[Senate Hearing 114-696]
[From the U.S. Government Publishing Office]



 
   AGRICULTURE, RURAL DEVELOPMENT, FOOD AND DRUG ADMINISTRATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2017

                              ----------                              


                        WEDNESDAY, MARCH 2, 2016

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 1:58 p.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Jerry Moran (chairman) presiding.
    Present: Senators Moran, Daines, and Merkley.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                      Food and Drug Administration

STATEMENT OF HON. DR. ROBERT CALIFF, M.D., M.A.C.C., 
            COMMISSIONER
ACCOMPANIED BY JAY TYLER, CHIEF FINANCIAL OFFICER


                opening statement of senator jerry moran


    Senator Moran. Good afternoon, everyone. We are having an 
abbreviated hearing today as a result of four votes being 
announced at 2:30.
    Dr. Califf, congratulations on your confirmation. Welcome 
to the Food and Drug Administration (FDA). Senator Merkley and 
I have agreed to withhold our opening statements, which should 
be to the benefit of all in the audience.
    [Laughter.]
    Senator Moran. And we will submit those for the record.
    And we are going to start with your testimony, then we will 
have a round of questions for as long as we are able until the 
votes are called. We will go a little bit until that time.
    So, Dr. Califf, we welcome your testimony as we begin the 
appropriations process for this year.


              summary statement of hon. dr. robert califf


    Dr. Califf. Thank you, Chairman Moran and Ranking Member 
Merkley. I was advised that my testimony could be sidelined, 
too, but I am happy to give it if you would like. I know your 
time is limited.
    Senator Moran. We would welcome you perhaps highlighting 
the things you want to make certain we know, and perhaps if you 
can do that rather than reading your statement, that is to all 
of our benefit.
    Dr. Califf. Great. Well, I will try to do this in one 
minute instead of five, and I appreciate being here. I also 
want to acknowledge Dr. Ostroff sitting behind me, who has just 
finished his term as Acting Commissioner, and I think he has 
done a wonderful job. We all owe him a debt of gratitude for 
stepping in with such equanimity and grace.
    You have got the budget in front of you. We think it is a 
very responsible budget, and several of the main priorities 
that I have in this, as you well know, are, first of all, the 
workforce at the FDA. Due to the increasing intensity of 
biological, agricultural, and engineering advances, we need a 
topnotch workforce, and much of our activity is devoted to 
that. And the second is shoring up the science base, which 
includes a heavy emphasis on quantitative analytics. One of our 
biggest priorities for this year is implementation of the Food 
Safety Modernization Act (FSMA).
    At the core of that is a quality system, which you have all 
participated in helping us develop. We appreciate the funding 
increase that we got last year. It has made a big difference, 
but we still have work to do there. And at the core of it is a 
quality system built on high-level analytics so that we can 
deploy FDA forces in the most efficient and effective manner.
    So at the core of it for me is that we are in a continuing 
evolution of the FDA as a science-based public health 
organization with a very broad scope of activities. There is an 
amazing array of details that we can talk about. They are 
specified in my testimony that we have submitted, and I look 
forward to taking your questions.
    [The statement follows:]
              Prepared Statement of Hon. Dr. Robert Califf
                            i. introduction
    Good afternoon Chairman Moran, Ranking Member Merkley, and Members 
of the Subcommittee, I am Dr. Robert Califf, 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 (FY) 2017 
Budget Request for FDA. I would like to thank the Subcommittee for its 
past investments in FDA, most recently for fiscal year 2016 funding, 
which have helped us meet the demands of our increasingly complex and 
diverse mission at home and abroad. For fiscal year 2017, FDA is 
requesting $5.1 billion to support our essential functions and priority 
needs.
    I am honored to have been chosen by the President and confirmed by 
Congress to lead the FDA. Thank you all for your willingness to share 
with me and my predecessor, Dr. Ostroff, your perspectives on ways the 
FDA can better serve the American people. My first priority as 
Commissioner is to strengthen and better support the FDA's talented and 
dedicated workforce. I will focus on the need to carry our critical 
priorities over the finish line. FDA's ambitious agenda currently 
includes implementation of the Food Safety Modernization Act, 
finalizing the Tobacco Deeming Rule, facilitating the development of 
medical counter measures, and making progress on the Combating 
Antibiotic Resistant Bacteria (CARB) initiative, and the Precision 
Medicine Initiative. I also want to further development of the FDA's 
science base that informs decisionmaking across drugs, medical devices, 
food safety, and more. FDA's work on the groundbreaking Sentinel 
system, supported by your mandate, demonstrates the power of the use of 
our new national digital infrastructure. We are increasingly able to 
rapidly develop evidence to inform FDA's decisionmaking, and giving us 
the ability to act quickly on safety issues, rather than having to wait 
for a new study every time a safety issue arises. I look forward to 
continued dialogue with you to gain support for FDA's important public 
health mission.
    ii. fda plays a critical role in america's public health system
    FDA is a science-based regulatory agency charged with an enormous 
and significant responsibility: to promote and protect public health. 
Our goal in carrying out our mission is to ensure the safety, 
effectiveness, and quality of human and veterinary drugs, biological 
products and medical devices; the safety of dietary supplements; as 
well as the safety and security of the vast majority of our nation's 
food supply. Additionally, the Agency regulates the manufacturing, 
marketing, and distribution of tobacco products, and seeks to reduce 
the use of tobacco products by minors and the detrimental effects of 
tobacco on the general population. FDA's relatively new authority to 
oversee tobacco products, as well as the Agency's heightened role in 
the food supply, has tremendously increased FDA's responsibilities and 
opportunities to promote and protect public health.
    FDA plays a unique and vital role in facilitating the availability 
of safe and effective products and treatments, while also protecting 
people from products that are promoted using false claims or may cause 
harm. FDA works with a broad array of stakeholders including industry, 
other government agencies, and the public, in order to achieve the best 
possible outcomes.
    Congress has recognized the dynamic role that FDA plays and the 
increasingly complex and inter-connected global environment in which we 
operate. As a result, FDA has been tasked with a multitude of new 
responsibilities and authorities in the public health arena, including 
the Drug Quality and Security Act (DQSA); the FDA Safety and Innovation 
Act (FDASIA); the FDA Food Safety Modernization Act (FSMA); and the 
Family Smoking Prevention and Tobacco Control Act (TCA). While FDA has 
stepped up to meet these essential public health responsibilities under 
current funding levels, successful implementation of these new 
authorities requires additional resources.
    III. FDA Has a Proven Track Record of Success
    FDA's accomplishments over the past year have been as substantial 
as any in the Agency's recent history. Across the areas of food safety 
and nutrition, medical product safety and innovation, tobacco control, 
and other areas of our work, our accomplishments demonstrate our 
ability to respond to evolving needs and opportunities--including the 
embrace of new approval pathways, innovative technologies, and cutting-
edge science.
    Moreover, given the importance of our work, FDA's budget is a 
bargain for American taxpayers. The products regulated by FDA account 
for more than 20 percent of every consumer dollar spent on products in 
the U.S.; individual Americans only pay about 2 cents per day to 
support oversight to help ensure that those products are safe and 
effective. This is a small price for life-saving medicines and 
treatments approved as fast as or faster than anywhere in the world, 
confidence in medical products that are relied on daily, and a food 
supply that is among the safest in the world.
    iv. fda's innovations improve and protect america's food supply
    Food Safety Modernization. Congress enacted FSMA in response to 
dramatic changes over the last 25 years in the global food system and 
in our understanding of foodborne illness and its consequences, 
including the realization that foodborne illness is a significant 
public health problem, is preventable, and is costly. FDA is 
modernizing our food-safety system, using quality systems and analytics 
to prevent foodborne illness before it occurs. These food system 
changes and the new FSMA mandates require transformative change in how 
FDA does its work.
    FDA published seven major proposed rules in 2013 and, after much 
stakeholder input, five of those became final in 2015: the preventive 
controls rules for human and animal food, the produce safety rule, the 
foreign supplier verification program rule and the third-party 
accreditation rule. These groundbreaking final rules will help food 
manufacturers, produce farmers, and food importers take steps to 
prevent food safety problems. The produce safety and foreign supplier 
verification rules, for the first time, establish enforceable science-
based safety standards for the growing and harvesting of produce and 
make importers accountable for conducting risk-based verification to 
determine that imported food meets U.S. safety standards. In addition, 
as part of these rulemakings we are establishing a program for the 
accreditation of third-party certification bodies to conduct food 
safety audits of foreign food facilities.
    Nutrition. Americans eat and drink about one-third of their 
calories away from home. To this end, on December 1, 2014, FDA carried 
out a congressional mandate to publish rules requiring that calorie 
information be listed on menus and menu boards in chain restaurants and 
similar retail food establishments, and on signs for vending machines. 
In 2015, FDA issued two guidances to help affected industries implement 
the menu labeling rule, one aimed at small businesses, and the second 
providing more detailed advice on how the rule works in the context of 
a diverse industry. FDA also listened to stakeholders and extended the 
compliance date for menu labeling.
          v. promoting innovative medical product development
    Medical Product Application Review. This year, through application 
of our efficient and flexible approval process, we again were able to 
approve a broad range of innovative medical products and treatments 
with the potential to make a positive difference in the lives of 
patients. These products included a new generation of targeted 
therapies that will be used to treat or prevent diseases that affect 
only a few individuals and additional products that will be used to 
treat diseases that affect large portions of the population. They 
involve novel approaches to therapy developed from the rapidly 
accelerating science of genomics and even new product categories, such 
as our approval of the first biosimilar biological product.
    We also enhanced engagement of patients in the development, 
approval and evaluation process. And we continued to make progress in 
our application of some of the most cutting edge areas of science and 
technology, such as precision medicine, which is helping us to advance 
biomedical understanding and provide targeted therapies that will allow 
us to better treat individual patients and diseases.
    FDA's rapid drug reviews and use of expedited programs for certain 
categories of drugs haves helped provide meaningful new products to 
U.S. patients quickly without compromising our safety and efficacy 
standards. In 2015, FDA approved 56 novel new drugs. These approvals 
included four new treatments for patients with multiple myeloma, two 
new drugs for patients with heart failure, and another robust year of 
approvals of drugs for rare or ``orphan'' diseases.
    In 2015, we also approved several important vaccines, including one 
for serogroup B meningococcal disease, the first seasonal influenza 
vaccine to contain an adjuvant (intended for people 65 years and 
older), and a new indication for anthrax vaccine to prevent disease 
following exposure to anthrax--the first vaccine to receive an approved 
indication based on the Animal Rule, which allows efficacy data 
generated in animal models to serve as the basis for the approval of 
medical countermeasures against chemical, biological, radiological or 
nuclear threats when human efficacy studies aren't ethical or feasible. 
We also saw the approval of several innovative devices that will make a 
positive difference in the lives of patients, including a device that 
extends the survival time of patients with brain cancer, and a 
transcatheter pulmonary valve that can be placed in certain patients 
with congenital heart disease, without requiring open heart surgery.
    We have also seen important progress in our device review program. 
Our average time to reach decisions on premarket approvals (PMAs) has 
dropped 36 percent since 2009. And in 2015, FDA approved 79 novel 
devices, the most since the start of the Medical Device User Fee 
Program. Most importantly, enhanced flexibility and an efficient 
approval process have come without lowering our standards for safety 
and efficacy.
    An important component of all of the medical product reviews is the 
use of interaction between product developers and our expert staff at 
FDA at critical points in product development. Our expert review teams 
``see it all'' and therefore play an important role in providing 
guidance and feedback to companies that is enabling more effective 
product development. The enhanced communication and growing expertise 
within FDA promotes earlier exit of products that will not pass muster 
and a much higher rate of approval on first review for products that do 
meet our rigorous criteria for safety and efficacy. The success of this 
approach highlights the need for talented people at the FDA--as medical 
products become more sophisticated the need for talented reviewers at 
FDA will grow.
    Opioid Medications. Prescription opioid analgesics are an important 
part of modern pain management; however, misuse and abuse of these 
products contribute to a serious and growing public health epidemic. 
After extensive internal review, the Agency has issued a detailed 
action plan that includes a new framework for considering the 
consequences of addiction, abuse and misuse not only on the individuals 
for whom the treatment is intended, but also upon the larger society 
that is affected by abuse and misuse. Additional post-market 
requirements for studies have been added. FDA continues to support 
development of antidotes to treat overdose, abuse deterrent 
formulations, non-addictive pain relievers, and medication-assisted 
treatments for dependence.
    Biosimilars. FDA has been developing its biosimilar program, an 
effort which led to the approval of the first biosimilar biological 
product in March 2015. And there are more applications in the pipeline. 
To prepare, FDA has produced a variety of guidancesin this area. FDA 
remains committed to strengthening the biosimilars pathway by 
continuing to work diligently to provide development phase advice to 
sponsors and evaluate applications submitted under this abbreviated 
pathway, and issue additional guidance as needed to provide clarity to 
stakeholders.
    Next Generation Sequencing and Precision Medicine. Our strengthened 
focus on regulatory science is helping to drive innovation. One 
illuminating example is our growing ability to apply the sophisticated 
technologies of next generation sequencing and precision medicine. FDA 
today is better prepared for and more engaged than ever in facilitating 
the development of these new technologies (as well as new uses for 
older technologies), with reasonable assurance of safety and 
effectiveness. These efforts help to achieve more precise diagnosis or 
treatment, through the development and review of state of the art 
diagnostics and drugs that are targeted to an individual's genetic 
blueprint. We continue to move forward on the White House's Precision 
Medicine Initiative to advance biomedical understanding by leveraging 
genomic advances, health information technologies, and new methods of 
analyzing large volumes of data. Recently, we launched FDA's 
precisionFDA web platform, a cloud-based portal that has already 
succeeded in enabling scientists from industry, academia, government 
and other partners to come together to foster innovation and develop 
the science behind next-generation sequencing. PrecisionFDA provides a 
clear example of regulatory science stimulating innovation.
    We are also working to refine clinical trial design and statistical 
methods of analysis to create more efficient studies that take 
advantage of advances in genomics and information technology to provide 
more rapid, less expensive and more reliable answers about medical 
products. For instance, we continue to support collaborative efforts in 
clinical trials, such as the NIH's Lung-MAP protocol for lung cancer.
    Drug Quality and Security Act. FDA is implementing the DQSA and 
working diligently to reduce the risks of compounded drug products in 
the U.S. Since enactment of the DQSA, FDA has conducted over 230 
inspections of compounders, many in response to reports of serious 
adverse events, product quality problems, or other complaints. FDA 
continues to identify serious problems during these inspections, 
including contamination in purportedly sterile drugs and in the sterile 
compounding environment, and other insanitary conditions that put 
patients at risk. FDA has also investigated serious adverse events 
associated with non-sterile drugs that were superpotent, as much as 
1000 times the labeled strength. As a result of these inspections, FDA 
has taken aggressive action to protect the American public from 
compounded drugs that could cause harm. Since enactment of the DQSA, 
FDA has issued over 75 warning letters to compounders and has worked 
closely with the Department of Justice on civil and criminal 
enforcement actions. Many compounders have recalled all of their 
sterile drugs and ceased sterile operations at FDA's recommendation. 
FDA has also been working diligently to implement sections 503A and 
503B of the Federal Food, Drug, and Cosmetic Act (as added by DQSA) by 
publishing draft and final policy documents while taking into 
consideration stakeholder input. FDA has issued 12 draft guidance 
documents, five of which were finalized, a proposed rule, and a draft 
memorandum of understanding related to interstate distribution of drugs 
compounded by state-licensed pharmacies and Federal facilities. FDA has 
consulted with the Pharmacy Compounding Advisory Committee, convened 
three intergovernmental working meetings with state representatives, 
and has actively engaged with more than 50 stakeholder groups during 
listening sessions. FDA will continue to work diligently on draft and 
final policy documents to implement the DQSA, and to engage with 
stakeholders on our proposed policies. We have also put out a draft 
guidance on the appropriate use of compounded products for animals. 
Even though not specifically included in the legislation, stakeholders 
have asked us to clarify our policy on animal drug compounding for 
years, which we are now doing.
   vi. fda works to reduce the impact of tobacco on the public health
Family Smoking Prevention and Tobacco Control Act.
    FDA closely monitors retailers' compliance with restrictions on 
tobacco product marketing and sales to youth--and takes strong 
corrective action when violations occur. In late 2015, FDA issued its 
first ever no-tobacco-sale-orders to retailers who continually violate 
the law. In addition, the Agency launched a second major public 
education campaign, ``Fresh Empire,'' targeting multicultural youth 
with powerful messaging about the dangers of tobacco products, all as 
part of the effort to reduce the number of young people who use tobacco 
products.
    Also for the first time, in 2015, FDA authorized the marketing of 
eight new tobacco products under the premarket tobacco application 
pathway. We have made significant progress and have taken many steps to 
improve timeframes in reviewing marketing applications. Our actions 
include increasing scientific staffing; providing feedback to industry; 
issuing multiple guidance documents; holding meetings with industry; 
hosting webinars; sending letters and other communications to clarify 
expectations for industry; and, finally, establishing performance goals 
that include timeframes for review of Substantial Equivalence (SE) 
reports for products that are not on the market.
       vii. fda tackles emerging, unique, and complex challenges
    Combating Antibiotic-Resistant Bacteria (CARB). FDA has made 
progress on each of the five goals of the President's National Action 
Plan for CARB. These goals are to slow the emergence of resistant 
bacteria and prevent the spread of infections caused by resistant 
bacteria; strengthen national one-health surveillance efforts to combat 
resistance; advance development and use of rapid and innovative 
diagnostic tests for identification and characterization of resistant 
bacteria; accelerate basic and applied research and development for new 
antibiotics, other therapeutics, and vaccines; and improve 
international collaboration and capacities for antibiotic-resistance 
prevention, surveillance, control and antibiotic research and 
development.
    On June 2, 2015, both human and animal health stakeholders came 
together in support of a one-health antibiotic stewardship forum hosted 
by the White House. Additionally, CDC and FDA launched the 
antimicrobial-resistant isolate bank of over 160 isolates composed of 
collections of carbapenem-resistant Enterobacteriaceae and other multi-
drug resistant bacteria of antibiotics that are approved for use in 
food- producing animals. FDA also is working closely with CDC and USDA 
on a data collection plan to verify the changes in on-farm antibiotic 
use that are expected to result from FDA's initiative to eliminate 
animal production uses (e.g., growth promotion) of medically important 
antibiotics in food-producing animals and to require 
veterinaryoversight for therapeutic uses of these drugs for the 
treatment, control or prevention of a specifically-identified disease. 
In support of this effort, FDA finalized changes to the Veterinary Feed 
Directive (VFD) regulation in June 2015 which took effect in October 
2015. FDA also published a proposed rule in May 2015 that includes 
additional reporting requirements regarding the sale and distribution 
of antibiotics that are approved for use in food-producing animals.
    Responding to Ebola. In a world where disease knows no borders, 
FDA's response to the Ebola outbreak in West Africa demonstrated how we 
used our scientific expertise and regulatory authorities to the fullest 
extent possible to address a tragic public health crisis of global 
impact. Our response involved collaborating with partners across 
government, pharmaceutical and diagnostic companies, international 
organizations like the World Health Organization, and our international 
regulatory counterparts. We played a key role in encouraging the 
appropriate study of and expediting the availability of diagnostic 
tests, investigational therapeutics, and vaccines, as well as 
investigating fraudulent products marketed to diagnose, prevent and 
treat Ebola. And many FDA commissioned corps officers of the U.S. 
Public Health Service served on the front lines, deployed in a 
humanitarian mission to provide care to patients at the Monrovia 
Medical Unit in Liberia, one of the West African nations that were hard 
hit by the outbreak.
    Medical Countermeasures. FDA's Medical Countermeasures mission is 
to promote national health and security by facilitating the development 
and availability of medical countermeasures (MCMs) such as drugs, 
biologics, vaccines, devices, and diagnostic tests. These products are 
used to diagnose, prevent, or treat conditions stemming from an attack 
with a chemical, biological, radiological, or nuclear material, or a 
naturally occurring emerging infectious disease, such as Ebola or the 
most recent outbreak of Zika virus in the Americas. Sixteen diagnostic 
tests have been authorized under FDA's Emergency Use Authorization 
authority in response to emerging infectious disease threats. MCMs have 
been approved for anthrax, plague, botulism, Acute Radiation Syndrome, 
and pandemic influenza, and several others are on an 
accelerateddevelopment track. FDA finalized the guidance ``Product 
Development Under the AnimalRule''; to date, eleven drug and biologic 
products have been approved under thisregulation. We also established a 
publicly available microbial DNA reference database to help advance 
diagnostic test development.
        viii. fda's fiscal year 2017 president's budget request
    The fiscal year 2017 Budget Request for FDA is $5.1 billion, an 
increase of 8 percent or $358.3 million compared to the fiscal year 
2016 enacted level. The budget includes $2.7 billion for budget 
authority--an increase of one-half of 1 percent or $14.6 million 
compared to fiscal year 2016; $2.3 billion for user fees \1\ an 
increase of twelve percent or $268.7 million compared to fiscal year 
2016. Mindful of the larger pressures on the Federal budget, we have 
focused our request on the most urgent needs for fiscal year 2017.
---------------------------------------------------------------------------
    \1\ Includes proposed Food Facility Registration and Inspection, 
Food Import, International Courier, Cosmetics, and Food Contact 
Substance Notification fees and proposed increase to the Export 
Certification fee.
---------------------------------------------------------------------------
    Food Safety. The fiscal year 2017 Budget provides $1.5 billion for 
food safety, an increase of $211.6 million above the fiscal year 2016 
level. The budget includes $1.3 billion for budget authority--an 
increase of 1 percent or $18.4 million compared to the fiscal year 
2016Enacted budget--and $209.8 million for user fees--an increase of 
$193.2 million compared to the fiscal year 2016 Enacted budget. The 
budget includes an increase of $25.3 million to improve food and feed 
safety through continued FSMA implementation.
    FDA's fiscal year 2017 budget will build on the fiscal year 2016 
investments and focus on two strategic areas of investment that are 
essential to the success of FSMA: state capacity to partner with FDA 
and the safety of imported food. The fiscal year 2017 budget request 
for state capacity building will be used primarily to fund state 
cooperative agreements and grants that support the essential state role 
in implementing FSMA's new produce safety rule requirements.
    Additionally, the fiscal year 2017 request will enable FDA to 
continue progress toward implementing the multifaceted new import 
safety system mandated by Congress, including the Foreign Supplier 
Verification Program (FSVP) rule, foreign food facility and produce 
inspections, and partnerships with foreign governments. Under the FSVP 
rule, importers must verify that imported food has been produced in a 
manner consistent with FSMA's new standards for produce safety and 
preventive controls.
    The user fee request for food safety includes $105.3 million in new 
resources to support the new import safety system and $61.3 million in 
new resources to further modernize the FDA inspection program.
    Medical Product Safety and Innovation. The fiscal year 2017 Budget 
request for FDA for Medical Product Safety and Availability is $2.8 
billion, an increase of $116.2 million above the fiscal year 2016 
Enacted level. The request includes $1.3 billion for budget authority--
an increase of 0.2 percent or $3.2 million compared to the fiscal year 
2016 Enacted level, $1.4 billion for user fees--an increase of 3 
percent or $38.0 million compared to the fiscal year 2016 Enacted 
level, and $75.0 million in new mandatory funding for the Vice 
President's Cancer Moonshot. With this request, FDA will improve 
medical product safety and innovation in five key areas: evaluating 
Precision Medicine-based diagnostics, improving the safety of 
compounded drugs, combating antibiotic resistant bacteria, supporting 
animal drug and medical device review, and improving cancer diagnostics 
and treatments.
    FDA requests $4 million in fiscal year 2017, an increase of $2.0 
million above fiscal year 2016 for Precision Medicine. With the 
majority of the increase, FDA will help advance Precision Medicine by 
establishing the National Medical Device Evaluation System (NMDES) to 
identify patients who benefit most or do not benefit from specific 
types of devices. FDA will also continue to invest in precisionFDA, 
which provides a crowd- sourced, cloud-based platform to advance 
regulatory science around NGS-based analytical tools and datasets.
    FDA requests $18 million, an increase of $1 million above fiscal 
year 2016, to enhance oversight of human drug compounding through 
increased inspection and enforcement activities, policy development and 
implementation, and state collaboration and coordination.
    For CARB, FDA requests $42 million to support continued work to 
address public health concerns associated with antimicrobial drug use 
in animals and to better protect antibiotic effectiveness for both 
human and animal populations. FDA will work in collaboration with USDA 
to support efforts to monitor antimicrobial drug use in food- producing 
animals.
    FDA requests an additional $2.9 million to support ongoing 
activities within the Animal Drugs Review Program and the Devices 
Program to achieve enhanced and predictable review performance that 
meets industry, congressional, and public expectations. The increased 
funding requested will enable FDA to continue to meet premarket animal 
drug review requirements by having the necessary review staff to carry 
out these activities. The request will also support ongoing review 
activities in theDevices Program to meet statutory requirements for the 
review of medical device applications.
    In fiscal year 2017, FDA requests $75.0 million in mandatory 
resources as part of the Vice President's Cancer Moonshot in order to 
accelerate progress in cancer--to reduce the number of people who 
develop cancer and to improve the outcome for those who do. In order to 
support the dramatic increase in the number, complexity, and strength 
of cancer diagnostics and therapeutics, FDA will establish an Oncology 
Center of Excellence to streamline collaboration across FDA's Human 
Drugs, Biologics, and Devices and Radiological Health Programs and to 
interface more effectively with the NIH and the clinical environment. A 
highly effective interface will be needed to deal with the 
proliferation of highly effective but complex combinations of targeted 
drug and biological therapies and immunotherapy, driven by 
sophisticated diagnostic testing and monitoring devices. There is hope 
that many forms of cancer will be cured or changed to chronic diseases.
    Infrastructure, Rent and Facilities. The fiscal year 2017 Budget 
Request provides an increase of $3 million over the fiscal year 2016 
Enacted level, for a total of $12 million, for urgent facility 
investments that will provide functioning offices and labs across the 
country to ensure FDA can execute its Food Safety and Medical Product 
Safety mission. This $3.0 million increase will be used to address 
repairs, improvements and mission support needs at FDA's owned 
laboratories and other critical owned facilities across the U.S.
                             ix. conclusion
    FDA's public-health mission is indispensable to the health and 
well-being of every American. We carry out our broad and expanding 
public health responsibilities effectively and with relatively few 
taxpayer dollars, despite dramatic expansions in our responsibilities 
as a result of new legislation, scientific and technological advances, 
and a globalized marketplace. The fiscal year 2017 Budget Request plans 
for efficient spending on programs that are essential to providing 
Americans with the safe foods and safe and effective medical products 
they expect. We look forward to answering your questions today and to 
working with you in the coming year.

