draft or final 
guidance documents for industry. In 2017, FDA announced its intention 
to consider how it might simplify the agricultural water standards and 
to extend compliance dates for those standards (for produce other than 
sprouts). FDA also recently announced its intention to continue to 
focus on Current Good Manufacturing Practice requirements during 
routine animal food facility inspections, but not to begin routine 
inspections for Preventive Controls requirements until the fall of 
2018.
    What steps is FDA taking to ensure that small businesses and 
producers understand and are able to comply with the FSMA requirements?
    Answer. FDA is engaging in and sponsoring a great deal of outreach 
and technical assistance to help small and very small farms and 
processors in understanding and complying with the provisions of the 
FSMA regulations.
    Beginning with the enactment of FSMA in 2011, FDA has been 
committed to providing tools to the food industry, particularly small 
businesses and producers, in meeting the requirements of the law. FDA 
recognizes that small and very small businesses and farmers face unique 
circumstances and challenges in implementing FSMA. FDA established 
phased-in compliance dates to provide small and very small businesses 
as well as producers additional time to comply with the preventive 
controls regulations (human and animal food), produce safety 
regulation, and foreign supplier verification program regulation. FDA 
also began operating a Technical Assistance Network (TAN), which is a 
web portal to which questions concerning application of and compliance 
with the FSMA regulations can be submitted for an individual response.
    FDA continues to engage in a number of activities intended to 
assist small and very small businesses as well as producers in advance 
of their FSMA compliance dates. To help ensure that our assistance is 
targeted to meet their needs, FDA partners with groups involved with 
specific communities to facilitate delivery of training and 
informational resources to achieve compliance with the FSMA 
regulations. For example, in 2016 FDA awarded a cooperative agreement 
to the National Farmers Union Foundation to develop and provide 
science-based, culturally specific food safety training, education, and 
outreach for local food producers and processors.
    FDA established a Produce Safety Alliance (PSA) to develop and 
deliver training on the produce safety regulation requirements that 
would be of particular assistance to small and very small farms, with 
training courses available since fall 2016. FDA also established the 
Food Safety Preventive Controls Alliance to develop and deliver 
training that will help small and very small facilities understand the 
preventive controls and foreign supplier verification program 
regulations requirements.
    In 2016, FDA awarded almost $22 million in cooperative agreements 
to 42 States to develop produce safety infrastructure which included 
outreach and technical assistance to farms in those states. In July 
2017, FDA announced an additional nearly $31 million in cooperative 
agreements to 43 States to begin and continue development of these 
State activities. FDA has also created a Produce Safety Network (PSN), 
which is a regionally-located staff of produce specialists whose 
primary focus is to develop relationships with the local farming 
community and assist in the implementation of the produce safety 
regulation.
    In addition, FDA has issued small entity compliance guides for the 
current good manufacturing practice (CGMP) and hazard analysis and risk 
based preventive controls regulations for both human and animal feed, 
intended to inform small and very small domestic and foreign human and 
animal food facilities about the CGMP and preventive controls 
regulations and enable them to better understand the requirements of 
the regulations.
    These guidances should be helpful to small and very small farms 
that also engage in on-farm manufacturing and processing. FDA also has 
issued a small entity compliance guide for the Mitigation Strategies to 
Protect Food Against Intentional Adulteration rule. FDA also intends to 
issue small entity compliance guides for the produce safety regulation 
and the other FSMA regulations.
                               cosmetics
    Question. Virtually every American uses personal care products 
daily, yet the safety laws for cosmetics and personal care products 
haven't been modernized since created in 1938. There is support among 
the industry- both large and small companies- as well as consumer and 
health groups to take significant steps to update oversight in this 
area. I have worked with Senator Collins to introduce a bipartisan bill 
to do just that.
    Will you commit to working with us to make meaningful updates, 
including evaluating the safety of ingredients in these prod?
    Answer. FDA shares your interest in the safety of cosmetics 
marketed to American consumers and commits to continuing dialogue on 
cosmetics issues.
