[Senate Hearing 113-786]
[From the U.S. Government Publishing Office]
S. Hrg. 113-786
PROTECTING THE PUBLIC HEALTH: EXAMINING FDA'S INITIATIVES AND
PRIORITIES
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HEARING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED THIRTEENTH CONGRESS
SECOND SESSION
ON
EXAMINING THE FOOD AND DRUG ADMINISTRATION'S INITIATIVES AND
PRIORITIES, FOCUSING ON PROTECTING THE PUBLIC HEALTH
__________
MARCH 13, 2014
__________
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Pensions
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
TOM HARKIN, Iowa, Chairman
BARBARA A. MIKULSKI, Maryland LAMAR ALEXANDER, Tennessee
PATTY MURRAY, Washington MICHAEL B. ENZI, Wyoming
BERNARD SANDERS (I), Vermont RICHARD BURR, North Carolina
ROBERT P. CASEY, JR., Pennsylvania JOHNNY ISAKSON, Georgia
KAY R. HAGAN, North Carolina RAND PAUL, Kentucky
AL FRANKEN, Minnesota ORRIN G. HATCH, Utah
MICHAEL F. BENNET, Colorado PAT ROBERTS, Kansas
SHELDON WHITEHOUSE, Rhode Island LISA MURKOWSKI, Alaska
TAMMY BALDWIN, Wisconsin MARK KIRK, Illinois
CHRISTOPHER S. MURPHY, Connecticut TIM SCOTT, South Carolina
ELIZABETH WARREN, Massachusetts
Derek Miller, Staff Director
Lauren McFerran, Deputy Staff Director and Chief Counsel
David P. Cleary, Republican Staff Director
(ii)
C O N T E N T S
__________
STATEMENTS
THURSDAY, MARCH 13, 2014
Page
Committee Members
Harkin, Hon. Tom, Chairman, Committee on Health, Education,
Labor, and Pensions, opening statement......................... 1
Alexander, Hon. Lamar, a U.S. Senator from the State of
Tennessee, opening statement................................... 2
Warren, Hon. Elizabeth, a U.S. Senator from the State of
Massachusetts.................................................. 22
Isakson, Hon Johnny, a U.S. Senator from the State of Georgia.... 24
Bennet, Hon. Michael F., a U.S. Senator from the State of
Colorado....................................................... 26
Enzi, Hon. Michael B., a U.S. Senator from the State of Wyoming.. 28
Casey, Hon. Robert P., Jr., a U.S. Senator from the State of
Pennsylvania................................................... 29
Roberts, Hon. Pat, a U.S. Senator from the State of Kansas....... 31
Baldwin, Hon. Tammy, a U.S. Senator from the State of Wisconsin.. 33
Murkowski, Hon. Lisa, a U.S. Senator from the State of Alaska.... 34
Witness
Hamburg, Margaret, M.D., Commissioner, Food and Drug
Administration, U.S. Department of Health and Human Services,
Silver Springs, MD............................................. 4
Prepared statement........................................... 6
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.:
Response by the Food & Drug Administration to questions of:
Senator Harkin........................................... 42
Senator Murray........................................... 45
Senator Sanders.......................................... 48
Senator Casey............................................ 49
Senator Bennet........................................... 52
Senator Baldwin.......................................... 53
Senator Warren........................................... 53
Senator Alexander........................................ 55
Senator Burr............................................. 57
Senator Burr and Senator Isakson......................... 58
Senator Burr, Senator Enzi and Senator Isakson........... 59
Senator Enzi............................................. 59
Senator Murkowski........................................ 62
Senator Hatch............................................ 63
Senator Isakson.......................................... 64
Senator Isakson and Senator Enzi......................... 66
Senator Kirk............................................. 66
Senator Roberts.......................................... 67
(iii)
PROTECTING THE PUBLIC HEALTH: EXAMINING FDA'S INITIATIVES AND
PRIORITIES
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THURSDAY, MARCH 13, 2014
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The committee met, pursuant to notice, at 9:32 a.m., in
room SD-430, Dirksen Senate Office Building, Hon. Tom Harkin,
chairman of the committee, presiding.
Present: Senators Harkin, Casey, Franken, Bennet, Baldwin,
Warren, Alexander, Enzi, Isakson, Roberts, and Murkowski.
Opening Statement of Senator Harkin
The Chairman. Good morning. The Senate Committee on Health,
Education, Labor, and Pensions will come to order. We have
convened this hearing to examine FDA's implementation of key
public health initiatives being undertaken by the agency,
including several significant reforms passed out of this
committee over the last few years.
Our Nation faces a variety of public health challenges in
this early part of the 21st century. There have been rapid
changes in where our products are made and how they're made and
where our food comes from. There have been major innovations,
including treatments that save lives, and a better and more
diversified food supply. But these new dynamics also present
new risks and greater challenges for regulatory oversight.
The HELP Committee has been able to address many of these
challenges in recent years, proving that things can still get
done in Washington. I want to thank Ranking Member Alexander
for being a great partner and also Senator Enzi and all the
members on this committee and their staffs. We've worked
together in a collaborative and bipartisan manner to address
these public health issues head on.
Let me just summarize a few. Last fall, a year after the
meningitis outbreak from compounded sterile drugs killed 64
people and sickened 751 patients across 20 States, we passed
the Drug Quality and Security Act, which clarifies and
strengthens oversight of compounded drugs.
In 2012, we passed the Food and Drug Administration Safety
and Innovation Act, which, along with authorizing several FDA
user fee programs, sped up patients' access to generic drugs,
modernized FDA's ability to regulate the global drug supply
chain, established tools to prevent and mitigate shortages of
prescription drugs, and implemented reforms to help bring
critical drugs and medical devices to market faster.
In 2011, we enacted the Food Safety Modernization Act, a
landmark law that brings America's food safety system into the
21st century to better protect Americans from contaminated food
and food-borne illness.
Finally, in 2009, the Family Smoking Prevention and Tobacco
Control Act, which this committee spearheaded, became law. It
gives the FDA the authority to regulate the manufacture,
distribution, and marketing of tobacco products to protect
public health. So this committee, I believe, has been very
active in addressing the health and safety needs of Americans.
I also want to take this opportunity to thank you,
Commissioner Hamburg, and to commend the FDA for the recent
proposal to update the Nutrition Facts Panel we see on packaged
food. The last update to these labels, in 2006, prompted
manufacturers to reduce trans fat in many of their products,
and I'm hopeful that this new proposal will further support
Americans in their efforts to make healthy decisions for
themselves and their families.
So this hearing will focus on FDA's implementation of these
reforms, as well as other key public health initiatives that
are now confronting us and being undertaken by the agency, and
other concerns to members of this committee. We are pleased to
have Commissioner Hamburg of the FDA here to talk to us about
their efforts and answer our questions.
I'll turn now to Senator Alexander for his opening remarks.
Opening Statement of Senator Alexander
Senator Alexander. Thanks, Mr. Chairman. Thanks for having
this very timely hearing.
Dr. Hamburg, thank you for being here today. We look
forward to visiting with you.
I'm going to devote most of my attention to the Drug
Quality and Security Act, which was signed into law last fall
to clarify FDA authority over compounding pharmacies. That's
very important to many States, but especially to Tennessee. The
fungal meningitis outbreak in 2012 was a nightmare for us, as
137 Tennesseans became sick and 16 others died from the
outbreak which was caused by contaminated steroid injections
distributed by a poorly regulated compounding facility in
Massachusetts.
While the final legislation, the law, was not as strong as
the bill that passed this committee, the law does make it clear
that either the FDA or the State is overseeing each compounding
facility. And just to review, the law says that large
facilities compounding sterile drugs without prescriptions now
have the ability to voluntarily register with the FDA as
outsourcing facilities committed to higher standards for
sterile compounded drugs, to report adverse events, put on
certain labels, and list all the products they make with the
FDA.
The legislation, the new law, kept State oversight of
traditional pharmacies, the corner drug store, and FDA
oversight over drug manufacturers. The FDA gets plenty of
criticism from time to time. But I want to give credit where
credit is due on this one.
You have responded to a crisis--and it was--as if it was a
crisis. You're off to a fast start in implementing this
important legislation, I appreciate that.
On December 4, just 1 week after the legislation was signed
into law, FDA published three guidance documents. It's been
just a little over 100 days since the President signed the law,
and in that time, 30 facilities have registered as outsourcing
facilities nationwide. They've done this voluntarily. And these
30 facilities have done this without receiving guidance on the
requirements they'll have to meet for the sterile drugs they
make. So that's a good sign. And I believe that once we have
more clarity, the number of outsourcing facilities will go up
significantly.
Now that the law is established, who is on the flag pole?
FDA and States can take the action necessary to make sure
compounded drugs are safer in the future. You've continued
inspections and enforcement actions, and you've sent numerous
warning letters, referrals to State boards, and publishing
inspection observations for many pharmacies.
In the question time, I hope to learn what policies you're
developing and when we will see the guidance on the quality
standards outsourcing facilities must comply with; and, No. 2,
what your enforcement priorities are and how you plan to
followup on the warning letters. The New England Compounding
Pharmacy had received a warning letter, and I want to ensure
there will be appropriate followup from the agency this time.
And, third, now that we've established who's on the flag pole,
how are you coordinating with States on what they're doing?
I thank you for your quick work in implementing this law,
and I look forward to hearing about future plans on some other
areas where the FDA's pace seems to be moving rather slowly. I
hope the way you've worked on compounding pharmacies might set
an example for how you might move ahead, for example, on the
Center for Tobacco Products. You've gotten $1.7 billion in user
fees to date for tobacco. Over 4,000 applications are filed.
You've acted on 34.
Congress also instructed FDA to set up a regulatory pathway
for biosimilars--that was March 2010--and established a
biosimilar user fee 2 years later. Almost 4 years later, we
don't have an approved biosimilar product in the United States,
and many questions linger.
My last example comes from the implementation of the Food
Safety Modernization Act. My understanding is that the FDA is
going to re-propose parts of the proposed regulation due to
widespread stakeholder concern about the cost and complexity of
these regulations after the law emphasized the need for a
science- and risk-based flexible approach.
I urge the FDA to improve responsiveness to congressional
inquiries. There is one letter I sent last July to which I have
not yet received a response. And in that light, I will send in
writing a question that Senator Fischer of Nebraska has that
she'd like answered. I won't deal with that orally, but I'll
provide that to you separately.
But all in all, Commissioner, I thank you for the FDA's
fast start on implementing the compounding pharmacy
legislation, and we welcome you to the hearing.
The Chairman. Thank you very much, Senator Alexander.
On behalf of the committee, I'd like to welcome our witness
today, Dr. Margaret Hamburg, the 21st Commissioner of the U.S.
Food and Drug Administration since 2009. She is the top
official of the FDA, an agency with the fundamental mission to
protect and promote the public health.
Dr. Hamburg received her M.D. from Harvard Medical School
and completed her residency at what is now New York
Presbyterian Hospital/Weill Cornell Medical Center.
Commissioner Hamburg has an impressive background as a doctor,
an NIH scientist, and has significant public health experience
from her previous post at New York's Department of Public
Health and Mental Hygiene and the U.S. Department of Health and
Human Services.
Dr. Hamburg, we thank you for sharing your expertise with
the committee and being here today. Your statement, which is an
extensive statement, which I got through yesterday and last
night, will be made a part of the record in its entirety. I'd
like to maybe give you up to 10 minutes to go through that, if
you would like, rather than just 5--however close you can keep
it, but below 10 minutes. And I'm going to request that the
record remain open for 10 days for Senators to submit
statements or questions for the record.
A couple of things--at 10:30, I have to leave. Both of us
have to leave.
Senator Alexander. Senator Enzi will stay.
The Chairman. OK. Good. I think Senator Franken said he
would take over at that time if we continue on beyond that
time. But we're managing a bill on the floor that we have to
leave for at 10:30.
Again, Dr. Hamburg, welcome and please proceed.
STATEMENT OF MARGARET HAMBURG, M.D., COMMISSIONER, FOOD AND
DRUG ADMINISTRATION, U.S. DEPARTMENT OF HEALTH AND HUMAN
SERVICES, SILVER SPRING, MD
Dr. Hamburg. Thank you very much, and I know that you are
pressed for time, so I wanted to keep my oral statement
relatively short. I really thank you, Mr. Chairman and members
of the committee, for the opportunity to be here to discuss
some of the important initiatives that FDA has been working on
with regard to the implementation of several new laws recently
passed with this committee's leadership: the Food Safety
Modernization Act, the Food and Drug Administration Safety and
Innovation Act, and the Drug Quality and Security Act.
I also really want to express my gratitude to you and the
members of the committee for championing the passage of these
landmark laws. They all represent remarkable accomplishments
done, as you noted, in a bipartisan way, and their importance
to public health really cannot be overstated.
We also welcome the opportunity to return to the committee
to provide a more detailed review of our implementation of the
2009 Family Smoking Prevention Tobacco Control Act, as you
requested, which really lays a strong foundation for protecting
the public health from the harms of tobacco products.
First, food safety. Reducing foodborne illness in the
United States is one of the FDA's most important
responsibilities. The toll that it takes on public health is
profound: an estimated 48 million illnesses, 128,000
hospitalizations, and 3,000 deaths every year from foodborne
illness. Moreover, the overall negative economic impact of
foodborne illness in the United States, including cost to
farmers, food processors, and consumers, may be as high as $77
billion per year.
Thanks to you and your colleagues, who enacted the Food
Safety Modernization Act, FDA now has tools to significantly
lessen these impacts. FSMA's central framework, as you know, is
aimed at building preventive measures across the food system
from farm to table, including produce safety, modern preventive
controls, guarding against intentional contamination,
modernizing oversight of imported foods, and ensuring safe
transport.
Over the past year, FDA has put forth seven proposed rules
on these topics for public comment. But new rules alone won't
get us to our goal. FDA must have the resources to implement
them; to provide the technical assistance to small food
processors, for example; to build the capacity of our States as
partners in this important effort; and also, very importantly,
to begin the long delayed process of better oversight of
imported foods, which are increasingly important in our food
supply.
Simply put, without a significant increase in resources, we
will not achieve FSMA's vision of a modern food safety system
and a safer food supply.
With respect to FDASIA, building on a successful model, the
Food and Drug Administration Safety and Innovation Act
reauthorized user fee programs for innovator drugs and medical
devices and also established two new important user fee
programs for biosimilars and for generic drugs. Coming at a
time of continuing budget constraints, this steady source of
funding is really essential for speeding safe and effective new
products to patients and providing predictability and
consistency for industry.
The law also gave FDA new authority to better protect the
drug supply chain in an increasingly global marketplace. In
addition, FDASIA provided the agency with new authorities to
combat drug shortages and also to stimulate antibacterial drug
development, enhanced development of pediatric medicines, and
encourage drug and device product innovation.
I want to highlight just a few of the successes that we've
already seen. As part of the negotiated agreement with
industry, FDA committed to meet much-enhanced performance goals
for medical device reviews. Since fiscal year 2010, we have
achieved a 27 percent decrease in the backlog of lower device
applications and a 10 percent decrease in average total review
time. For higher risk devices, we've seen a 43 percent decrease
in the backlog and a 32 percent decrease in average total
review time.
Recognizing the need to stimulate investments in
antibacterial drugs, FDASIA created incentives for their
development. Since the passage of FDASIA, FDA has granted 41
qualified infectious disease product designations under this
new program, which I think is a promising start. I'm pleased
that after a series of interventions, including use of new
authority provided under FDASIA, the number of new drug
shortages declined very significantly from 251 to 117 between
2011 and 2012, and then fell even further to 44 in 2013.
However, there do continue to be shortages that persist for
longer periods, and we're working aggressively with all the
tools at our disposal to prevent and mitigate them.
With respect to the Drug Quality and Security Act, the last
time, as was noted, that I appeared before this committee, we
were in the midst of a nationwide public health crisis related
to the fungal meningitis outbreak caused by compounded
medications. Thanks, truly, to this committee's leadership, we
now have the Drug Quality and Security Act, which contains
important provisions relating to compounding oversight and also
outlines steps to an interoperable system to identify and trace
certain prescription drugs.
As was noted, within 1 week of passage of DQSA, FDA took
several actions to begin implementation, including the issuance
of three draft guidances, three notices soliciting nominations
for drugs that can and cannot be compounded, and significant
stakeholder outreach has been undertaken. As of this week, 35
firms have, in fact, registered with FDA as outsourcing
facilities. We intend to continue inspections of compounding
pharmacies and to take enforcement actions as appropriate to
protect patients.
So without a doubt, FDA's responsibilities have undergone
huge transformation through these important new laws. Our
commitment to implementing the responsibilities entrusted to
this agency by Congress to improve the lives of the American
public, to protect their health, safety, and welfare is
unwavering.
We are committed to working closely with you on these
important new laws, as well as so many other issues. We really
believe that our work is vital and the partnership with you is
vital, and that we are making a difference in the lives of
Americans.
Thank you.
[The prepared statement of Dr. Hamburg follows:]
Prepared Statement of Margaret A. Hamburg, M.D.