    Senator Moran. Commissioner, thank you very much. Let me, 
first of all, agree with you and express my appreciation for 
the relationship and the work by Dr. Ostroff at FDA. I very 
much value his service to the Agency and to the American 
people, who, in my view, are safer because of his work. And so, 
thank you for that service, and we look forward to it 
continuing.
    Let me start with a complaint, however.
    [Laughter.]
    Senator Moran. And one of the things that I have, at least 
in my view when I became chairman of this committee, we have 
worked at developing a relationship with FDA, and I appreciate 
that we have that. But I am concerned that the FDA is often 
slow in communicating with us and with our staff, that many 
times, in fact today was a perfect example. I would guess that 
many questions will be submitted to the FDA in writing for the 
record. A timely response is not always the case, and 
specificity of answering those questions is often lacking.
    And so, in an attempt to suit you up today on your first 
hearing before this subcommittee, Dr. Califf, I would ask if 
you would assure me that you will do everything as the 
commissioner to see that our subcommittee, its members, get 
appropriate, full, complete, and timely responses to inquiries 
we make to the FDA.
    Dr. Califf. In my consideration of joining the FDA and 
taking this job, outspokenness was one of the criteria that was 
said about me, and it is the case that I do think the FDA can 
do a better job of explaining what it is doing and of 
communicating. I have also had a hard lesson coming to the FDA 
in learning about issues with regard to trade secrets, and I 
will just call them social mores that exist about how things 
roll out that you are well aware of.
    But taking all that into account, we are going to step up 
our communications. I can promise you that we will do that. I 
am an old intensive care unit doctor. I carry a cell phone. I 
am used to being called 24 by 7, and if you feel that 
communication is slow, just call me. I am here.

                            ARSENIC IN RICE

    Senator Moran. Thank you very much. Let me ask a specific 
question about rice and arsenic. Last week during the budget 
meeting in the House, Dr. Ostroff noted that the FDA was making 
the risk assessment for arsenic in rice a priority. When do you 
plan to move, and what exactly are you planning to release in 
that regard?
    Dr. Califf. Well, as you well know, the issue here is 
estimating the risk associated with arsenic that is in rice, 
and estimating the benefits of rice, which has been a staple of 
the American diet. My ancestors down between Charleston and 
Hilton Head actually farmed rice for a living, so I have a 
little history here.
    The assessment is complicated because the data are 
imperfect. It is in a multiagency review. I think you are well 
aware of that. It is a very high priority for us to get this 
out. We know that people are waiting. I am not able to give you 
the specifics of what will be in it, but we are working on it 
very hard with other Federal agencies.
    Senator Moran. This decision potentially has significant 
consequence to a lot of people, from producers to consumers, 
and I would ask that you initiate a broad discussion among 
those affected by this decision before a conclusion is reached. 
Is that something you intend to do?
    Dr. Califf. Yes, I would say there has already been a good 
bit of discussion, but there certainly will be a lot of 
discussion about it.
    Senator Moran. Are there other foods that are involved in 
this topic besides rice?
    Dr. Califf. This particular decision is a rice decision, 
which, of course, comes in many preparations, including infant 
formulas and nutritional aspects, so, you know, it is an 
important decision. We are well aware of that. It will affect 
people, and we want to make sure we take that into account.
    Senator Moran. Thank you very much. Let me now turn to the 
ranking member, Senator Merkley.

                         TOBACCO RELATED ISSUES

    Senator Merkley. Thank you, Mr. Chairman, and 
congratulations, Dr. Califf. There are plenty of fascinating 
and really important issues that the FDA deals with, and the 
one I wanted to start off with is related to the tobacco 
deeming regulation. That regulation has now been in the Office 
of Management and Budget (OMB) since October 2015. The basic 
rules are that it is not supposed to be there more than 90 days 
with one 30-day extension. That would be 120 days. As of today 
we are at 134 and counting.
    So it has been a mystery year after year after year that 
this deeming regulation has not been finished because while 
essentially we have been not acting, the addiction rate for e-
cigarettes has increased dramatically. They are targeted at 
kids with all kinds of flavors--Scooby Doo, Double Dutch 
Chocolate. You name it, you can find it. And to have a product 
targeted to children that is that effective is troublesome 
since it means the likelihood of a lifetime of nicotine 
addiction with related health consequences, and certainly a lot 
of expenses for our healthcare system as well.
    So what is going on? Is this ever going to emerge from OMB?
    Dr. Califf. I can assure that it will emerge, and just--as 
I think you know, I am a cardiologist. I had a very busy 
clinical practice and intensive care units, so I have probably 
seen as many people die or have strokes, or heart attacks, or 
renal failure due to tobacco-related issues as almost anyone on 
earth at this point. So I am strongly committed to get this 
out. You are also well aware of the complexity. We had 135,000 
comments. There are many views about the details that were 
aired that we have been working through.
    But I do not think you will find anybody more committed to 
getting this out than I am. I have seen the consequences of 
tobacco-related illnesses, and we need to take care of this.
    Senator Merkley. Well, I do appreciate that your personal 
background gives you that direct insight because some type of 
special change is needed here because for 2011, 2012, 2013, 
2014, 2015, now we are in 2016, very responsible individuals 
who have said they care a lot about this issue, that they care 
a lot about kids, they care a lot about people, say we are 
doing everything we can, we will have it in a short period of 
time. And it just never happens. So I am hoping the new energy 
you bring and your perspective can say let us get this done.
    Let me just note that between 2013 and 2014, e-cigarette 
use tripled among middle and high school students in 1 year. 
And so, obviously the targeting of children is very effective, 
and it is hurting a lot of people, and this is something where 
we can actually make a difference for the good. So I do hope 
you take your personal experiences and pry this out into the 
public space, and hopefully it will include a ban on all of 
these kid targeting flavors, and hopefully it will include caps 
that are difficult for children to take off so that we do not 
have as many poison cases as we have had with children. That is 
my hope, my hope and my prayer.
    Dr. Califf. Well, I mean, as you know, we are instructed by 
law to take care of the children with the Tobacco Act, and we 
plan to do it. Chairman Upton this morning in a meeting--I was 
with him--pointed out that we can all understand the FDA better 
if we think about our own families. And I have a son, a 
brilliant rocket scientist son, who became addicted to nicotine 
at age 12 in North Carolina, so this is not a matter of 
intelligence or willpower. It is something that we need to 
protect children from. And 400,000 people a year are dying from 
tobacco-related illnesses even now, so we have work to do here.
    Senator Merkley. Thank you, doctor.

                     AGRICULTURE AND BIOTECHNOLOGY

    Senator Moran. The Senator from Montana.
    Senator Daines. Thank you, Mr. Chairman. Thank you for the 
efficiency with which you run this committee. I greatly 
appreciate it.
    Dr. Califf, congratulations to you as well on your recent 
confirmation, and thank you for coming before this committee.
    As you know, the United States is a world leader in food 
production, in food safety, and the FDA plays a critical role 
in maintaining our global leadership in those fields. In my 
home State of Montana, agriculture is our number one industry, 
and our farmers, our ranchers, whether they produce wheat, 
cattle, sugar, beets, pulse crops, or other products, play a 
critical role in not only feeding the United States, but also 
the world.
    And one important way Montana is able to do that is by 
having a world-class research facility at the land grant 
university, Montana State University (MSU). In fact, I was 
particularly proud when I heard that MSU was able to endow its 
first Montana plant sciences chair who is a world leader in 
cereal genetics and started earlier this year.
    Moving forward, it is critical that Washington not get in 
the way and push policies that have the potential to hinder or 
even discriminate against ag research and technology that has 
proven to be effective, proven to be safe, and proven to be 
productive. In particular, the prospects for biotechnology 
continue to be bright. Whether it is enhancing production by 
increasing crop yields or helping protect the environment by 
requiring fewer pesticides, or reducing demand for water, for 
example, or even lower food costs for families, I view biotech 
as essential to the future of our food supply.
    So with that as background, my question is, there was a 
decision made in November of 2015 by the FDA to deny a petition 
to require mandatory labeling of biotech in food products. Do 
you agree with that decision?
    Dr. Califf. Well, this is a decision that was really 
mandated by law in the opinion of the FDA because in order for 
the FDA to mandate a label, it would be required that there be 
a material difference, for example, as measured by a change in 
the nutritional composition of what you eat for a genetically 
engineered product versus a non-genetically engineered product. 
And we have been unable to detect such differences at this 
point, which explains our decision.
    Senator Daines. So as a food safety agency, it sounds like 
you would believe, and I do not want to put words in your 
mouth, but do you believe the FDA should make its decisions 
based on sound science rather than unsubstantiated claims that 
might not be supported by evidence?
    Dr. Califf. We are firmly committed at the FDA to base our 
decisions and policies on the best science that we can possibly 
get.
    Senator Daines. Yeah, it is good to have a doctor running 
it. Thank you, and I agree with you. And to bring this issue 
home, for example, in Montana on the eastern side of our State, 
sugar beets are a major crop. They are an economic driver for 
our State, and, in fact, the source of hundreds of jobs, and 
most sugar beets are grown utilizing biotechnology. But the 
sugar that results from the processing of a conventional sugar 
beet versus a biotech sugar beet is identical in both 
nutritional value and composition, I think to the point that 
were just describing there.
    If a biotech food product, like sugar beets in the example 
provided, is deemed by the FDA to be safe for human 
consumption, meet the same quality standards as a non-biotech, 
and is nutritionally and essentially the same as a non-biotech 
counterpart, should it be regulated by the FDA any differently?
    Dr. Califf. Well, the law tells us it should not be labeled 
specifically for that if the quality is as you described. But I 
also want to take the chance here to stress something that you 
said. This is vitally dependent on a robust agricultural, 
biomedical research enterprise, which is not predominantly 
located at the FDA. We have great people, and Susan Main is 
here today who leads that.
    But it is very important to have first-rate universities 
that are doing the kind of research that you described where 
you are. In my previous career at Duke University, we had great 
biology and botany, but NC State, you know, is world class in 
the broader agricultural sciences, and I had the chance to do a 
lot of work with those folks. So what we are really dependent 
on is a first-rate research enterprise that delivers the 
science that we need to make good decisions, so any decision 
would depend on the specifics of what was measured about the 
plant that you are discussing.
    Senator Daines. Well, I am out of time, but I want to thank 
you, Commissioner Califf, for the thoughtful remarks. And 
moving forward, I do believe it is important that the FDA 
remains focused on its mission to helping ensure the United 
States has a safe food supply and abstains from marketing or 
labeling mandates that would have no bearing on food safety. So 
thanks for your remarks.
    Dr. Califf. I would like to add, Senator, that we did issue 
a guidance on voluntary labeling so those who wish to do so 
have a specified way to do that for those. Who think it should 
be labeled as such.
    Senator Daines. Thank you.

                   FOOD SAFETY MODERIZATION ACT CFSMA

    Senator Moran. Thank you, Senator. Commissioner, let me 
turn my attention, our attention, to FSMA and the topic of 
guidance documents. How many guidance documents is FDA working 
on, and does FDA anticipate releasing--how many do they intend 
to release in regard to FSMA implementation?
    Dr. Califf. Well, Senator Moran, this has been a 
fascinating issue for me because essentially thanks to 
Congress, we are implementing an entire new structure to 
prevent food-borne illness and problems, rather than reacting 
to it. So this means an entire system is having to be put into 
place.
    As you know, five out of the seven major rules have already 
been issued. We have two more rules to come out shortly, and 
then emanating from those rules will be a whole series of 
guidance documents. And what I have come to understand about 
this particular area that is really fascinating and of 
emblematic of where America should be, is a system that starts 
at the farm, works at the county, works at the State, and 
includes the Federal Government.
    And as guidance documents are put out, and I cannot give 
you an exact number because it will depend somewhat on how 
things go. It is really the interpretation of the rules that 
gives people the information they need to for implementation. 
And since this is not the Federal Government saying here is 
exactly how you have to do it, it is really a discussion 
occurring among multiple parties. There has to be some 
flexibility in here so that we get it right.
    And you might even imagine the exact way things are 
implemented could vary depending on the circumstances in 
particular regions or with particular issues. So we are 
committed to issuing the guidance documents that are needed so 
that this is done right and it prevents food-borne illness.
    Senator Moran. And something you just said is a reminder to 
me to remind you and FDA, when your inspectors are reviewing 
practices and making a determination whether compliance is 
occurring, the guidance documents are just guidance. And the 
entity being reviewed can perform compliance in a different way 
than the guidance documents. That is true?
    Dr. Califf. Yes. So let me tell you why--I am actually 
excited about this topic. A lot of my career was built on doing 
multinational human clinical trials, and the first one we did 
was so big about 20 years ago, the FDA was not prepared for the 
inspection. So we ended up with meat inspectors looking at our 
electrocardiograms out in hospitals around the world, and it 
just was not ideal.
    And so, you know, before I got here, wise people figured 
out that our inspectors need to be aligned with a particular 
center so that there is a continuity between the expertise and 
the center and what the inspectors are doing. And when you have 
that expertise, it gives you the flexibility for the inspectors 
to look at the built-in quality as opposed to just reading a 
document and saying you have to do it this way.
    And, you know, I am really pleased to say this is well 
under way. It is a critical part of FSMA, so people inspecting 
farms and food places will have expertise in that area, and 
they will be connected to the center so that if there are 
issues rather than just relying on rote memory, they will be 
able to deal with it. Now, you know, whenever you have a 
complex system it is never perfect. People will need to let us 
know so we can adjust if there are problems.
    Senator Moran. You are making the point that I wanted to 
make sure was clear because even though a producer or a 
processor may not follow the guidelines, they still could be in 
compliance. And I want to make sure that your inspector would 
know that.
    Dr. Califf. Yeah, so----
    Senator Moran. It is about the result. It is not about--I 
mean, FSMA is designed in a way to create safe food, not a 
regulatory checklist. And I think that is what you just told me 
that you agree with.
    Dr. Califf. I agree with that, but I do want to pick a 
little finer point here----
    Senator Moran. Okay.
    Dr. Califf. [continuing]. Because in general, I can speak 
to this from hospital quality which has similar issues. The 
process typically is closely related to the outcome that you 
want. So when you deviate from a standard process that has been 
proven to be effective, then you need to have a good reason for 
doing it, and there often are good reasons. And I have been on 
the other side of the inspection, so I feel like I understand 
when a good reason may be in play.
    But I would not want anybody to believe that we can throw 
the process out the window here. I mean, the whole reason to 
have FSMA is so that we can share knowledge, and people on the 
farms and in the food processing places can know what the best 
standard for quality is. And our inspectors should know that 
quite well, too, because if we did not have that, we would have 
total chaos and no standard.
    So we are going to be flexible, but, you know, we have got 
to have people understand that process leads to the quality. 
Does that make sense?
    Senator Moran. It does. Related topic, what is the status 
of the personnel necessary to pursue compliance of FSMA? Are 
you in hiring mode?
    Dr. Califf. We have done a lot of hiring. We are still in 
hiring mode, and again, thanks for the funding because it is 
has made a huge difference. We are having to increase the 
workforce and the realignment. Remember previously it was 
geographically organized. Now we are saying, you know, you have 
got a particular job to do with a particular industry. And so, 
it is not just hiring people. It is also a tremendous amount of 
team building, and the things that you would do if you are 
building a first rate in a company.
    Senator Moran. Education and training.
    Dr. Califf. Yeah, and, you know it is a complex process. We 
have States and counties involved in doing a lot of the work. 
It is well underway, and I think it is going really well. We 
are excited about it.
    Senator Moran. Thank you, doctor. Senator Merkley.

                          OPIODS AND ADDICTION

    Senator Merkley. I want to turn to the current Senate 
conversation about opioids and opioid addiction and the 
overdoses that are occurring. The FDA has come under criticism 
for not always using an advisory panel on opioids. With Zohydro 
approved back in 2013, the FDA did have an advisory panel. It 
recommended 12-2 against approval, but FDA approved it anyway. 
And then the following year the FDA approved two additional 
opioids, but decided not to convene an advisory panel. What was 
the reason? Was it that FDA did not want to hear about the 
concerns from medical professionals, or why would on such an 
important issue--with so many addiction-related issues, why 
would the FDA have wanted to trash their advisory panel system?
    Dr. Califf. Well, let me be clear. There is no interest at 
the FDA in trashing the advisory panel system. As you know, we 
have recently taken a very deep look at opioids. It is right 
that people are upset. I know you are dealing with it today on 
the Senate floor. It is a national epidemic, more people dying 
from overdoses than from auto accidents, which is a startling 
statistic.
    So we have a very deep eight-point plan that was just 
published in the New England Journal with everything from 
having advisory panels on almost everything to reframing the 
whole issue. You know, the question is how do you consider a 
situation where maybe half of opioids that are prescribed are 
actually diverted to someone for whom the prescription was not 
written. How do you consider the societal effects in addition 
to the effects on the person for whom the treatment is 
prescribed?
    So this is a major point of emphasis. We are changing our 
tactic on this. And I guess the way I like to describe it is we 
are fighting a battle here against a very tough opponent. I 
think the FDA has always tried to do the best job it could, but 
the opponents have gotten tough very quickly, and we are having 
to change our tact here. We are going to do that.
    Senator Merkley. So I know you were not at the FDA last 
year when the FDA approved OxyContin for children without an 
advisory panel. It just kind of defies logic, and so I want to 
ask the question again. Why did the FDA decide to do away with 
advisory panels on these dangerous drugs?
    Dr. Califf. Let me address the two that you brought up 
specifically, Zohydro and pediatric OxyContin. And it will take 
just a minute, if it is okay. I know we are pressed for time.
    This Zohydro issue, it is true the panel took a vote that 
you have recited, but it also specified that there were 
criteria that might make it okay. Their problem was they were 
concerned about the post-market system that was in place. And I 
have learned there was a feeling at the FDA that the 
requirements of the advisory panel were met, so it was not felt 
that it was really disagreeing with the advisory panel. It was 
listening to the advisory panel and making the changes.
    But on that one, we are in complete agreement. If had we to 
do it over again, we would have met with the advisory panel 
again and reviewed the issues.
    And on the pediatric OxyContin, this is a very important 
one, and I think technically I do not think it is correct to 
simply call it an approval. OxyContin has been available for 
children. There are about 10,000 children a year, and if you 
have ever seen a child with sickle cell disease, for example, 
which is one of the serious illnesses for which chronic opioids 
are needed for very severe pain, or a child dying of cancer, 
the drugs are being prescribed, and we think for children, 
mostly appropriately so. Pediatricians would not use these 
drugs ad hoc.
    So the only change that was made was to make proper dosing 
available in the label as opposed to changing fundamentally the 
way the drug was used. And it was associated with a very 
profound post-market commitment to make sure we are able to 
track what is done with OxyContin. Having said that, we learned 
a lot by seeing what happened, and I should note that I was at 
the FDA when this happened because I was at Medical Products 
and Tobacco. So I do not want to be shirking responsibility 
here.
    But seeing the public reaction to this, we are going to 
have two consecutive pediatric advisory panels to review all of 
our approaches to opioids and children. They are already 
scheduled. They will be very intensive, and we will certainly 
listen to the advice.
    Finally, if I could just note one other thing about this, 
we do have a letter that was recently in the Boston Globe from 
the American Academy of Pediatrics and from the chair of the 
Standing Pediatric Advisory Committee of the FDA saying that 
they thought our decision was the correct decision to give 
doctors dosing information so they would know the right doses 
to use when these drugs are indicated. But, you know, having 
said that, we are going to use advisory panels to review these 
things.
    Senator Merkley. Mr. Chairman, could I ask one more 
question here?
    Senator Moran. Yes.