                Questions Submitted by Senator Tom Udall
    Question. Last year, FDA issued a long overdue rule, known as the 
deeming rule, to enable the agency to begin to oversee e-cigarettes, 
cigars, and other previously unregulated tobacco products. FDA was 
responding, in part, to the thousands of flavored e-cigarettes that 
have flooded the marketplace in recent years--flavors such as cotton 
candy, gummy bear, root beer float, and banana split. While youth use 
of e-cigarettes dipped last year, youth use of e-cigarettes exceeds use 
of regular cigarettes. As the Surgeon General reported last year, use 
of e-cigarettes by youth is a public health concern and use of any 
product containing nicotine by youth, including e-cigarettes, is 
unsafe.
                                deeming
    I am concerned that FDA announced in May a three-month delay in 
enforcement of future deeming rule compliance dates and that the 
Administration has delayed filing legal briefs defending the deeming 
rule from industry challenges. While there is debate about whether e-
cigarettes could help some adult smokers to quit regular cigarettes, we 
should all be able to agree that FDA oversight is needed to protect 
kids and public health. FDA should be aggressively addressing the 
flavors and marketing practices that are increasing e-cigarettes' 
appeal to youth.
    During the Subcommittee's hearing, you indicated that FDA was 
looking at aspects of the deeming rule. Which aspects of the deeming 
rule you are examining?
    Answer. On July 28, 2017, FDA announced a comprehensive approach to 
the regulation of nicotine which includes the Agency's plan to begin a 
public dialogue about lowering nicotine levels in combustible 
cigarettes to non-addictive levels through achievable product 
standards. The Agency intends to issue an Advance Notice of Proposed 
Rulemaking (ANPRM) to seek input on the potential public health 
benefits and any possible adverse effects of lowering nicotine in 
cigarettes. The comprehensive approach also includes, among other 
things, a reconsideration of aspects of the implementation of the final 
deeming rule with an eye towards fostering innovation where innovation 
could truly make a public health difference, and making sure FDA has 
the foundational regulations it needs in place to make the entire 
program transparent, predictable, and sustainable for the long run.
    FDA shares the concerns about youth use of e-cigarettes. On August 
8, 2017, FDA announced it would pursue a strategic, new public health 
education campaign aimed at discouraging the use of e-cigarettes and 
other electronic nicotine delivery systems (ENDS) by kids. The Agency 
plans to expand its ``The Real Cost'' public education campaign this 
fall to include messaging to teens about the dangers of using these 
products while developing a full-scale campaign that will launch in 
2018. The campaign is just one component of the Agency's efforts to 
restrict youth access, limit youth appeal, and reduce youth exposure to 
toxic chemicals from all tobacco products. FDA continues to enforce 
existing regulations specifically aimed at addressing youth access to 
ENDS and other newly-regulated products, including banning the sale of 
tobacco products to those under age 18, requiring age verification by 
photo ID, and prohibiting free samples. Since August 2016, FDA has 
issued over 6,400 warning letters to brick and mortar and online 
retailers for selling newly-regulated tobacco products such as e-
cigarettes to minors.
    On August 4, 2017, FDA issued a guidance that extended the 
deadlines for the submission of marketing applications for those 
products that became newly-regulated by last year's deeming rule and 
were on the market as of August 8, 2016. Applications for newly-
regulated combusted products--such as most cigars, pipe tobacco, and 
hookah tobacco--would be submitted by August 8, 2021. Applications for 
newly-regulated non-combusted products--such as most e-cigarettes--
would be submitted by August 8, 2022. For newly regulated products on 
the market as of August 8, 2016, FDA anticipates that manufacturers 
will be able to continue marketing products while FDA reviews product 
applications submitted by the revised filing dates.
    With this additional time, FDA intends to issue other foundational 
rules and guidances--addressing topics such as the type of information 
FDA expects to be included in marketing applications--that will help 
make the product review process more efficient, predicable, and 
transparent, while still upholding the FDA's public health mission.