Introduction
Mr. Chairman and members of the committee, I am Dr. Margaret
Hamburg, Commissioner of Food and Drugs at the Food and Drug
Administration (FDA or the Agency), which is part of the Department of
Health and Human Services (HHS). Thank you for the opportunity to be
here today to provide an overview of the important actions and
initiatives FDA has been working on over the last year, including
implementation of several new laws passed with this committee's
leadership: the FDA Food Safety Modernization Act (FSMA), Public Law
111-353; the Food and Drug Administration Safety and Innovation Act
(FDASIA), Public Law 112-144; and the Drug Quality and Security Act
(DQSA), Public Law 113-54.
I would like to express my gratitude to you and the members of this
committee for championing passage of these landmark laws, all of which
directly impact the public health. Their importance cannot be
overstated, and the breadth of their provisions touch and guide so much
of what we do every day. I appreciate the opportunity to provide this
committee with an overview of the Agency's implementation of various
provisions of these laws. I'd also like to take this opportunity to
share FDA's broader strategic efforts to enhance areas such as
innovation, quality and safety, smart regulation, and the increasing
globalization of the food and medical products we regulate.
fsma implementation
In January 2011, building on the bipartisan work of Congress, the
President signed FSMA, the most sweeping reform of our Nation's food
safety laws in more than 70 years. I commend this committee for its
leadership in passing this landmark legislation. As you know, FSMA aims
to enhance the safety of the U.S. food supply by shifting the focus
from responding to contamination to preventing it. The modernization of
FDA's regulatory framework for the oversight of food is one of the most
challenging initiatives in FDA's history, but one that will have public
health and economic benefits that could save thousands of lives and
billions of dollars annually.
Preventive Standards
I would like to highlight the Agency's activities related to the
seven foundational rules that form FSMA's central framework aimed at
systematically building preventive measures across the food system,
from the farm to the table. This framework is comprised of measures to
keep produce safe, implement modern preventive controls in human and
animal food/feed facilities, modernize oversight of imported foods,
guard against intentional contamination, and help ensure the safe
transport of food and feed. Since January 2013, FDA has released seven
proposed rules on these topics for public comment.
The proposed rules were the result of extensive outreach by FDA
with consumers, government, industry, researchers, and many others.
Since their release, we have made every effort to solicit input on the
proposed rules, not only through the standard rulemaking process, but
also by participating in webinars, listening sessions, public meetings,
and other activities with industry, consumer, and other stakeholder
groups across the country and internationally.
Based on our conversations, the Agency has learned a great deal,
and, in some areas, our thinking has evolved. For example, with regard
to the preventive controls for human food rule and the produce safety
rule, we recognize that the new safety standards must be flexible
enough to accommodate reasonably the great diversity of the produce
sector, practical to implement, and based on the best available
science. To achieve this goal, we believe that significant changes will
be needed to key provisions of the two proposed rules affecting small
and large farmers. We intend to publish revised proposed rule language
on certain provisions by early summer 2014 and accept comments on those
provisions. We value our ongoing dialog with produce farmers and others
in the sector on the proposed rules, and we want to ensure that we
implement FSMA in a way that improves public health protections while
minimizing undue burden on farmers and food processors.
FDA also recognizes that FSMA will only be as effective as its on-
the-ground implementation. Our implementation strategy includes
collaborating with industry, Federal, State, and local partners, tribal
and territorial authorities, and foreign governments to ensure mutual
reliance and appropriate and efficient oversight and compliance. It is
also a concerted effort, prior to enforcement, to facilitate compliance
through education, technical assistance, and regulatory guidance.
Resources
Our work together to improve the safety of our food supply requires
two fundamental steps. The first was to give FDA authority and tools to
modernize the food safety system, which FSMA did. The second is to give
FDA the capacity to carry out the numerous changes embodied in the law.
The President's fiscal year 2015 budget proposes a registration fee and
an import user fee that will help FDA meet its food safety obligations
under FSMA, while also benefiting industry and our State, local,
territorial, and tribal partners.
We are, of course, grateful for the additional food safety funding
that the Agency has received to date through the appropriations
process. As documented in the FSMA capacity and funding report that
Secretary Sebelius submitted to Congress in May 2013, however,
implementing the law in a manner that achieves its food safety goals,
while minimizing costs and disruptions for industry, will require
additional resources above FDA's current base funding for food safety.
For example, we need to invest in training and new tools to modernize
FDA and State inspection activity in keeping with FSMA's science-based
prevention framework and to improve the quality and consistency of
inspections. We need to invest in guidance, training, and other
technical assistance for small- and mid-size growers and processors.
And we need to invest in building FSMA's innovative new import
oversight system, which is vital to support international trade in safe
food. FDA looks forward to working with you and the stakeholder
community to develop these user fees.
Looking Forward
It is gratifying to FDA that in our meetings around the country, we
have received broad support for moving forward in implementing FSMA in
a timely and appropriate manner in light of its importance to food
safety and to the economic success of the food industry. We will
continue our collaborative approach as we move down the pathway to
final rules and to full implementation of FSMA. Successfully
implementing the broad prevention framework required by FSMA is
critical to food safety and consumer confidence in the food supply and
is an important priority for the Agency.
fdasia implementation
In 2012 the Congress passed--and on July 9, 2012, President Obama
signed into law--FDASIA, reauthorizing user fee programs for innovator
drugs and medical devices and establishing two new user fee programs
for generic drugs and biosimilar biological products. The law also gave
FDA new authority to better protect the drug supply chain, which is
critical in an increasingly global marketplace. In addition, FDASIA
provided the Agency with new authorities to combat drug shortages and
stimulate antibacterial drug development, made permanent programs to
enhance development of products used to treat pediatric populations,
included provisions intended to encourage drug innovation, made a
number of important changes to medical device regulation, and added a
number of other important provisions.
User Fee Program Implementation
FDASIA includes the fifth authorization of the Prescription Drug
User Fee Act (PDUFA V), which was first enacted in 1992, and the third
authorization of the Medical Device User Fee Act (MDUFA III), which was
first enacted in 2002. Two new user fee programs, for generic drugs and
for biosimilar biological products, build on the successes of these two
established user fee programs. Coming at a time of continuing budget
restraints, this steady source of funding is essential to support and
maintain FDA's staff of experts who review the thousands of product
submissions we receive every year, and do so in a timely and thoughtful
manner. Over the years, our user fee programs have ensured predictable,
consistent, and streamlined premarket programs for industry and have
helped speed patient access to safe and effective new products.
PDUFA
PDUFA V addressed many of the top priorities identified by public
stakeholders, the top concerns identified by industry, and the most
important challenges identified within FDA. PDUFA V enhancements
included increased interaction during regulatory review of New
Molecular Entity New Drug Applications (NME NDAs) and original
Biologics License Applications (BLAs); regulatory science enhancements
to expedite drug development; development of important new guidance for
drug developers; a commitment to develop a structured framework for
benefit-risk assessment; various enhancements to the drug safety
system; and requirements for electronic submissions and standardization
of electronic application data. This additional work was funded by a
modest 6 percent increase in PDUFA user fees.
MDUFA
Reauthorization of the medical device user fee program has helped
to expedite innovative new products to market by boosting the medical
devices regulatory review capacity through hiring new review staff.
MDUFA III represented a commitment between the U.S. medical device
industry and FDA to increase the efficiency of regulatory processes in
order to reduce the total time it takes to make decisions on safe and
effective medical devices. It was the result of more than a year of
public input, negotiations with industry representatives, and
discussions with patient and consumer representatives.
Prior to MDUFA III, beginning in 2010, we put in place a series of
reforms designed to improve predictability, consistency, and clarity in
the device review process.\1\ We were seeing results from these reforms
before enactment of MDUFA III,\2\ but the additional user fee funding
authorized under FDASIA enhances our ability to implement positive
changes for patients and industry. Under MDUFA III, FDA is authorized
to collect user fees that will total approximately $595 million over 5
years. With this additional funding, plus stable appropriated funding,
FDA intends to hire more than 200 full-time-equivalent (FTE) workers
over the course of MDUFA III. Between passage of MUDUFA III and October
1, 2013, we have hired more than 90 new employees in support of the
medical device review process.
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\1\ For example, in January 2011, FDA's Center for Devices and
Radiological Health (CDRH) announced a Plan of Action that included 25
specific actions we would take in 2011 to improve the predictability,
consistency, and transparency of our premarket programs. The following
month, CDRH announced its Innovation Initiative, which included several
proposals to help maintain the position of the United States as the
world's leader in medical device innovation, including the creation of
a new approach for important new technologies. See FDA, ``CDRH Plan of
Action for 510(k) and Science,'' available at http://www.fda.gov/
aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/
cdrhreports/ucm239448.htm, and documents cited therein.
\2\ For example, in 2011, CDRH, for the first time, began reducing
what previously was an increasing backlog of unresolved 510(k)
submissions. In addition, in February 2012, CDRH reported that the
``not substantially equivalent'' (NSE) rate for 510(k) submissions had
decreased to 5 percent in 2011 from a peak of 8 percent in 2010. See
Testimony of Jeffrey Shuren, M.D., J.D., before the U.S. House of
Representatives, Committee on Energy and Commerce, Subcommittee on
Health (February 15, 2012), available at http://www.fda.gov/NewsEvents/
Testimony/ucm290707.htm.
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In exchange for the additional user fees, FDA committed to meet
much-enhanced performance goals for the device review process.
Preliminary data indicate that FDA has the potential to meet all of its
fiscal year 2013 MDUFA III performance goals, and the program has
already seen a 27 percent decrease in the backlog of 510(k)'s compared
to fiscal year 2010, a 10 percent decrease in average total time for
review of 510(k)'s compared to fiscal year 2010, a 43 percent decrease
in the backlog of Premarket Approval (PMA) applications compared to
fiscal year 2010, and a 32 percent decrease in average total time for
review of a PMA application compared to fiscal year 2009. Also, FDA is
providing substantially more detailed quarterly reporting on our
progress in implementing those performance goals, and our quarterly
performance reports are online and available to the public.\3\ These
reports are also presented and discussed at FDA-conducted, quarterly
meetings with representatives from medical device member organizations.
---------------------------------------------------------------------------
\3\ See CDRH, ``MDUFMA Reports,'' available at http://www.fda.gov/
medicaldevices/deviceregulationandguidance/overview/
medicaldeviceuserfeeandmodernizationactmdufma/ucm
109210.htm.
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In addition, FDA and the medical device industry agreed in MDUFA
III to have an independent contractor conduct a two-phase assessment
for performing technical analysis, a management assessment, and program
evaluation, required to objectively assess FDA's premarket review
processes for medical devices. Phase 1 of this assessment required the
publication of high-priority recommendations within 6 months of
contract award.\4\ The following high-priority recommendations were
published on December 11, 2013:
---------------------------------------------------------------------------
\4\ See Booz Allen Hamilton, ``Evaluations and Studies of Premarket
Device Reviews under Medical Device User Fee Amendments (MDUFA) II/III
for the Food and Drug Administration--MDUFA II/III Evaluation_Priority
Recommendations'' (Contract No. HHSF223201010017B, Order No. 22313004)
(Dec. 11, 2013), available at http://www.fda.gov/downloads/medical
devices/deviceregulationandguidance/overview/mdufaiii/ucm378202.pdf.
Develop criteria and establish mechanisms to improve
consistency in decisionmaking throughout the review process;
Provide mandatory full staff training for the three
primary information technology (IT) systems that support MDUFA III
reviews;
Identify metrics and incorporate methods to better assess
review process training satisfaction, learning, and staff behavior
changes; and
Adopt a holistic, multi-pronged approach to address five
quality component areas to standardize process life-cycle management
activities and improve consistency of reviews.
The remainder of the Phase 1 assessment is currently in process and
is expected to be completed in June 2014.
Generic Drug User Fee Amendments of 2012
One of FDA's major undertakings since July 2012 has been putting in
place the infrastructure for a new user fee program under the Generic
Drug User Fee Amendments of 2012 (GDUFA) that will expedite the
availability of low-cost, high quality generic drugs. The program has
already achieved several milestones, including making significant
strides in reducing the backlog of pre-GDUFA applications and enhancing
review efficiencies. FDA has completed scientific review of
approximately 40 percent of GDUFA backlog applications, since the
program launch. In addition, FDA has conducted completeness assessments
for over 1,500 drug master files and has launched the creation of a
public list of drug master files available for reference \5\ to
expedite review of applications containing referenced active
pharmaceutical ingredients. Further, FDA held a public meeting on June
21, 2013, to discuss regulatory science priorities to expand the
availability and quality of generic drugs and solicit input from
stakeholders. The Agency streamlined the hiring process to recruit new
scientific reviewers, project managers, investigators, and support
staff, and met its ambitious year-one GDUFA hiring goal by bringing on
board at least 25 percent of GDUFA program hires by October 1, 2013.
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\5\ www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/
UCM332875.xls.
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Last, FDA has facilitated development of the most comprehensive
list of generic drug industry participants: more than 3,500
manufacturing and testing facilities have submitted self-identification
information to FDA during the fiscal year 2013 annual reporting period,
enhancing the quality and transparency of our knowledge of the generics
industry.
Biosimilars User Fee Act (BsUFA)
The Biologics Price Competition and Innovation Act, which was
enacted as part of the Affordable Care Act, established a new
abbreviated approval pathway for biological products shown to be
``biosimilar to'' or ``interchangeable with'' an FDA-licensed
biological product. Approved biosimilars are expected to be less
expensive than the reference products, providing clinicians and their
patients access to more affordable treatments that are biosimilar or
interchangeable.
BsUFA addresses many of the top priorities identified by public and
industry stakeholders and the most important challenges identified by
FDA in bringing biosimilar products to market. The BsUFA program is
similar to the PDUFA program in that it includes fees associated with
marketing applications, manufacturing establishments, and products.
However, there are some differences between BsUFA and PDUFA because of
the nascent state of the biosimilars industry in the United States. For
example, there are currently no FDA-approved biosimilar biological
products; accordingly, the BsUFA program includes fees for products
that are in the development phase to generate fee revenue in the near-
term and to enable sponsors to have meetings with FDA early in the
development of biosimilar biological product candidates.
In March 2013, FDA published draft guidance for industry entitled
``Formal Meetings Between the FDA and Biosimilar Biological Product
Sponsors or Applicants.'' \6\ This draft guidance provides
recommendations to industry on formal meetings between FDA and sponsors
or applicants relating to the development and review of biosimilar
biological products regulated by the Center for Drug Evaluation and
Research (CDER) and the Center for Biologics Evaluation and Research
(CBER). The guidance assists sponsors and applicants in generating and
submitting a meeting request and the associated meeting package to FDA
for biosimilar biological products.
---------------------------------------------------------------------------
\6\ http://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/UCM345649.pdf.
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Development of Antibacterial Drugs
Recognizing the need to stimulate investments in antibacterial
drugs, Congress passed--and the President signed into law--the
Generating Antibiotic Incentives Now (GAIN) title of FDASIA to create
an incentive system. The primary framework for encouraging
antibacterial development authorizes FDA to designate human
antibacterial or antifungal drugs that are intended to treat ``serious
or life-threatening infections'' as ``qualified infectious disease
products (QIDP).'' With certain limitations set forth in the statute, a
sponsor of an application for an antibacterial or antifungal drug that
receives a QIDP designation gains an additional 5 years of exclusivity
to be added to certain existing exclusivity periods. A drug that
receives a QIDP designation is also eligible for designation as a fast-
track product, and the application for that drug is eligible for
priority review. Between July 9, 2012 (when the GAIN title of FDASIA
went into effect), and February 19, 2014, FDA granted 40 QIDP
designations representing 27 unique molecules. Consistent with the
statute, on June 12, 2013, FDA issued a proposed rule to establish a
legislatively mandated list of ``qualifying pathogens'' that have the
potential to pose a serious threat to public health and make public the
methodology for developing the list, as required by FDASIA.
In addition to this initiative under FDASIA, FDA's Center for
Veterinary Medicine (CVM) has introduced a judicious-use strategy to
help protect the efficacy of anti-microbial drugs that are currently
used in animal agriculture but are also important for treating human
infection (``medically important antimicrobials''). The plan includes
phasing out the use of medically important antimicrobials for food
animal production uses, such as to enhance growth or improve feed
efficiency, and bringing under veterinary oversight all remaining
therapeutic uses of such drugs in food-producing animals in order to
ensure such uses are consistent with the judicious-use principles in
CVM's recently issued Guidance for Industry (GFI) #213 entitled ``New
Animal Drugs and New Animal Drug Combination Products, Administered in
or on Medicated Feed or Drinking Water of Food-Producing Animals:
Recommendations for Drug Sponsors for Voluntarily Aligning Product Use
Conditions with GFI #209.'' \7\ FDA is committed to the success of this
initiative as an element of its overall strategy to address the public
health problem of antimicrobial resistance.
---------------------------------------------------------------------------
\7\ http://www.fda.gov/downloads/animalveterinary/
guidancecomplianceenforcement/guidance
forindustry/ucm299624.pdf.