                              OPIOD LABELS

    Senator Merkley. So I am glad to hear the commitment to 
advisory panels going forward. Did you require on the label 
warnings about the addiction properties? Is that on all the 
opioids now?
    Dr. Califf. Yes.
    Senator Merkley. And if not, is that something that can be 
done right away?
    Dr. Califf. It is on all the opioids, but we are going to 
strengthen the labels, which is part of the plan that you see. 
And one thing that happened is there were a whole series of 
things done for long-acting opioids, so-called ER/LA, extended-
release and long-acting. And we are just updating this 
information to put out sterner warnings.
    So I think if you read what is in the label, it is pretty 
clear what the problems are, but we have learned that it has 
not gotten through, and we need to get to prescribers because 
the prescribing really needs to be brought under control.
    Senator Merkley. Well, I can tell you it does not get 
through because just recently, for example, my daughter had her 
wisdom teeth extracted, and so when she came home and she had 
her prescription, I said to her, you know, we have to be very 
careful of these because of the dangers of addiction, and it 
was one of those, ``oh, Dad'' moments. Now, if the dentist had 
talked to her about the dangers of addiction that would have 
carried some weight, if the pharmacist had talked with her 
about the dangers of addiction.
    But it was crazy to her. What is this crazy idea that she 
is hearing from her dad. And as I have talked to people, very 
few get any sort of education from their doctors about the 
substantial risks involved. And just think in Oregon, four 
million people last year, 100 million opioid pills prescribed. 
One hundred million.
    Dr. Califf. Well, if I may, I feel qualified to talk about 
this because up until 10 months I was a pretty busy practicing 
doc. I started in intensive care, and then had an outpatient 
practice. So, you know, recently it was not so big because I 
had administrator responsibilities, but still saw it all.
    The medical practice issue here is profound, and I know you 
all are going to be dealing with it actually today. It is our 
stated position in the New England Journal there should be 
mandatory education. And a really critical thing as you talk 
about this, to back up one second, we spent all day yesterday 
with our science board in a public meeting. One of your 
colleagues actually came out to the FDA to give some public 
testimony.
    A really critical thing here is mandatory education, but 
not just about opioids because, you know, the pain that people 
have is real. There are 10 to 12 million Americans with severe 
chronic pain, and we also heard from them. And so, the doctors 
need to be trained about how to deal with pain and then how to 
deal with the opioid part of pain.
    We have a voluntary program which is part of the RIMS 
commitment that companies have to pay for it, but independent 
CME providers do it. But one problem with voluntary education 
is that people most likely to volunteer to take it are the ones 
who probably need it the least. So we are officially in favor 
of mandatory education, and we think it is one of the most 
important things that could be done.
    Senator Merkley. Thank you.

                     CENTER FOR VETERINARY MEDICINE

    Senator Moran. Commissioner, I saw recently that the 
Director of the Center for Veterinary Medicine announced that 
she was leaving the agency. And I would ask you and encourage 
you to consider the appointment of a veterinary medicine 
practitioner, a doctor of veterinary medicine, to that 
position. Have you thought about what is next in this regard?
    Dr. Califf. I have. We will do a national search, and, you 
know, by standard we need to have it open to all types of 
people who might apply. I will note that I have a proclivity 
towards veterinarians right now. My future daughter-in-law, we 
have a family wedding coming up in Colorado. She is actually a 
Wyoming native, has just graduated from the Cornell Veterinary 
School. So I have heard the veterinarians' perspective on this, 
and personally I have sort of a love of veterinarians because 
of that, but we have to open it up to everyone.
    Being a medical doctor and now in charge of the FDA, I 
understand what you are saying, the concerns, the deep science 
concerns, you know. It would mean that someone from that 
background could be very helpful and someone with experience 
out in the field.

                              BIOSIMILARS

    Senator Moran. Thank you. Let me talk a moment about 
biosimilars and highlight language that was included in the 
omnibus spending bill directing the commission to respond, the 
FDA to respond. And what the language says is--first of all, I 
would preface this by saying there are lots of folks in the 
industry who would like to have input, understanding analysis 
as the biosimilar program is developed, naming labeling, 
interchangeability, and indication extrapolation. And our 
language in the appropriation bill that you are now operating 
under directed that the committee be provided with an estimated 
timeline by which the Agency will finalize all pending draft 
biosimilar guidance documents and regulations.
    The committee expects to receive this report no later than 
60 days after enactment. Enactment occurred in December, and we 
have not had a response to that directive. What is the status, 
and what can we expect?
    Dr. Califf. Well, it sounds lame to say I am going to have 
to get back with you on the details of the timing, but we will 
get back with you. I will just point out, I was in charge of 
the clinical trial for the first biologic in cardiology, and 
ended up working a lot with biologics. So I am well aware of 
the issues. They are complex, but I think we are very close.
    I will give a shout out to Janet Woodcock and her team who 
have been working on this. They are not only regulators. They 
are world authorities on the chemistry and biology of biologic 
drugs.
    So we are going to get this as quickly as we can. I mean, 
after all, we have 59 compounds in the pipeline now for the 
biosimilar program. So if we do not get this out soon, it is 
going to be difficult for people to navigate and know what they 
need to do.
    So I hear you, and we will get back with you.
    [The information follows:]
    
    
    
    
    
    
    
    
                 GAO REPORT ON FDA'S IT INFRASTRUCTURE

    Senator Moran. Let me highlight a Government Accountability 
Office (GAO) report that was released in December of 2015 on 
FDA's information technology infrastructure. That report made a 
recommendation that FDA define schedules and milestones for 
incorporating into its IT plan elements that align the Agency's 
mission and business strategies, and fully implement the plan.
    I have gotten interested in IT. We have seen lots of 
problems in Federal agencies and their use of IT, and I would 
highlight the GAO report for your consideration and 
information, and encourage the FDA to take an active role in 
meeting the recommendations of the GAO report. This matters a 
lot to efficiency and good government.
    Dr. Califf. Well, let me just say it was an interesting 
experience to come from a major university with a lot of 
Federal funds and then to step inside of the Federal system on 
IT, so I appreciate your concerns. And what I would say is that 
in the past, the primary issue at the FDA has been considered 
to be protecting all of the highly protected trade secret 
information that is under constant attack, and that has gone 
well. We have done that well.
    But I am pleased to say we hired a new CIO just as I came 
on board. He is a great guy. He has experience in the Federal 
Government and the private sector. We read the GAO report and 
we are complying with it. Not only that, we are working closely 
with the GAO to close the gaps.
    And what it pointed out was there was a plan for IT inside 
the FDA, but not a marriage of the IT plan with the overall 
strategic plan of the organization. And I can assure you in a 
science-based organization, if you do not have good knowledge 
management infrastructure, and the way the FDA works it is a 
lot of transactions, a lot like a business. People put in 
applications, and they have to be dealt with. If you do not 
have those systems working, you have got a real deficit that is 
going to hurt you, so we are very focused on it. And I am 
confident we will comply.
    Senator Moran. We have just a few more minutes. The vote 
has been called, but let me ask Senator Merkley if he has any 
brief, short follow-up questions that he would like to make 
sure he asks.

                                 OPIODS

    Senator Merkley. Thank you, Mr. Chairman. I want to go back 
to the opioid situation, and I mentioned the number of pills in 
Oregon, the 100 million pills prescribed for the population in 
1 year of 4 million. It seems like there must be ways to take 
this on. So many people say, hey, I needed eight pills, and I 
had 30 left over or whatever. And not only are they not getting 
from their doctors about the addiction risk, they are also not 
being told, and these represent a significant problem, these 
leftover pills, so this is what I want you to do. This is how 
you get rid of those pills. This is how you return them to me, 
or this is how you----
    So is it worth thinking about a smaller number of 
prescribed initially? And the way, I was shocked to read that 
the number--the percent--that virtually everyone who suffered 
an opioid overdose--I think it was 90 percent of those who 
suffered an overdose, were able to go back and easily fulfill--
get a prescription filled again even after their overdose. In 
other words, there is something--maybe we do not have a 
tracking database, people are getting prescriptions in various 
places.
    What can we do? It is crazy, 100 million pills in the State 
of Oregon?
    Dr. Califf. There is no doubt about this, and I should 
reveal that in my academic career just before coming to FDA, I 
was involved in the National Institute on Drug Abuse (NIDA) 
network to deal with opioid abuse, the National Institutes of 
Health (NIH)-funded network. We oversaw a project Kaiser was 
doing to organize its health system to offer alternative team-
based approaches to pain to reduce opioid prescription. And we 
had a grant from NIDA together with the CMS Innovation Center 
to develop electronic health record systems to identify and 
intervene people who were high risk in rural southern counties 
in West Virginia, Mississippi, and North Carolina. So I have 
done a lot of work on this topic.
    You are fair to call it crazy, and if I could take 1 
minute. I know you have got to go vote. Ten years ago there was 
a call for America's doctors to stamp out pain. It was a 
quality measure in hospitals. Doctors were taught that you had 
to get the pain level down to zero, and that was the goal. 
There obviously was an overreaction. It is extreme. It has 
created a national epidemic. We have got to rein it in.
    The FDA has a role. We are not going to shirk our 
responsibility. I believe our directions are currently clear, 
but if you talk to doctors, none of them read medical drug 
labels. I did not either. It is the derivative instructions 
that go to the doctor and the education.
    So we are one of multiple Federal agencies, and the 
Congress, and the States that need to work together. Remember 
that medicine is regulated mostly at the State level. We are 
prohibited from regulating the practice of medicine. We are 
going to be very outspoken about this along with you, and we 
have got to put practical things in place.
    One just quick comment about arbitrary restrictions on 
numbers of days. It is complicated because many of the people 
actually do need opioids for chronic pain. We had amazing 
testimony by someone from Walter Reed yesterday who was 
involved with tens of thousands of veterans that have had 
amputations. And many of them are in extended living facilities 
or other places where they cannot easily get back to the doctor 
to get their prescriptions refilled.
    So I would urge against an arbitrary restriction, but we 
have got to work together to convince doctors that they need to 
exert the most care with the fewest possible pills prescribed. 
And there are clear instructions for disposal of the medication 
if you do not need everything that is in your bottle.

                               CONCLUSION

    Senator Moran. Dr. Califf, thank you very much. Thank you 
for your testimony today. I was impressed with your level of 
knowledge and expertise, and I wish you well as you lead the 
Food and Drug Administration. My intention, as I indicated when 
we visited in my office, that I would have expected to have a 
conversation today about Zika, about opioids, which Senator 
Merkley clearly was interested in, and about cancer--the cure 
of cancer, and the moonshot effort. I welcome those 
conversations to continue. We can do that one-on-one.
    But my hope is that a few months into your job as we get 
through the appropriations process, that we would invite you 
back, that you would accept that invitation, and we would give 
not only Senator Merkley and I, but other members of this 
subcommittee the chance to have a more in-depth conversation 
about a variety of issues facing the FDA.
    Dr. Califf. I would really appreciate that opportunity. As 
my testimony submitted for the record says, we need the 
interchange and the guidance to get it right because we base 
everything we do on science, and we must insist that we get 
better and better at the science. But policy obviously involves 
an intersection of culture and science, and you are the 
intersection. So we look forward to working with you.
    Senator Moran. Thank you very much. And, Mr. Tyler, thank 
you for joining us. You have been very good at handing notes to 
the Commissioner.
    [Laughter.]