    This additional time will not only help manufacturers develop 
higher quality and more complete applications, but also allows FDA 
additional time to explore clear and meaningful measures to make 
tobacco products less toxic, appealing, and addictive, with an intense 
focus on youth. In particular, the Agency is pursuing product standards 
for ENDS that would address known risks. This could include measures on 
battery safety and child-resistant packaging, and product labeling to 
prevent accidental child exposure to liquid nicotine. The FDA also 
intends to issue an Advance Notice of Proposed Rulemaking (ANPRM) to 
seek public comment on the role that flavors--including menthol--in 
tobacco products play in attracting youth. The FDA also intends to 
issue an ANPRM to request information on how ``premium cigars'' should 
be defined, the health effects of these products, and their patterns of 
use. Additionally, the Agency plans to explore additional restrictions 
on the sale and promotion of ENDS, including restrictions on how 
products may be sold and advertised, to further reduce youth exposure 
and access to these products.
    Question. Will you commit to not delay enforcement of the deeming 
rule beyond the current three-month delay?
    Answer. On July 28, 2017, FDA announced a comprehensive approach to 
the regulation of nicotine which includes the Agency's plan to begin a 
public dialogue about lowering nicotine levels in combustible 
cigarettes to non-addictive levels through achievable product 
standards. The Agency intends to issue an Advance Notice of Proposed 
Rulemaking (ANPRM) to seek input on the potential public health 
benefits and any possible adverse effects of lowering nicotine in 
cigarettes. The comprehensive approach also includes, among other 
things, a reconsideration of aspects of the implementation of the final 
deeming rule with an eye towards fostering innovation where innovation 
could truly make a public health difference, and making sure FDA has 
the foundational regulations it needs in place to make the entire 
program transparent, predictable, and sustainable for the long run.
    FDA shares the concerns about youth use of e-cigarettes. On August 
8, 2017, FDA announced it would pursue a strategic, new public health 
education campaign aimed at discouraging the use of e-cigarettes and 
other electronic nicotine delivery systems (ENDS) by kids. The Agency 
plans to expand its ``The Real Cost'' public education campaign this 
fall to include messaging to teens about the dangers of using these 
products while developing a full-scale campaign that will launch in 
2018. The campaign is just one component of the Agency's efforts to 
restrict youth access, limit youth appeal, and reduce youth exposure to 
toxic chemicals from all tobacco products. FDA continues to enforce 
important existing regulations specifically aimed at addressing youth 
access to ENDS and other newly-regulated products, including banning 
the sale of tobacco products to those under age 18, requiring age 
verification by photo ID, and prohibiting free samples. Since August 
2016, FDA has issued over 6,400 warning letters to brick and mortar and 
online retailers for selling newly-regulated tobacco products such as 
e-cigarettes to minors.
    On August 4, 2017, FDA issued a guidance extending the deadlines 
for the submission of marketing applications for those products that 
became newly-regulated by last year's deeming rule and were on the 
market as of August 8, 2016. Applications for newly-regulated 
combustible products--such as most cigars, pipe tobacco and hookah 
tobacco--would be submitted by August 8, 2021. Applications for newly-
regulated non-combustible products--such as most e-cigarettes and other 
Electronic Nicotine Delivery Systems (ENDS)--would be submitted by 
August 8, 2022. For newly regulated products on the market as of August 
8, 2016, the Agency anticipates that manufacturers will be able to 
continue marketing products while FDA reviews product applications 
submitted by the revised filing dates.
    Importantly, the compliance policy described above does not affect 
any current requirements from the deeming rule that have already gone 
into effect. For example, the deeming rule provisions regarding 
mandatory age and photo-ID checks to prevent illegal sales to minors 
remain in effect and are subject to enforcement by FDA. It also will 
not affect future deadlines for other provisions of the rule, 
including, but not limited to, required warning statements, ingredient 
listing, health document submissions, harmful and potentially harmful 
constituent reports, and the removal of modified risk claims, such as 
``light,'' ``low,'' or ``mild,'' or similar descriptors.