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Breakthrough Therapies
FDASIA created a powerful new tool to facilitate the development
and review of ``breakthrough therapies,'' instructing FDA to take
actions appropriate to expedite the development and review of a drug or
biologic, if preliminary clinical evidence indicates that it may offer
a substantial improvement over available therapies for patients with
serious or life-threatening diseases. This offers real opportunities to
get promising drugs more quickly to patients who need them. In fact,
using this new approach, FDA recently approved two advanced treatments
for rare types of cancer and one for hepatitis C. As of December 31,
2013, CDER had received 121 requests for breakthrough therapy
designation, and CDER has already granted the breakthrough therapy
designation to 36 potential innovative new drugs, many of which have
been for rare disease indications, that have shown encouraging early
clinical results in treating conditions such as cystic fibrosis,
hepatitis C infection, and breast cancer.
Pediatrics
FDASIA strengthened and made permanent provisions to improve the
safety and effectiveness of drugs, biological products, and medical
devices intended for use in pediatric populations. It made permanent
the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric
Research Equity Act (PREA), and authorized certain funding associated
with pediatric device development. We recently marked the 16-year
anniversary of BPCA and the 10-year anniversary of PREA and are pleased
to report that, since passage of those important pieces of legislation,
labeling for more than 500 drug products have been revised to contain
information about use of products in pediatric populations.
Under FDASIA, PREA was amended to require the submission of initial
pediatric study plans, typically at the end of Phase 2. This provision
provides an opportunity to improve the pace of pediatric drug
development by requiring sponsors to submit pediatric study plans early
in a product's development program; it is consistent with FDA's stated
regulatory objectives and facilitates alignment with European efforts
in the arena of pediatric product development. FDA implemented this
provision in early January 2013. In addition, FDA has published draft
guidance to industry, ``Pediatric Study Plans: Content of and Process
for Submitting Initial Pediatric Study Plans and Amended Pediatric
Study Plans.''
FDA has also issued a Final Rule, as required under FDASIA,
relating to the tracking of pediatric use of devices. This rule
requires applicants to include in certain premarket submissions readily
available information on pediatric subpopulations who suffer from the
disease or condition that the device is intended to treat, diagnose, or
cure. The information submitted will be used to help FDA better track
the number of approved devices for which there is a pediatric
subpopulation that suffers from the disease or condition that the
device is intended to treat, diagnose, or cure. FDA would like to use
this data to identify unmet pediatric needs in medical device
development.
Rare Disease Initiatives and Other Rare Disease Programs
FDASIA added a number of new provisions for rare diseases,
including the rare pediatric disease priority review voucher program,
consultation with external experts on rare diseases, and a pediatric
rare diseases public meeting. Under PDUFA V, CDER has a rare diseases
program that is fully staffed and operational, and a rare diseases
liaison in CBER has been planned. Also, a 3-day public meeting on
complex issues in rare disease drug development, which included the
pediatric rare diseases public meeting, was recently held on January 6-
8, 2014.
FDASIA also broadened the circumstances under which a sponsor of a
device approved under the humanitarian device exemption (HDE) pathway
could make a profit, in order to further encourage the development of
medical devices for rare diseases and conditions, without undermining
the incentive for sponsors to develop these devices for pediatric
populations. To encourage the development of medical devices intended
to benefit patients in the treatment and diagnosis of rare diseases,
sponsors of certain devices for rare diseases or conditions may apply
for marketing approval under the HDE pathway, which allows the sponsor
to seek FDA approval for the device by demonstrating only a reasonable
assurance of safety and not a reasonable assurance of effectiveness.
FDA approval of an HDE authorizes an applicant to market a device
subject to certain profit and use restrictions set forth in section
520(m) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
Previously, only sponsors of devices that were intended and labeled for
use in pediatric patients after the date of the enactment of the
Pediatric Medical Device Safety and Improvement Act of 2007 could seek
to make a profit on their HDE-approved devices. FDASIA expanded this
profit prohibition exemption to include HDE-approved devices intended
for the treatment or diagnosis of a disease or condition that does not
occur in pediatric patients or that occurs in pediatric patients in
such numbers that the development of the device for such patients is
impossible, highly impracticable, or unsafe. FDA has approved five HDE
supplements for HDE device sponsors, under this modified provision.
Patient Engagement
In accordance with our commitments in PDUFA V, FDA has initiated
the Patient-Focused Drug Development Program. The objective of this 5-
year effort is to more systematically obtain the patient's perspective
on a disease and its impact on patients' daily lives, the types of
treatment benefit that matter most to patients, and the adequacy of the
available therapies for the disease. As part of this commitment, FDA is
holding at least 20 public meetings over the course of PDUFA V; each
will focus on a specific disease area. We have already held patient
meetings on several major diseases.
CDRH launched a comprehensive Patient Preference Initiative last
year. This Initiative builds upon our 2012 Benefit-Risk Guidance
entitled ``Factors to Consider When Making Benefit-Risk Determinations
in Medical Device Premarket Approvals and De Novo Classifications,''
\8\ which outlines the principal factors that FDA considers, including
patient perspectives on meaningful benefits and acceptable risks, when
making benefit-risk determinations during the premarket review process
for certain medical devices. This guidance outlines a strategy for how
patient preference results should be compared to other sections of an
application.
---------------------------------------------------------------------------
\8\ CDRH, ``Guidance for Industry and Food and Drug Administration
Staff--Factors to Consider When Making Benefit-Risk Determinations in
Medical Device Premarket Approvals and De Novo Classifications'' (March
28, 2012), available at http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/UCM296379.pdf.
---------------------------------------------------------------------------
CDRH established the Patient Preference Initiative to address
issues not in the guidance, such as available methods, tools, and
approaches that can be used to collect patient views, how to establish
and evaluate the validity of the data, and how patient preference data
may be used in a broader context of the total product cycle of medical
devices.
The Initiative intends to provide the information, guidance, and
framework necessary to incorporate patient preferences on the benefit-
risk assessment of medical devices into the full spectrum of CDRH's
regulatory processes and to inform medical device innovation by the
larger medical device community. CDRH held a 2-day public workshop in
September 2013 to engage and solicit information on patient preference
from stakeholders, including patients, health care providers, industry,
and academic leaders. CDRH has also recently completed an obesity pilot
study that has developed new tools that can be used to measure patient
preferences. Finally, CDRH is working to expand both the number of
patient Special Government Employees and the ways in which FDA uses
these expert patients throughout the Agency.
In addition to these efforts, CDER established the Professional
Affairs and Stakeholder Engagement program that will serve as a focal
point and enhance two-way communication and collaboration with health
professional organizations and patient advocacy and consumer groups
about drug products.
Drug Shortages
Drug shortages pose a significant public health threat, affecting
individual patients from across the United States, including patients
who are in need of drugs to treat life-threatening diseases such as
cancer, serious infections, and malnutrition. The number of new drug
shortages in the United States rose steadily between 2005, when FDA
began tracking 60 new shortages and the all-time high in 2011, when 251
new shortages were reported. After a series of interventions, including
a presidential Executive order, enactment of FDASIA, FDA outreach, and
work with the pharmaceutical community, the number of new drug
shortages declined significantly in 2012 to 117 and fell even further
to 44 in 2013. However, shortages continue to persist for longer
periods, and at the end of 2013, FDA was tracking 97 total shortages
that began in 2013 or earlier.
Preventing drug shortages has been, and continues to be, a top
priority for FDA. Recognizing the importance of this issue, we have
increased substantially the resources we devote to drug shortages and
expanded our work to prevent them. While the Agency cannot solve the
problem alone, working in partnership with manufacturers and other
stakeholders, and within the current statutory and regulatory
framework, FDA helped prevent 170 shortages in 2013, 282 shortages in
2012, and 195 shortages in 2011. FDA has also identified future actions
that can help prevent shortages, including important work to support
new manufacturing methods that promise high-quality drug manufacturing,
that would help to ensure patients have needed access to lifesaving
medicines and could help revitalize pharmaceutical manufacturing.
Responding to notifications about potential shortages has enabled
FDA, working with other groups, to prevent a significant number of drug
shortages. Going forward, there is important additional work to do to
reduce the factors that lead to shortages. In October 2013, the Agency
released a Strategic Plan (``the Plan''),\9\ called for in FDASIA, both
to improve the Agency's response to imminent or existing shortages and
to advance longer-term approaches for addressing the underlying causes
of shortages to prevent supply disruptions from occurring in the first
place. The Plan also recognizes the important role of other groups in
preventing drug shortages and highlights opportunities for drug
manufacturers and others to prevent drug shortages by promoting and
sustaining quality manufacturing.
---------------------------------------------------------------------------
\9\ http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/
UCM372566.pdf.
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Supply Chain
Title VII of FDASIA strengthens drug safety by giving FDA new
authorities to protect the integrity of an increasingly global drug
supply chain in which nearly 40 percent of finished drugs and 80
percent of APIs are imported. Title VII allows FDA to protect the
global drug supply chain by: (1) increasing FDA's ability to collect
and analyze data to enable risk-informed decisionmaking, (2) advancing
risk-based approaches to facility inspection, (3) partnering with
foreign regulatory authorities, and (4) driving safety and quality
throughout the supply chain through strengthened enforcement tools.
Since enactment of FDASIA, FDA has been working diligently to
implement the title VII supply chain authorities in a meaningful way
that strives to maximize its public health impact. For example, FDA
issued a proposed rule to extend the Agency's administrative detention
authority to include drugs intended for human or animal use, in
addition to the authority that is already in place for foods, tobacco,
and devices; issued draft guidance defining conduct that the Agency
considers delaying, denying, limiting, or refusing inspection,
resulting in a drug being deemed adulterated; and issued draft guidance
addressing specification of the unique facility identifier system for
drug establishment registration.
The Agency already had taken steps toward development of a risk-
based inspection schedule, prior to FDASIA. However, the enhancements
provided by FDASIA will further assist the Agency in responding to the
complexities of an increasingly globalized supply chain. For example,
provisions in FDASIA that permit FDA to request records in advance or
in lieu of an inspection and that require firms to submit a unique
facility identifier will allow FDA to increase its inspectional
efficiency and its knowledge base.
In addition, FDA hosted a public meeting in July 2013 to solicit
comments from the public about implementation of title VII generally,
and to specifically address the provisions related to standards for
admission of imported drugs and commercial drug importers, including
registration requirements and good importer practices.
Title VII implementation requires not only the development of new
regulations, guidance, and reports, but also major changes in FDA
information systems, processes, and policy--a challenging task, given
that title VII was not additionally funded through user fee support or
otherwise. However, FDA has worked to make progress in each of these
areas, prioritizing the Agency's efforts to achieve the greatest public
health impact and deploy its limited resources most effectively.
Unique Device Identification (UDI) System
On September 20, 2013, FDA announced the Final Rule for a UDI
system,\10\ which, once implemented, will provide a consistent,
standardized, unambiguous way to identify medical devices. The UDI
system will be phased in over several years, focusing first on the
highest-risk medical devices. Once fully implemented, the UDI system
rule is expected to have many benefits for patients, the health care
system, and the device industry. It will provide improved visibility as
devices move through the distribution chain, enhancing the ability to
quickly and efficiently identify marketed devices when recalled and
improve the accuracy and specificity of adverse event reports; it will
also offer a clear way of documenting device use in electronic health
records and clinical information systems.
---------------------------------------------------------------------------
\10\ FDA, ``Final Rule: Unique Device Identification System,''
Docket No. FDA-2011-N-0090, 78 Fed. Reg. 58786 (Sept. 24, 2013),
available at http://www.gpo.gov/fdsys/pkg/FR-2013-09-24/pdf/2013-
23059.pdf.
---------------------------------------------------------------------------
Health Information Technology (Health IT)
Pursuant to section 618 of FDASIA, FDA, in collaboration with the
Federal Communications Commission (FCC) and the HHS Office of the
National Coordinator for Health IT (ONC), will soon publish on our
respective Web sites a report containing a proposed strategy and
recommendations on an appropriate risk-based regulatory framework
pertaining to health IT that promotes innovation, protects patient
safety, and avoids duplicative regulation. FDA, FCC, and ONC convened a
working group of external stakeholders and experts under ONC's Health
IT Policy Committee to provide appropriate input on the strategy and
recommendations for this report. This working group held open meetings,
made documents and information discussed available to the public, and
solicited public input during every meeting and through a public
docket. In developing the report, FDA, FCC and ONC took into account
all of ONC's Health IT Policy Committee's recommendations. The
committee adopted in full the external stakeholder working group's
recommendations.
Complementary to the FDASIA section 618 report in development, on
September 25, 2013, FDA published its final guidance on mobile medical
applications (mobile medical apps).\11\ FDA issued the mobile medical
apps guidance to provide clarity and predictability for manufacturers
of mobile apps. This guidance informs manufacturers, distributors, and
other entities about how FDA intends to apply its regulatory
authorities to software applications intended for use on mobile devices
that perform the same functions as traditional medical devices.
---------------------------------------------------------------------------
\11\ CDRH, ``Mobile Medical Applications: Guidance for Industry and
Food and Drug Administration Staff '' (September 25 2013), available at
http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/UCM263366.pdf.
---------------------------------------------------------------------------
Consistent with FDA's existing oversight approach, which considers
functionality rather than platform, the Agency intends a tailored
approach. The Agency intends to exercise enforcement discretion for the
majority of mobile apps as they pose low risk to consumers. FDA intends
to focus its regulatory oversight on the subset of mobile apps that are
medical devices that present risks to patients if they do not work as
intended. FDA has cleared more than 75 such mobile medical apps since
the late 1990s.
Implementing FDASIA is a considerable undertaking, requiring
detailed planning to integrate these tasks with the rest of FDA's
workload. All told, the 140-page law called for multiple deliverables
of all types, including more than 30 proposed and final rules, more
than 40 draft and final guidance documents, more than 20 reports to
Congress, and many other additional reports, assessments, public
meetings, and plans. FDA continues to meet most of its FDASIA
milestones and is on track to implement more provisions very soon. To
help the public keep track of our progress on these and other
provisions, we established a FDASIA web portal that includes a link to
our 3-year implementation plan, which we update regularly.\12\
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\12\ http://www.fda.gov/regulatoryinformation/legislation/
Federalfooddrugandcosmeticactfdc
act/significantamendmentstothefdcact/fdasia/ucm20027187.htm.
---------------------------------------------------------------------------
dqsa implementation
This past fall, Congress passed--and on November 27, 2013, the
President signed--DQSA. This new law contains important provisions
relating to the oversight of compounding of human drugs and outlines
steps to an interoperable system to identify and trace certain
prescription drugs as they are distributed in the United States.
Compounding
Title I of DQSA, the Compounding Quality Act, removes certain
provisions from section 503A of the FD&C Act that were found to be
unconstitutional by the U.S. Supreme Court in 2002. By removing these
provisions, the new law removes uncertainty regarding the validity of
section 503A, which will be applicable to compounders nationwide. In
addition, the new law creates a new section 503B in the FD&C Act. Under
section 503B, a compounder can become an ``outsourcing facility.'' An
outsourcing facility will be able to qualify for exemptions from the
FDA approval requirements and the requirement to label products with
adequate directions for use, but not the exemption from current good
manufacturing practice (CGMP) requirements. Outsourcing facilities must
comply with CGMP requirements, will be inspected by FDA according to a
risk-based schedule, and must meet certain other conditions, such as
reporting adverse events and providing FDA with certain information
about the products they compound.
If compounders register with FDA as outsourcing facilities,
hospitals and other health care providers that purchase drugs necessary
to meet the medical needs of their patients can provide patients with
drugs that were compounded in outsourcing facilities, subject to CGMP
requirements and Federal oversight.
On December 4, 2013, a week after the bill was signed, FDA took
several actions to implement the Compounding Quality Act. These
included issuance of three draft guidances related to implementation of
sections 503A and 503B of the law, three Federal Register Notices
soliciting nominations for various lists of drugs that can and cannot
be compounded, and significant stakeholder outreach.
Since then, FDA has solicited nominations for members of the
Pharmacy Compounding Advisory Committee and published a list of
compounders that have registered with FDA as outsourcing facilities
under section 503B of the law. As of February 28, 2014, 30 companies
had registered.\13\ FDA has also scheduled a 50-State meeting for March
20-21, 2014, to discuss implementation of the Compounding Quality Act.
---------------------------------------------------------------------------
\13\ Company list, facility information, and information about what
it means to register as an outsourcing facility are available at http:/
/www.fda.gov/Drugs/GuidanceCompliance
RegulatoryInformation/PharmacyCompounding/ucm378645.htm.
---------------------------------------------------------------------------
New problems continue to be identified at compounding pharmacies
across the country, and FDA intends to continue its inspection and
enforcement efforts to address these problems using currently available
resources. FDA intends to continue proactive and for-cause inspections
of compounding pharmacies and plans to take action, including
enforcement actions, as appropriate to protect the public health.
Track and Trace
DQSA also outlines critical steps to build an electronic,
interoperable system to identify and trace certain prescription drugs
as they are distributed in the United States. The development of the
system will be phased in with new requirements over a 10-year period.
These requirements will include placing unique product identifiers on
individual drug packages and providing product and transaction
information at each sale with lot level information, in paper or
electronic format.