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Moran. I would take the opportunity to formally 
conclude this hearing as soon as I find the magic words.
    For members of the subcommittee, any questions that you 
would like to submit for the record should be turned into the 
subcommittee staff within 1 week, which is Wednesday, March the 
9th. We would appreciate if we could have responses from the 
FDA within 4 weeks of that time.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
               Questions Submitted by Senator Jerry Moran
                            cancer moonshot
    Question. The budget requests $755 million in mandatory funds for 
new cancer-related research activities, of which $75 million would be 
transferred from NIH to FDA to develop a virtual Oncology Center of 
Excellence.
    It is my understanding that the $75 million in mandatory funding 
for the Cancer Moonshot would be available for 5 years. How does that 
work? Would this funding only be used for infrastructure/IT, or would 
it be used for staffing? Would the mandatory funding need to be 
reauthorized, or is it a one-time cost?
    Answer. FDA is conducting a needs assessment to ensure a successful 
implementation of the Oncology Center of Excellence. Until business and 
systems requirements are fully documented, funding should be 
distributed equally across all 5 years, allocating $15 million per 
year.
    Preliminary budget estimates for fiscal year 2017 include a mix of:
  --IT funding to support system enhancements and innovation for 
        oncology related activities and improve analytic capabilities 
        in CBER, CDER and CDRH (each Center has multiple IT systems 
        that may need major or minor enhancements to support oncology 
        efforts)
  --Funding for executive recruitment search efforts to hire a 
        dedicated Oncology Center of Excellence Program Director and 
        senior staff
  --Funding for FTEs to support oncology activities across medical 
        product areas: drugs, biologics, and devices
  --Funding for FTEs to document business and systems requirements: 
        business project managers, information technology specialists, 
        systems engineers and other support disciplines.
    After the first 5 years, FDA will assess whether additional funding 
is necessary for the Oncology Center of Excellence.
    Question. Should Congress not move forward with the mandatory 
funding for the Cancer Moonshot, how much money would you need in 
fiscal year 17 to begin moving forward with the virtual Oncology Center 
of Excellence?
    Answer. Mandates such as the Oncology Center of Excellence can be 
challenging to implement without appropriate funding. Based on the 
magnitude of establishing a new structure to support the Oncology 
Center of Excellence, the minimum funding needed in fiscal year 2017 
would be $15million in budget authority, consistent with the 
distribution methodology over 5 years as described above. FDA regulates 
multiple product areas for drugs, biologics and devices, in addition to 
building, enhancing and maintaining various IT systems needed to 
automate the regulatory review processes.
                             fsma--produce
    Question. The produce industry has expressed concerns about the 
possibility of having some of their packinghouses subject to the 
preventive controls rule while other packinghouses would be subject to 
the produce rule. The produce industry has worked closely with FDA to 
ensure that there are commodity specific, risk based standards put in 
place under the produce rule.
    Would you agree that it makes no sense for produce facilities, 
because of ownership structure, to not be handled under the produce 
rule and instead under the preventive controls rule?
    Answer. In September, 2015 FDA launched a FSMA Technical Assistance 
Network (TAN) to provide technical assistance to industry, regulators, 
academia, consumers and others regarding FSMA implementation. FDA is 
using information specialists and subject matter experts to respond to 
questions related to the FSMA rules and programs. These questions are 
being tracked and trended to assist FDA in prioritizing FSMA guidance 
and training. FDA is also establishing a technical assistance network 
to support FDA food safety staff (FDA and State) performing inspections 
and compliance activities. FDA is identifying a cadre of experts to be 
available to assist inspectors and compliance staff with technical and 
policy questions including queries about regulation requirements and 
applicability.
    Question. Don't you think this would create added complexity, 
confusion, and cost when the real focus should be on food safety?
    Answer. Under FSMA, farms packing and holding covered produce are 
subject to the produce safety rule, and facilities required to register 
are subject to the preventive controls for human food rule. Our 
preventive controls and produce safety regulations adhere to the 
statutory framework. Accordingly, produce packing houses that fall 
under the new farm definition and pack covered produce are covered by 
the produce safety rule. Produce packing houses that do not fall under 
the new farm definition are facilities covered by the preventive 
controls for human food rule.
    We acknowledge the circumstances that result from the framework and 
have used our authority to minimize the practical effect of this 
dichotomy to the extent possible. First, we expanded our definition of 
``farm'' to include more packinghouses than before. However, it was 
important to us for the definition to reflect what farms are in the 
real world. As a result, we did not include all packinghouses, such as 
those businesses with a limited relationship to a farm, within that 
definition.
    Second, we expect that the specific steps necessary to ensure the 
safety of produce would generally be the same for on-farm and off-farm 
produce packing houses. For example, several of the CGMP requirements 
in the preventive controls rule that would apply to an off-farm produce 
packing facility (like provisions for employee health and hygiene, the 
plant and its grounds, sanitary operations and facilities, and 
equipment and utensils) have analogous counterparts in the produce 
safety rule. In addition, although an off-farm produce packing facility 
would be required to establish and implement a food safety plan and 
establish preventive controls food safety management components, we 
expect that, in general, off-farm produce packing houses can look 
toward the produce safety rule for guidance. We expect that an off-farm 
produce packing facility's food safety plan would focus on a few key 
preventive controls, which reflect similar measures in the produce 
safety rule. For example, we expect that the food safety plan for an 
off-farm produce packing facility would include preventive controls 
such as maintaining and monitoring the temperature of water used during 
packing. We also expect that an off-farm produce packing facility would 
establish sanitation controls to address the cleanliness of food-
contact surfaces (including food-contact surfaces of utensils and 
equipment) and the prevention of cross-contamination from insanitary 
objects and from personnel to food, food packaging material, and other 
food-contact surfaces. These preventive controls are also reflected in 
the produce safety rule.
                      fsma--supplier verification
    Question. There is a great deal of concern and confusion regarding 
the provisions in the final rule for Human Consumption dealing with 
situations when a facility is not required to implement a preventive 
control specifically with respect to the requirement for written 
assurances from customers.
    Does FDA intend to issue additional guidance on this section and if 
so when? With the final rule effective in close to 6 months, would FDA 
exercise enforcement discretion for this provision?
    Answer. FDA understands there is some concern about written 
assurances from customers required under certain provisions of the 
regulations on preventive controls for human and animal food as well as 
the regulation on foreign supplier verification programs, and we 
continue to have dialogue with industry to better understand their 
concerns and identify areas of confusion. We are considering guidance 
in this area, as well as other options for addressing the written 
assurance provisions before the first facilities have to comply with 
the preventive controls regulations on September 19, 2016.
                   fsma--technical assistance network
    Question. FDA has developed a Technical Assistance Network (TAN) to 
share information among consumers, industry, regulators and other 
stakeholders working to implement FSMA.
    Are the questions and answers submitted to TAN made public? If not, 
what is FDA's rationale for not making the questions and answers 
public?
    Answer. The individual questions and answers submitted to FDA's 
Technical Assistance Network (TAN) are not currently posted on FDA's 
web site. The TAN process is intended to address questions from 
individuals and firms. The posting of questions and answers FDA 
provides through the TAN process is not a substitute for FDA following 
the good guidance practice requirements (21 USC 371(h); 21 CFR 10.115) 
for communicating its current thinking on regulatory issues to a wider 
audience. In addition, FDA is in the process of developing answers to 
frequently asked questions for posting on the web site. Further, FDA is 
developing guidance documents that are being informed by the questions 
received through TAN. FDA will be better able to provide comprehensive, 
organized information through guidance documents to a broad audience 
while using a process that includes public input.
    The Department of Agriculture Food Safety Inspection Service (FSIS) 
has a similar system called ``AskFSIS'' which functions very well as a 
way to share information with industry and provide answers in a timely 
fashion. It's a helpful, searchable tool, and the content is public so 
everyone has access to the same answers. This also provides 
efficiencies so that the same questions aren't asked again and again.
    Question. Have you engaged in any discussions with FSIS to learn 
from their experience?
    Answer. Yes, FDA engaged in lengthy and productive discussions with 
FSIS from May through September 2015 before launching the FDA FSMA 
Technical Assistance Network in September 2015. Representatives from 
FDA visited the FSIS Technical Service Center in Omaha, Nebraska in May 
2015 to learn about their system and processes. The following features 
of the AskFSIS system and processes were adopted by FDA: the staffing 
structure including administrators and Subject Matter Experts to answer 
questions; the use of an IT platform (Knowledge Management System) that 
provides an internal searchable database of questions and answers to 
promote consistency in responses and tracking of responses; and 
trending responses to identify those that are frequently occurring so 
as to inform FDA's guidance documents. The FDA TAN has been well-
received by our stakeholders, and we believe that our early engagement 
with FSIS helped us build a solid foundation for our success.
                        fsma--inspection process
    Question. Under FSMA FDA is tasked to develop and implement a 
comprehensive program to train investigators on a wide range of issues 
including what the regulations require and how inspections should be 
conducted. It is essential that regulations are enforced consistently 
from one region to another, and by both Federal and state officials.
    Given the breadth of the new FSMA rules, what specific resources 
will inspectors have at their disposal during facility inspections when 
technical questions arise?
    Answer. For Preventive Controls inspection and compliance work, FDA 
is developing an electronic resource library that will include the 
following resource tools to aid FDA's food safety staff (including 
state employees performing inspections on FDA's behalf) before, during, 
and after inspections: special instructions and assignments; FDA 
guidance documents; links to commodity specific processing videos; fact 
sheets describing commodity specific processes and potential hazards 
and controls; and a contact list identifying subject matter experts by 
area of expertise.
    For issues relating to sprouts, FDA also plans to have a resource 
library that would include resources such as the Produce Safety Rule, 
FDA guidance, Sprout Safety Alliance training materials and resources, 
and subject matter expert contacts lists to provide technical and 
policy support to regulators inspecting sprout operations for 
compliance with the Produce Safety Rule and the Federal Food, Drug and 
Cosmetic Act.
    For Produce Safety, FDA is establishing a network of regionally-
based FDA personnel who will coordinate with state and other partners 
to fully implement and foster industry compliance with the Produce 
Safety Rule. This network will provide scientific and technical support 
to regulators performing inspections.
    Question. Has the FDA considered creating a hotline or phone number 
for inspectors to contact FDA experts?
    Answer. In September 2015, FDA launched a FSMA Technical Assistance 
Network (TAN) to provide technical assistance to industry, regulators, 
academia, consumers and others regarding FSMA implementation. FDA is 
using information specialists and subject matter experts to respond to 
questions related to FSMA rules and programs. FDA is tracking and 
trending these questions to assist FDA in prioritizing FSMA guidance 
and training. FDA is also establishing a technical assistance network 
to support FDA food safety staff (FDA and State) performing inspections 
and compliance activities. FDA is identifying a cadre of experts that 
will be readily available to assist inspectors and compliance staff 
with technical and policy questions including queries about regulation 
requirements and applicability.
    Question. It is foreseeable that a facility may disagree with an 
inspector's conclusions and/or interpretation of the rules.
    How will these differences be resolved?
    Answer. If a facility disagrees with the interpretations of the 
rules and conclusions reported during an inspection, the first step in 
the process should be contacting the District Office or state if 
applicable. Technical experts in the relevant Center (i.e., Center for 
Food Safety and Applied Nutrition or Center for Veterinary Medicine) 
would be engaged in questions regarding rule interpretation and 
application.
    If the facility does not believe the District Office or state has 
been responsive, or they do not understand the process for how to 
proceed next, then the facility should contact the ORA Ombudsman's 
office. The facility also may contact the ORA Ombudsman's office (or 
the FDA Ombudsman's office) for matters it believes are appropriate to 
raise in a different venue.
    Question. When a facility disagrees with an observation reported on 
a FDA Form 483 (Notice of Inspectional Observations), how should it 
appeal that decision?
    Answer. If a facility disagrees with an observation reported on a 
FDA Form 483, it would be able to appeal that decision using the same 
mechanisms utilized for all other inspections. As stated in the 
previous response, the first step in the process should be contacting 
the District Office or state if applicable. If that does not resolve 
the matter, for an FDA decision, a firm can file a formal request for 
review. FDA regulations (21 CFR 10.75) provide a mechanism for any 
interested person to obtain formal review of any FDA decision by 
raising the matter with the supervisor of the employee who made the 
decision.
    Question. Will the FDA provide a centralized, timely mechanism for 
companies/facilities to appeal an FDA enforcement action?
    Answer. If a facility disagrees with an observation reported on a 
FDA Form 483, it would be able to appeal that decision using the same 
mechanisms utilized for all other inspections. First, the firm can 
contact the issuing district office, as stated in the previous 
response. If that does not resolve the matter, the firm can file a 
formal request for review. FDA regulations (21 CFR 10.75) provide a 
mechanism for any interested person to obtain formal review of any FDA 
decision by raising the matter with the supervisor of the employee who 
made the decision.
    Question. Do you agree that a formal appeals process would also 
help identify areas where additional inspector training would be 
helpful?
    Answer. See our responses to previous questions describing the 
review process. FDA agrees that if a state, District Office, or ORA 
Ombudsman Office have been routinely contacted by regulated entities 
challenging inspectors' conclusions and/or interpretation of the rules 
for similar reasons it would potentially help identify areas for 
improvement. FDA could then consider this information when designing 
and administering subsequent inspector trainings to help prevent 
similar future disputes.
                        fsma--deficiency letters
    Question. On May 2, 2014, FDA released its Operational Strategy for 
Implementing the FDA Food Safety Modernization Act, and that document 
contained a list of administrative compliance tools including 
``voluntary correction achieved at the district level through 
deficiency letters . . . . to document significant safety-related 
deficiencies and request corrective action within a specified period of 
time.''
    What is a ``deficiency letter''? Please explain why this new 
enforcement tool is necessary and provide specific examples of 
situations that would lead to a deficiency letter?
    Answer. A deficiency letter is a potential new tool that FDA is 
considering using to inform a firm of observed violations that appear 
to pose a significant public health concern and FDA's expectations 
regarding a timely and effective response to address the identified 
concern. The deficiency letter would be issued within a relatively 
short time period after FDA made observations of non-compliance which, 
if not corrected quickly, could affect public health. Further, a 
deficiency letter would describe the enforcement tools available to FDA 
if, after Agency review, the firm has not adequately corrected the 
violation(s) and FDA continues to have the same level of concern.
    As contemplated, the intent of the deficiency letter would be to 
immediately, and in a formal way, advise the firm of the situation and 
to seek expedited compliance for those violations that present a 
significant public health concern. If the firm does not resolve the 
deficiency promptly, and further review within FDA supports the 
seriousness of the violation, FDA would determine what additional 
Agency action is necessary.
    The deficiency letter would have the potential to expedite FDA 
actions to protect public health. We believe the deficiency letters 
could enhance FDA's existing tools which include the Form FDA-483, 
Advisory Letters, and other enforcement tools, potentially decreasing 
the need for their use, but not replacing them.
    Our current thinking is that FDA would issue a deficiency letter 
only when the likely outcome of the observed violation would have 
significant public health implications. The specific criteria that 
would trigger a deficiency letter are still under development.
    Question. Please explain in detail the process FDA will be using 
for issuing deficiency letters including the following: who will issue 
them, who will review them, under what circumstances will they be 
issued, how much time will a facility be given to respond, will they be 
publicly available?''
    Answer. FDA is still considering whether to use deficiency letters 
as a possible compliance tool. If we decide to use deficiency letters, 
we will establish written standards for determining when to use 
deficiency letters, including the level of substantiation needed to 
support issuance. We also would establish written procedures for 
issuing and responding to deficiency letters.
    Question. How will deficiency letters fit into FDA's current 
administrative process?
    Answer. As contemplated, the intent of the deficiency letter would 
be to achieve expedited compliance for those violations that present 
the most significant public health concern. Thus, deficiency letters, 
if employed, would be a more targeted tool than warning letters. If a 
firm does not expeditiously correct the violation, FDA would be 
prepared to take further administrative or enforcement action to 
protect public health.
    Question. What is the implication/consequence of getting a 
deficiency letter?
    Answer. As deficiency letters are currently contemplated, a firm 
receiving a deficiency letter would be informed of any violations that 
pose the most significant public health concern. The deficiency letter 
would inform the firm that it should address such a violation in an 
expeditious manner. If the firm does not correct the violation in an 
appropriate timeframe, the firm would likely be subject to further 
administrative or enforcement action.
                           fsma--spent grain
    Question. The Committee understands that FDA is working on 
clarifying guidance on its dried Distiller's Grains rules. The 
Committee took action last year on delaying the implementation of the 
new rule while distillers awaited this guidance.
    Please inform the Committee when this guidance will be completed, 
provide response to what it would contain, and if the intent of the 
limitation contained in Sec. 750 will be complied with.
    Answer. Animal food, including distillers grains used for animal 
food, must be safe for its intended use and not adulterated. In 
September 2015, FDA finalized the Preventive Controls for Animal Food 
(PCAF) rule that established new regulations for current good 
manufacturing practices (CGMPs) and hazard analysis and risk-based 
preventive controls for animal food. This rule addressed a range of 
animal food, including byproducts of human food production used as 
animal food. Distillers grains from the alcoholic beverage industry are 
considered human food byproducts.
    FDA is currently developing guidance for industry to assist 
implementation of the rule. In the coming months, we are planning to 
issue draft guidance on compliance with the CGMPs and draft guidance 
for human food producers with byproducts going to animal food. Other 
guidance documents, including a draft guidance document on the hazard 
analysis and risk-based preventive controls requirements, will follow. 
We intend to issue these draft guidances before the applicable 
compliance dates for the PCAF rule. The guidance documents are part of 
a broader effort to foster and support compliance that also includes 
education, training, and FDA's Technical Assistance Network (through 
which firms can get answers to how the rule applies to their particular 
operation).
    FDA also assures the Committee that as we move forward with 
implementation of the PCAF rule, we will comply with the requirements 
of Sec. 750.
                                listeria
    Question. Did FDA's 2013 quantitative risk assessment study include 
data regarding the risk of Listeriosis associated with consumption of 
frozen vegetables and frozen food entrees?
    Answer. No. The 2013 quantitative risk assessment, issued jointly 
with the USDA Food Safety and Inspection Service, focused on deli foods 
and did not include data on frozen vegetables or frozen food entrees. 
The ``Interagency Risk Assessment: Listeria monocytogenes in Retail 
Delicatessens'' may be viewed at http://www.fda.gov/downloads/food/
foodscienceresearch/risksafetyassessment/ucm370243.pdf.
    Question. What relative risk of Listeria monocytogenes related 
illnesses does FDA believe frozen foods such as frozen vegetables and 
frozen food entrees pose compared to other foods historically known to 
be associated with Listeria monocytogenes?
    Answer. The quantitative risk assessments on Listeria monocytogenes 
that FDA has conducted to date have addressed frozen foods such as ice 
cream and other frozen dairy products, but have not addressed other 
frozen foods such as frozen vegetables and frozen food entrees.
    Question. Will FDA continue to distinguish between frozen ready-to-
eat foods (RTE) and frozen not ready-to-eat (NRTE) foods when frozen 
NRTE foods bear validated cooking instructions?
    Answer. FDA evaluates each situation in which a hazard, such as 
Listeria monocytogenes or Salmonella, is detected in a frozen food on a 
case-by-case basis. Where cooking instructions are present on the label 
of a frozen food, FDA will consider such factors as whether it is 
reasonable that a consumer or food service facility would thaw the 
frozen food for consumption without following package cooking 
instructions, or whether a consumer would follow recipes in which a 
frozen food would be thawed and included as an ingredient in a fresh, 
uncooked food such as salsa or a dip.
    Question. Will FDA align with global regulatory policy and treat 
the presence of Listeria monocytogenes in RTE foods on the basis of 
whether the RTE food does or does not support the growth of Listeria 
monocytogenes?
    Answer. FDA currently is discussing international standards on 
Listeria monocytogenes in RTE foods that vary based on whether the RTE 
food does or does not support the growth of Listeria monocytogenes. To 
further internal dialogue, in December 2015, FDA convened a meeting of 
the CFSAN Food Advisory Committee (FAC) to consider, among other 
things, whether FDA should treat the presence of Listeria monocytogenes 
differently in RTE foods, depending on whether the food supports the 
growth of Listeria monocytogenes. A majority of the FAC voting members 
(7 of 11 voting members) recommended that FDA should not treat the 
presence of Listeria monocytogenes differently in RTE foods, depending 
on whether the food supports the growth of Listeria monocytogenes. FDA 
intends to take the recommendations of the FAC into account in its 
internal deliberations.
    More information about the December 2015 FAC meeting, including the 
agenda, presentations, background information, transcripts and final 
FAC recommendations, can be found at: http://www.fda.gov/
advisorycommittees/
committeesmeetingmaterials/foodadvisorycommittee/ucm471769.htm.
    Question. Will FDA align its testing guidance to reflect current 
USDA practice? Specifically, will FDA change its recommendation on when 
a firm should speciate Listeria and encourage food manufacturers to 
follow up on a single finding of Listeria spp. on a food contact 
surface with corrective actions followed by additional testing?
    Answer. FDA currently is internally discussing better alignment of 
FDA's 2008 draft testing guidance to current USDA practices. To inform 
those discussions, in December 2015, FDA convened a meeting of the 
CFSAN Food Advisory Committee (FAC) to consider, among other things, 
whether FDA should change its recommendations on speciation of Listeria 
and appropriate follow up to a positive finding of Listeria species 
(spp.) on a food contact surface. The FAC recommended that ``FDA should 
follow the Food Safety and Inspection Service (FSIS) approach for 
Listeria spp. detected on a food-contact surface, if it tests positive 
then corrective action should be taken.'' FDA intends to take the 
recommendations of the FAC into account in its internal deliberations.
                                  zika
    Question. It is my understanding that several vaccine platform 
technologies have been developed over the last several years and could 
now be called upon to try to quickly develop vaccines for medical 
countermeasures, as well as emerging infectious diseases, like Zika.
    Can you explain FDA's role working with other agencies and 
companies to advance vaccine candidates for emerging infectious 
diseases?
    Answer. FDA works closely with other components of the Department 
of Health and Human Services--including the Office of the Assistant 
Secretary for Preparedness and Response (ASPR) and its Biomedical 
Advanced Research and Development Authority (BARDA), the National 
Institutes of Health (NIH), and the Centers for Disease Control and 
Prevention (CDC)--as well as with medical product developers, 
counterpart national regulatory authorities, and other international 
organizations (e.g., World Health Organization (WHO)) to advance the 
development and availability of medical products (including drugs, 
vaccines, and diagnostic tests) to respond to emerging infectious 
disease outbreaks as quickly and effectively as possible.
    FDA's efforts include providing scientific and regulatory advice to 
product developers and U.S. government agencies that support medical 
product development to help speed development programs. Specific 
activities include clarifying regulatory requirements through agency 
guidance and meetings, reviewing and providing input on pre-clinical 
and clinical trial designs, and expediting the regulatory review of 
data as they are received from product developers. As needed, FDA 
expedites the review of Investigational New Drug (IND) applications and 
related amendments, which are required for FDA-regulated clinical 
trials of drugs and vaccines to proceed. In addition, FDA collaborates 
with WHO and international regulatory counterparts--including the 
European Medicines Agency, Health Canada, and many others--under 
confidentiality agreements to provide technical support and scientific 
advice and to exchange information about investigational products in 
support of international product development efforts.
    Question. What resources are needed to respond quickly and nimbly 
to emerging infectious diseases and other potential threats to our 
public health security?
    Answer. Emerging infectious diseases and other threats to our 
public health security--such as the deliberate use of chemical, 
biological, radiological/nuclear agents--may occur without warning. 
Responding quickly and effectively to such no-notice events has 
required resources beyond what base resources can support. For example, 
to support the response to the Ebola epidemic in West Africa, Congress 
authorized $5.4 billion in supplemental funding in fiscal year 2015, 
which included $25 million for FDA. FDA is using this supplemental 
funding to support ongoing Ebola response activities, including:
  --Working closely with interagency partners, product developers, the 
        World Health Organization (WHO) and international regulatory 
        counterparts to encourage and facilitate the development and 
        assessment of vaccines, drugs and diagnostic tests;
  --Collaborating with West African health authorities to facilitate 
        access to investigational products as necessary (e.g., for 
        flare-ups) through appropriate mechanisms until approved 
        products are available;
  --Maintaining the availability of diagnostic tests under FDA's 
        Emergency Use Authorization authority; and
  --Supporting regulatory science to help facilitate Ebola medical 
        product development and review.
    To support response to the Zika virus outbeak, the Administration 
has requested approximately $1.9 billion in supplemental funding 
including $10 million for FDA. If appropriated, FDA will use the $10 
million supplemental Zika funding to support highly targeted regulatory 
science research required to enhance the efficient development and 
regulatory review of medical products and blood screening assays for 
Zika virus; collaboration with and technical support to international 
partners' response efforts; and FDA staff to support the development, 
review, regulation, and surveillance of vaccines, diagnostics and 
therapies.\1\
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budget_amendments/emergency_supplemental_2-22-16_zika.pdf
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                                tobacco
    Question. Public Health England, the English version of the U.S. 
Center for Disease Control and Prevention, stated that e-cigarettes are 
95 percent less harmful than a combustible cigarette. Moreover, 
England's government health plan, the National Health Service states 
that, ``There is evidence that e-cigarettes can help people stop 
smoking.'' And it is reported that the National Health Service will 
likely begin prescribing e-cigarettes as a cessation tool in 2016.
    Do you share the view of Public Health England and the National 
Health Service related to reducing the harm associated with combustible 
tobacco through e-cigarettes?
    Answer. Specific to individual health risk, the Public Health 
England Report's estimate of 95 percent lower risk of e-cigarettes 
compared to tobacco cigarettes relied upon evidence from a prior paper 
(Nutt, D. J., L. D. Phillips, D. Balfour, et al., ``Estimating the 
Harms of Nicotine-Containing Products Using the MCDA Approach,'' 
European Addiction Research, 20(5):218-225, 2014) to assess the 
relative harm of electronic nicotine delivery systems (ENDS) products. 
The Nutt et al (2014) paper employed an analysis model that quantified 
the relative health harms of 12 tobacco products using a series of 14 
harm criteria. The expert panel determined that while cigarettes scored 
100 percent in their assessment of maximum relative harm, ENDS products 
were rated to have only 4 percent maximum relative harm, which 
contributed to Public Health England's assessment that ENDS are around 
95 percent safer than smoking combusted cigarettes. The Report's use of 
the Nutt et al (2014) paper has several limitations, and the Nutt et al 
(2014) paper itself observed that it was reporting outcomes based on 
the decision-conferencing process from a group of experts who were 
selected without any ``formal criterion,'' though ``care was taken to 
have raters from many different disciplines'' and primarily based on 
geographic location ``to ensure a diversity of expertise and 
perspective''. In addition, the authors of the Nutt et al (2014) paper 
acknowledge that there is a ``lack of hard evidence for the harms of 
most products on most of the criteria''. The authors of the Nutt et al 
(2014) paper did not explain what scientific information was available 
to the experts upon which they should base their ratings and they did 
not explain the derivation of the quantitative assessment of each harm 
criterion. It is unclear if the authors of Nutt et al (2014) paper 
carried out or referenced a quantitative risk analysis, a standard 
practice when assessing relative risk, nor did the authors indicate 
that they used mean levels of exposure to harmful or potentially 
harmful constituents HPHCs in users or other quantitative evidence as 
an approximation of risk. FDA does not find the results reported in the 
Nutt et al (2014) paper to be sufficiently conclusive on the relative 
risks of using different tobacco products.
    FDA is also aware of the National Health Service's position on 
prescribing e-cigarettes as a cessation tool. No e-cigarettes have been 
approved by FDA as a cessation product. Moreover, consumers often don't 
know how much nicotine these devices deliver, making them unreliable 
for cessation efforts. There are a number of FDA-approved cessation 
tools on the market that have proven safety and effectiveness and FDA 
will continue to support and encourage research into cessation tools, 
including the potential role of e-cigarettes.
    The final deeming rule gives FDA the tools it needs to answer 
important questions about e-cigarettes and how they are made, marketed 
and used to help establish whether, how, and to what extent they are 
beneficial or harmful and to whom. Furthermore, subjecting e-cigarettes 
to FDA's tobacco product authorities will give manufacturers an 
incentive to conduct research and submit data to establish any 
potential public health benefit of e-cigarettes.
    There are distinctions in the hazards presented by various 
nicotine-delivering products. Cigarette smoking is the major 
contributor to the death and disease attributable to tobacco use. Given 
this, some have advanced the view that certain new non-combustible 
tobacco products (including ENDS products such as e-cigarettes) may be 
less hazardous, at least in certain respects, than combustible 
products, given the known carcinogens in smoke and the dangers of 
secondhand smoke.
    Scientific evidence may demonstrate that certain products are less 
harmful than others at an individual level, but the Tobacco Control Act 
directs FDA to also take into account the impact on the health of the 
population as a whole, including both users and non-users of tobacco 
products, in making regulatory decisions about these products.
    Much remains to be learned about the risks of e-cigarettes to 
health, as well as their possible benefits. E-cigarettes could benefit 
public health if they encourage people who would otherwise not quit 
smoking to stop smoking altogether, while not encouraging youth or 
others to start use of tobacco products or encouraging former users to 
relapse back to tobacco use. On the other hand, e-cigarettes could be a 
detriment to public health. E-cigarettes have the potential to re-
normalize smoking, encourage youth to initiate smoking, and/or prompt 
users to continue or to escalate to cigarette use--in effect, reversing 
the meaningful progress tobacco control initiatives have achieved to 
date. Other reported e-cigarette risks include dermal exposure to 
nicotine, childhood poisoning events, and physical harm from defective 
products (such as exploding batteries). Anecdotes illustrating both 
benefits and harms abound, but it is empirical scientific evidence that 
should drive the actions taken with respect to e-cigarettes.
    Question. FDA is committed to using an evidence-based approach to 
the application of the principles of harm reduction to tobacco 
regulatory policy.
    Does the FDA believe in the concept of tobacco harm reduction? Do 
you believe that adult smokers have the right to know about the risks 
and relative risks of different tobacco products and products with 
nicotine derived from tobacco?
    Answer. Section 911 of the Federal Food, Drug, and Cosmetic Act, as 
amended by the Tobacco Control Act, provides a pathway for companies to 
seek FDA authorization to market a modified risk tobacco product. In 
deciding whether to issue an order authorizing the marketing of a 
modified risk tobacco product, FDA takes into account a variety of 
factors such as the relative health risks to individuals of the 
product, the likelihood that existing users of tobacco products who 
would otherwise stop using tobacco products will switch to the product, 
and the likelihood that persons who do not use tobacco products will 
start using the product.
    FDA is committed to using an evidence-based approach to the 
application of the principles of harm reduction to tobacco regulatory 
policy. The Agency is also committed to providing the public with the 
most accurate health information and evaluating the products under our 
jurisdiction based on sound scientific evidence.
    FDA has communicated the existence of a continuum of risk of 
nicotine-delivering products to the public. For example, in the 
proposed deeming rule, FDA asked for comments, data, and research 
regarding how various new tobacco products should be regulated based on 
the continuum of nicotine-delivering products and the potential 
benefits associated with these products, especially e-cigarettes.
    There are distinctions in the hazards presented by various 
nicotine-delivering products. Cigarette smoking is the major 
contributor to the death and disease attributable to tobacco use. Given 
this, some have advanced the view that certain new non-combustible 
tobacco products (such as e-cigarettes) may be less hazardous, at least 
in certain respects, than combustible products, given the known 
carcinogens in smoke and the dangers of secondhand smoke.
    Scientific evidence may demonstrate that certain products are 
indeed less harmful than others at an individual level, but FDA must 
also take into account the impact on the health of the population as a 
whole, including both users and non-users of tobacco products, in 
making regulatory decisions about these products.
    Much remains to be learned about the risks of e-cigarettes to 
health, as well as their possible benefits. E-cigarettes could benefit 
public health if they encourage people who would otherwise not quit 
smoking to stop smoking altogether, while not encouraging youth or 
others to start use of tobacco products or encouraging former users to 
relapse back to tobacco use. On the other hand, e-cigarettes could be a 
detriment to public health. E-cigarettes have the potential to re-
normalize smoking, encourage youth to initiate smoking, and/or prompt 
users to continue or to escalate to cigarette use--in effect, reversing 
the meaningful progress tobacco control initiatives have achieved to 
date. Other reported e-cigarette risks include dermal exposure to 
nicotine, childhood poisoning events, and physical harm from defective 
products (such as exploding batteries). Anecdotes illustrating both 
benefits and harms abound, but it is empirical scientific evidence that 
should drive the actions taken with respect to e-cigarettes.
    CTP has identified e-cigarettes as an immediate research priority 
area, and has funded over 75 research projects since 2012 to better 
understand e-cigarette initiation, use, perceptions, dependence, and 
toxicity. This ongoing and funded research will provide important 
information about these products including a better understanding of e-
cigarette users, reasons for use, abuse liability, user perceptions, 
and health effects.
    Question. How will FDA share with adult tobacco consumers the 
different risks associated with different tobacco products?
    Answer. FDA is committed to providing the public with the most 
accurate health information and evaluating the products under our 
jurisdiction based on sound scientific evidence.
    FDA has communicated the existence of a continuum of risk of 
nicotine-delivering products to the public. For example, in the 
proposed deeming rule, FDA asked for comments, data, and research 
regarding how various new tobacco products should be regulated based on 
the continuum of nicotine-delivering products and the potential 
benefits associated with these products, especially e-cigarettes.
    Under the Tobacco Control Act, FDA has authority to issue an order 
authorizing a product to be marketed as a modified risk tobacco product 
after taking into account a variety of factors such as the relative 
health risks to individuals of the product, the likelihood that 
existing users of tobacco products who would otherwise stop using 
tobacco products will switch to the product, and the likelihood that 
persons who do not use tobacco products will start using the product. 
To date, FDA has not authorized the marketing of any modified risk 
tobacco product. FDA is currently conducting scientific review of eight 
modified risk tobacco product applications to determine whether the 
applicant has provided sufficient scientific evidence for FDA to issue 
an order allowing the products to be marketed as modified risk tobacco 
products.
    Although industry has introduced newer forms of tobacco products 
that are not currently regulated under FDA's tobacco product 
authorities, it is important to note that, if such products are deemed 
subject to FDA's tobacco product authorities, manufacturers may not 
market these products as modified risk tobacco products unless they 
request and receive authorization from the Agency.
                              biosimilars
    Question. The joint explanatory statement of the House and Senate 
Appropriations Committee on the Consolidated Appropriations Act, 2016 
(Public Law 114-113), expresses the need for FDA to provide the public 
with a greater opportunity to review and comment on all regulatory 
standards for the approval and oversight of biosimilar drugs. 
``Therefore, FDA is directed to provide the Committees with an 
estimated timeline by which the agency will finalize all pending draft 
biosimilars guidance documents and regulations. The Committee expect[s] 
to receive this report no later than 60 days after enactment.'' This 
law was enacted on December 18, 2015.
    Please provide your response to this request. If you do not have 
that information, please explain why you have not responded to this 
request and when you intend to do so.
    Answer. The requested report is currently in clearance. The Draft 
Guidance on Labeling for Biosimilar Products was released on FDA's 
website on March 31, 2016.
    Question. Please provide us with an estimated timeline for 
publishing draft and final biosimilars guidances for the topics that 
are listed on FDA's 2016 guidance agenda.
    Answer. The Food and Drug Administration (FDA) has worked 
diligently to issue multiple guidances on biosimilar products since 
enactment of the Biologics Price Competition and Innovation Act of 2009 
(BPCI Act). While FDA will continue to work on drafting guidances, 
reviewing submitted comments, and finalizing guidances in fiscal year 
2016, FDA anticipates issuing the biosimilar guidances listed in our 
guidance agenda within the next 12 months. Please keep in mind that 
while these are our best estimates, they are subject to change and 
factors such as workload and a shift in priorities could influence the 
timeframe.
     internet/social media advertising and promotional labeling of 
                           prescription drugs
    Question. In 2014 the FDA issued draft guidance for industry usage 
of Internet/social media platforms. Earlier this year, the FDA put out 
its guidance agenda for 2016 listing new and revised guidance's that 
are to be published this year. This list included a bullet on 
``Internet/Social Media Advertising and Promotional Labeling of 
Prescription Drugs and Medical Devices--Use of Links to Third-Party 
Sites''.
    Can you tell us what the timeline is for producing this guidance, 
and will this be the final guidance for the draft put out in 2014?
    Answer. The draft guidance issued in 2014 referenced above is the 
``Internet/Social Media Platforms with Character Space Limitations--
Presenting Risk and Benefit Information for Prescription Drugs and 
Medical Devices'' draft guidance. This draft guidance is not the 
document listed on the guidance agenda for 2016. The guidance agenda 
lists the ``Internet/Social Media Advertising and Promotional Labeling 
of Prescription Drugs and Medical Devices--Use of Links to Third-Party 
Sites'' draft guidance. FDA continues to work toward publishing this 
and other draft and revised draft guidances listed on the 2016 guidance 
agenda.
    Question. Are you working with stakeholders in crafting this 
guidance, and if so do you intend to do so further before putting out 
the updated guidance?
    Answer. FDA has worked with stakeholders since November 2009, when 
we held a Part 15 public hearing to gather input from our stakeholders 
(e.g., industry, healthcare professionals, consumers, patient groups, 
Internet vendors, advertising agencies, and other interested parties) 
on how FDA can best provide guidance on the promotion of FDA-regulated 
medical products (including prescription drugs for humans and animals, 
prescription biologics, and medical devices) using the Internet and 
social media tools.
    When this draft guidance is published, FDA will invite comments 
from our stakeholders on the draft. After providing this opportunity 
for public comment, we will review all comments received and carefully 
consider suggested changes, if any, as we prepare a final version of 
the guidance document.
                  inspections--risk based inspections
    Question. As FDA moves toward a more, targeted, risk-based, and 
efficient inspection model for importing drugs, food, and medical 
devices this will require better data about these facilities and the 
companies we are importing from. In the Omnibus, $5 million was 
included for foreign high-risk inspections to continue efforts to 
develop and ``utilize a targeted, risk-based, and efficient inspection 
model that incorporates commercially available information on high-risk 
establishments for onsite verifications.''
    Can you elaborate on the risk-based decisionmaking and how you are 
utilizing commercial data to prioritize inspections?
    Answer. FDA continues to improve our risk-based decisionmaking 
inspection models for multiple product areas. In our drug inventory, 
FDA is employing a site selection surveillance inspection model that 
runs annually on all facilities in the FDA's inventory allowing for 
risk-adjusted parity between the foreign and domestic inventory. 
Several ongoing efforts target improvements to the quality and scope of 
data feeding into the risk models. Improved accuracy and completeness 
of data related to the inventory of foreign manufacturing sites under 
FDA oversight leads to improved risk model outcomes and enhanced 
inspection planning efficiencies. To that end, FDA uses commercially 
available data (e.g., the data on businesses available through FDA's 
enterprise contract with Dun and Bradstreet) and commercial in-country 
services to verify the accuracy of firm information that feeds into the 
risk models.
    In the food arena, FDA continues to work with our foreign 
counterparts to develop and implement Systems Recognition agreements. 
Systems Recognition agreements allow FDA to leverage the findings of 
the country with whom we have an agreement to help target Agency 
resources and increase efficiencies in our inspection model. We 
continue to work towards identifying a Unique Facility Identifier (UFI) 
that will allow for more comprehensive commercial data to be attached 
to an entity. In addition, the Agency continues to work to incorporate 
Geographic Information System (GIS) data with our inventory to extend 
the capabilities of our risk model. GIS data allows for the analysis of 
additional layers of data that can be pivotal in making risk-based 
determinations.
                    inspections--data bounce process
    Question. It is my understanding that in 2013 the FDA's Southwest 
Import District Dallas Office created a program called the Data Bounce 
Process. Please provide a summary of this program, and input on whether 
it is something that could be replicated or expanded upon.
    Answer. Several years ago, FDA's Southwest Import District (SWID) 
initiated a project in which some SWID offices accepted entry data from 
importers of medical devices prior to entry. Via a stand-alone 
automated process, the SWID staff checked this entry data against 
existing FDA databases in an effort to verify accuracy of the importer-
supplied data. This process helped provide short-term feedback on 
whether importer-supplied data matched what FDA has in its own systems. 
Some firms have requested that FDA make this available to all firms 
importing products FDA regulates. While the agency appreciates this 
feedback, we have concluded that this limited operation cannot be 
effectively replicated on a large scale. FDA currently processes more 
than 34 million import admission decisions each year, and we do not 
have the IT capability to process a large number of additional test 
cases. If the program was expanded, additional test cases could easily 
number several million each year. Therefore, FDA is honing its 
targeting system to allow for the automated processing of entries where 
data are complete, accurate, and could fall into lower risk categories. 
In doing so, we may provide automated releases which increase 
efficiencies in terms of minimizing delays and enhancing targeting of 
high risk goods.
    We also believe it is helpful where possible to provide instant 
feedback regarding the acceptability of data necessary for import 
processing. We are pursuing a similar process through the Automated 
Commercial Environment (ACE) system. ACE has the capability to screen 
electronic import submissions and indicate where data is lacking or 
fails to match syntax such that the entry is not acceptable for 
processing. This functionality is currently available in ACE. We also 
are examining opportunities to enhance our IT systems and develop 
outreach programs to provide immediate feedback to the import filer 
when the data they provide does not match the information in our 
systems.
                       medical device inspection
    Question. Concerns exist with the lack of consistency, 
transparency, and predictability in the FDA medical device inspection 
process, including discrepancies in how facilities inside the US are 
inspected versus facilities outside the US, as well as FDA barriers to 
markets outside the US for products that are available to patients in 
the US. For example, typically five days is sufficient for the FDA to 
complete an overseas inspection and determine the suitability of the 
location to provide product into the US market while inspections inside 
the US can run several weeks, and even months. These discrepancies lead 
to variations in inspection standards and potentially competitive 
advantages for those who choose to manufacture outside the US.
    How does the FDA plan to address the discrepancies between 
inspections performed by FDA within and outside the US?
    Answer. A variety of factors are considered when planning and 
conducting inspections inside and outside the US. The majority of both 
domestic and foreign FDA inspections last 1 week or less but some 
inspections both inside and outside the US can last several weeks or 
longer. Medical Device inspections are conducted using FDA's Quality 
System Inspection Technique (QSIT), where some (Level I) or all (Level 
II) subsystems of the firm's quality system are evaluated. The average 
time to complete a domestic QSIT Level I inspection is 37 hours; 52 
percent of domestic inspections are QSIT Level I. The average time to 
complete a domestic QSIT Level II inspection is 58.5 hours; the 
remaining 48 percent of domestic inspections are QSIT Level II. Foreign 
inspections are always QSIT Level II and take an average of 61.4 hours. 
In situations where a firm has had a previous inspection with a 
significant number of violations or a firm has received a warning 
letter, the inspection may last longer because the agency needs to 
confirm the completion of promised corrective actions and ensure no 
additional problems create a public health risk. In addition, when FDA 
identifies a large number of violations in the first few days of an 
inspection, FDA may extend the length of the inspection to ensure we 
can fully assess all quality systems and rule out additional concerns.
    FDA is also engaged in an extensive Program Alignment initiative, 
which will create commodity-specific programs for the inspection of 
medical devices and radiological health products. Program Alignment 
allows FDA to address the increasing breadth and complexity of our 
mandate to protect the public health, address the impact of 
globalization on the food and medical product supply chains, and the 
ongoing trend of rapid scientific innovation and increased biomedical 
discovery. Program Alignment allows investigators with specialized 
knowledge of medical devices and radiological health products and 
related policies and procedures to focus on inspections of those 
products rather than expecting investigators to specialize in multiple 
product areas. Additionally, FDA is working to streamline existing 
processes, which are intended to improve effectiveness and consistency 
of inspections performed inside and outside the US.
    Further, FDA allows sponsors to submit the results of a third party 
audit in lieu of a routine surveillance inspection conducted by FDA 
personnel. Specifically, certain types of audits conducted under the 
Medical Device Single Audit Plan (e.g., those that are accepted as 
substitutes for routine inspections) may be deemed to satisfy 
regulatory requirements of multiple international jurisdictions, and 
provide flexibility to device sponsors and establishments.
    Question. There are reports of FDA withholding/rescinding a 
company's Certificate for Foreign Governments (CFG), essentially 
prohibiting the ability to serve markets outside the US, in instances 
when their products are able remain on the market in the US.
    What is the FDA's process for rescinding and reinstating CFG?
    Answer. A Certificate to Foreign Government (CFG) is an indication 
to a foreign government that FDA requirements are met at the time of 
its issuance. Firms request certificates to facilitate shipments to 
foreign countries.
    FDA/CDRH will not issue a CFG to a firm that has been issued a 
Warning Letter for Quality Systems violations. Before FDA/CDRH will 
issue that firm a CFG, FDA/CDRH must have assurance that the firm 
addressed the violations. Once FDA/CDRH confirms the issues are 
addressed through an inspection or a submission to FDA from the firm, 
FDA will issue a letter stating that the violations appear to have been 
adequately addressed. Only then will FDA issue a CFG to the firm.
    FDA/CDRH does not currently rescind CFGs once issued and we have 
not rescinded any certificates since 2009. CDRH previously rescinded 
certificates if we became aware that a firm was in violation of the 
Quality System regulation. It was difficult to physically retrieve 
rescinded certificates, however, because in most cases CDRH found the 
certificate had already been sent to the foreign country.
                                generics
    Question. Recently the FDA has proposed a series of initiatives, 
which, together with the slowdown in generic drug approvals, are 
contributing to cost increases (labeling rule, same size guidance, 
Quality Metrics Guidance, delay in guidance for interchangeable 
generics).
    Has FDA examined the collective effects of public health and cost 
to patients from the implementation of all these proposals? If not, can 
FDA undertake that examination and report back to the committee?
    Answer. One of the initiatives identified in your question is a 
rule and the other three initiatives are guidance documents. The 
processes governing consideration of the economic impact of proposed 
rules and guidance documents are different, as outlined below.
    With respect to the proposed rule on Supplemental Applications 
Proposing Labeling Changes for Approved Drugs and Biological Products, 
any final rule that is adopted will reflect FDA's consideration of 
public comments and would be accompanied by an analysis of the economic 
impact of the regulatory change described in the final rule. This 
regulatory impact analysis would be based on the framework described in 
Executive Orders 12866 and 13563, and use the best available techniques 
to quantify anticipated present and future benefits and costs. The 
regulatory impact analysis would help ensure that any regulation is 
adopted only upon a reasoned determination that its benefits justify 
its costs, and is tailored to impose the least burden on society, 
consistent with obtaining regulatory objectives. As part of the final 
regulatory analysis, FDA will estimate all of the benefits and all of 
the costs of the final rule. These benefits and costs will include any 
potential effects on public health and cost to patients from the 
implementation of the final rule but will not include the cumulative 
effects of other proposals or guidance documents. The effects of 
regulations and guidance documents currently in place are included in 
the baseline used as the starting point for estimating the effects of 
the rule.
    The process for consideration of guidance documents, including 
those mentioned in your question, is governed by FDA's Good Guidance 
Practices (GGP) regulations (see 21 CFR 10.115). FDA's GGP regulations 
do not require an examination of the costs or impact to the public 
health associated with following the recommendations described in 
guidance. Should the recommendations described in guidance cause a 
particular hardship to its relevant stakeholders, those stakeholders 
may propose an alternative approach as long as that alternative 
approach satisfies the relevant statutes and regulations. If a guidance 
requests or requires that members of the public obtain, maintain, 
submit, retain, report, or publicly disclose information, the Office of 
Management and Budget (OMB) must first grant approval of these requests 
or requirements as an information collection request (ICR) in 
accordance with the Paperwork Reduction Act. Before the ICR is reviewed 
and approved by OMB, FDA estimates the total time, effort, or financial 
resources involved in providing the information and publishes a notice 
in the Federal Register requesting comments from the public on specific 
elements outlined in the Paperwork Reduction Act.
    Industry, consumers and other stakeholders play a significant role 
in the agency's guidance development processes. FDA welcomes 
suggestions of topics for guidances, and in certain instances solicits 
draft proposals. For example, FDA may issue a ``Request for 
Information'' in the Federal Register to gain input on certain topics 
or participate in public workshops to engage with industry and other 
stakeholders on topics for which the Agency is considering developing 
guidance. After a draft guidance is published, comments are reviewed 
and considered by FDA in preparing the final guidance documents. The 
public can provide comments on any guidance document at any time.
                          dietary supplements
    Question. Within FDA's Center for Food Safety and Nutrition 
(CFSAN), how many FTE's are dedicated to enforcement activities? Of 
that number, how many are focused specifically on enforcing dietary 
supplement regulations?
    Answer. The Office of Compliance is the focal point for enforcement 
activities within CFSAN, with eight (8) FTEs dedicated to dietary 
supplement enforcement. The Office of Dietary Supplement Programs 
(ODSP) is the CFSAN lead for policy development and strategic 
management of the dietary supplement program, which includes compliance 
strategy and safety assessments as well as guidelines and regulations. 
ODSP has authorization for 26 FTEs. Most of ODSP's FTE's devote at 
least some of their efforts towards enforcement, but none are focused 
specifically on enforcement. CFSAN leverages its dietary supplement 
enforcement activities by partnering with other organizations within 
FDA, including the Office of Regulatory Affairs, that work on 
compliance and enforcement matters.
    Question. In 2015, how many enforcement actions did FDA bring 
against dietary supplement manufacturers and marketers? How many 
dietary supplement good manufacturing practice inspections did FDA 
conduct in 2015? How many serious adverse events were reported to FDA 
last year? How many unique dietary supplement formulations were 
involved in these reports? How many new dietary ingredient 
notifications were filed with the Agency in 2015? And lastly, how many 
FTEs are devoted to dietary supplement enforcement and regulatory 
programs (including inspections of dietary supplement facilities)?
    Answer. In fiscal year 2015 FDA issued the following warnings and 
brought the following enforcement actions against dietary supplement 
(DS) manufacturers and marketers:
  --49 Import Detentions (detentions without physical examination)
  --6 Untitled Letters
  --83 Warning Letters
  --6 Injunctions [Entered by District Courts]
(Data retrieved from FDA's Compliance Management Services database)
    In fiscal year 15, FDA:
  --Conducted 482 Dietary Supplement GMP inspections. Of those, 445 
        were of domestic facilities and 37 were of foreign facilities.
  --Received 5,336 serious adverse event (AE) reports for products 
        regulated by FDA's Center for Food Safety and Applied 
        Nutrition. Of those serious adverse events reported, 3,098 were 
        for dietary supplements with 3,529 unique product names 
        reported (some AEs report multiple products).
  --Received 35 new dietary ingredient notifications.
    FDA devotes just over 100 FTEs to dietary supplement enforcement 
and regulatory programs, including inspections of dietary supplement 
facilities. Approximately 26 of those FTEs are located in CFSAN's 
Office of Dietary Supplement Programs (ODSP), which serves as the CFSAN 
lead for policy development and strategic management of dietary 
supplement program, including enforcement and regulatory programs. 
CFSAN's Office of Compliance has approximately 8 FTEs focused on 
dietary supplement enforcement activities.
    Additionally, ORA devotes several FTEs to dietary supplement 
enforcement and regulatory programs, allocated in fiscal year 15 as 
follows: approximately 8.45 FTE for sample collections and analyses; 54 
FTEs expended for inspections for domestic and foreign dietary 
supplement firms; and 5 FTEs in the Office of Enforcement and Import 
Operations, Division of Enforcement, providing support for dietary 
supplement enforcement and regulatory program activities.
    Question. Given that the Office of Dietary Supplement Programs 
(ODSP) within the Center for Food Safety and Applied Nutrition (CFSAN) 
at FDA was only created in December 2015, what is the budget and FTE 
count for ODSP for the remainder of 2016? What is the proposed budget 
and FTE count for fiscal year 2017?
    Answer. In fiscal year 2016, the Center for Food Safety and Applied 
Nutrition provided the Office of Dietary Supplement Programs (ODSP) a 
budget of $4.6 million to include funding for payroll and non-payroll 
requirements. The fiscal year 2016 budget includes 26 approved 
positions (FTE). The proposed fiscal year 2017 budget for ODSP is $5.9 
million and includes additional funds for hiring to reach the approved 
level of 26 FTE.
    Question. What does the Office of Dietary Supplement Programs 
(ODSP) within the Center for Food Safety and Applied Nutrition (CFSAN) 
at FDA consider to be the top enforcement priorities in the dietary 
supplement industry for fiscal year 2017? How were these priorities 
selected?
    Answer. Using risk based prioritization, the Office of Dietary 
Supplement Programs (ODSP) has determined that in fiscal year 2017 it 
will use its current authorities and available resources to monitor the 
safety of dietary supplement products and take compliance and 
enforcement actions, such as:
  --Taking action to remove from the market supplement products that 
        are dangerous to consumers;
  --Taking action, in conjunction with FDA's Center for Drug Evaluation 
        and Research, to remove from the market products that contain 
        undeclared pharmaceutical agents and are labeled as dietary 
        supplements;
  --Enforcing the dietary supplement good manufacturing practices (GMP) 
        regulations, giving priority to cases with GMP violations that 
        meet the following criteria:
        --Potentially compromise product safety;
        --Fail to ensure product quality due to lack of testing, 
            procedures, and records; and
        --Result in consumer deception, when, for example, 
            manufacturers do not verify the identity of their raw 
            materials
  --Taking action against supplement products that bear claims to treat 
        diseases which can result in serious risk of harm to the 
        consumer (such as egregious claims of benefit in treating 
        serious diseases) or widespread economic fraud.
    These priorities reflect a risk-based determination of how ODSP's 
limited resources can best be deployed to protect the public health.
    Question. What is the status of FDA's effort to finalize the draft 
New Dietary Ingredient notification guidance?
    Answer. FDA published its draft guidance for industry entitled 
``Dietary Supplements: New Dietary Ingredient Notifications and Related 
Issues'' (the NDI Draft Guidance) for public comment in July of 2011. 
FDA reviewed public comments and met on several occasions with 
industry, consumers, and members of Congress to better understand the 
concerns raised. We considered the views expressed at those meetings 
and the many public comments received on the draft guidance as we 
worked on revisions to provide additional explanation and 
clarification. The comments received on the original draft guidance 
caused FDA to conclude that the best course of action would be to 
reissue the guidance as a revised draft that contains clarifications on 
several key issues that were the subject of confusion or 
misinterpretation. We are currently in the later stages of preparing a 
revised draft guidance, and we hope to publish the revised draft 
guidance in the near future. All interested individuals and groups will 
have an opportunity to review and comment on the revised draft guidance 
before FDA issues any final guidance.
    Question. How many facilities are registered as dietary supplement 
manufacturers with FDA through biannual registration as required by the 
Food Safety Modernization Act?
    Answer. As of March 2, 2016, there are a total of 12 744 
(6,522domestic and 6,222 foreign) facilities that have selected food 
product categories that indicate that they manufacture/process, pack, 
or hold dietary supplements. Of this total, 7,164 (3,876 domestic and 
3,288 foreign) registrations were renewed during the 2014 Biennial 
Registration Renewal period (October 1, 2014 through December 31, 
2014). Under current food facility registration regulations at 21 CFR 
1.233(g), the type of activity conducted at a facility is optional 
information and is not required to be submitted with a registration 
submission; therefore not all registrations include this information. 
Currently, there are a total of 4,953 (1,482 domestic and 3,471 
foreign) facilities that manufacture/process, pack, or hold dietary 
supplements that have provided activity type information identifying 
themselves as ``manufacturers/processors.''
                      over-the-counter antiseptics
    Question. The Food and Drug Administration (FDA) is currently re-
writing the 1994 tentative final monograph for over-the-counter (OTC) 
antiseptics. In the 1994 tentative final monograph, FDA delineated 
several categories associated with antiseptic hand washes, including 
one specific to food handlers and recognized that different categories 
of users need different regulatory treatment due to the possible risk 
to public health (78 Fed.Reg.76444).
    Does the FDA intend to recognize the different categories 
associated with antiseptic hand washes included in the 1994 tentative 
Final Monograph?
  --If not, does FDA intend to include food handlers as a part of the 
        2013 Consumer Hand Wash Monograph?
  --If so, does FDA intend to specify different regulatory conditions 
        that would be associated with antiseptic washes used in the 
        context of food preparation?
  --And, if this is the case, does FDA intend to have a more 
        substantive dialogue with stakeholders to ensure clarity about 
        how the rule will be applied in the consumer and food 
        preparation sectors?
    Answer. In 1994, FDA identified a category of nonprescription 
(over-the-counter) antiseptics marketed for use in food handling and 
processing, and requested relevant data and information regarding these 
antiseptic products (59 FR 31402 at 31440). FDA continues to consider 
antiseptics for use by food handlers to be a separate and distinct 
monograph category from consumer antiseptic monographs, which are 
labeled and marketed for different intended uses and which raise 
different issues. The consumer wash rulemaking is not intended to 
affect products indicated for use by the food industry. In fact, the 
2013 consumer antiseptic wash proposed rule specifically mentions that 
antiseptics for use by the food industry would not be discussed in that 
proposed rule (78 FR 76444 at 76446). We intend to consider over-the-
counter antiseptic products for use by the food industry separately 
from consumer wash antiseptics. FDA intends to communicate with 
stakeholders at the time of publication of the final rule on consumer 
antiseptic hand washes.
    Question. If FDA does not intend to include food handlers in the 
final monograph, will it be explicitly stated in the regulation and 
material associated with its release in order to prevent confusion 
about what should or should not be used by food establishments?
    Answer. In 1994, FDA identified a category of nonprescription 
(over-the-counter) antiseptics marketed for use in food handling and 
processing and requested relevant data and information regarding these 
antiseptic products (59 FR 31402 at 31440). FDA continues to consider 
antiseptics for use by food handlers to be a separate and distinct 
monograph category from consumer antiseptic monographs, which are 
labeled and marketed for different intended uses and which raise 
different issues. The consumer wash rulemaking is not intended to 
affect products indicated for use by the food industry. In fact, the 
2013 consumer antiseptic wash proposed rule specifically mentions that 
antiseptics for use by the food industry would not be discussed in that 
proposed rule (78 FR 76444 at 76446). We intend to consider over-the-
counter antiseptic products for use by the food industry separately 
from consumer wash antiseptics. FDA intends to communicate with 
stakeholders at the time of publication of the final rule on consumer 
antiseptic hand washes.
                                 ______
                                 