                                 ______
                                 
              Questions Submitted by Senator Patrick Leahy
          helping farmers comply with food safety regulations
    Question. The FDA is still in the long drawn-out process of 
implementing new regulations under the Food Safety Modernization Act 
(FSMA). This is something that our farmers and food companies in 
Vermont have been watching very closely, especially for produce farmers 
who will be covered under the new regulations and have compliance dates 
that begin in 2018. However, there has already been significant market 
pressure for farms of all sizes to demonstrate food safety compliance 
now, regardless of whether they are fully subject to the new 
requirements. It is critical that the FDA and USDA both provide support 
to farmers in order to build the needed capacity to adapt to this 
changing food safety regulatory landscape. In addition, food safety 
training and technical assistance should not be one-size-fits-all, but 
rather tailored to meet the needs of agricultural operations across the 
country that vary in types and farm size.
    I have heard reports from farmers in Vermont that they feel there 
is a shortage of information flowing from the FDA, and a growing need 
for trainings that are tailored to the unique needs of small- and mid-
scale diversified farms and local food processors.
    The FDA has stated that it will provide additional guidance for 
trainers to use in assessing the equivalency of their training 
programs, and it has provided some funding to support the development 
of training programs tailored toward local food producers. However, at 
this point very little information has been provided regarding the 
timelines and processes for these much needed equivalent and 
alternative trainings, yet compliance starts in 2018. It is imperative 
that the FDA provide sufficient resources in order to offer a diverse 
array of farmer food safety capacity-building efforts to help American 
produce farms of all sizes and stages of development in order to face 
these new Federal food safety requirements, access markets, and promote 
public health.
    What are the specific processes and timelines that the agency will 
follow in issuing alternate training and equivalency criteria for 
farmers as quickly as possible?
    Answer. FDA recognizes that this is the first FDA regulation 
specific to produce farms, which can make implementation challenging 
for farmers. FDA is actively engaged in activities to ensure that 
farmers have the training, guidance, and other technical assistance 
targeted to meet their needs and delivered in a timely manner based on 
the phased in compliance dates in the final rule. FDA has also 
announced its intention to extend the compliance dates for agricultural 
water provisions in the rule (other than for sprouts).
    Specifically, FDA is actively engaged in activities that will 
assist with ensuring that training is and continues to be available to 
farmers. FDA established a Produce Safety Alliance (PSA) to develop and 
deliver training on the produce safety requirements that would be of 
particular assistance to farmers. PSA training courses have been 
available since fall 2016. In August 2016, FDA announced a partnership 
with the National Farmers Union, through a Cooperative Agreement, to 
develop and provide science-based, culturally specific food safety 
training, education and outreach, for local food producers and 
processors. The emphasis is on those involved in diversified, 
sustainable, organic, and identity-preserved agricultural operations; 
beginning and socially disadvantaged farmers; value-added farm 
businesses and small-size processors; and direct and intermediate 
supply chain participants.
    In August 2016, FDA announced a partnership with the University of 
Arkansas at Fayetteville, through a Cooperative Agreement. The 
partnership is to develop and implement food safety training, 
education, outreach, and identification of technical assistance 
resources for key tribal stakeholders, including farmers, packers, and 
manufacturers/processors that grow, harvest, pack, manufacture/process, 
or hold food covered by FSMA. Moreover, FDA partnered with the U.S. 
Department of Agriculture's National Institute of Food and Agriculture 
to provide a National Coordination Center and four Regional Centers to 
provide training opportunities for owners and operators of farms, small 
food processors, and small fruit and vegetable wholesalers. These 
Regional Centers are also responsible for providing technical 
assistance to farms and offer yet another mechanism for delivering 
training in a form and manner that meets farms' needs. One of the four 
Regional Centers is based at the University of Vermont.
    In 2016 and 2017, FDA awarded a combined nearly $53 million in 
cooperative agreements to 43 States to develop produce safety 
infrastructure, which included outreach and technical assistance to 
farms in those states. FDA has also created a Produce Safety Network, 
regionally-located staff consisting of produce specialists whose 
primary focus is to develop relationships with the local farming 
community and assist in the implementation of the produce safety 
regulation. The FSMA Collaborative Training Forum is co-led by FDA and 
USDA and involves all public and private entities engaged in FSMA 
training, especially those serving small and very small businesses. The 
members of the Forum are actively working to identify and address any 
information gaps in the various training materials and help ensure that 
training programs meet farms' needs.
         added-sugar nutritional labeling for maple and honey:
    Question. I understand that the FDA is setting a new compliance 
date for the updated nutrition facts label. I am a strong supporter of 
transparency and giving consumers information about what is in the 
foods they buy. However, I believe consumers should not be misled into 
thinking that sugar has been added to products like maple syrup and 
honey, which by their nature are pure single ingredient products.