Ten years after enactment, the system will facilitate the exchange
of information at the individual package level about where a drug has
been in the supply chain. The new system will:
Enable verification of the legitimacy of the drug product
identifier down to the package level;
Enhance detection and notification of illegitimate product
in the drug supply chain; and
Facilitate more efficient recalls of drug products.
This system will enhance FDA's ability to help protect consumers
from exposure to drugs that may be counterfeit, stolen, contaminated,
or otherwise harmful. The system will improve detection and removal of
potentially dangerous drugs from the drug supply chain to protect U.S.
consumers. Failure to comply with the requirements of the law can
result in penalties.
Drug manufacturers, wholesale drug distributors, repackagers, and
many dispensers (primarily pharmacies) will be called on to work in
cooperation with FDA to develop the new system over the next 10 years.
The law requires FDA to develop standards, guidance documents, and
pilot programs and to conduct public meetings, in addition to other
efforts necessary to support efficient and effective implementation.
FDA developed a schedule for implementing the law's requirements.\14\
In addition, last month we established a docket and requested comments
on standards for the interoperable exchange of information for tracing
of human, finished, prescription drugs, in paper or electronic
format.\15\
---------------------------------------------------------------------------
\14\ http://www.fda.gov/Drugs/DrugSafety/
DrugIntegrityandSupplyChainSecurity/Drug
SupplyChainSecurityAct/ucm382022.htm.
\15\ https://www.Federalregister.gov/articles/2014/02/20/2014-
03592/standards-for-interoperable-exchange-of-information-for-tracing-
of-human-finished-prescription-drugs.
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fda's efforts to protect the public health--now and in the future
FDA's mission is to promote and protect the public health, and
FDA's core responsibilities include ensuring the safety and efficacy of
medical products while fostering medical product innovation, overseeing
the safety and nutritional quality of four-fifths of America's food
supply, the safety of the blood supply and animal feed, and regulating
tobacco products. These responsibilities are enormous and the products
FDA regulates represent over 20 cents of every consumer dollar spent on
products in the United States.
Quality and Safety
Quality and safety are integral to FDA's mission. Food safety and
medical product quality depend primarily on the industry, requiring
top-level management commitment; a clear and in-depth knowledge of the
product and the system; supply chain management throughout the entire
life of a product; proactive and continuous management of risk; and
continuous and consistent monitoring of quality management systems and
processes. Unfortunately, serious quality lapses in recent years have
presented serious public health challenges, most notably those
involving foodborne illness, drug shortages, and the compounding of
unsafe drugs. Food safety and medical product quality issues lead to
higher risks to public health, increased costs, inefficiencies,
shortages and recalls, market damage, and, ultimately, loss of consumer
trust. FSMA, FDASIA, and DQSA respond to these challenges and present
the opportunity to re-think traditional approaches to quality.
FDA plans to redouble its prevention efforts through a focus on
quality. The Agency will promote the adoption of quality policies,
practices, and standards, both domestically and internationally, aimed
at reducing risks in the manufacturing, production, and distribution of
FDA-regulated products.
FDA is already taking concrete steps to prioritize quality in the
day-to-day work of staff across the Agency. For example, CDRH continues
to advance the Case for Quality Initiative for medical devices and has
established a Voluntary Compliance Improvement Program pilot. CDER is
moving toward creating a new Office of Pharmaceutical Quality to
highlight and consolidate quality principles and review throughout the
life cycle of drugs. And the Office of Foods is fostering broad,
consistent industry implementation of modern preventive practices under
FSMA.
Ultimately, all stakeholders globally must work individually and
collectively to foster food safety and medical product quality.
Industry, regulators, international organizations, health
professionals, purchasers, and consumers all have a role in demanding
products that are what they say they are and do what they say they will
do, delivered through a system that ensures the security and quality of
the product.
Diet and Health
In addition to implementing FSMA's prevention framework for food
safety, FDA is implementing a wide range of other high-priority food
safety and nutrition initiatives aimed at improving consumer access to
safe and nutritious food and to the information they need to choose a
healthy diet.
For example, FDA has begun a public process to further reduce Trans
Fat in the American diet and thereby reduce the risk of heart disease.
We recently announced our tentative determination that partially
hydrogenated oils, which contain industrially produced Trans Fat, do
not meet the criteria for ``generally recognized as safe'' status under
the statute. If, after reviewing the comments and scientific
information submitted, FDA finalizes this determination, such oils
would become unapproved food additives. That would make their use
unlawful, unless a company or other petitioner could prove to FDA that
one or more specific uses are safe. We have specifically solicited
comment on how such a determination might impact small businesses and
whether any special considerations could be made to reduce any burden
on small businesses.
We are also addressing concerns raised about the proliferation of
caffeine uses in energy drinks, conventional foods and dietary
supplements, including products that are readily available and
attractive to children. We do not have a concern about the use of
caffeine within its traditional boundaries, but we are working with the
scientific community and the food industry to ensure that higher levels
of caffeine added to new foods and marketed for new purposes meet the
relevant safety standards and bear any labeling that may be appropriate
to help ensure safe use.
Several initiatives are underway at FDA to provide information to
consumers that can help them make healthier food choices and thus could
improve their diets in ways that can reduce the risk and economic costs
of chronic disease. Last month, First Lady Michelle Obama announced
FDA's plans to update the iconic 20-year-old Nutrition Facts Label
based on updated scientific information and data about consumer eating
patterns. Among other things, the recently issued proposed rules to
update the label propose changes that better highlight the calorie
content of food, which is one tool to enable consumers to choose diets
that can reduce the tragically high incidence of obesity in the United
States. We expect and welcome a wide range of comments on the proposed
label changes and look forward to working with industry, consumers, and
nutrition experts to improve the food label.
In a similar vein, FDA is working on a final regulation
implementing the legislative requirement for nutrition labeling of
standard menu items in certain chain restaurants and similar retail
food establishments with 20 or more locations. Again, the focus is on
calories, so that consumers can readily know what they are getting and
can make informed choices when eating out. We expect to issue the Final
Rule this year.
Globalization
Just over a decade ago, FDA was responsible for overseeing a
largely domestic market of foods and medical products comprised of
manufacturers and producers within its borders who were relatively easy
to oversee. Contrast that with today's marketplace, where information
and goods flow freely across borders, and the development and
production of FDA-regulated products has become increasingly complex,
fragmented, and global.
These worldwide products create new public health challenges for
the Agency. FDA's historical regulatory approaches and tools--such as
hoping to intercept products at the border--are outdated and often
insufficient. Border inspections will remain important but cannot reach
even a small fraction of the 24 million U.S. food and medical imports a
year. To effectively protect the health of Americans, FDA must continue
to transform itself--from a primarily domestic agency to one that uses
innovative global strategies to secure our vast worldwide supply chain.
Globalization demands that we think, act, and engage globally.
Acknowledging that we cannot respond to these challenges alone, over
the next 5 years, FDA will continue expanding its regulatory
enterprise, including medical product and food regulators at the
international, Federal, and State levels, to build a stronger global
product safety net.
Through global coalitions of regulators, FDA will continue
developing procedures for more comprehensive and systematic information
sharing and deployment of resources, with an ultimate goal of mutual
reliance--a point where FDA and other regulators can rely on each
other, as well as on private third parties, to protect and improve
product safety.
``Smart'' Regulation
In the midst of rapid scientific development and an increasingly
global and complex marketplace, FDA's mission of promoting and
protecting the public health has become even more challenging. FDA must
address these new challenges expeditiously, as it continues to meet its
core responsibilities. Public trust in FDA oversight breeds confidence
in our regulated industries, at home and in the global marketplace. In
order to keep the public trust and maintain FDA's global leadership
role in fostering innovation, we must employ smart regulation.
The term ``smart regulation'' embodies the concept that protecting
the public health while encouraging innovation is an attainable goal
and it is attainable through smart, sound, science-based regulation.
Smart regulation also necessitates that FDA remain dynamic; continually
respond to changing situations, new information, and new challenges;
and that it always brings the best possible science to bear.
Regulation, when done right, can be a pathway toward meaningful
innovation; instill consumer confidence in products and treatments;
prevent recalls that threaten industry reputation and consumer trust;
and spur industry to excellence.
Over the last few years, FDA has worked hard to keep the public
trust and maintain its global leadership role in fostering innovation
by deploying smart regulatory approaches to streamline and modernize
its regulatory programs and minimize regulatory uncertainty for
industry, without compromising safety. This commitment will continue
into the future.
Regulatory Science
The 21st century has seen rapid advances in biomedical research.
New cutting-edge technologies that have led to thousands of new drug
candidates include: the sequencing of the human genome; combinatorial
chemistry, a new method of chemical synthesis that makes it possible to
prepare thousands of compounds in a single process; biosynthesis, which
enables scientists to synthesize complex chemicals in living cells; and
high throughput screening, which allows researchers to quickly conduct
millions of genetic, chemical, or pharmacological tests. In addition,
cutting-edge electronics and materials science have the power to
transform medical devices, and research on nanotechnology-based
materials will provide a better understanding of the safety of the use
of nanomaterials in food, over-the-counter drugs, and cosmetics. FDA's
regulatory science research agenda is critical to help translate new
technologies and basic science discoveries into safe and effective
real-world diagnostics, treatments, and cures and reduce the time,
complexity, and cost of product development.
In 2011, FDA recognized that advancing regulatory science was
necessary to enable FDA to keep abreast of emerging technologies, and
indeed, to stay ahead of the curve. That year, the Agency released its
strategic plan entitled ``Advancing Regulatory Science at FDA.'' \16\
Since that time, FDA has been modernizing its scientific infrastructure
by enhancing its internal research capacity and access to outside
scientific expertise, and by expanding external collaborations. Early
efforts have included:
---------------------------------------------------------------------------
\16\ http://www.fda.gov/ScienceResearch/SpecialTopics/
RegulatoryScience/ucm267719.htm.
The Medical Countermeasures Regulatory Science Program--
this program funds a number of projects conducted by internal FDA
scientists, external organizations, and public-private partnerships;
The Biomarker Qualification Program--this program was
established to support CDER's work with external scientists and
clinicians in developing biomarkers;
Modernizing Toxicology Safety Assessments--FDA has worked
in collaboration with the National Center for Toxicological Research to
modernize toxicology safety assessments;
The Entrepreneurs in Residence Program in CDRH--this
program enables the Center to recruit world-class entrepreneurs and
innovators to join highly qualified FDA scientists to develop solutions
that impact innovation; and
Public-Private Partnerships--these partnerships include:
the Centers for Excellence at the University of Maryland and Georgetown
University and the virtual Center of Excellence in Regulatory Science
formed with the State of Arkansas, which promote cross-disciplinary
regulatory science training, scientific exchanges, and research; and
the Medical Device Innovation Consortium, a partnership between FDA,
NIH, CMS, medical device companies, patient advocacy groups, and non-
profit organizations, such as the Pew Charitable Trusts, to advance
regulatory science for devices.
In addition, in October 2013, FDA issued a report entitled ``Paving
the Way for Personalized Medicine: FDA's Role in a New Era of Medical
Product Development'' to help the industry capitalize on advances in
personalized medicine. FDA has long understood that therapies targeted
toward individual patients were a major wave of the future.
Stewardship
During these challenging fiscal times, maximizing public health
value from each Federal dollar has become increasingly demanding for
FDA as the Agency attempts to keep pace with the dramatic technological
and market-based changes, impacting how foods, drugs, biologics, and
devices are produced. From personalized medicine and nanotechnology to
the globalization of our food and medical product supplies to an array
of new laws passed by the Congress that expand FDA's oversight
responsibilities, these complicated issues do not always include
additional resources to support FDA's new responsibilities. Therefore,
it is critical that FDA continues to effectively and efficiently
utilize its limited resources to increase productivity while also
maintaining program integrity.
In today's era of budget constraints and ever-increasing
requirements to do more with less, it is imperative that FDA takes a
hard look at how it approaches its work to identify ways to modernize
and maximize efficiency. The Agency will continue to prioritize
recruiting, developing, and retaining a high-quality workforce;
fostering a culture of continuous improvement; emphasizing customer
satisfaction; and embracing excellence from its programs. FDA has
established operational excellence and accountability objectives to
align resource planning, allocation, and management with the Agency's
strategic priorities to better ensure timely delivery of services
critical to the fulfillment of FDA's mission.
FDA must be an organization that delivers smart regulation through
lean management that relies on the best available evidence and science
to drive decisionmaking. Responsible stewardship of our public funding
and user fees requires collaboration across FDA to perform the mission-
specific core regulatory activities, which engage not only the
regulatory science disciplines but also Agency experts in policy,
planning, informatics, analysis, management, and communications. FDA is
continuing to invest in a talented and diverse workforce that can help
to fulfill the Agency's important public health and regulatory roles.
FDA is improving its systems and process for hiring, paying, training,
assessing, and retaining staff.
The Agency is fostering a culture of continuous improvement that
includes encouraging programs to prioritize actions that have the most
public health impact, communicating with and learning from others to
innovate and solve problems, and quickly reassessing when outcomes are
not ideal or do not move forward. FDA is also developing performance
metrics that align with program requirements to help drive outcomes.
Focusing on customer improvement and expectations of excellence,
both internally and externally, FDA is allowing for more timely
information sharing and collaboration. This includes systems that track
critical resources and support functions.
Conclusion
FDA's responsibilities have undergone huge transformations through
such important laws as FSMA, FDASIA and DQSA. Our commitment to
implementing the responsibilities entrusted to the Agency by Congress,
to improve the lives of the American public with integrity, is
unwavering. We look forward to continuing and improving on the critical
work we do.
I am happy to answer any questions you may have.
The Chairman. Thank you very much, Dr. Hamburg. We'll start
a round of 5-minute questions. I have two tracks I want to go
on. I don't know if I can get them in in 5 minutes, but I'll
try. I'd like to have you address, if you can--perhaps I'll
submit the question in writing--sodium consumption and the
reduction of sodium in our foods.
But I really want to focus my question on opioids. In 2002,
doctors in America wrote 144 million prescriptions for opioids,
144 million. Ten years later, they wrote 241 million
prescriptions for opioids. In 1999, 4,030 people died from
prescription opioids overdose, and 16,651 died in 2010, more
than heroin, opium, everything else combined. That's OxyContin,
Percocet, Vicodin, all those.
On October 25, 2013, the FDA approved a new hydrocodone,
Zohydro. Forty experts urged the FDA to reconsider its
approval, and here's a statement they made,
``In the midst of a severe drug addiction epidemic
fueled by overprescribing of opioids, the very last
thing the country needs is a new, dangerous, high-dose
opioid.''
One expert said, ``It's a whopping dose of hydrocodone
packed in an easy to crush capsule. It will kill people as soon
as it's released.'' And then I found in the newspaper this
morning--the Washington Post, where I'm getting some of this
information--I don't know if it's right, but I'm just reporting
what they said. The advisory panel, your advisory panel, voted
11 to 2 against approving Zohydro, and yet the FDA went ahead
and approved it.
What I find startling is that in the United States, we have
5 percent of the world's population, but we have 99 percent of
the world's consumption of hydrocodone. Hydrocodone-based pain
killers are the most prescribed pharmacy drugs in the United
States--as I said, 241 million for hydrocodone. It was 131
million prescriptions in 2011.
I didn't realize we were so painful in this country. What's
happened? We had a hearing on pain here last year. I may have
to have another one. Pain clinics, all these--you go to a
doctor, and they're prescribing pain killers, opioids. People
go back and get them refilled. You've got a pain, you go to the
doctor, and they prescribe this. What's happening to our
doctors in this country?
We had a panel here last year that said a lot of it is not
physiologically caused. It may have a physiological
manifestation, but it's not physiologically caused. And now the
FDA comes along and approves what I understand to be something
that is 10 to 20 times more powerful than OxyContin when your
advisory panel voted 11 to two.
There was an editorial in the Post this morning plus
another story in the Post. Could you address that, please?
Dr. Hamburg. As you know, it's a very complex problem, a
very serious public health threat. We are working very hard to
address what FDA can do to make sure that patients with
legitimate pain needs get what they need, but also to recognize
the serious addiction potential of these drugs and that we need
to do what we can internally and, of course, work more broadly
with all the components. As you noted, prescriber practices is
an important component of this overall problem.
With respect to your question on Zohydro, let me address it
as best I can. Hydrocodone is a very important opiate for the
treatment of legitimate pain, and we do have many medical needs
for both acute and chronic pain management. Hydrocodone, up
until the approval of Zohydro, was only available in a product
that also included acetaminophen, which has significant liver
toxicity.
As you know, some patients respond to different drugs
differently, and some can tolerate hydrocodone much better than
they can tolerate other opiate drugs. But at the lower doses,
where it was available in the combination product, there are
serious risks, if you upped the dose of the hydrocodone, of
liver toxicity and serious life-threatening complications from
the acetaminophen. So this product is unique in terms of its
availability as a single hydrocodone product without that
associated liver toxicity risk.