                Questions Submitted by Senator Roy Blunt
    Question. In the Ag-Omnibus end-of-year funding bill for the FDA, 
we included language to have the compliance date for the FDA final menu 
labeling regulations be in-line with FDA completing and publishing 
final guidance that has been in the works for over a year. We thought 
it is only fair for those who are regulated to have the answers to 
their numerous questions/concerns, to allow them to forward and allow 
adequate time to properly comply with these regulations.
    Can you tell us the status of the guidance?
    Answer. On September 11, 2015, FDA issued the draft guidance for 
industry, ``A Labeling Guide for Restaurants and Retail Establishments 
Selling Away-From-Home Foods--Part II (Menu Labeling Requirements in 
Accordance with 21 CFR 101.11).'' FDA received a wide range of 
substantial comments from a variety of stakeholders. FDA is carefully 
considering all comments received as we work to finalize the guidance. 
We expect to publish the final guidance in the spring of 2016.
    Question. Are you planning to incorporate some of the comments and 
provide some flexibility that many of the regulated establishments are 
seeking, into the final document?
    Answer. FDA appreciates the extensive input received from 
stakeholders throughout the process of establishing requirements for 
menu labeling and in developing guidance to assist industry in 
complying with the regulations. The menu labeling regulations provide 
flexibility for covered establishments, such as the ability to choose 
among several options for determining calorie and other nutrition 
information for standard menu items. The draft guidance reflects the 
flexibility of the regulations. We are carefully considering the 
comments and will incorporate changes as appropriate. We will also work 
flexibly and cooperatively with establishments covered by the menu 
labeling final rule to facilitate compliance. We will provide 
educational and technical assistance for covered establishments and for 
our state, local, and tribal regulatory partners. We believe this 
cooperative approach will facilitate successful implementation in a 
practical way.
    Question. I am concerned that many believe the industry has been 
the only reason for the delay in the menu labeling implementation. Do 
you agree that the FDA had a predominant role in the delay? The FDA 
took 3\1/2\ years to finalize the regs (April 1, 2011 Proposed Rule 
followed by Dec. 1, 2014 Final Rule) and then another 10 plus months to 
issue draft guidance when the FDA itself could not answer the questions 
from the regulated businesses such as grocery stores and others?
    Answer. The successful development and implementation of a complex 
rulemaking such as menu labeling requires sustained dialogue and close 
collaboration with the affected industry and other key stakeholders. We 
recognize that implementing menu labeling requirements nationwide in a 
collaborative manner has taken a significant amount of time and 
resources.
    As we developed the menu labeling rule, we became increasingly 
aware of the complexity of the American retail food industry, 
particularly with respect to foods prepared away from home. FDA 
received a wide range of substantial comments on the proposed rule from 
consumers, various food industries, trade associations, and other key 
stakeholders.
    As we move toward implementation, to assist stakeholders with 
further understanding the menu labeling requirements we have been 
meeting and will continue to meet with industry groups to discuss the 
requirements. We will also continue to provide webinars and 
presentations and respond to industry questions submitted to the 
Agency's menu labeling inbox. We will work flexibly and cooperatively 
with establishments covered by the menu labeling final rule to 
facilitate compliance. We will also provide educational and technical 
assistance for covered establishments and for our state, local, and 
tribal regulatory partners. We believe this collaborative approach will 
facilitate compliance with the requirements in a flexible and practical 
way.
    As you know, the House passed legislation to make some changes to 
the FDA menu labeling regs so certain entities would have a better 
opportunity to implement and comply with these regulations. I was 
joined by Senator King in introducing the Senate companion bill. The 
bill does not exempt supermarkets, convenience stores, or delivery 
operations from the menu labeling regulations, but allows some 
practicality for providing nutritional information to customers based 
on the different ways that foods are prepared and sold across various 
venues and formats.
    For instance, the House passed bill has provisions such as:
  --Preserving local foods or fresh items that may only be sold at one 
        or two store or restaurant locations.
  --Allowing for use of a menu or menu board in a prepared foods area 
        or next to a salad bar instead of individually labeling every 
        item
  --Allowing an establishment 90-days to take corrective actions to fix 
        an error and clearly stating that oversight authority rests 
        with FDA (and states/municipalities that work with FDA) ;
  --Allowing items that are normally ordered off-premises (pizza 
        delivery) to have nutritional information posted as the 
        ordering decision is made online as a means for compliance.
    None of these provisions impact FDA's oversight or enforcement 
authority and no entity that is currently regulated under the menu 
labeling regulations would be exempt.
    Question. FDA did not provide flexibility in these areas in the 
draft guidance that the agency released last September. Are there any 
provisions in this bill that FDA is planning on adopting as part of 
this final guidance you are working on?
    Answer. FDA's menu labeling draft guidance reflects the Agency's 
current thinking on the menu labeling regulation (21 CFR 101.11) and 
does not impose new requirements. Rather, the draft guidance explains 
the Agency's interpretation of the regulation and contains 
recommendations for ways that industry can meet the menu labeling 
requirements. Industry may use other approaches that satisfy the 
regulations.
    We understand that H.R. 2017, referred to as the ``Common Sense 
Nutrition Disclosure Act of 2015,'' is still under consideration in 
Congress. If this bill, as currently written, should become law, FDA 
would have to engage in rulemaking to amend the current requirements 
and revise any associated guidance.
                                 ______
                                 