    Have you looked into this issue related to the labeling of sugars 
in honey and maple syrup? Will you commit to work on this issue to find 
solutions in order to avoid consumer confusion for these single 
ingredient pure foods like maple syrup and honey so that we do not 
adversely impact farmers and producers?
    Answer. FDA announced on June 13, 2017, its intention to extend the 
compliance dates for the Nutrition Facts label final rule. After 
careful consideration, FDA determined that additional time would 
provide manufacturers covered by the rule with guidance from FDA, and 
would help them be able to complete and print updated Nutrition Facts 
labels for their products before they are expected to be in compliance. 
FDA will provide details of the extension through a Federal Register 
notice.
    The Nutrition Facts label final rule defines ``added sugars,'' in 
part, to include sugars that are either added during the processing of 
foods, or are packaged as such, which includes packages of sugar or 
containers of honey. The Agency has heard concerns from the honey 
industry about declaring added sugars on a jar of honey since no sugar 
is added to the product. The Agency has also heard similar concerns 
from the maple syrup industry. Providing industry more information 
about the labeling of ``added sugars'' on pure honey, maple syrup, and 
other single ingredient sugar products--is an Agency priority, and FDA 
is working to address the complex issues related to this labeling 
concern. FDA plans to invite further comment in the near future and 
intends to follow up with the maple syrup and honey industries and 
other stakeholders at a later date.
            maple nutritional labels and deceptive marketing
    Question. We also must crack down on food manufacturers that use 
the word ``maple'' on their labels or utilize maple related graphics on 
their packaging, when there is not any maple syrup in their products. I 
am concerned that consumers are being misled into thinking that these 
manufactured food products contain maple syrup, because to most 
consumers ``maple'' is not viewed merely as a characterizing flavor as 
is the case with a grape or orange soda. Instead, ``maple'' is 
synonymous with the ingredient maple syrup. This must be addressed by 
the FDA because these foods that are masquerading as maple syrup-
flavored only serve to deceive and mislead consumers, and can cause 
economic harm to American maple syrup producers and food producers 
using real pure maple syrup.
    Maple syrup as a premium ingredient has a material bearing on the 
price and consumer acceptance of food products that contain it, which 
is why it is frequently an ingredient named in the foods or displayed 
on its packaging. What steps will the FDA take to exercise its legal 
authority to investigate and take action against misbranded ``maple'' 
products in interstate commerce that give consumers the erroneous 
impression that such maple syrup is present in the foods they are 
purchasing?
    Answer. FDA's regulations address labeling requirements for 
characterizing ingredients and flavors. Those regulations provide a 
basis to allow firms to include statements that are truthful and not 
misleading on their labels. In addition, they provide a framework for 
identifying maple ingredients or maple flavors in products, whether 
involving the use of real maple syrup, or maple flavors derived from 
maple sources, or the use of maple flavor that is derived from other 
natural or artificial components. If maple flavor is derived from maple 
sources other than maple syrup, such as maple sugar or maple extract, 
FDA would not object to that product being represented as containing 
natural maple flavor. However, if the characterizing flavor is derived 
from a non-maple source, such as fenugreek or an artificial flavor, the 
food must be labeled as ``artificially flavored'' in accordance with 21 
CFR 101.22(i)(1)(ii) and 101.22(i)(2).
    Under FDA's regulations, the term ``maple'' is not synonymous with 
``maple syrup.'' Such a reading would require, among other things, 
evidence that consumers perceive the terms to be synonymous and a 
change in FDA's regulations. The process for requesting FDA to issue, 
amend, or revoke a regulation is described in 21 CFR 10.30 (Citizen 
petition).