The advisory committee met, actually, before we put in
place more stringent labeling requirements around the use of
this class of drugs that we think are important for assuring
appropriate use for patients with legitimate pain. It is
approved as a Schedule II drug, which means that there are
additional restrictions on prescribing. Physicians have to have
a special license. There are limits on prescriptions--no
refills. There are special security precautions and
requirements that have to be undertaken with respect to the
storage of the drug and reporting requirements.
It's a Schedule II drug, which has these additional
requirements to limit its use and, hopefully, to make sure that
it is prescribed and used appropriately for pain where it is
required. In addition, there is a REMS for this drug product
that places further restrictions on the use and also requires
the company to make available physician training for its
appropriate use.
So we recognize that this is a powerful drug. But we also
believe that, appropriately used, it serves an important and
unique niche with respect to pain medication, and it meets the
standards for safety and efficacy. Recognizing its addiction
potential and understanding, of course, the broader context of
the serious problem of opiate medication abuse and misuse in
this country, we weigh carefully risks and benefits.
We hope that as a Nation, we can make progress in
addressing all of the issues that contribute to this ongoing
and very serious opiate misuse and abuse epidemic, and we will
continue to push hard. We also are trying to ensure that work
is going forward with respect to the science and technology of
abuse deterrent formulations so that, hopefully, we can move in
that direction going forward.
The Chairman. Thank you, Commissioner. I have followup
questions, but my time is out. I'll submit those in writing.
Senator Alexander.
Senator Alexander. Thanks, Mr. Chairman.
Dr. Hamburg, I've complimented you and the FDA for your
fast start on implementing the compounding pharmacy. I'd like
to just discuss that with you a little bit. I think we
understand each other on this. One of the reasons, in my
opinion, for the tragedy was some confusion about who was on
the flag pole, whose job it was to regulate the Massachusetts
facility.
My understanding is that now the law clears that up, that a
compounding pharmacy that compounds sterile drugs may choose to
be regulated by you, or, if not, they're regulated by the
States. Is that right?
Dr. Hamburg. First, let me thank you for your leadership on
this issue and the important issue of trying to clarify through
legislation important aspects of the compounding pharmacy law
and requirements for oversight. I would say that this is a
very, very important step forward in terms of that effort and
also really defining a new role for the FDA.
I do have some concerns, and I think that you're aware that
FDA, as the legislation was being shaped, was concerned about
the fact that even with clarifying 503A, so we now know that it
does apply nationwide, it is still possible that a compounding
pharmacy could be in compliance with some aspects of 503A,
compounding a specific product for a specific patient with a
prescription, ET cetera, but might be out of compliance with
other components, such as compounding an FDA approved drug or
other aspects. So there still is an opportunity for some
confusion there.
With respect to 503B, we are concerned that since it is
voluntary and companies can choose to register with us and be
under our oversight, some may not.
Senator Alexander. True.
Dr. Hamburg. And if they sort of hide out as 503A
traditional compounders, we may not even know that they exist.
Senator Alexander. I've only got 5 minutes here, so I want
to get to--yes, I understand that. And the Senate bill, of
course, wanted to go further, but the law didn't go that far.
But, fundamentally, you've got 35 facilities that have already
agreed to be regulated by you, and at the same time, you're
able to and are--I mean, you're issuing warning letters to
others.
Dr. Hamburg. Yes.
Senator Alexander. So I have a couple of questions on that.
On your followup to the warning letters, I also understand that
some States are indicating, I've heard, that they may require
an outsourcing facility that has chosen to be regulated by the
FDA also to be regulated by the State as a pharmacy. Have you
heard that? That wasn't really the intent of the legislation.
It was to permit a facility to choose one or the other.
Dr. Hamburg. I have not heard that specific concern. States
vary, as you know, considerably in terms of their laws and
their resources for the oversight of compounding pharmacies.
What I have heard from States is that when there are these
large facilities that are manufacturing high-risk sterile
injectable products, they often don't feel equipped to provide
that regulatory oversight. So they hope that those facilities
will register with FDA.
Senator Alexander. But at least under the law,
manufacturers, you've got. You regulate manufacturing.
Dr. Hamburg. Right.
Senator Alexander. Outsourcing facilities are all yours.
The rest are the States'. But when will you be issuing more--I
guess you call them draft quality standards----
Dr. Hamburg. Yes.
Senator Alexander [continuing]. So that the other
compounding pharmacies will know what will be expected of them
if they choose to be an outsourcing facility.
Dr. Hamburg. We are working to develop the good
manufacturing practices guidelines for those outsourcing
facilities, and we'll get that out as quickly as we can. I
think that these kinds of facilities understand the sort of
broad framework that they can expect in terms of good sterility
practices, ET cetera. But this is very, very important and a
high priority for us, and we will be moving forward.
Senator Alexander. Do you have any estimate of how many of
these facilities that compound sterile drugs exist that are
eligible to be outsourcing facilities? Do you have any idea?
Dr. Hamburg. We really don't know what that number is, and
we're hoping that now, as we implement this important new law
and begin this process, we'll begin to get a much better sense.
And, of course, we are also increasing our partnership with the
States, and, actually, we're having a second 50-State meeting
next week to help strengthen the communication, both the
understanding of what this new law means for all of us and also
to make sure we've got the right systems for communication.
We've also been doing a lot of outreach with healthcare
providers, hospital systems, ET cetera, because we hope that
they will see this, the outsourcing facility mechanism, as what
is best for their patients in terms of assuring quality and
regulatory oversight, and that it will become the standard of
care so that more and more companies will declare themselves to
us and we will be able to work with them in this way.
Senator Alexander. That is my hope, too, and I'll be
anxious to watch this as it moves along.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Alexander.
I have in order here Senator Warren, Senator Isakson,
Senator Bennet, Senator Enzi, Senator Murphy, and Senator
Casey, and now Senator Franken.
Senator Warren.
Statement of Senator Warren
Senator Warren. Thank you very much, Mr. Chairman and
Ranking Member Alexander.
Welcome, Dr. Hamburg. It's good to see you here today. The
CDC estimates that more than 2 million people develop
antibiotic resistant infections in the United States every
year. There's increasing scientific evidence that the overuse
of antibiotics in animal agriculture is contributing to the
rise in antibiotic resistance.
The more we use an antibiotic, the less effective it
becomes at fighting resistant infections. If we continue to use
30 million pounds of antibiotics in food animals every year,
which is about four times as much as we use in people, we're
likely to have a lot more resistant infections and fewer
antibiotics that work when we need them.
So the FDA's most recent guidance documents on this subject
concluded that the use of antibiotics in animal agriculture for
production purposes, to promote growth in animals--and I'll
quote you here--``may contribute to antibiotic resistance.''
But the FDA says that antibiotic use for disease prevention is
all right. And you've asked pharmaceutical companies that sell
antibiotics to animal growers to voluntarily withdraw their FDA
approvals for those uses.
Now, we've heard preliminary reports that all 27 companies
that manufacture animal antibiotics agreed to comply with this
directive and will submit supplemental new drug applications to
revise their labels. Surely, the removal of production uses
from the market is a good first step, and I'm hopeful that this
is going to lead to decreasing use of antibiotics.
But the FDA's guidance doesn't guarantee the prudent use of
antibiotics in the context of disease prevention. Even with
every animal drug company agreeing to comply with the FDA's
most recent guidance, there could still be a lot of antibiotic
use in animals that is ostensibly for disease prevention, but
it is still far more than necessary and will continue
increasing resistance.
So how will these guidances and the FDA's review of
labeling changes ensure that we're reducing the antibiotic use
in agriculture and decreasing the risks of perpetuating
resistance?
Dr. Hamburg. Thank you for the question. It's such an
important topic, and it's actually one that, on a personal
level, I've been working on for most of my career. I really am
encouraged by some of the steps that we are taking now, and I
think they will make a real and an enduring difference.
As you noted, we put forward the guidance asking for
companies, both innovator manufacturers and generics, to show
us how, over a period of time, they will remove the products
for the growth promotion purposes, what we call non-judicious
use of the antibiotics. We've been very encouraged.
There was a 90-day period for the companies to report to us
their plans for how they would voluntarily comply. That just
closed, and we've gotten preliminary indications of very full
participation. We'll obviously review what they have put in
writing to make sure that we are comfortable, and we'll work
with them if we don't think it adequately addresses.
With respect to your question about how we ensure that
these antibiotics don't continue to be used inappropriately,
although not targeted for the growth promotion, for prevention
purposes, we're also going to be moving the oversight of the
use of these products to the supervision of a veterinarian,
which isn't the case now. So it'll be much more like what
you're familiar with, with a prescription from a doctor and the
release of a drug. The same will be true with veterinary
oversight of the use of these products for the preventive and
treatment purposes.
Of course, there will always be a need for antibiotics to
treat animals for important illnesses they may have, and, also,
there is a role for prevention. But we want to make sure that
it's appropriate and adequately supervised, and, especially,
that is of importance when they are antibiotics of importance
for human medical needs as well.
Senator Warren. I appreciate that, and I'm running out of
time here. So I'll just make the note about the use--moving
this over so that veterinarians have to prescribe. Again, I
think it's a very good first step.
But veterinarians are permitted to prescribe for anything
that's on-label use. And so long as they are permitted to use
it effectively for prevention of disease, that means there's
the possibility of just continuing to keep these drugs out in
circulation, keeping them out there all the time, even with the
approval of a veterinarian, and I'm just concerned.
I'll submit the rest of my questions for the record so we
can go back to this in detail, including how you're going to
track it.
Dr. Hamburg. Yes. And I'm happy to discuss it further, and
we will be able to work in oversight of the prescribing
practices of veterinarians in ways that may be reassuring to
you.
Senator Warren. I appreciate that and just want to
encourage you along these lines. Thank you very much, Dr.
Hamburg.
The Chairman. Thank you, Senator Warren.
Senator Isakson.
Statement of Senator Isakson
Senator Isakson. Thank you, Mr. Chairman.
Dr. Hamburg, thank you for being here, and thanks for your
service. I'm sure you're probably aware that skin cancer is
reaching epidemic proportions in the United States. In fact,
one person an hour dies now from melanoma, not to mention
disfigurement of squamous cell and basal cell and other skin
cancers. The last time the FDA approved an application for an
enhanced ingredient for sun screening capability was in 1990.
And there are some applications that have been pending longer
than a decade for action.
Senator Reed, my Democratic co-sponsor, and myself--and
you're familiar with, I think, some of the initiatives we've
taken--will be introducing along with members of the House some
legislation to make more transparent and more rapid the
determination in terms of skin care ingredients in products. We
don't want to, in any way, legislate what FDA should approve.
But we want to get a more transparent and a more effective
system of evaluating these important ingredients for this
terrible cancer.
Would you commit to work with our offices on this to ensure
that we get a more rapid response to these determinations?
Dr. Hamburg. Absolutely, and I would agree with you that it
has been taking too long. We are eager to work with you on that
particular legislation. We are moving forward on our evaluation
of the sun screen additives and getting back to sponsors on our
assessments. We also are looking at whether we can modernize
the overall framework for how some of the over-the-counter
products submit applications and are overseen to really try to
streamline it and make it more responsive to our modern world.
Senator Isakson. We'll certainly work with you and your
office to be a positive influence. We don't want to make the
decision, but we want to get the decisions to be made, and we
know that's your responsibility.
Dr. Hamburg. Absolutely.
Senator Isakson. My second question has arisen in my State
from a couple of companies that have asked me questions. I'm
not going to get into a specific question of their product, but
I do want to ask you about the length of time it takes for FDA
to respond to an appeal of an FDA decision.
A particular case was brought to my attention where a
decision was made by FDA, and the company governed by that
decision appealed the decision based on scientific facts and
determinations that were submitted. It's been 2 years, and they
still haven't gotten an answer.
Last July, when they called for an update, they were told
the decision was pending and would be there any day, and that's
been 8 or 9 months ago. So what can people expect on an appeal
of a determination by the FDA in terms of a reasonable time
within which to get an answer to that appeal?
Dr. Hamburg. I think it would depend on the product, the
nature of the appeal, the regulatory pathway that the appeal
was being undertaken. So I can't give you a one-size-fits-all
answer. But I would say that I recognize how important it is to
make sure that these processes work well and that they are
clearly understood by the companies in terms of what timelines
will be.
I think it's, no doubt, an area where we can often be more
efficient and responsive than we have been, and we really are
committed to trying to do the best job possible. But, not
knowing the specifics here, I can't tell you when--I do believe
I saw a letter from you, and we are moving forward on that in a
relatively timely way. But I will get back to you on your
specific query.
More broadly, I would say that over the last couple of
years, we've been working very hard to really streamline and
modernize our regulatory systems to address some of the
business process issues that slow things down and to recognize
the importance of good, clear communication with companies
around these kinds of activities.
Senator Isakson. And I understand with breakthroughs in
medical science and pharmaceuticals and devices, sometimes
devices use pharmaceuticals within themselves, and you've got
to determine which one they are.
Dr. Hamburg. That is true.
Senator Isakson. That can get very complicated.
Dr. Hamburg. Yes. In this arena, as in many other arenas,
the world in which our authorities were first established looks
very different today. That's why we had to modernize through
FDASIA and FSMA, updating the compounding pharmacy laws, ET
cetera. We're always needing to really look at whether our
systems match the real world needs.
Senator Isakson. I appreciate your attention very much. My
time is almost up, so I'll just say I'm going to submit another
question that is very important with regard to FDA's
considering the regulation of medical IT.
Dr. Hamburg. There is a great deal of interest in that
topic.
Senator Isakson. We need to look at Congress'
responsibility in that as well. So I'll look forward to talking
to you about that. Thank you for your service.
Dr. Hamburg. Thank you.
The Chairman. Thank you, Senator.
Senator Bennet.
Statement of Senator Bennet
Senator Bennet. Thank you, Mr. Chairman. I'd like to thank
you and the Ranking Member, Senator Alexander, for holding this
important hearing.
Commissioner, welcome back. I want to take a minute before
I ask my question to thank you for the FDA's work over the last
few years. It hasn't been easy to implement a comprehensive FDA
reform bill while beginning to also implement a track-and-trace
and compounding bill. You came out to my home State of Colorado
in 2011 and listened to many people in our bioscience community
all across the State who were having difficulty communicating
back and forth with the FDA, and you made a commitment then
that things were going to get better.
I can tell you honestly that I've heard from many people
back home that they've seen a very positive change at the FDA,
and I think a lot of that is due to your leadership. Nothing is
perfect, but I hear consistently how much things have improved
at the FDA. And on behalf of my constituents, I want to thank
you for that.
Dr. Hamburg. Thank you.
Senator Bennet. I also was pleased to see the
implementation of a bill that I worked on with Senators Burr
and Hatch that created a breakthrough therapy designation for
drugs that have shown dramatic results early in the approval
process. To date, over 40 treatments have received this
designation.
We passed that bill--if you had asked me if we'd be sitting
here today with 40 drugs, I would have said you're delusional.
But that is, in fact, what's happened. Drugs that are trying to
cure various kinds of cancer, cystic fibrosis, hepatitis C, and
many other life-threatening conditions.
I visited a number of Colorado patients who are receiving
breakthrough therapies, and I can tell you firsthand that it
has truly made a lifesaving difference for many who tell me
that their dream is only to live a normal life. That's all they
want to do, like everyone else, something the rest of us take
for granted.
So as a result of this effort to get drugs to patients more
efficiently, we've seen a number of people writing to our
office asking for more direct dialog with FDA regarding
groundbreaking drugs that should be considered to be
breakthrough therapies. And while no one wants to unduly
influence the science and data that FDA looks at, I believe
there should be an avenue for patients to inform the FDA of
their opinions about what might be considered for breakthrough.
So, Commissioner, in light of all the work that FDA has
already done, I wonder whether you can talk a little bit about
the effect this new designation has had at the agency and for
the industry and for patients, and whether you might be willing
to have more open dialog with patients to consider information
they would supply with respect to breakthrough therapy
designation. I apologize for the long windup, but I'm excited
to see something in our government working well, and I wanted
to give you an opportunity to talk about it.
Dr. Hamburg. I could give you an answer that would be very
long, too. I'll try to be succinct, though. But it's been such
an important and exciting new opportunity for us, and we
appreciate that it was included in the legislation. Frankly, it
has been much more popular and successful than we had
anticipated. The other side of that is that we actually didn't
get new resources to implement this program.
But we have been able to identify a very large number of
exciting drugs that really hold promise to treat serious, often
life-threatening illnesses. We've been able already to approve
three different products for four different indications under
this breakthrough therapy pathway. And I think that we will
continue to see it as a very important program.
It underscores, I think, another set of important points
that have broader ramifications for our work at the FDA. One of
the aspects of it that's been so successful is the early
engagement with the FDA review teams and senior level
scientists at the FDA to really help shape what the best
development strategy is, so that we can ask and answer all the
critical questions to address the safety and efficacy
questions, but actually move it through the system as quickly
as possible so these promising drug candidates can get to the
people who need them. And in that regard, the opportunity for
engagement of patients is critical.
In another aspect of FDASIA and our FDA work, we actually
have been also establishing a series of meetings with patients
around some critical disease areas to get their input in terms
of how the disease or condition manifests itself in their
lives, how we should be thinking about patient-reported
outcomes in many instances as an integral part of our study
designs, and how to really make sure that we are helping to
address critical unmet medical care and public health needs
while trying to help speed innovation and product development.