              Questions Submitted by Senator Steve Daines
         fda final rule deadlines and market stability lead-in:
    Question. On May 1, 2015, the FDA published a Proposed Rule to be 
added to their 1994 Tentative Final Monograph (TFM) for Healthcare 
Antiseptics. Yet, the FDA as indicated that this proposed rule will not 
be finalized until January 2018, despite having received significant 
public input and concerns with the proposed rule. This delay has left 
companies in limbo, not knowing whether their new products will need to 
meet a coming finalized rule to enter the market or for existing 
products to remain on the market and whether that finalized rule will 
address their concerns. As an example, this turbulence in the market 
has caused a 25 percent revenue reduction in 2015 for BioScience 
Laboratories, a Montana company, and they are currently facing 
additional staff reductions.
    Mr. Commissioner, will the FDA continue to delay addressing 
concerns with this proposed rule regarding the 1994 Temporary Final 
Monograph (TFM) for Healthcare Antiseptics and continue to delay 
publishing a final rule?
    Answer. In 1994, FDA published a proposed rule with the agency's 
tentative determinations as to which ingredients were generally 
recognized as safe and effective for use in nonprescription 
antiseptics. Since 1994, FDA's safety standards, our ability to detect 
and measure antiseptics in the body, and the scientific knowledge about 
the impact of widespread antiseptic use have evolved. For the past 
several years, FDA has been actively engaged in this issue. In 2005 and 
again in 2014, FDA sought the advice of an FDA advisory committee made 
up of outside scientific and medical experts. As you know, on May 1, 
2015, we published a healthcare antiseptics proposed rule (HCA PR(80 
FR25166), which is part of a larger, ongoing review of antiseptic 
active ingredients by FDA. The HCA PR proposed that all active 
ingredients used in healthcare antiseptic products marketed under the 
OTC drug monograph system need additional safety and effectiveness 
data. In doing so, it proposed to revise certain testing criteria, 
identified important scientific data gaps for active ingredients used 
in certain over-the-counter healthcare antiseptic products, and 
requested additional data to support the ingredients' safety and 
effectiveness.
    Because of the complexity of the HCA PR, FDA provided a public 
comment period of 180 days after publication, which closed on October 
28, 2015. Moreover, the public and regulated industry had 12 months 
after publication of the proposed rule, or until April 30, 2016, to 
submit data or new information. Responsive comments on any new data or 
information may now be submitted for an additional 60 days, until June 
30, 2016. Upon the close of the final comment period, FDA will review 
all data and information submitted to the record in order to complete a 
final rule. FDA intends to issue the final rule on healthcare 
antiseptics by January 15, 2018, which is approximately 18 months after 
the final comment period closes.
                               follow-up
    Question. Additionally, will you commit to reducing market 
turbulence to the full extent possible by preventing such delays in 
addressing public concerns with proposed rules and publishing final 
rules in a timely manner, as well as clearly indicating when those 
final rules will go into effect?
    Answer. Senator, we understand your concerns. However, because of 
the complexity of the healthcare antiseptics proposed rule, FDA 
provided a public comment period of 180 days after publication, which 
closed on October 28, 2015. Moreover, the public and regulated industry 
had 12 months after publication of the proposed rule, or until April 
30, 2016, to submit data or new information, and comments on any new 
data or information may now be submitted for an additional 60 days, 
until June 30, 2016. Upon the close of the final comment period, FDA 
will review all data and information submitted to the record in order 
to complete a final rule. FDA intends to issue the final rule on 
healthcare antiseptics by January 15, 2018, which is approximately 18 
months after the final comment period closes. In the proposed rule, FDA 
proposed that any final rule would become effective 1 year after the 
date of the final rule's publication in the Federal Register.
    Notice and comment rulemaking is a lengthy and multistep process. 
Major steps for FDA rulemaking generally include determination that a 
rule is needed and what the rule should say; review of relevant data; 
drafting, reviewing, and finalizing the proposed rule; publishing the 
proposed rule; a public comment period and review of the comments; 
revising the proposed rule as appropriate; possibly convening an 
advisory committee meeting, meeting with interested parties, or both; 
reviewing the draft final rule and finalizing it, and publishing the 
final rule in the Federal Register.
    Even while FDA is moving forward to finalize the healthcare 
antiseptic rule, FDA has a very broad mandate and multiple public 
health priorities, with limited resources to address these priorities. 
FDA's Center for Drug Evaluation and Research (CDER) is responsible for 
regulating the safety and efficacy of both prescription and 
nonprescription human drugs. Like FDA as a whole, CDER must continually 
balance multiple important public health priorities, of which the OTC 
Drug Review, which includes healthcare antiseptics, is one. CDER does, 
and will continue to, consider the OTC Drug Review, and the antiseptic 
rulemakings in particular, among its priorities as it endeavors to 
appropriately allocate staff and resources within the context of all 
CDER responsibilities.
                                 ______
                                 
