[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\
---------------------------------------------------------------------------
\1\ https://www.whitehouse.gov/sites/default/files/omb/assets/
budget_amendments/emergency_supplemental_2-22-16_zika.pdf
---------------------------------------------------------------------------
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.
---------------------------------------------------------------------------
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.]