Senator Bennet. My time is up because of my long wind-up,
but I want to thank you.
And, Mr. Chairman, I want to thank you, because your
leadership in including this really has made a material
difference. I think as we see the FDA exercising its muscles
around this one part of the pipeline, my hope is that, as you
sort of implied, we're going to be able to see it across the
FDA as we think about how to make sure that the United States
maintains its leadership in bioscience going into the 21st
century. So thank you.
Dr. Hamburg. Thank you.
The Chairman. Thank you, Senator Bennet. But, again, my
thanks to you, because you were the person on this committee
who spearheaded that effort for a couple of years, and so I'm
very grateful for you sort of taking that over and running with
it. I appreciate it very, very much.
Senator Enzi.
Senator Enzi. Thank you, Mr. Chairman.
The Chairman. And you, too. Senator Roberts was also--I
forgot. Both Bennet and Roberts were on that issue, now that I
think about it. Thank you.
Senator Enzi.
Statement of Senator Enzi
Senator Enzi. Thank you, Mr. Chairman. That used up 10
seconds of my time.
[Laughter.]
I would followup on what Senator Warren was asking about,
the animal antibiotics. That's very important in Wyoming, and
now there's a proposed veterinary fee directive. She comes from
a very heavily populated State. I come from a very sparsely
populated State and one that's underserved by large animal
veterinarians. So we have some different problems with that.
In light of her one question taking up all 5 minutes, I'm
going to submit that one in writing.
Dr. Hamburg. OK.
Senator Enzi. I worked with Senator Tester on the Tester
amendment which was the Food Modernization Act that provides
specific accommodations for preventive controls in the law for
small farmers and producers. What is the status of the
implementation of that?
Dr. Hamburg. The Tester amendment, in particular, or more
broadly?
Senator Enzi. Yes, in particular.
Dr. Hamburg. One of the things--as we have been doing
outreach in response to developing our proposed rules and now
as we are taking comments--one of the things more broadly than
just the Tester amendment is the impact on small farmers and
the fact that we have a system where there are very different
types of food producers, and we need to find a way to ensure
greater food safety, but not impose undue burdens.
Senator Enzi. I'll submit that one with more detail, too.
Dr. Hamburg. OK.
Senator Enzi. I have heard a number of concerns from food
producers about the overly prescriptive framework when
considering the preventive controls for human food. What
concerns me even more is that it doesn't appear as though the
FDA has adhered to the requirements of the Administrative
Procedures Act in how it went about publicizing the proposed
rule.
Can you provide this committee with a commitment that
you'll adhere to the requirements of the Administrative
Procedures Act on further rulemaking?
Dr. Hamburg. I certainly can. And I had not heard that
concern. I would say, if anything, we have really done a
remarkable job in terms of outreach and engagement and taking
comment and responding to comment. So I will go back and ask
some questions about that, and we'll certainly followup with
you.
Senator Enzi. We'll provide more detail on that, too, then.
For my next question, we're concerned about the abuse
deterrent formulations, of course, to make pills harder to
crush and inject and use. If the agency establishes a clear
pathway and standards for abuse deterrent claims, companies, of
course, I think, will continue to invest in this kind of
research. I've been troubled to hear from the drug
manufacturers who are working toward that and who would like to
adopt abuse deterrent formulations that they are kind of
stymied and confused by the FDA's lack of clear and consistent
standards.
When do you plan to finalize the guidance, and can we
expect the guidance to also include generic versions? It's
integral in the fight for prescription drug abuse to use all
the available tools, and the regulatory uncertainty is slowing
down the particular tool, and I think that's unacceptable. So
could you commit to me to finalize the guidance in maybe the
next 6 months?
Dr. Hamburg. I think the guidance is very important and
lays out how we're thinking about it. I think, in all honesty,
the science and the technology also needs to be developed here,
though. We really need to incentivize companies to work hard on
this. That's what we want to do. We want to be able to provide
them with as much clarity as possible, because it's such an
important area, and we need to develop abuse deterrent
approaches for these powerful drugs.
Senator Enzi. But there's no time table laid out for it?
Dr. Hamburg. I am not sure what the timeframe is. I know we
issued the guidance maybe a few months ago when--a year ago,
and so we----
Senator Enzi. I'll submit that as well, because I know it's
a very complicated thing, and I would like a fairly extensive
answer on it. I appreciate the efforts on it.
There's also a new pathway to approve biosimilars, and I
was very involved in crafting the bipartisan proposal to create
a pathway, and then helped lead discussions to ratify a user
fee to support that program. You mentioned resources earlier.
And I'm very interested in how both are implemented and
particularly committed to ensuring that the implementation is
consensus-driven with the original law.
Again, I'm looking for a commitment that the FDA will be
transparent, that you'll issue guidance as needed to ensure we
all understand, and also give the stakeholders, which, of
course, would include us, the opportunity to engage with you
around the key policy questions before the final decisions are
made.
Dr. Hamburg. Absolutely committed to that. We are standing
up the program, as you well know, and have had many discussions
with companies that are either developing or interested in
developing biosimilars as part of that new program and pathway.
Senator Enzi. Thank you, and I've got some additional
questions, but my time is out. So thank you.
The Chairman. Thank you, Senator Enzi. Let's see. Where are
we now? Senator Murphy, Senator Casey.
Statement of Senator Casey
Senator Casey. Mr. Chairman, thank you very much.
Dr. Hamburg, we're grateful for your presence here and your
good work. I wanted to try to get to at least two areas. One is
on this issue of naloxone, and the question of whether law
enforcement and others should be able to administer this drug
in the case of an overdose to reverse it. In particular, I
wanted to highlight an element of legislation. Tom Udall,
Senator Udall, has Senate bill 1657, which is the Increasing
the Safety of Prescription Drug Use Act of 2013.
One of the provisions asks the FDA to reconsider the status
of naloxone as a prescription drug. I just wanted to have you
speak to that. I know you can't make a determination here
today, but I just wanted to have you speak to that issue in
terms of its value in the context of law enforcement, but, more
particularly, as a way to deal with a crisis situation when
there's an overdose.
Dr. Hamburg. Naloxone, as you know, is a very, very
important medicine in terms of being able to reverse opiate
overdose and certainly used on a very frequent basis and very
effectively in the healthcare setting. We have been concerned
that many opportunities when it could save a life have been
limited because they occur in the community, not in a
healthcare setting.
We've actually encouraged and reached out to manufacturers
of this product to consider coming in to us with a formulation
that could be provided as an auto injector or nasal inhaler
that could be more available in community settings. Law
enforcement or others, potentially, could take advantage of
this kind of formulation, and it could, I think, save lives. So
we're encouraged, actually, by the response that we've had from
the manufacturers, and we will continue to work on this
important issue.
Senator Casey. I appreciate that. I know that the chairman
has raised this issue. A lot of people are working on this. It
is stunning, as Chairman Harkin said, the numbers we've seen.
The one number that I keep coming back to is people who abuse
prescription drugs are 19 times more likely to abuse heroin--
just stunning.
Our State of Pennsylvania unfortunately has a third place
finish that we did not want to have in terms of heroin abuse.
So it's substantial, and we're seeing it not in the
stereotypical fashion, not urban communities or places where
you might--you know, the popular image of this kind of abuse is
in big cities. We're seeing it in rural areas and small towns.
So it's very substantial.
Let me just move to one more issue that the chairman also
raised--Zohydro, if I'm pronouncing that right. One issue that
the chairman raised is the question of the advisory committee
recommending against the approval of the product. But also,
apparently, the product was approved without any abuse
deterrent properties. Is that correct?
Dr. Hamburg. That is correct.
Senator Casey. I guess a related question to what the
chairman asked is the concern that I think a number of us
have--and I'm sure you share this concern--about the
implications of allowing this new product on the market without
these abuse deterrent properties. Can you speak to that?
Dr. Hamburg. I would love it if we had abuse deterrent
formulations that were actually meaningful and effective at
deterring abuse in all instances. We are moving in that
direction. We put out, as was noted, guidance for how we would
be thinking about reviewing and approving abuse deterrent
formulations. What they would need to be able to demonstrate--
because it doesn't do any good to label something as abuse
deterrent if it actually isn't abuse deterrent.
Right now, unfortunately, the technology is poor. There's
one abuse deterrent formulation that is in the marketplace,
recently approved. It's abuse deterrent in terms of immediate
crushing for uses, injection or for sniffing. It doesn't
prevent abuse or misuse when taken orally, and it's, frankly,
not where we need to be. It's an important step forward. It
demonstrates utility and opportunity, but we need to continue
to work with companies and the broader scientific and
engineering community to come up with better abuse deterrent
formulations that will really work.
We also are committed to working on developing non-opioid
pain medicines, because that would make a huge difference as
well. You know, acute and chronic pain needs to be treated.
Opiates are very effective for acute pain and less effective
for chronic pain. But we don't have a lot of good alternatives
at the present time. So that's another commitment that FDA has
made, to work with companies to try to develop non-opioid pain
medicines that really will make a difference for patients.
Senator Casey. Thank you. I'm out of time. I'll submit some
more for the record. Thank you.
Senator Franken [presiding]. We'll go next to Senator
Roberts.
Statement of Senator Roberts
Senator Roberts. Thank you, Mr. Chairman.
Dr. Hamburg, thank you so much for coming. I know your time
is very valuable. This is a Senator Enzi question, too. It's
the same question he asked. I think he pretty well summed it
up. But it gets pretty specific, so I'd like to go through it,
and I think your answer to Senator Enzi was yes. That's the
answer I'm looking for. So we'll give that a try.
There is concern, as you know, from our food industry
leaders about the implementation of the Food Safety and
Modernization Act, specifically, concerns related to the
preventive controls for human food, a proposed rule that I
believe is still open for comment. They are specifically
interested in the proposed rule mentioning testing and supplier
verification requirements in the preamble, but does not provide
the specific requirements in the rule.
This can get pretty expensive, to say the least, and there
is a whole host of organizations, which I will not go into,
that are very worried about this. Can you assure me that you
will not finalize the rule with these more prescriptive testing
and supplier verification requirements, the ones that are so
expensive, unless they go through a full notice and comment
period regulatory process, including the revised economic
analysis? And can you also assure me that this will not be
issued as an interim final rule?
Dr. Hamburg. What I can assure you is that we have really,
from the very beginning, tried to reach out to all of the
different stakeholders, hear their concerns, and we've done
lots of public meetings, visits, meetings with specific groups
and individuals, all trying to get input. It has been a complex
set of rules to put forward with many different, sometimes
competing interests and concerns.
We have gotten a lot of response back. We're going to be
carefully going through all of the comments when the different
comment periods end on the rules. We may well reissue codified
language on certain key provisions because of some of the kinds
of concerns that you've raised, and I have heard the concerns
about some of the economic impacts and analyses as well. So,
yes, we will work in a very deliberate, transparent way and
continue to try to drill down on these critical questions so
that we end up with something that will really work.
Senator Roberts. I appreciate that. I think that's a long
yes, and I thank you for going into that. In the Food and Drug
Administration Safety and Innovation Act, we asked the GAO to
look into how regulations and guidance, policies and practices
could be modified, streamlined, expanded, or discontinued in
order to reduce or prevent such drug shortages. This was also
discussed at length with the FDA staff during the drafting of
the legislation.
Can you tell me where the FDA is in regards to their
internal review of their regulations and what's been done to
address instances in which the FDA policies are or were leading
to drug shortages?
Dr. Hamburg. I think a huge amount of progress has been
made in the drug shortage area. Certainly, our team, which has
been expanded as well, has been working, I think, long hours
and very diligently to address both existing shortages and
eminent potential shortages in this country. Obviously,
industry plays a critical role, and the shortages that occur
generally occur because of issues with either their supply
chains of products or, importantly, quality concerns in the
manufacturing.
But we have seen real improvement in the number of
shortages in recent years. The passage of FDASIA has helped to
strengthen progress that was being made and really enables us
to institutionalize important ways of interacting with industry
and important activities within FDA. So we are moving forward
and, I think, have made real progress, and I think we have
systems that are working and need to continue to be
strengthened, of course.
Senator Roberts. I understand you're making progress. And
pardon me for the interruption. I have about 11 seconds here.
But where is your internal review of the regulations? Where
would you say that stands now? Are you halfway done, or where
are we?
Dr. Hamburg. I'm not quite sure when you say the internal
review with respect to regulations. We had some delays in
getting the reports up to you----
Senator Roberts. Well, it's an ongoing process.
Dr. Hamburg [continuing]. But we are----
Senator Roberts. But you're getting there.
Dr. Hamburg. We're getting there, and I really do think
that it is a system that is working.
Senator Roberts. OK. I appreciate that.
Thank you, Mr. Chairman.
Senator Franken. Before we go to Senator Baldwin, I just
want to thank Senator Roberts for your work on the compounding
bill.
Senator Roberts. Well, thank you, Mr. Chairman. I
appreciate that. I'm happy to compound with you any time.
[Laughter.]
Senator Franken. OK. We'll go to Senator Baldwin.
Statement of Senator Baldwin
Senator Baldwin. Thank you. And I want to thank, in their
absence, Chairman Harkin and Ranking Member Alexander for
convening this hearing and giving us the opportunity to ask
questions of you. Welcome, Dr. Hamburg.
Dr. Hamburg. Thank you.
Senator Baldwin. Wisconsin is home to a vibrant community
of innovative medical device companies. There's always
interesting things going on. Wisconsin innovators are making
significant contributions to medical treatment with
breakthrough technologies, such as a state-of-the-art colon
cancer screening test and a pioneering sepsis detection device.
In the last several years, the FDA has taken some
encouraging steps to enhance patient access to safe devices and
to spur product innovation, and we're very excited about some
of those, in particular, the FDA's pilot program of parallel
review that allows both the FDA and CMS to simultaneously
review innovative devices for market approval and coverage
determinations. This will help streamline the process for
companies and the patients who are served by those innovations.
So, Commissioner, the FDA Center for Devices recently
indicated that the agency plans on establishing a new pathway
to accelerate the approval of certain devices for patients with
serious unmet medical needs. Under this approach, as I've
heard, some of the data that typically is collected in device
studies could be submitted to the FDA once the device is
already approved for use with patients.
This proposal not only has the potential to improve
treatment options for patients in need, but also to empower
smaller companies to bring new and cutting edge technologies to
market by allowing them to target their resources most
efficiently and effectively throughout the approval process. So
I'm hoping that today you could elaborate on the development of
this new pathway and, specifically, if you could tell me how
the FDA will assure predictability throughout the process for
the device companies, and, importantly, how the agency will
make sure that the needed evidence is collected in a post-
market setting to guarantee patient safety.
Dr. Hamburg. That's an important question. There's so much
exciting innovation in the medical device arena. The center has
been working hard in a number of arenas to really harness those
opportunities in science and technology for innovation--the
innovation pathway, the entrepreneurs and residence program--
and looking now at how we can learn, in some ways, from the
drug center and pathways there to try to build in some new
mechanisms, recognizing that really understanding safety and
effectiveness and benefits to patients of a product has to be
sort of a life cycle of the product approach, and that as we
look at the preapproval, we also have opportunities to deepen
our understanding in real world use with post-marketing
surveillance and collection of data and additional studies that
are continued.
That's been a theme on the drug side for quite a number of
years and continuing now, and I think that is part of the
Center for Devices strategic plan going forward. As you noted,
this approach of really integrating post-market studies into
the overall assessment and ongoing understanding of a device is
very, very key, and it's being shaped, and we are going to be
eager to work with industry and patients and consumers and
other stakeholders as it moves forward.
Senator Baldwin. Thank you. We'll follow this and look for
more details with great interest.
Mr. Chairman, I'm going to submit some additional questions
for the record, but thank you again for the opportunity.
Senator Franken. Thank you. We'll do that.
Senator Murkowski.
Statement of Senator Murkowski
Senator Murkowski. Thank you, Mr. Chairman.
Dr. Hamburg, welcome. We appreciate all that you do. There
have been good questions asked about FDA approval of certain
drugs, drug shortages. These are issues that I have concern
with. But in fairness to your time, I want to shift to a couple
of subjects that probably have not been brought up.
One is the shellfish ban that the Chinese have imposed on
shellfish coming out of parts of Alaska and the West Coast.
This is an issue that might be very narrow in its scope, but
has great impact in certainly a portion of my State, impacting
some basically family-owned businesses that are really taking a
real hit right now.
We sent a letter on March 6 to encourage that there be a
delegation to go to China to discuss this issue with the
Chinese to see if we can't get faster resolution of this. I
understand from NOAA that this meeting is scheduled in China
for March 21. The U.S. delegation is going to include NOAA,
USTR, and USDA's Foreign Ag Service, but not FDA.
The question to you this morning is: Can you give me any
assurances that we are fast-tracking a resolution of this
issue, what FDA's role is, and if you will be sending somebody
as part of that delegation, and, if not, why not?
Dr. Hamburg. Well, this is an issue that, obviously, has
great importance. It is something where NOAA and the Department
of Commerce has the lead in terms of the interactions with the
Chinese. We have been providing information and support to
them, as well as information about public health assessments to
our Chinese counterparts as well.