              Questions Submitted by Senator Jeff Merkley
                                tobacco
    Question. The longer the tobacco deeming regulation takes, the more 
attempts there will be to include things like the House's language last 
year, which would have changed FDA's deeming date, and kept e-
cigarettes essentially unregulated.
    What effect the House's provision last year would have had on 
access to tobacco products, and the deeming regulation?
    Answer. This language contained in last year's House bill aimed to 
treat newly deemed products in a way roughly modeled on how the TCA 
treated newly regulated products when the law was enacted. 
Specifically, the grandfather date of February 15, 2007, would be 
changed to the effective date of the deeming final rule, and new 
tobacco products introduced between the new grandfather date and 21 
months afterwards would be permitted to stay on the market as long as 
an SE report was submitted by the end of the 21 month period. This 
proposed language would have eroded FDA's ability to regulate certain 
tobacco products to protect public health. Specifically, the House bill 
would exempt from FDA review those tobacco products that were marketed 
before the effective date of the deeming final rule. As a result, these 
products, including currently marketed flavored e-cigarettes, and novel 
tobacco products like certain dissolvables, would have been allowed to 
stay on the market indefinitely without oversight or a scientific 
evaluation of their risks, potentially threatening public health. Those 
tobacco products that come on the market after the 21 month transition 
period would be subject to FDA's premarket authority and would need a 
marketing order before being sold.
                                opioids
    Question. FDA has been under fire recently for approving opioids 
without convening, or against the recommendations of, your advisory 
panels, especially when the pills are flooding the market. In response, 
the Agency recently announced a series of steps including re-examining 
the ``risk-benefit'' paradigm for opioids to consider public health 
effects; convening an advisory panel for any new opioids that don't 
have abuse deterrent properties; and adding additional warnings on 
labels, among other things.
    Could you walk us through each of these decisions and the outcomes 
you expect they will provide? Specifically, on the risk-benefit 
paradigm, what will FDA consider that it wasn't already--addiction 
potential, number of opioids already on the market, anti-deterrence 
methods?
    Answer. These actions are part of a number of actions the Agency 
outlined in a plan to reassess the approach to opioid medications 
announced in February. The plan is focused on policies aimed at 
reversing the epidemic, while still providing patients in pain access 
to effective medication. This comprehensive action plan will help to 
mitigate the problem of opioid abuse and confront the epidemic. There 
are four main pillars to the plan described below.
  --Transparency: FDA will be more transparent and open in the approval 
        process for this category of drugs. FDA plans to convene an 
        expert advisory committee before approving any new drug 
        application for an opioid that is not in an abuse-deterrent 
        formulation (ADF). Additionally, we're going to engage the 
        Pediatric Advisory Committee to make recommendations on 
        pediatric opioid labeling before any new labeling is approved. 
        The advisory committee process is going to provide opportunity 
        for public input, which is going to help us better understand 
        and answer the concerns people have about these drugs.
  --Improving Communication: Requiring labeling changes and updates to 
        Risk Evaluation and Mitigation Strategies (REMS), FDA hopes to 
        improve communication with the medical community about opioids. 
        Through labeling, our goal is to provide better information to 
        doctors about the risks of these drugs and how to safely 
        prescribe them. In March 2016, FDA released new labeling 
        changes to immediate release opioid labeling that incorporate 
        elements similar to the labeling of the extended-release/long-
        acting opioid analgesic products. In addition, FDA will 
        evaluate updates to our Risk Evaluation and Mitigation Strategy 
        (REMS) program requirements for opioids with the goal of 
        increasing the number of prescribers who receive training on 
        pain management and improve the safe prescribing of opioids to 
        decrease inappropriate prescribing. That effort will complement 
        work being done at the Department level and at the CDC to help 
        ensure that opioids are prescribed appropriately. We believe 
        that improving prescribing practices is a key component of 
        ending this public health crisis. The nearly 250 million 
        prescriptions for these types of pain killers written each 
        year--enough for every adult in the U.S. to have a bottle of 
        pills--is clear evidence of the work ahead of us.
  --Post Marketing: FDA recently strengthened the requirements for 
        drugmakers to conduct post-market analysis of opioid 
        analgesics. This information, especially about long-term use, 
        is currently lacking and we need more and better evidence on 
        the risks of misuse and abuse associated with long-term opioid 
        use and to better understand predictors of addiction, among 
        other issues.
  --Product Development: In March, the FDA issued draft guidance with 
        its recommendations for studies that should be conducted to 
        show that a generic copy of a brand-name abuse-deterrent opioid 
        formulation is as abuse-deterrent as the brand-name drug. We 
        believe the availability of less costly generic products with 
        abuse-deterrent properties may help accelerate prescribers' 
        uptake of abuse deterrent formulations. In addition, FDA is 
        working to improve access to naloxone, which is effective at 
        treating overdoses. The FDA is reviewing options, including the 
        possibility of over-the-counter availability, to make naloxone 
        more accessible.
    Question. Is there anything FDA could do to try to curb the number 
of pills that doctors prescribe, such as shortening the standard course 
of treatment for acute injuries, so there aren't as many pills left 
over?
    Answer. There is no standard course of treatment for acute injuries 
described in labeling for opioid analgesics. That is because the 
duration of treatment will vary depending on the type of injury. It is 
generally left to the discretion of the treating healthcare provider to 
decide how many pills to prescribe once the decision has been made to 
prescribe an opioid analgesic.
    Question. FDA has contributed significantly to improving the safety 
and safe use of opioid analgesics. We are continuing our work to ensure 
prescribers have the information they need to understand the risks 
associated with opioid analgesics, as evidenced by the recently 
announced sweeping changes FDA is requiring to the immediate-release 
(IR) opioid analgesic labeling, which include safety-related 
information similar to that added to the extended-release and long-
acting (ER/LA) opioid analgesic labeling in 2014. FDA is also requiring 
changes to the indications for these products to better emphasize that 
opioid analgesics should be prescribed in situations where non-opioid 
analgesics are not adequate. Further, the ER/LA Opioid Analgesics Risk 
Evaluation and Mitigation Strategy (REMS) requires that drug sponsors 
make available prescriber education to better inform healthcare 
professionals about the risks and appropriate use of these drugs. It is 
the Agency's hope that the significant actions it has taken, along with 
broader Departmental efforts, will lead to more careful and thoughtful 
prescribing, and more appropriate use of these drugs.
    What role does FDA play in educating doctors and pharmacists about 
the risks of these drugs?
    Answer. The primary tool FDA uses to educate doctors and 
pharmacists about the risks of prescription drugs, including opioids, 
is the FDA-approved product labeling. The purpose of the drug labeling 
is to give healthcare professionals the information they need to 
prescribe drugs appropriately; to understand the patients for whom the 
drugs are considered safe and effective; the way the drugs are intended 
to be used; and the risks and benefits associated with their use. In 
April 2014, FDA finalized sweeping changes to the labeling for 
extended-release and long-acting (ER/LA) opioid analgesics to help 
prescribers better understand the risks of misuse, abuse, neonatal 
opioid withdrawal syndrome, addiction, overdose, and death associated 
with these drugs and to more clearly describe the patient population in 
whom these drugs should be used. On March 22, 2016, FDA sent letters to 
sponsors of immediate-release (IR) opioid analgesics requiring changes 
similar to those finalized for the ER/LA opioid analgesics in 2014. 
These changes to the labeling, once finalized, are expected to 
emphasize that opioid analgesics should be prescribed only when other 
treatment options are inadequate or ineffective. For both ER/LA and IR 
opioid analgesics, the new labeling better enables prescribers to make 
decisions based on a patient's individual needs, given the serious 
risks associated with opioids. FDA intends these changes to enable not 
only a more careful and thorough approach to determining whether opioid 
analgesics should be prescribed for a particular patient, but also to 
allow prescribers to better assess whether the serious risks associated 
with opioids, are offset by the benefits opioids may provide in 
managing pain for an individual patient.
    FDA also uses other tools to educate prescribers about opioid 
risks. For example, the ER/LA Opioid Analgesics Risk Evaluation and 
Mitigation Strategy, approved in 2012, requires manufacturers of the 
ER/LA opioid analgesics to make available, for free or at nominal cost, 
education courses from for healthcare professionals who prescribe ER/LA 
opioid analgesics. These continuing education courses educate 
prescribers about the risks of these opioid analgesics, as well as 
safer prescribing and use practices for these drugs. Manufacturers of 
ER/LA opioid analgesics are also required to conduct an assessment of 
the REMS and submit a REMS assessment report to the Agency for review. 
On May 3-4, 2016, FDA convened a joint session of the Anesthetic and 
Analgesic Drug Products and the Drug Safety and Risk Management 
Advisory Committees to discuss the results of the 36th month ER/LA 
Opioid Analgesics REMS Assessment submitted by the manufacturers of the 
ER/LA opioid analgesics in July 2015. The Agency sought the committees' 
comments as to whether the REMS for this class of drugs assures safe 
use; is not unduly burdensome to patient access to the drug; and, to 
the extent practicable, minimizes the burden to the healthcare delivery 
system. In addition, the Agency sought the committees' comments on any 
modifications to the ER/LA Opioid Analgesics REMS, including possible 
expansion of the scope and content of prescriber education, and whether 
to expand the REMS program to include immediate-release opioids. FDA is 
evaluating potential modifications to the REMS program requirements for 
opioids after considering advisory committee recommendations and 
reviewing existing requirements.
    In addition, the Agency utilizes publications such as drug safety 
communications (DSCs) to inform prescribers and patients of safety 
issues that should be considered when prescribing and using these 
drugs. For example, on March 22, 2016, FDA issued a DSC regarding risks 
of serotonin syndrome for some opioids, and for adrenal insufficiency 
and androgen deficiency for all opioids, regardless of indication. 
Further, FDA officials recently published a note in the Journal of the 
American Medical Association expressing the Agency's dedication to 
improving the safety of these drugs, and setting forth the Agency's 
plan to achieve this goal in the coming months.
    Question. Why not require an advisory panel for all new opioids, 
whether or not they have an abuse deterrent formula?
    Answer. Seeking advice from external experts on matters related to 
opioids, including related to this emerging area of science, is a 
cornerstone of the FDA's 2016 Opioids Action Plan. While we're 
continuing to learn more about the impact that approved abuse-deterrent 
(AD) products are having in the community, and supporting research and 
development of additional technology, the agency plans to seek advisory 
committee recommendations on new, non-AD brand-name products, and on 
new AD brand-name products when they raise novel issues. We hope that 
this public discussion will allow for greater transparency around the 
FDA's decisionmaking regarding opioid products during this period of 
reassessment of our policies and regulatory approach to 
opioids.Judicious use of Advisory Committees is grounded in the 
recognition that advisory committee meetings demand significant 
resource commitments by advisory committee members, sponsors and other 
public participants, as well as for the FDA itself. FDA works to ensure 
that the finite resources of its advisory committee program are devoted 
to consideration of the matters in which the agency would most benefit 
from the advice of outside experts.
    Question. Are there new abuse deterrence methods on the horizon?
    Answer. Ultimately, the 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. However, 
we are still in the early stages of abuse-deterrent product 
development--the market has a small number of products using abuse-
deterrent technologies, and the agency is assessing each opioid drug 
product's safety and efficacy on a case-by-case basis. Since the draft 
guidance on the evaluation and labeling of abuse-deterrent opioids was 
issued on January 9, 2013, the FDA has approved six extended-release 
long-acting opioids with labeling describing the product's abuse-
deterrent properties consistent with the draft guidance: OxyContin 
(April 16, 2013); Targiniq ER (July 23, 2014); Embeda ER (October 17, 
2014); Hysingla ER (November 20, 2014); MorphaBond (October 2, 2015); 
and Xtampza (April 26, 2016).
    The abuse-deterrent properties of those six products are based on 
data and described in terms consistent with those set forth in the 
FDA's 2015 guidance on the topic, Abuse-Deterrent Opioids--Evaluation 
and Labeling. FDA is prohibited by law from disclosing confidential 
information about a unapproved applications (e.g., 21 CFR 314.430) and 
is therefore unable to comment on drugs in development or in the FDA 
review process. Further, consistent with longstanding Agency practice, 
we do not discuss the substance of any matters pending before the 
Agency. However, FDA expects these technologies to improve and expects 
products containing abuse deterrent properties (both innovator and 
generic) to become more widely available.
    Abuse-deterrent does not mean abuse-proof. Abuse-deterrent opioids 
are intended to deter abuse by making the products less vulnerable to 
attempts to manipulate the product for abuse by the oral, nasal, or 
intravenous routes. However, the products must be able to deliver the 
opioid in order to provide analgesia and so will remain susceptible to 
abuse to some extent.
    While FDA is gathering data on the impact that approved ADFs are 
having in practice, and supporting research and development of 
additional ADF technology, the agency is also asking for advisory 
committee recommendations on all new non-ADF products to determine 
whether the benefit of non-AD products continues to offset the risks. 
FDA hopes that this public discussion will allow for greater 
transparency around the agency's decisionmaking regarding opioid 
products during this period of reassessment of our policies and 
regulatory approach to opioids.
                     food safety modernization act
    Question. The budget request for FSMA implementation is modest, to 
say the least. Last year, when FDA's budget was submitted, I was very 
appreciative that it finally included a realistic request to implement 
FSMA, and not one that relied on user fees that didn't stand a chance 
of happening. Congress took that request very seriously and provided 
full funding--so you know what our commitment is.
    Even then, according to FDA's own documents--there was still going 
to be a funding gap of approximately $166 million needed to 
successfully implement FSMA. So in a lot of ways, this budget request 
feels like a step backwards, even though I know we are all in agreement 
that FSMA has to be done right.
    What happens, or does not happen, if you get exactly what you ask 
for in budget authority, and no new user fees? How much additional 
funding, no matter the source, would be a responsible level this year 
to continue to fully support FSMA implementation?
    Answer. The fiscal year 2017 President's Budget includes a total of 
$1.5 billion in proposed resources for food safety. The budget would 
increase food safety funding by $211.6 million over fiscal year 2016. 
Specifically to support FSMA implementation, the budget proposed an 
increase of $25 million in budget authority. The budget also includes 
two key proposed user fees to support implementation, an import user 
fee ($105.3 million) and food facility registration and inspection fee 
($61.3 million). The sum of these increases represents the total 
resources needed for FDA to effectively implement FSMA. For example, if 
FDA does not receive the additional integrated food safety funds 
requested, we will have to reduce our planned support of State produce 
safety regulatory programs aligned with FDA's Produce Safety rule. It 
would in turn hamper education and outreach efforts to farmers.
    Question. The biggest part of your proposed increase is $11.3 
million for cooperative agreements and grants to implement the produce 
safety rule. While state and local efforts are no doubt critical, it's 
concerning that there is no money to train FDA staff. Was the money 
provided last year for this effort enough? Are FDA staff fully trained 
and prepared for this entirely new way of doing business?
    Answer. Training on the Produce Safety rule will be very important 
for both FDA and State regulators, as FDA will be working 
collaboratively with the National Association of State Departments of 
Agriculture and our State, local, and tribal partners to implement a 
produce safety regulatory program. fiscal year 16 investments support 
ongoing work on training plans and materials for the Produce Safety 
Alliance pre-requisite training; the Produce Safety Regulator Training 
will be developed and delivered to FDA and State personnel beyond 
fiscal year 16. As compliance requirements phase in, additional FDA and 
State personnel will be identified for training.
    Quesiton. Enforcement of the both Preventative Control for Human 
and Animal Foods rules begins in September of this year, but guidance 
documents, which are important for industry to understand what's 
expected of them, haven't been published yet. When do you expect to 
publish them, and how long will that process take? Does FDA, and in 
turn the states and localities, have everything needed to begin 
enforcement of this rule, in a consistent way?
    Answer. FDA is currently developing guidance documents related to 
the key FSMA rules, including the preventive controls rules for both 
human and animal food. These documents are part of a broader effort to 
foster and support compliance that also includes outreach; education 
and training programs, particularly for small and midsized firms; and 
FDA's Technical Assistance Network, through which regulated industry 
and other members of the public can get answers to specific questions 
about how the rules apply. The outreach and guidance development 
process will continue for years to come, but our goal is for key draft 
guidance documents to be available before the applicable compliance 
dates.
    We are currently on track to issue draft implementation guidances 
on preventive controls for human food and on Current Good Manufacturing 
Practices for animal food in the coming months. Additional draft 
guidance documents on specific hazards and controls are on target for 
issuance later this year.
    We are working with our state, local, and tribal partners to ensure 
that the new FSMA rules are implemented consistently and in a manner 
that encourages voluntary compliance. Adequate funding will help ensure 
the success of these efforts.
    Question. Funding was provided to train approximately 1,000 state 
and local inspectors in fiscal year 16 or about 20 in each state. More 
than 3,000 state, local and tribal entities will be involved in FSMA 
implementation. How many additional people will be trained this year?
    Answer. FDA's regulator training is being phased in over 3 years 
based on the staggered compliance dates in the Preventive Controls for 
human food rule, with a focus on large firm inspections in year 1 
(fiscal year 2017). FDA is on target to train 2,000 FDA and State food 
safety staff in 2016 in the Food Safety Preventive Controls Alliance 
Human and Animal Food courses, as a pre-requisite to the Preventive 
Controls regulator courses. In addition, the 2,000 FDA and State food 
safety staff will also receive modernized Good Manufacturing Practice 
(GMP) training for human food facilities and new GMP training for 
animal food facilities. In fiscal year 2016, FDA's Preventive Controls 
regulator courses will be offered to the subset of the 2,000 FDA and 
State food safety staff that will cover the large firm inventory. Food 
Safety staff is defined as investigators/inspectors, managers, 
compliance officers and Subject Matter experts, in both FDA and State.
    Question. The budget also proposes $14 million to implement the 
Foreign Supplier Verification Rule, which is vital considering that 
food imports continue to grow. The first enforcement of this rule is 
slated to begin in early 2017, although that timeline varies. Will this 
request be enough?
    Answer. In fiscal year 2017, FDA is proposing an additional $14 
million in budget authority to support the Foreign Supplier 
Verification Program (FSVP). FDA would use these additional resources 
to hire staff to perform FSVP inspections, provide training and 
technical assistance to FDA staff and importers, and continue outreach 
on the new FSVP requirements.
    Since FSVP is an entirely new program, FDA will need to assess the 
need for additional resources when we have more experience with the 
inventory of importers subject to FSVP and compliance rates.
                      genetically modified salmon
    Question. Obviously, I was concerned for multiple reasons when the 
FDA approved GMO salmon last year to go into our food supply. First, I 
have grave concerns about what will happen when one of these fish is 
inadvertently released, and second, I am concerned that it won't be 
labeled as GMO. So I worked to include language in the Omnibus to keep 
the salmon out unless it was labeled or FDA published final labeling 
guidance. In response, FDA issued an import alert to hold any GMO 
salmon at the border, or return it.
    To my first concern, how is FDA planning to work with the fish 
producers to make sure that none of these fish actually make it into 
the wild stock and do irreparable harm to the environment for native 
salmon?
    Answer. The approved application pertaining to AquAdvantage Salmon 
provides for specific conditions including that the GE salmon will be 
raised only in the two land-based, contained facilities in Canada and 
Panama that are described in the application. Under this approval, no 
other facilities or locations, in the United States or elsewhere, are 
authorized for breeding or raising AquAdvantage Salmon. There are no 
additional ``fish producers'' who may raise these salmon. As the 
sponsor and new animal drug application (NADA) holder, AquaBounty is 
the sole ``fish producer'' under the approved application.
    In terms of assuring that the GE salmon do not escape the two 
facilities allowed under the application, the facilities in Canada and 
Panama have a series of multiple and redundant levels of physical 
barriers to prevent eggs and fish from escaping. The facilities use 
land-based tanks--rather than ocean net pens, which are not allowed 
under the approved application. The first level of barriers (Primary 
Containment) includes items such as metal screens on tank bottoms, 
stand pipes, and incubator trays to prevent the escape of eggs and fish 
during hatching or rearing. Tanks also have covers, nets, jump fences, 
and screened overflow tanks to prevent escape over the sides of the 
tanks or incubators. Tank netting also keeps predators such as birds 
from entering the fish tanks at the outdoor facilities in Panama. All 
tank drains and stand pipes have covers or sleeves permanently attached 
to them. In order to prevent eggs or small fish from passing through 
the pipes or plumbing there is a closed septic system and additional 
screens and chlorine pucks are used to kill any escaped fish in the 
main drain area.
    Several additional sets of barriers, also in series (Secondary, 
Tertiary, and sometimes Quaternary Containment), add increased physical 
security to these primary containment measures described above. These 
barriers are designed to prevent fish from entering the drainage system 
or sedimentation pools and the local river (in the case of the Panama 
facility) and include floor drain covers, barrier screens inside the 
drains, drum and sock filters, and a series of sedimentation ponds with 
outlet filters.
    To augment physical containment, strict security measures and 
equipment are in place at both facilities. This includes locked gates 
for entry and exit to the properties, the presence of guard dogs, 
perimeter fences with barbed wire, and monitoring systems.
    In addition to these physical containment measures, the approval 
also includes biological containment measures: producing only one sex 
of fish and making the female fish sterile via triploidy induction (a 
method used in finfish and shellfish to prevent their sexual maturation 
and make them sterile).
    To ensure that AquaBounty maintains these physical and biological 
containment measures, they must follow record-keeping and reporting 
requirements, including ensuring that the triploidy process is within 
specifications and monitoring physical containment, including reporting 
of any likely or actual breaches of physical containment.
    Furthermore, even if AquAdvantage Salmon could somehow escape and 
migrate to the Pacific Ocean, there is no reasonable potential for 
hybridization between escaped AquAdvantage Salmon and native Pacific 
salmon, which are of a different genus, Oncorhynchus. Farm-raised 
Atlantic salmon on the west coast of the United States and Canada that 
have escaped in the Pacific Ocean have not interbred with wild Pacific 
salmon and, to date, there has been no compelling evidence of any 
colonization and establishment (i.e., self-sustaining populations) of 
Atlantic salmon in these areas
    As a result of these and other conditions included in the approval, 
there is a very low likelihood that AquAdvantage Salmon could escape 
their conditions of confinement and, in the unlikely event they did 
escape, it is extremely unlikely that they would establish and 
reproduce conditions at the facility sites.
    Question. Can you make a guarantee that these fish, grown in other 
countries, will be contained?
    Answer. The approved AquAdvantage Salmon application allows the GE 
salmon to be raised only in the two land-based, contained facilities in 
Canada and Panama that are described in the application. Additionally, 
these facilities are separately regulated by the relevant regulatory 
bodies in each respective country. Under this approval, no other 
facilities or locations, in the United States or elsewhere, are 
authorized for breeding or raising AquAdvantage Salmon.
    If other countries choose to produce GE salmon that will not enter 
U.S. commerce, those countries will regulate those facilities. FDA does 
not have jurisdiction to regulate products that are produced outside 
the United States and never enter the United States.
    Question. As you know, FDA approved AquaBounty's production plan to 
produce GM salmon eggs in Canada and ship them to Panama for fish 
production. If the company wanted to grow the fish in the U.S., what 
steps would it have to take to gain FDA approval?
    Answer. FDA's approval of the application pertaining to 
AquAdvantage Salmon does not allow production and grow out of the 
salmon in any facilities other than those in Canada and Panama. If the 
sponsor proposes to begin producing GE salmon in the United States (or 
at additional locations outside of the United States with the intent to 
import food from them into the United States), it first must submit a 
supplemental new animal drug application to FDA for the new production 
facilities, and this supplemental application will require its own 
National Environmental Policy Act analysis of potential environmental 
impacts of those facilities.
    Question. What repercussions will there be if there is an escape?
    Answer. Under the FD&C Act, a new animal drug that does not comply 
with its approved application is considered ``unsafe'' and an unsafe 
new animal drug is ``adulterated.'' 21 U.S.C. Sec. Sec. 360b(a); 
351(a).
    The FD&C Act also deems adulterated any food that contains an 
unsafe new animal drug. 21 U.S.C. 342(a)(2)(C)(ii). FDA may take 
enforcement action against adulterated drugs and foods, including 
refusing admission to imported foods and drugs that appear to be 
adulterated.
    Among the conditions included in the approval, AquaBounty must 
maintain physical and biological containment measures and report any 
likely or actual breaches of physical containment. If any such breach 
occurred in violation of a condition established in the approved 
application, AquAdvantage Salmon would be deemed ``unsafe'' and 
adulterated under these provisions and, therefore subject to FDA 
enforcement action, including seizure of adulterated product.
                                 ______
                                 
               Questions Submitted by Senator John Tester
                             premium cigars
    Question. Given that premium cigars are enjoyed by adults in 
moderation, and are inherently less attractive to underage smokers than 
other tobacco products, how are you taking into account the unique 
nature of cigars when promulgating tobacco regulations?
    Answer. Although all cigars are harmful and potentially addictive, 
it has been suggested that different kinds of cigars (e.g., small 
cigars, cigarillos, large cigars, premium cigars) may have the 
potential for varying effects on public health if there are differences 
in their effects on youth initiation, the frequency of their use by 
youth and young adults, and other factors.
    In the proposed deeming rule, FDA sought comment on two options for 
regulating categories of cigars: option one would deem all cigars 
subject to FDA's tobacco control authorities, and option two would 
exclude premium cigars. FDA also asked what additional restriction(s) 
may or may not be appropriate for different kinds of cigars.
    FDA reviewed all comments, data, and information submitted to the 
docket regarding this matter, and will address the issue in the final 
deeming rule.
                                 ______
                                 