    FDA shares your concern for the truthful labeling of food products, 
and FDA intends to continue to monitor the marketplace for potentially 
false and misleading labeling. If a food does not contain the 
ingredient maple syrup, the label cannot include the term ``maple 
syrup'' in the ingredient statement or as a part of the statement of 
identity. FDA will consider taking action, as appropriate, consistent 
with our food safety priorities and resources, against products that 
are misbranded.
    Further, FDA shares your desire to avoid consumer confusion. In 
September 2016, FDA developed an FDA Consumer Update to help educate 
consumers about the differences in the ways that ingredients and 
flavors are declared on product labels, including ``maple'' and ``maple 
syrup.'' The Update is available at: https://www.fda.gov/ForConsumers/
ConsumerUpdates/ucm521518.htm. FDA may develop additional educational 
materials if further needs are identified. Furthermore, FDA has worked 
with the maple syrup industry and would be willing to meet with them to 
discuss available data and other industry information on consumer 
perceptions regarding maple and maple syrup.
                      fighting the opioid epidemic
    Question. Addiction to opioids has ravaged the nation in recent 
years. According to the National Institutes of Health (NIH), more than 
two million Americans suffer from opioid addiction today, with the 
number of prescriptions written for opioids having tripled in the past 
20 years. Overdose deaths from heroin and opioids has also more than 
tripled in the past two decades.
    This epidemic has had devastating consequences. I watched with 
interest the recent announcement by the FDA on its intention to take 
steps to address the crisis by exploring new opioid formulations 
designed to deter abuse, and by engaging stakeholders to evaluate the 
impact of opioid addiction on addicts, their families, and communities 
nationwide.
    In addition to the FDA's recent announcement, what other ways can 
the agency continue to take steps to address the nationwide opioid 
epidemic?
    Answer. The FDA Commissioner has made reducing the scope of the 
epidemic of opioid addiction his highest initial priority. As a first 
major step in combatting this crisis, FDA recently created an Opioid 
Policy Steering Committee which is considering what more the Agency can 
do to confront the challenges of opioid addiction and opioid-related 
overdoses and deaths.
    Bringing together some of the Agency's senior leaders and members, 
the Committee has begun by exploring three questions: whether mandatory 
education for healthcare professionals who have the capability to 
prescribe opioids is needed; whether extra risk management steps for 
opioid prescription need to be taken; and whether a change to the 
current FDA framework used to assess the risk of abuse and misuse 
during the drug review process is needed.
    While the Committee has begun with these core questions, it has a 
broad mandate to consider whatever additional questions FDA should be 
seeking to answer. The Committee will solicit input, and engage the 
public. FDA is committed to looking at all facets of this complex issue 
and collaborating on various approaches. To pursue these policies, FDA 
plans to continue to have public dialogue through various forums and to 
share additional steps and information FDA is considering in addressing 
these challenges. FDA continues to collaborate with fellow HHS agencies 
as part of a coordinated Departmental strategy around addressing the 
opioid crisis.
    Question. Regarding the FDA's recent announcement to explore new 
opioid formulations designed to deter abuse, has the agency also 
considered exploring opioid-alternatives to treat and mange pain?
    Answer. FDA continues to support efforts to better understand the 
treatment of pain, especially as it relates to balancing the need to 
effectively treat pain with the public health crisis related to opioid 
use disorder and overdose. Currently, there are both opioid and non-
opioid drugs approved by FDA for the management of pain.
    FDA has a number of programs, such as Fast Track and Breakthrough 
Designation, which are intended to facilitate the development and 
expedite the review of products that are intended to treat a serious 
condition for which there is an unmet medical need. Novel non-opioid 
medications with the potential to provide effective pain relief may be 
appropriate designations, but it will be a product-specific 
determination.

                          SUBCOMMITTEE RECESS

    Senator Hoeven. Again, I want to thank everyone for coming 
today, most of all the Commissioner. Again, we look forward to 
working with you.
    Dr. Gottlieb. Thanks a lot.
    Senator Hoeven. We are adjourned.
    [Whereupon, at 11:15 a.m., Tuesday, June 20, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]