We are not going to be formally part of the delegation, but
we will be in contact with them. We'll be working with them and
supporting them, and we also do have an office in China to
provide additional support. So we will have input, but we are
not in the lead on this. Our focus is really on the public
health assessment.
Senator Murkowski. Well, I understand. I appreciate that.
My only concern is that if there are issues that arise in this
meeting that speak to the specific jurisdiction of FDA, I would
hate for things to be held----
Dr. Hamburg. And we will be available to them--and they
know it--24 hours a day to provide that technical support.
Senator Murkowski. All right. Then I would like to turn to
a subject that I have brought up before this committee, and no
offense to the chairman here, but we often refer to this alien
species of fish as a Frankenfish. No offense to Senator Franken
here in any way, shape, or form.
Senator Franken. Offense taken, however.
[Laughter.]
Dr. Hamburg. There's actually an inflatable Frankenfish
that I've seen.
Senator Murkowski. Now, see, that's even worse.
Senator Franken. That is worse.
Senator Murkowski. That is worse.
[Laughter.]
I don't want to consume my time here talking about how bad
the name is. We'll refer to it as genetically engineered fish,
and, specifically, salmon. You know that I have very, very
strong concerns and reservations. I don't need to show you
pictures of beautiful wild Alaska salmon. I have them here.
But I will show you a picture of the eelpout, which is
where the DNA is taken from--this kind of slimy, ugly eel,
bottom-feeding fish--that is injected into a beautiful chinook
salmon in an effort to cause these fish to grow quicker so that
they can get to a market more readily. I continue to strongly
oppose, strongly oppose, FDA approval of genetically engineered
salmon. I don't believe that the FDA has adequately studied the
environmental effects, the economic impacts, not only on the
wild salmon themselves, but our seafood markets, and let alone
the potential health impacts on humans.
Given the concerns that I have and many, many others have,
can you assure me that FDA is prepared to deny approval of the
sale of GE salmon to consumers if your agency determines that
it cannot guarantee that it's safe to eat?
Dr. Hamburg. If we could guarantee that it wasn't safe to
eat, then it would not pass our approval standards.
Senator Murkowski. All right, because what we're looking
for is--we want this assurance, and we don't know that it is
safe to eat. We don't believe that it has been determined that
this genetically engineered salmon would be safe to eat. We
also haven't been able to determine whether or not it would
impact negatively and jeopardize the wild Alaska salmon.
So I would ask again that you look very critically at this.
The threat, I believe, is not only to humans for consumption of
this bizarre fish, but is a threat to our wild stocks. And then
if, in fact--if, in fact--FDA should advance to a level of
approval for sale to consumers, I have been demanding that the
agency provide very clear labeling to consumers that that is,
in fact, what they would be purchasing for consumption.
So what I'm seeking is, first of all, a level of assurance
that if it's not safe to eat, it's just not going to be out
there for sale, but if it is determined that it should be
allowed, that there be clear labeling allowed.
Dr. Hamburg. I know time is limited. It's a complicated
issue. I can assure you of a couple of things. One is that we
have been taking a very, very systematic, science-based
approach to the review of this application. It does represent
the first in its class, so to speak, and so it's very, very
important as a product in and of itself and also the pathway
for review and approval.
We also undertook an environmental assessment, as I think
you know, to address your concerns, vis-a-vis, the wild salmon
populations. We published in December 2012 our preliminary
findings and sought comment. Actually, we got--I think it was
33,000 or 35,000 comments, so this is a topic that people care
a lot about.
We're going through those comments, taking them very
seriously. And we will be moving forward in a deliberate,
science-driven way, reflecting all of the important inputs,
including, obviously, the perspectives that you've brought
forward today and earlier, as we consider this product
application.
Senator Murkowski. Mr. Chairman, my time has expired.
But perhaps, Dr. Hamburg, you and I would have an
opportunity to discuss further not only GE salmon, but progress
that we're making in other areas.
I have some other questions that I will submit for the
record, and I would ask that you pay particular attention to
the level of inquiry about how we are doing with ALS research
and the joint meetings that we have been having with
stakeholders and how we can advance a cure for ALS.
Dr. Hamburg. OK.
Senator Murkowski. Thank you.
Thank you, Mr. Chairman.
Senator Franken. Senator Murkowski, do any of the questions
that you have for the record include reference to Frankenfish?
[Laughter.]
Senator Murkowski. No, your----
Dr. Hamburg. Do you want to screen those?
Senator Franken. Well, we'll include them, then.
Senator Murkowski. Thank you, Mr. Chairman.
Senator Franken. Senator Hatch may be coming, but I'll take
a round of questioning.
First of all, welcome.
Dr. Hamburg. Thank you.
Senator Franken. I want to start by thanking Chairman
Harkin and Ranking Member Alexander for calling this important
hearing and for the leadership that they've both shown
regarding policy issues within the FDA's purview. It's been a
pleasure working with both of them on reform of a number of FDA
policies, most recently the pharmacy compounding legislation
that passed into law in November, which I helped to develop
with them and Senator Roberts.
I want to thank you, Dr. Hamburg, for working with us so
closely on that. In your testimony, you noted your quick
implementation of the laws allowing new companies to register
as outsourcing facilities, what we call outsourcing facilities,
already. This was a critical component of our bill. Can you
tell the committee why this is so important? How does this new
option improve public health and prevent new outbreaks?
Dr. Hamburg. Well, this was targeted on high-risk products,
sterile injectables, that we know can become contaminated, and
when they do, there are very serious consequences for health.
This will enable, for those companies that choose to register
with us, a higher level of assurance in terms of good
manufacturing practice and adherence with the kinds of
manufacturing procedures that need to be undertaken to make
these products safe.
So we think that this is hugely important. As I mentioned
earlier, we certainly hope that companies will choose to go
this pathway, and that, importantly, the marketplace will view
this as an appropriate standard of care for the health, safety,
and protection of their patients, and that healthcare systems
will really seek out those that have not just registered--
because that's the first step--but actually submitted
applications and become outsourcing facilities with us and are
part of our program of ongoing oversight, which would include
regular inspections to ensure compliance with these important
manufacturing procedures and safety protections.
Senator Franken. Thank you for that answer. Dr. Hamburg, as
you know, I'm proud to represent Minnesota, where we have a
true culture of innovation, particularly in my State's medical
device industry. I spend a lot of time with startup device
companies, which serve as a major source of innovation within
that industry and innovation for the next lifesaving therapies
for patients.
These entrepreneurs and their investors are pretty
tenacious, and they spend years doing R and D before they see a
dime of profit in the hopes of creating a therapy that improves
lives. I've been doing my part to fight for our device industry
in Minnesota and around our country, the American device
industry, and that's why I've been fighting the device tax
since it was first proposed, and I'm working now to find a
bipartisan solution to repeal the tax once and for all.
I want to do everything I can to help make sure our
companies which face international competition are able to
succeed. So in this vein, another area I've done a lot of work
on is making sure that the process of review is streamlined as
much as possible. And FDA--and I've seen this--FDA and the
industry have different cultures. I've often seen the FDA and
the device industry sort of talk past each other.
In Minnesota, we did something that I think is remarkable
to bridge the difference between the cultures. The FDA and
Minnesota's own LifeScience Alley, which happens to be the
largest State-based life science trade association in the
country, formed a partnership that I've worked hard to support.
It's called the Medical Device Innovation Consortium, as you
know. This public-private partnership is the first of its kind,
and it's goal is to create efficiency and quality of
regulation, and it studies regulatory science.
Can you tell me what progress has been made in advancing
innovation and benefiting patients because of the creation of
this organization?
Dr. Hamburg. Well, thank you for the question. I actually
felt badly that I forgot to mention it when I was responding to
Senator Baldwin as an element of what exciting things are
happening in the area of medical device innovation. It is a
public-private partnership, as you mentioned, and I think it
has gotten off to a very good start.
It was announced--I think we, together, launched it not too
long ago, and it has doubled in size. I think there are 38 or
so different members, and it spans device companies, consumer
groups, patient groups, research organizations, and the FDA is
part of it. I think what's exciting about it is that it has
created a research agenda to really focus on how we can advance
the underlying science so that we can get the promise of
science to people more quickly.
It is focused on a number of critical areas. One is new
clinical trial designs so that we can ask and answer critical
questions more efficiently and, hopefully, also encourage more
device manufacturers to do their first human studies in the
United States rather than overseas where it might be cheaper
and less cumbersome. It's focused on patient-reported outcomes
and how to actually integrate that into device development,
which is so very important across all medical conditions and
products, but devices, in particular.
Also, one of the things that excites me is developing
computer simulations and models so that you could actually
study some of these devices in that context instead of in
animal models or in people in the early stages so that you can
really, No. 1, manipulate things and play with it more, but
also reduce cost and potential risks to patients, but still
really get important information to, again, move things that
have promise into the marketplace and making a difference in
people's lives.
So I think it's a wonderful public-private partnership.
Thank you for your leadership in helping to make it possible.
We are very committed to working with it, and we are seeing
benefits already, and we see, more importantly, the foundation
for lots more progress.
Senator Franken. Thank you for your role in that and for
your excitement about it. I am, too.
Senator Enzi for a second round.
Senator Enzi. Thank you, Mr. Chairman.
I'd like to revisit the goals you immediately identified
when you took the helm at the FDA in modernizing how the agency
considers new therapies and closing the regulatory science gap.
Those goals are ones we obviously all share.
That said, there is a continued level of frustration among
patients and manufacturers that the FDA lags behind other
countries in both timeliness and up-to-date understanding of
critical responsibilities, including clinical trial design,
valid end points for assessing the value of new therapies, and
how the risk evaluation and mitigation strategies are tools to
both protect patients and allow access to higher-risk products
where patients are desperate for treatment.
In Senator Harkin's opening statement and questions, he
mentioned a case where the committee voted against a product
and then was overridden by the FDA. I'll talk about a little
different situation, and that's dealing with multiple
sclerosis.
FDA recently made a decision to break with an overwhelming
advisory committee vote to support the safety and effectiveness
of a novel therapy for multiple sclerosis, and then the agency
chose not to approve the drug, despite it having been approved
in 30 other jurisdictions based on the same data set. Can you
explain the logic behind the agency's decisions? What did the
FDA see that the advisory committee could not?
Dr. Hamburg. First, let me address your broader question
about us, in terms of--we are, I think, at the cutting edge in
terms of review and approval of new products. If you look at
drugs approved in recent years, I think about three-quarters of
them were approved in the United States first.
And on devices, apart from the highest risk devices, we
are, I think, at par with comparable other countries in terms
of review times, ET cetera. We do ask for more clinical data
often on the higher risk devices. So I think there's some urban
mythology about where we stand in comparison to review times
and leadership there, and I would have to say the PDUFA, the
user fee programs for both devices and drugs, have made a real
difference in our ability to be as competitive as possible.
With respect to the role of advisory committees and the
decisionmaking within the FDA, the advisory committees are a
very important component of the review process, but they are
not determinative, as you well know. We seek expert advice in
many ways, including advisory committees. Advisory committees
are not used with every product that is reviewed, of course.
But it's sometimes frustrating for me, I have to say, when
people ask questions about a specific product and why we didn't
approve it. That information is commercial confidential
information that we're not allowed to share without permission
of a company.
But I can assure you that the FDA review teams take their
job very, very seriously, going through in a systematic way the
data that is available to them, assessing safety and efficacy
and overall risk-benefit and the benefit to patients. There
often are things that are not obvious but that make a real
difference in terms of a decision that's made.
Senator Enzi. And the advisory committee isn't----
Dr. Hamburg. The advisory committee is a very important
part of our input on a decision. I would say the majority of
times, our ultimate decision aligns, but not always.
Senator Enzi. But you're saying they're lacking information
that the people at FDA would have? So they're not getting the
full story?
Dr. Hamburg. I think that there are many components to the
review, and the advisory committee is an important piece of it.
But the advisory committee is not spending time with the
patient level data that the review teams are, and there are, I
think, aspects of the review that the advisory committee is not
always engaged in. But we value their input. We take their
input very seriously, and we do try to engage subject-matter
experts to the greatest degree that we can.
Senator Enzi. The only reason this one came--that I noticed
this one is that it had been approved in 30 other jurisdictions
already, using the same data set. So those other jurisdictions
are considered wrong, too. And that's a decision, I guess, that
the FDA can make, and we do want you to keep us safe.
My time has run out.
Senator Franken. Would you care to ask another question?
Senator Enzi. Well, it would be your turn.
Senator Franken. I know, but go ahead.
Senator Enzi. I know that the FDA is underway in its
implementation of the Generic Drug User Fee Act, and it's my
understanding that not all first generic applications have been
approved on the same day as the patent expiration. Is there a
reason for that?
Dr. Hamburg. Well, this is a program that, as I think you
know, we've had serious backlogs in. That was a big part of why
the user fee program was begun with the passage of FDASIA. We
are moving forward in implementing that, hiring up, addressing
the backlog in critical ways, and, also importantly, addressing
the issues of expanding our inspectional capacity so that we
can do those critical inspections, which increasingly are often
overseas.
We're not where we need to be yet. But we're committed to
moving forward, and we have made progress, but there's a lot
more work to be done.
Senator Enzi. I'll submit some additional information that
I'd like on that, like how many applications the agency has
received for these first generic products and how many have
missed the approval at the earliest possible date and what
you're doing to ensure that the future generic applications are
reviewed. So I'd be interested in some more detail on that.
Dr. Hamburg. Of course.
Senator Enzi. Again, I thank you for being here today to
answer our questions. We don't get this opportunity very often,
and you've done an outstanding job. Thank you.
Dr. Hamburg. Thank you.
Senator Franken. Thank you, Senator Enzi.
When we did the reauthorization of the FDA user fees, I
worked closely with you when you were ranking member of this
committee and with Chairman Harkin to make sure that devices
that are approved through the 510(k) process didn't have to go
back to the agency every time an insignificant change was made
to the device, such as the color of the label or the packaging
was changed.
I know just recently, FDA sent the 510(k) modifications
report to Congress, and I wanted to first congratulate you on
that. I understand that FDA held a public meeting in advance of
preparing the report and engaged in a healthy dialog with
interested parties. I appreciate all that you did to work with
the industry.
Again, this is about working with the industry, in this
case, to develop the report. I think it's, again, another great
example of FDA-industry collaboration and communication. What
have you learned from the industry as a result of this
collaboration? And as you prepare the draft guidance on this
topic, which I understand to be the next step, do you
anticipate that this sort of FDA-industry collaboration will
continue?
Dr. Hamburg. This kind of collaboration is key. I would add
patients in as well, because I think at the end of the day, our
goal is to provide the best medical devices for their needs.
But I think it has been very valuable in helping us to better
understand the way in which this industry works.
As you well know, it's not a one-size-fits-all industry in
terms of the very small device companies and much larger device
companies with very different needs and experience. And the
range of device products is expanding rapidly and getting more
and more complex. So we really do need to work together to be
able to keep progress moving forward and, ultimately, to
deliver what patients need.
But I wouldn't say that the interactions are always easy,
but it's been very valuable to listen and learn. We've tried to
be as responsive as possible, and I think it's making a
difference.
Senator Franken. No, they shouldn't necessarily always be
easy.
Dr. Hamburg. Right.
Senator Franken. As part of FDASIA, I worked with Senator
Alexander on a provision that created new incentives for
medical device companies to develop products to treat rare
conditions. In your written testimony, you noted that you have
approved five new products under our provision. Thank you again
for your work.
Can you explain why it is so important to reward innovators
for developing products to treat rare conditions? In this case,
it was rare conditions that adults had, if a treatment for
pediatric use had already been approved. Can you talk about why
it's important to have these incentives?
Dr. Hamburg. I think it's very important that we have the
right incentives to get companies to invest in developing
technologies where there may not be a huge marketplace, where
the return on investment will not necessarily be clear, but
where there is essential medical need and where these products
really will matter in addressing an individual's--either a
pediatric patient or adult patients--medical needs and
requirements.
So I think we see this on the device side, and we see it on
the drug side, that you cannot always assume that these
important healthcare and public health needs will be addressed
without looking at what the opportunities are, what the
barriers are, and are there incentives to help ensure that work
goes on in these key, often under-addressed areas.
Senator Franken. Well, I'm glad we've had success on these
five new products.
Senator Enzi, any more questions?
[No verbal response.]
Senator Franken. OK. Great.
Well, then, thank you, Dr. Hamburg, for your testimony and
for your service.
This hearing is adjourned.
[Additional material follows.]
ADDITIONAL MATERIAL
Department of Health & Human Services,
Food and Drug Administration,
Silver Spring, MD 20993,
November 6, 2014.
Hon. Tom Harkin, Chairman,
Committee on Health, Education, Labor, and Pensions,
U.S. Senate,
Washington, DC 20510.
Dear Mr. Chairman: Thank you for providing the Food and Drug
Administration (FDA or the Agency) with the opportunity to testify at
the March 13, 2014, hearing entitled ``Protecting the Public Health:
Examining FDA's Initiatives and Priorities,'' before the Committee on
Health, Education, Labor, and Pensions. This letter is a partial
response for the record to foods and veterinary medicine questions
posed by several members of the committee.