            Questions Submitted by Senator Patrick J. Leahy
                                opioids
    Question. I have for years pushed the FDA to promote safer 
alternatives to powerful prescription painkillers, and to remove from 
the market older, less safe drugs. The FDA's announcement last month to 
expand access to abuse-deterrent formulations of these powerful drugs 
is a step in the right direction in response to my concerns. However, 
the FDA can and must do more.
    What plans do you have to ensure the FDA is doing everything in its 
power to help address the significant opioid crisis we are facing in 
this country?
    Answer. Prescription opioids with abuse-deterrent properties will 
not fix the problem, but they can be part of a comprehensive approach 
to combat the opioid epidemic. While the FDA has a responsibility to 
regulate drugs and help educate prescribers, addressing this epidemic 
requires the collaboration of multiple Federal agencies, state 
governments, professional organizations, and other stakeholders.
    FDA is changing the Agency's approach to opioid medications. The 
Agency's opioids action plan, announced on February 4, will focus on 
policies aimed at reversing the prescription opioid epidemic while 
still providing patients in pain access to effective relief. This plan 
includes concrete steps toward reducing the impact of opioid abuse on 
American families and communities. The plan includes a call for a re-
examination of the risk-benefit paradigm for opioids, changes to 
immediate-release opioid analgesic labeling, improved access to 
naloxone, and new advisory committee meetings to provide 
recommendations on pediatric approval issues and any new opioid that 
does not have abuse-deterrent properties. The Agency will provide 
updates on progress with the goal of sharing timely, transparent 
information on a regular basis.
    The Agency's action plan is part of the Health and Human Services 
(HHS) initiative to address the opioid epidemic which is working 
towards three broad goals: 1) opioid prescribing practices to reduce 
opioid use disorders and overdose 2) the expanded use of naloxone, used 
to treat opioid overdoses and 3) expanded use of Medication-assisted 
Treatment (MAT) to reduce opioid use disorders and overdose . 
Evaluation is a critical component of the initiative to identify what 
works and how the most effective interventions can be taken to scale.
                    fda standard for raw milk cheese
    Question. I continue to be very worried about the potential impact 
that the FDA's non-toxigenic E. coli standard for raw milk cheeses 
could have on cheese producers in Vermont and across the United States.
    The FDA's move to a standard for non-toxigenic E. coli that 
requires a thousand-fold decrease in the presence of non-toxigenic E. 
coli in raw milk cheeses could severely limit the production of raw 
milk cheeses across the country. In December, I helped to lead a 
bicameral and bipartisan letter to your Deputy Commissioner for Foods 
and Veterinary Medicine, Mike Taylor, asking several specific questions 
about the new standard and how it was developed, but the agency's 
response did not specifically answer all of our questions.
    In our letter, we asked whether the science upon which this 
standard is based has been subject to peer review. In response, the 
agency cited four different articles. While the articles do support the 
use of non-toxigenic E. coli as an indicator organism for food safety, 
they do not recommend the same level that the FDA has called for in raw 
milk cheeses. The first citation offered does not even seem to be in 
line with the agency's new standard, with the abstract specifically 
stating that with regards to raw cow milk samples, ``No relationship 
was detected between E. coli or the total bacterial count and the 
presence of pathogenic bacteria.'' In general, the scientific papers 
referenced do not seem to be particularly relevant to the issues laid 
out in our letter, with one article discussing the results from samples 
of raw milk in Malaysia. Therefore, I ask again:
    Does the body of scientific evidence specifically support a 
thousand-fold decrease in the presence of non-toxigenic E. coli in raw 
milk cheeses?
    Answer. First, we would like to clarify that the decrease in the 
level of non-toxigenic E. coli in cheeses in the Compliance Policy 
Guide (CPG) is not one thousand-fold, but instead is one hundred-fold, 
if one compares the maximum permissible levels. Prior to the 2010 
revision of the CPG, if one sample had a test result of 10,000 cfu/g or 
greater, the product was considered violative. Under the current CPG 
also, if one sample has a test result of 100 cfu/g or greater, the 
product would be considered violative. Of course, there is a second 
criterion in the 2010 CPG, namely, 10cfu/g. However, under this 
criterion, multiple samples from the same lot of product would have to 
exceed it before the product would be deemed violative.
    Regarding the references provided in the letter of Deputy 
Commissioner Michael Taylor, the references, including the abstract you 
quoted, were intended to show that there is support in the scientific 
literature for the use of non-toxigenic E. coli as an indicator of 
fecal contamination and insanitary conditions of production. For the 
2010 CPG, we relied on the available peer reviewed literature (over 70 
scientific papers), which showed that non-toxigenic E. coli is 
generally not present in raw milk, and that when it is present, it is 
usually at very low numbers, i.e. <100 cfu/g. The literature also shows 
that the cheese making process, coupled with aging, substantially 
reduces any non-toxigenic E. coli present. With this information, we 
concluded that there should not be E. coli in cheese unless the milk 
used was of poor quality, or the cheese was produced under unhygienic 
conditions. This conclusion has been supported by the results of our 
2014-15 cheese sampling program in which the vast majority of 1606 raw 
milk cheese samples met the 2010 criteria.
    That said, as you may be aware, we have paused our testing for non-
toxigenic E.coli in cheese as we take another look and engage 
stakeholders regarding what role this indicator organism should have in 
identifying insanitary conditions and process failures for both 
domestic and foreign cheese and how the results of such testing may be 
used in support of preventive measures. We intend to further engage our 
stakeholders in the artisanal sector and scientific experts in dialogue 
on this issue. We will seek public comment on such issues as the use of 
a single bacterial criterion for both pasteurized and raw milk cheese, 
and the appropriate use(s) of non-toxigenic E. coli as an indicator 
organism in pasteurized and raw milk cheese. Based on this dialogue and 
input, we will consider and make changes in the 2010 CPG as 
appropriate.
                    fda standard for raw milk cheese
    Question. There is a strong desire for transparency in rulemaking 
and in the process that leads to policy change. I feel strongly, as do 
our cheesemakers and food safety advocates, that science and data must 
guide these decisions. The American Cheese Society has requested data 
to be released on the FDA's raw milk sampling program. I have been told 
that your staff had initially agreed to share that data. Transparency 
in this case, and access to this data, could help American raw milk 
cheesemakers determine if and where changes need to be considered to 
ensure the production of safe cheese. Access to this data would also 
help to educate producers and inspectors to ensure that they are 
working together to continually enhance public health and welfare.
    Has the FDA been working to respond to the American Cheese 
Society's request for data? And if so when can they expect the FDA to 
finally release the data they had been promised?
    Answer. The FDA received a request from the American Cheese 
Society, dated February 22, 2016, for data from the Listeria 
Environmental Sampling Program and the Raw Milk Cheese Program. We are 
diligently working to compile the requested information. The request is 
currently being processed under the Agency's Freedom of Information Act 
program. In addition, an external report is being prepared for 
stakeholders that will discuss the results of the FDA's fiscal year 
2014/15 surveillance sampling assignment on raw milk cheese.
     generic competition/pharmaceutical products subject to a rems
    Question. An essential step for generic drug manufacturers seeking 
to create a low-cost generic drug is to obtain samples of the brand-
name drug they wish to replicate so they can conduct bioequivalence and 
other testing for FDA approval. Unfortunately, some brand-name 
companies appear to be impeding generic competition by refusing to 
provide such samples, either by imposing their own restrictions, or by 
claiming that distribution of their product is prohibited because of an 
FDA-approved safety protocol known as a ``REMS''.
    Additionally, some brand-name companies appear to be impeding 
generic competition by refusing to work with potential generic 
competitors to develop a single, shared safety REMS which in certain 
cases the FDA requires prior to approving the generic product.
    Federal law expressly bars pharmaceutical companies from using REMS 
restrictions to block generic competition. Furthermore, in December 
2014, the FDA issued guidance describing a process the Agency has 
developed to reassure brand-name drug companies that providing sample 
product to a generic competitor would not violate a REMS. Nevertheless, 
numerous generic companies continue to report difficulties in obtaining 
samples or negotiating a single, shared REMS, thus foreclosing 
competition.
    In your experience, are some brand-name companies engaging in the 
practices described above, even after the adoption of FDA's December 
2014 protocol?
    Answer. Yes. FDA has received more than a hundred inquiries from 
generic companies that want to develop generic drugs but tell us they 
are unable to because they cannot get access to supplies of the 
reference listed drug (RLD) to do testing. This is a problem that 
affects both REMS drugs and non-REMS drugs: in fact, the number of non-
REMS products about which we have received these inquiries is actually 
larger than the number of products subject to REMS about which we have 
received inquiries.
    The problem often arises when generic companies are not able to get 
access to the RLD through normal distribution channels (i.e., via 
wholesalers) because limitations on the distribution of the drug are in 
place. The brand company might limit the distribution of the product on 
its own initiative for a variety of different business reasons (for 
example, by selling through a central or small group of pharmacies, 
some of which may identify themselves as specialty pharmacies). For 
drugs with a REMS, an element to assure safe use (such as a pharmacy 
certification requirement) might impact the way the product is 
distributed.
    We understand that some brand companies have refused to sell the 
RLD to generic companies for testing or have included provisions in 
their contracts with pharmacies/third parties that prohibit the sale of 
the RLD to generic companies for testing purposes. We have referred 
such matters that have been brought to our attention to the Federal 
Trade Commission (FTC) and encouraged generic companies to also raise 
these matters with the FTC. We have taken a number of additional steps 
as well.
    Some brand companies have argued that selling the RLD to the 
generic firm for testing/development would be a violation of their 
REMS. To address this, we have developed a process, where appropriate, 
for informing the brand company in writing that FDA will not consider 
provision of the RLD for these purposes to be a violation of the REMS. 
We do this by reviewing the bioequivalence study protocols of companies 
that want to develop generic versions of these REMS drugs to assess 
whether their protocols have safety protections comparable to those in 
the applicable REMS. If we determine that they do, we send the brand 
company a letter stating so and informing them that selling the RLD to 
the generic company for testing and development will not be considered 
a violation of the REMS. (This process is described in the December 
2014 draft guidance referenced in this question).
    However, while these letters make clear that such sales will not 
subject the brand company to REMS-related enforcement action, some 
brand companies have argued that they have independent business reasons 
for not selling the RLD to the generic firm that are unrelated to their 
REMS and/or that they have no obligation to do so.
    Finally, we note that we also continue to have concerns about brand 
companies blocking or delaying approval of generic drugs using the 
single, shared system REMS requirement. This is a separate problem from 
the RLD access issue described above. The development of a single, 
shared system (which is mandated by the Federal Food, Drug, and 
Cosmetic Act for REMS that include certain elements, unless FDA waives 
the requirement for one of the reasons set forth in the Act \2\) 
necessitates discussion and negotiation between the competitor brand 
and generic company and agreement on the terms of the single shared 
system REMS and how it will operate before the generic product can be 
approved. Brand companies therefore have an incentive to delay generic 
competition for their products by refusing to agree to single, shared 
system REMS terms and otherwise prolonging the negotiations over a 
single, shared system REMS. We see prolonged negotiations and inability 
to agree on the terms of a single, shared system REMS regularly.
---------------------------------------------------------------------------
    \2\ Section 505-1(i)(1)(B)
---------------------------------------------------------------------------
    Question. If yes, would additional tools or legislative changes 
assist the Agency or other entities in addressing such behavior?
    Answer. The Administration has not taken a position on pending 
legislation in this area.
    Question. Could such practices be further addressed by creating a 
specific cause of action for generic manufacturers to sue in court to 
obtain the samples they need and/or to secure good faith and timely 
negotiation on developing a single, shared system of distribution for 
products that are subject to a REMS?
    Answer. The Administration has not taken a position on pending 
legislation in this area.
    Question. How long does the FDA's process normally take to review 
and approve a generic company's REMS protocol, and are there steps FDA 
could take to expedite this review?
    Answer. The timing of the review of bioequivalence study protocols 
for drug products subject to a REMS with elements to assure safe use 
varies based on several factors. These protocols require review by the 
two separate divisions within the Office of Generic Drugs' (OGD's) 
Office of Bioequivalence: the Division of Bioequivalence and the 
Division of Clinical Review. Because review staff in these divisions 
must prioritize workload to accommodate projects with GDUFA goal dates, 
the timing of protocol review therefore depends on the complexity of 
the protocols, the size of the queue, and competing workloads.
    OGD has taken a number of steps to streamline and shorten the 
process for submission and review of bioequivalence protocols. The 
December 2014 draft guidance described above provides step-by-step 
guidance to prospective generic applicants on how to submit these 
protocols and what to include in them. This draft guidance was issued 
in order to streamline the process, improve the quality of submissions 
received by the Agency, and thereby reduce review time. OGD has also 
assigned dedicated staff to coordinate the review of these protocols 
across the different OGD offices and divisions. OGD continues to 
evaluate the protocol review process and engage in process refinements 
and improvements where possible to assure timely and efficient protocol 
reviews.
                       labeling of generic drugs
    Question. In 2013, the FDA issued a proposed rule that would ensure 
that generic drug companies can update their safety labels when they 
learn new information. This proposed rule is tremendously important 
because more than 80 percent of consumers take the generic version of a 
drug when it is available. We need generics to be able to improve their 
labeling, and be held accountable when they fail to do so.
    Unfortunately, the FDA's proposed rule remains caught up in 
regulatory limbo. Last year, the FDA reopened its rulemaking to 
consider an industry-backed alternative that would turn existing 
labeling rules on their head. The industry proposal would ensure that 
after a generic drug enters the market, no drug company could update 
its label immediately upon learning of adverse side-effects. Labeling 
updates would be delayed, and drug companies could not be held 
accountable if they failed to update their safety information.
    One of my constituents, Diana Levine, was able to seek justice 
after she was injured by a mislabeled drug precisely because of the 
rules the drug companies are now trying to overturn.
    I am gravely concerned by the drug companies' proposal. I am also 
concerned by the FDA's delay in completing the rulemaking on its 
initial proposal, which is widely supported by patient groups and 
safety advocates.
    The Unified Agenda for Regulatory and Deregulatory Actions 
currently states a release date for the final rule of July 2016, 
following several previous postponements. Is the rule on track to be 
released at that time?
    Answer. The proposed rule is intended to improve the communication 
of important drug safety information to healthcare professionals and 
patients. FDA has received a great deal of public input from 
stakeholders during the comment periods on the proposed rule regarding 
the best way to accomplish this important public health objective.
    These comments include a summary of FDA's meeting with the Generic 
Pharmaceutical Association (GPhA) on September 8, 2014, to listen to 
their comments and views regarding the proposed rule. In addition, on 
March 27, 2015, FDA held a public meeting at which any stakeholder had 
the opportunity to present or comment on the proposed rule, or on any 
alternative proposals intended to improve communication of important, 
newly acquired drug safety information to healthcare professionals and 
the public. In the February 18, 2015, notice announcing the public 
meeting, FDA reopened the docket for the proposed rule until April 27, 
2015, to allow for the submission of written comments concerning 
proposals advanced during the March public meeting.
    FDA is carefully considering comments submitted to the public 
docket established for the proposed rule from a diverse group of 
stakeholders including: consumers and consumer groups, academia 
(including economists), healthcare associations, drug and pharmacy 
associations, brand and generic drug companies, law firms, state 
governments, and Congress, including comments proposing alternative 
approaches to communicating newly acquired safety-related information 
in a multi-source environment (see Docket No. FDA-2013-N-0500).
    Question. The Unified Agenda, available at http://www.reginfo.gov/
public/do/eAgendaViewRule?pubId=201604&RIN=0910-AG94, currently lists 
an anticipated publication date of April 2017 for the final rule on 
``Supplemental Applications Proposing Labeling Changes for Approved 
Drugs and Biological Products.'' The dates for rules in the Unified 
Agenda are projected dates that may be adjusted to reflect ongoing work 
on specific rules.Will the FDA commit to work expeditiously to complete 
the rulemaking process, with a focus on consumers and patient safety?
    Answer. The proposed rule is intended to improve the communication 
of important drug safety information to healthcare professionals and 
patients. FDA has received a great deal of public input from 
stakeholders during the comment periods on the proposed rule regarding 
the best way to accomplish this important public health objective.
    These comments include a summary of FDA's meeting with the Generic 
Pharmaceutical Association (GPhA) on September 8, 2014, to listen to 
their comments and views regarding the proposed rule. In addition, on 
March 27, 2015, FDA held a public meeting at which any stakeholder had 
the opportunity to present or comment on the proposed rule, or on any 
alternative proposals intended to improve communication of important, 
newly acquired drug safety information to healthcare professionals and 
the public. In the February 18, 2015, notice announcing the public 
meeting, FDA reopened the docket for the proposed rule until April 27, 
2015, to allow for the submission of written comments concerning 
proposals advanced during the March public meeting.
    FDA is carefully considering comments submitted to the public 
docket established for the proposed rule from a diverse group of 
stakeholders including: consumers and consumer groups, academia 
(including economists), healthcare associations, drug and pharmacy 
associations, brand and generic drug companies, law firms, state 
governments, and Congress, including comments proposing alternative 
approaches to communicating newly acquired safety-related information 
in a multi-source environment (see Docket No. FDA-2013-N-0500).
                                 ______
                                 
              Questions Submitted by Senator Tammy Baldwin
    Question. I am encouraged by the FDA's increased attention to the 
growing epidemic of prescription opioid misuse and abuse and the need 
to improve treatment options for chronic pain. As you mentioned in your 
recent article in the New England Journal of Medicine \3\, there is 
little high-quality evidence on the safety and efficacy of opioids as a 
long-term treatment for chronic pain. It is critical that we fill the 
gap in research and promote the development of safer treatments that 
pose less risk of addiction for patients experiencing chronic pain.
---------------------------------------------------------------------------
    \3\ Califf, Robert M., M.D., Janet Woodcock, M.D., and Stephen 
Ostroff, M.D. ``A Proactive Response to Prescription Opioid Abuse.'' 
New England Journal of Medicine, 4 Feb. 2016. .
---------------------------------------------------------------------------
    How is the FDA collaborating with other government agencies, 
including the National Institutes of Health, to prioritize the 
development of non-addictive therapies for chronic pain and to generate 
high-quality evidence to support their use?
    Answer. To help combat the opioid epidemic, the FDA is encouraging 
drug development efforts that make it harder to abuse opioids, and the 
agency looks forward to the day, hopefully soon, when the majority of 
opioids in the United States are marketed in effective abuse-deterrent 
forms. However, development of and transition to use of opioids with 
meaningful abuse-deterrent properties is only one component of a multi-
pronged approach to addressing abuse of opioid medications. For 
example, the FDA is also working to support the efficient development 
of non-opioid alternatives for treating pain that have lower (or no) 
abuse potential. Encouraging the development of these products requires 
both scientific and translational development work. FDA has past and 
ongoing work in this area, supported through our participation in the 
ACTTION Public Private Partnership \4\ (PPP) in a wide variety of 
areas.
---------------------------------------------------------------------------
    \4\ ACTTION: Analgesic, Anesthetic, and Addiction Clinical Trial 
Translations, Innovations, Opportunities, and Networks
---------------------------------------------------------------------------
    ACTTION is working to improve study methods for developing novel, 
safe, and effective analgesic drug products. Through scientific 
assessment of FDA's clinical trial databases and publically available 
data, the PPP plans to develop novel and evidence-based approaches to 
improve the design of analgesic clinical trials. The PPP also 
coordinates scientific workshops that bring together key experts, 
including stakeholders from industry, professional organizations, 
academia, and government agencies.
    Additionally, as part of the FDA's recently announced plan aimed at 
reversing the opioid epidemic, the agency has contracted with the 
National Academy of Medicine to provide us with advice on how we should 
incorporate current evidence about the public health impact of opioid 
use, both for people who are prescribed opioids and for non-patients, 
into regulatory activities concerning opioids. We look forward to the 
recommendations from NAM and other experts about reassessing our risk-
benefit paradigm for opioids based on the current state of the science.
    FDA also continuously strives for enhanced collaboration between 
NIH and FDA. FDA leadership recently participated in a meeting of the 
FDA-NIH Joint Leadership Council, an organization through which senior 
leaders from both agencies address ways to facilitate new processes, 
such as FDA review of combination therapies and its consideration of 
rare disease trials with fewer patients enrolled. The participants on 
the FDA-NIH Joint Leadership Council work together to help ensure that 
regulatory considerations form an integral component of biomedical 
research planning, and that the latest science is integrated into the 
regulatory review process. Such collaboration and integration advances 
the development of new products for the treatment, diagnosis, and 
prevention of common and rare diseases, as well as enhances the safety, 
quality, and efficiency of the clinical research and medical product 
approval process.
    Question. How will the FDA in fiscal year 2017 improve post-market 
surveillance of medical devices? And, in addition to recalling such 
devices when they are found to be unsafe for patients, how will the 
agency better protect patients from adverse effects and complications 
while said devices are under investigation?
    Answer. FDA takes device post market safety very seriously. There 
will always be limitations to how much CDRH can learn about a device 
before it goes to market, diligent postmarket surveillance can identify 
safety signals, prevent patient harm, and lead to device improvements. 
The Center for Devices and Radiological Health's (CDRH) current 
postmarket surveillance tools, such as passive reporting, limit our 
ability to rapidly address safety concerns.
    For this reason, FDA has proposed the development of a national 
evaluation system for medical devices (system).
    In 2011, the Institute of Medicine (IOM) published a report 
recommending that FDA develop and implement a comprehensive medical 
device postmarket surveillance strategy to collect, analyze, and act on 
medical device postmarket performance information. In 2012 and 2013, 
CDRH set out a vision and strategy \5\ for creating such a system. In 
2015, two multi-stakeholder groups issued reports \6\ supporting the 
vision and made recommendations providing further direction for 
establishing this system. Further, CDRH's 2016-2017 Strategic 
Priorities \7\ include increasing access to and use of real-world 
evidence to support regulatory decisionmaking. The development of the 
post market evaluation system is integral to meeting those goals.
---------------------------------------------------------------------------
    \5\ http://www.fda.gov/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm301912.htm.
    \6\ http://www.brookings.edu/events/2015/02/23-future-of-medical-
device-safety-and-innovation;www.brookings.edu/about/centers/health/
projects/development-and-use-of-medical-devices/mds/2016-planning-
board.
    \7\ http://www.fda.gov /downloads/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDRH/CDRHVisionandMission/
UCM481588.pdf.
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    The principal challenge for implementing the system is lack of 
funding. The system needs investment from various stakeholders to 
operate and build on existing infrastructure and to establish and 
operate a governing body. The fiscal year 17 President's Budget 
contains a request for $1.8 million for the system. While the long-term 
vision for the system involves multi-stakeholder participation and 
investment, in order to garner meaningful financial support from the 
private sector, the NES needs a core investment. We would like others 
in the medical device ecosystem, such as payers and professional 
societies, to also have an important role in the development of this 
system. Finally, this investment will support precision medicine. One 
of the biggest problems facing the success of Precision Medicine is the 
challenge of determining which devices are best suited for which 
patients because of the high cost of developing evidence. Data that can 
answer these questions is generated every day as a part of routine 
clinical practice (evidence from clinical experience or ``real world'' 
data).
    To better protect patients from potential adverse events or 
outcomes while a postmarket device safety issue is under evaluation, 
the FDA communicates clear and easily understood information about the 
risks and benefits of a device to patients and healthcare providers. 
FDA uses a range of tools to disseminate information widely, including 
our website and through letters and meetings with healthcare providers 
and patient groups.
    To support increased communication on potential safety issues, in 
December 2015, CDRH released a draft guidance called ``Public 
Notification of Emerging Postmarket Medical Device Signals (`Emerging 
Signals').'' An emerging signal is new information about a medical 
device used in clinical practice that the FDA is monitoring or 
analyzing; that has the potential to impact patient management 
decisions and/or alter the known benefit risk profile of the device; 
that has not yet been fully validated or confirmed; and for which the 
FDA does not yet have specific recommendations.
    Historically, FDA has communicated important information we learned 
about in the postmarket context after completing an analysis of 
available data and, in most cases, after having reached a decision 
about relevant recommendations for the device user community. This 
guidance is designed to inform the public of our evolving efforts to 
share information in a more timely way that allows patients to make the 
most informed medical decisions with their healthcare provider as close 
to real-time and based on the most current data as possible.
    FDA has taken additional important steps to facilitate the 
identification and evaluation of postmarket safety concerns. FDA issued 
a final rule establishing a unique device identification system to 
provide a standardized way to identify devices across different 
information sources including electronic health records and device 
registries using unique device identifiers (UDIs).
    Question. The 2015-2020 Dietary Guidelines recognized that sugar 
that is added to increase the palatability of naturally tart fruits, 
like cranberries, can aid a healthy dietary pattern by supporting the 
consumption of fruits and vegetables. In considering the proposed added 
sugar DV for labeling, what is the FDA doing to ensure that consumers 
will be not be misled on the healthfulness of nutrient dense products 
that contain added sugar, when comparing similar fruit products with 
equal or more intrinsic sugars and calories?
    Answer. An added sugars declaration on the Nutrition and Supplement 
Facts labels, if finalized, would be just one piece of information that 
consumers can use to help them construct a healthful dietary pattern. 
We recognize that the added sugars declaration would be new information 
that consumers would not have seen before; therefore, in collaboration 
with Federal and other partners, we plan to engage in educational and 
outreach activities for consumers and health professionals about the 
use of information on the Nutrition and Supplement Facts labels, 
including any information about added sugars, if finalized. In the 
education and outreach activities, FDA plans to indicate that consumers 
should consider all of the information on the label, including total 
sugars and calories, when constructing a healthful dietary pattern, and 
not focus on just one specific nutrient.
    Question. Artisan cheesemakers in Wisconsin have expressed concerns 
over the uncertain regulatory climate for raw milk cheese production. 
In particular, FDA's approach in conducting sampling at cheese 
facilities as it reviews raw milk cheese and non-toxigenic E. coli 
levels created a great deal of uncertainty and concern within the 
industry, despite the industry's attempts to work with FDA. Though 
cheese producers cooperated extensively in providing samples, FDA did 
not share the results from those tests in a timely way with individual 
businesses or the industry. When can cheesemakers and their industry 
groups expect to receive comprehensive results from the Listeria 
Environmental Sampling Program and the Raw Milk Cheese Sampling 
Program?
    Answer. An external report is being prepared for stakeholders that 
will discuss the results of the FDA's fiscal year 2014/15 surveillance 
sampling assignment on raw milk cheese. We expect that report to issue 
in the coming months. FDA will release results of Listeria sampling 
conducted at cheese firms, as resources allow.
    Question. As the FDA works to complete its guidance document on 
environmental Listeria, is there any quantitative data on incidence and 
levels of Listeria monocytogenes in frozen foods such as frozen 
vegetables and frozen food entrees? In frozen foods where Listeria 
monocytogenes has been implicated in the reportable food registry, does 
FDA have any quantitative data? If so, please share that data with the 
subcommittee.
    Question. FDA recently queried the database for Reportable Food 
Registry submissions and found thirty-eight (38) primary submissions 
for Listeria monocytogenes in frozen foods between 2009 and the 
present. Of these submissions, nine (9) met the criteria for reportable 
food and were classified as Class I recalls because there is a 
reasonable probability that the use of or exposure to the product will 
cause serious adverse health consequences or death to humans or 
animals. Twenty-seven (27) submissions were considered non-reportable 
because the food failed to meet the Class I recall standard or because 
it did not meet the criteria of a reportable food (e.g., the food is 
not regulated by FDA or the report is not submitted by a manufacturer, 
processor, packer or holder of food required to be registered with FDA 
under section 415 of the Federal Food, Drug, and Cosmetic Act). Two (2) 
submissions are awaiting decisions on recall classification.
    FDA occasionally collects quantitative data from frozen food 
products on an as needed basis to assist in an investigation but has 
not conducted a comprehensive survey of the frozen food industry. In 
two investigations in the past 2 years, FDA collected quantitative 
data. In one investigation involving an ice cream outbreak, the data 
revealed that 99.4 percent of samples of the ice cream involved in the 
outbreak contained detectable L. monocytogenes at levels ranging from 
less than 0.03 cells of L. monocytogenes per gram to greater than 208 
cells per gram. In the second investigation involving frozen vegetables 
subject to recall, FDA collected samples from thirty-three (33) product 
lots stored in the firm's warehouse freezer. Eight (8) lots (24 
percent) tested positive for the presence of L. monocytogenes.
    Question. The fiscal year 16 omnibus included report language that 
asked the Administration for a timeline for updating the dietary 
reference intake (DRI) for sodium as part of the fiscal year 17 budget 
request. An update was not included in the fiscal year 17 budget 
request. Can you share the specific 2016 timeline and plan for the 
update of the sodium DRI as requested in the Omnibus report?
    Answer. FDA has prioritized updating the DRI for sodium and is 
collaborating with the Centers for Disease Control and Prevention and 
other Federal agencies to update the DRI for sodium as expeditiously as 
possible. A detailed timeline is not yet available.

                          SUBCOMMITTEE RECESS

    Senator Moran. Again, Commissioner, thank you, and, Acting 
Commissioner Ostroff, thank you very much for your leadership 
of the agency.
    And we stand adjourned.
    [Whereupon, at 2:42 p.m., Wednesday, March 2, the 
subcommittee was recessed, to reconvene subject to the call of 
the chair.]