If you have further questions, please let us know.
Sincerely,
Thomas A. Kraus,
Associate Commissioner for Legislation.
______
Response by the Food & Drug Administration to Questions of Senator
Harkin, Senator Murray, Senator Sanders, Senator Casey, Senator Bennet,
Senator Baldwin, Senator Warren, Senator Alexander, Senator Burr,
Senator Isakson, Senator Enzi, Senator Murkowski, Senator Hatch,
Senator Kirk and Senator Roberts
Senator Harkin
delayed tobacco and menu labeling regulations
I understand that both the menu labeling final rule, called for in
the Affordable Care Act, and the proposed tobacco deeming rule, called
for in the Family Smoking Prevention and Tobacco Control Act are under
review by OMB. In both cases, regulatory action has been significantly
delayed despite the fact that timely regulation has the potential to
have a significant positive impact on public health. In regards to menu
labeling, a final rule that covers chain restaurants and the full range
of similar retail establishments, including movie theaters, grocery
stores, and convenience stores--as I intended as the author of this
provision--will ensure that Americans have access to the information
they need to make healthy decisions for themselves and their families.
When it comes to the tobacco deeming rule, coverage of novel tobacco
products--such as e-cigarettes and liquid nicotine--will protect
Americans from unregulated products and help prevent a new generation
from becoming addicted to nicotine.
Question 1. Can you explain some of the obstacles that have
prevented FDA from acting more quickly in both of these instances? And,
going forward, if FDA were to assert their authority over e-cigarettes
through the deeming rule, can you tell me what the timeline would be
for actually regulating these products?
Answer 1. With respect to menu labeling, some of the issues in
implementing this provision proved to be complex as we engaged in the
rulemaking process. An example of this is the need to determine which
entities are covered by the term ``restaurants and similar retail food
establishments.'' Since the proposed rule was published in April 2011,
FDA has reviewed approximately 900 comments that were submitted and
considered a number of issues raised, including the menu labeling
rule's applicability to various establishments. Please be assured that
we are working diligently to complete the final rules as quickly as
possible.
Regarding tobacco, on April 25, 2014, FDA published a proposed rule
to extend the Federal Food, Drug, and Cosmetic Act (FD&C Act) tobacco
product authorities to cover additional products that meet the
statutory definition of ``tobacco product,'' such as electronic
cigarettes (e-cigarettes). This proposed rule is the first step toward
establishing an appropriate regulatory framework for these products.
The development and clearance of the proposed deeming rule involved
a large number of complex issues, including addressing the broad array
of products that would be covered by the scope of this proposed
rulemaking. FDA and other Federal agencies involved in this regulatory
process required ample time to fully review and analyze these issues.
FDA cannot speculate on the timeframe for completing a final deeming
rule, which will largely depend upon the number and complexity of
comments that FDA receives regarding the proposed rule.
sodium
Question 2. Upwards of 100,000 lives could be saved annually if
sodium levels in packaged and restaurant foods were cut in half--which
is why nearly 4 years ago the Institute of Medicine recommended FDA
initiate a process to set national standards for the sodium content of
foods. What has the agency been doing to address sodium consumption?
Answer 2. Since the release of the Institute of Medicine (IOM)
report outlining strategies to reduce sodium intake, FDA has been
carefully considering the challenges involved in sodium reduction. In
2011, we jointly published a notice in the Federal Register, with the
U.S. Department of Agriculture's (USDA) Food Safety and Inspection
Service, inviting comment on a number of issues related to sodium
reduction, including issues identified in the IOM report, to help us
better understand current challenges and opportunities. We also co-
sponsored a public meeting with other Federal agencies to promote
discussion of these issues. FDA is working with industry and other
stakeholders to promote gradual, achievable, and sustainable reductions
of sodium over time. We believe these efforts have built a strong
foundation for future action. FDA is looking for ways to further
encourage sodium reduction and has been working on the technical
research and assessments for the development of draft voluntary targets
for sodium reduction in foods.
As part of FDA's recently proposed revision of the Nutrition Facts
Label, we recommended a daily value of 2,300 mg for sodium based on the
tolerable upper intake level for sodium established in 2005 by the IOM
and current sodium recommendations from other consensus reports. The
current daily value is 2,400 mg. A daily value of 2,300 mg is much
lower than the average daily consumption in the United States today
which is 3,400 mg/day, based on data from the National Health and
Nutrition Examination Survey (NHANES). While FDA is proposing a daily
value of 2,300 mg, it is asking for comment on whether a daily value of
1,500 mg would be more appropriate and alternative approaches for
selecting a dietary value for sodium. The comment period was originally
scheduled to close on June 2, 2014, but was extended until August 1,
2014.
trans fat
Question 3. Last November, FDA issued a critical preliminary
determination to withdraw ``Generally Recognized as Safe'' (GRAS)
status for partially hydrogenated oil, a critical first step toward
phasing dangerous trans fat out of the food supply. How long do you
anticipate it will take to issue and implement a final rule on the GRAS
status of partially hydrogenated oil?
Answer 3. On November 8, 2013, FDA published a notice in the
Federal Register announcing its tentative determination that partially
hydrogenated oils (PHOs) are not generally recognized as safe (GRAS)
for any use in food. In the notice, FDA requested comments on its
tentative determination as well as other issues associated with the
tentative determination. The initial 60-day comment period was extended
an additional 60 days and closed on March 8, 2014. FDA received over
1,500 comments in response. After a complete evaluation of the comments
received and other available information, FDA will issue any final
determination regarding the use of PHOs in food.
dietary supplements
Question 4. Senator Hatch and I met with you in 2012 to discuss our
concerns with the FDA's ``New Dietary Ingredient Notifications and
Related Issues'' draft guidance for dietary supplements issued on July
5, 2011. Would you please provide us an update on the status of FDA's
work to develop and issue a new draft guidance that addresses our
concerns?
Answer 4. As you know, FDA announced in June 2012 that it would
revise and reissue the draft guidance on new dietary ingredient
notifications and related issues (the NDI guidance). The purpose of
issuing a revised draft guidance is to clarify matters that were not
clear in the original draft of the NDI guidance and that were subject
to misinterpretation. The revised draft is currently undergoing Agency
clearance.
In order to understand and respond to the various issues raised
about the original draft guidance, FDA has had a number of meetings
with industry to discuss their concerns. Some of the key issues that
will be addressed in the revised draft are (1) the development of a
process to identify and document the universe of ``pre-DSHEA''
ingredients that are exempt from NDI notification requirements (grand
fathered list of ingredients); (2) what constitutes ``chemical
alteration'' of an existing ingredient, such that it becomes a new
dietary ingredient that requires an NDI submission; and (3) the
treatment of synthetic copies of botanical ingredients. These are
difficult issues to resolve, but FDA is committed to issuing revised
draft guidance as soon as possible, which will provide stakeholders an
additional opportunity to comment on these matters.
fsma
In writing the Food Safety Modernization Act, Congress emphasized
the importance of creating new regulations that worked with existing
environmental and conservation efforts underway at Federal agencies. We
included this provision because after an outbreak of E. coli in spinach
in 2006, many buyers required farmers to remove existing conservation
practices, damaging the landscape and throwing away the Federal
investment in stewarding our natural resources.
Given this experience, I was glad to see strong statements about
the importance of conservation priorities in the preamble of the
proposed produce regulations, but I was concerned that that same
language was not included in the regulatory text. Without additional
protections for conservation in the regulations, we risk repeating
events of the past.
Question 5. Can you please discuss how the agency plans to
strengthen the produce safety regulations so that they more fully
protect conservation practices and address the co-management of
conservation and food safety?
Answer 5. FDA received several comments to the docket recommending
that language related to conservation priorities, most notably language
aimed at clarifying FDA's intent with regard to threatened and
endangered species, be included in the final codified text. On
September 19, 2014, FDA released proposed revisions to the proposed
rule on produce safety. In response to concerns that the produce safety
regulation may inadvertently promote practices that may adversely
affect wildlife and animal habitat, including impacts on threatened or
endangered species, we are proposing to include a new provision (
112.84) to explicitly state that the standards for the growing,
harvesting, packing, and holding of produce for human consumption would
not authorize or require covered farms to take actions that would
constitute the ``taking'' of threatened or endangered species in
violation of the Endangered Species Act, or require covered farms to
take measures to exclude animals from outdoor growing areas, or destroy
animal habitat or otherwise clear farm borders around outdoor growing
areas or drainages. FDA consulted with USDA's National Resources
Conservation Service and the U.S. Fish and Wildlife Service to inform
our current thinking on this issue. FDA is seeking comment on the
supplemental notice of proposed rulemaking until December 15, 2014.
FDA also is exploring the possibility of developing joint guidance
documents that would involve other Federal agencies that have a
significant role in food safety and conservation. Our efforts will be
much more focused on guidance development after the publication of the
final rule in 2015.
I am glad to see that the agency is undertaking an environmental
review of the produce safety regulations. There are a number of
potential environmental impacts with the proposed regulations, and it
is important to balance new regulatory requirements with environmental
considerations. Recently the agency extended the comment period on the
scoping process for the Environmental Impact Statement in order to seek
further public input.
Question 6. Can you please describe the agency's process for
developing an EIS, seeking public comment on the EIS, and incorporating
environmental considerations into the final regulations?
Answer 6. FDA's goal is to implement the FDA Food Safety
Modernization Act (FSMA) in a way that improves public health
protections while minimizing undue burden on farmers and other food
producers. In August 2013, FDA announced its intent to prepare an
Environmental Impact Statement (EIS) to evaluate the potential
environmental effects of the proposed produce safety rule and also
announced the beginning of the scoping process. During the scoping
process, FDA solicits public comments to identify issues to be analyzed
in the EIS.
The scope of the EIS includes consideration of alternatives to a
range of actions. To facilitate public input during the scoping
process, FDA identified a number of issues and a range of potential
alternatives to be considered in the EIS. Alternatives were identified
for provisions of the proposed produce rule that, if finalized, may
significantly affect the quality of the human environment. Alternatives
were identified for the following key provisions: (1) microbial
standard for agricultural water used during growing activities for
covered produce (other than sprouts) using a direct water application
method, (2) minimum application intervals for biological soil
amendments of animal origin, (3) measures related to animal grazing and
animal intrusion, and (4) scope of proposed rule and implications to
land use and land management. FDA invited comment on whether there are
other issues it should consider for in-depth analysis in the EIS and
any alternatives related to these issues. FDA also held a public
meeting in April 2014 as part of its ongoing efforts to seek public
input on the issues and alternatives that the Agency should consider
when preparing the EIS.
The public scoping period was extended twice, ultimately to April
18, 2014. FDA is now in the process of reviewing all comments received.
The Agency will consider these comments in preparing a draft EIS. FDA
will consider any potential significant environmental impacts
identified during the scoping phase in the draft EIS, and then will
consider public comments received on the draft EIS in the preparation
of the final EIS and the final rule. This includes determining whether
mitigation steps are needed for environmental impacts, and, if so, what
those steps will involve.
Senator Murray
food safety
Question 1. Under the Food Safety Modernization Act, FDA
investigators and inspectors will need to be well-trained in proper
auditing of food safety systems. Until now, investigators have
primarily inspected food facilities for physical evidence of hazards.
Inspectors and investigators will need to take a more proactive
approach when carrying out these activities under the Food Safety
Modernization Act. They will need to be able to understand and evaluate
the efficacy of a facility's food safety system and analyze whether the
facility is complying with that system.
Can you provide a timeline for the implementation of a
comprehensive training program for FDA inspectors, including State and
local partners?
Answer 1. FDA recognizes the need to establish training programs
for Federal and State regulators who will oversee compliance with the
new FSMA regulations, when finalized, to ensure consistency in the
performance and quality of inspections regardless of the regulatory
entity that performs such inspections. To implement FSMA, FDA will need
to work closely with State agencies and other partners to oversee
compliance with the new requirements. FDA has funded the creation of
three private-public university-based alliances--the Produce Safety
Alliance (PSA), the Food Safety Preventive Controls Alliance (FSPCA),
and the Sprouts Safety Alliance (SSA). These alliances are responsible
for providing standardized curricula and establishing mechanisms to
train industry and regulators on the requirements of the produce safety
and preventive controls rules for human and animal food. This will help
promote widespread industry compliance with the rules and provide for
consistent regulatory inspections by State and Federal officials. More
information about the Alliances is available on the Internet at http://
www.fda.gov/Food/GuidanceRegulation/FSMA/ucm293423.htm.
Further, we expect to collaborate with State regulatory partners
under the Partnership for Food Protection (PFP) umbrella, which
includes representatives from the Association of Food and Drug
Officials (AFDO) and the National Association of State Departments of
Agriculture (NASDA), to develop training and tools targeted for use by
regulators when performing inspections and other types of oversight
activities to ensure industry compliance with the new prevention-
oriented standards.
Finally, FDA's Office of Regulatory Affairs University (ORAU)
offers an extensive course catalog of instruction, both traditional in-
classroom and distance-learning formats. We envision collaborating with
our State regulatory partners to develop and deliver FSMA-related
training targeted specifically for regulators by using the alliances'
standardized curricula and ORAU regulator training. We also envision
that Federal and State regulators will be trained together using
qualified trainers to ultimately establish a cadre of investigators who
will conduct inspections to assess compliance with FSMA rules on the
farm and in food facilities. We expect the Alliances and others to
begin conducting training before the compliance dates of the final
regulations.
antibiotics in animals
The use of antibiotics in food animals is an issue of concern for
many people at home in Washington State. According to the Centers for
Disease Control and Prevention, the widespread use of antibiotics in
food-producing animals contributes to the emergence of antibiotic-
resistant bacteria in these animals and is linked to the occurrence of
antibiotic-resistant infections in humans. I was pleased to see FDA
take steps to address the use of antibiotics in food animals by
announcing Industry Guidance 213 and the Veterinary Feed Directive
proposed rule in December 2013.
As you know, Guidance 213 defines the appropriate uses of
antibiotics in food animals as only for ``the treatment, control, and
prevention of specific diseases . . . necessary for assuring the health
of food-producing animals.'' It calls on pharmaceutical companies to
change product labels on antibiotics so that they are not allowed to be
used for growth promotion or other production purposes. This is a good
first step to curb the use of antibiotics in animal feed for growth
promotion purposes, but more clarification is needed on FDA's intent to
address the use of antibiotics for disease prevention purposes. I have
heard concerns that this guidance may not address existing
inappropriate uses of antibiotics for disease prevention purposes.
Question 2. What steps will you take to ensure the appropriate use
of antibiotics for disease prevention? Will you encourage
pharmaceutical companies to tighten existing antibiotic approvals so
that only legitimate disease prevention is allowed?
Answer 2. FDA agrees that it is important to ensure that the use of
medically important antimicrobial drugs for prevention purposes is
judicious and appropriately targeted to address specifically identified
animal health risks. FDA has developed a ``judicious use'' strategy
aimed at phasing out the use of medically important antimicrobial drugs
for non-therapeutic purposes (e.g., feed efficiency and growth
promotion) and providing for veterinary oversight over the remaining
therapeutic uses of such drugs, as established in Guidance for Industry
#209 (GFI #209) in April 2012. The Agency finalized Guidance for
Industry #213 (GFI #213) in December 2013, which outlined a voluntary
process for the animal pharmaceutical industry to align their affected
products with the recommendations in GFI #209. In December 2013, we
also issued a proposed rule intended to revise the Agency's Veterinary
Feed Directive (VFD) regulation to improve the efficiency of the VFD
program and facilitate the process of bringing the use of medically
important antimicro-bials in animal feed under the oversight of
licensed veterinarians.
Once production uses are removed from affected medicated feed
products, such products can only legally be used for prevention
purposes if the labeling of the product includes an FDA-approved
prevention indication. If a medicated feed product were to be used for
an unapproved disease prevention purpose, FDA could initiate action on
the grounds that such use caused the drug to be unsafe under section
512(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21
U.S.C. 360b(a) and adulterated within the meaning of section
501(a)(5) of the FD&C Act, 21 U.S.C. 351(a)(5).
In addition, acknowledging the importance of this concept, GFI #213
outlines several important factors that veterinarians should consider
when determining the appropriateness of a preventive use. These factors
include whether: (a) there is evidence of effectiveness, (b) such a
preventive use is consistent with accepted veterinary practice, (c) the
use is linked to a specific etiologic agent, (d) the use is
appropriately targeted to animals at risk of developing a specific
disease, and (e) no reasonable alternatives for intervention exist.
The Agency believes veterinary oversight of these products is a
critical element for ensuring that the above factors are considered in
determining the specific situations where prevention use is necessary
and appropriate. FDA intends to work with veterinary and animal
producer organizations to reinforce the importance of these principles.
Question 3. How does FDA plan to collect, analyze, and provide to
Congress and the public comprehensive data on the implementation of
Guidance 213 and its effect on the amount of antibiotics used in food
animals?
Answer 3. FDA is committed to updating the public on the progress
that drug sponsors have made in aligning their products with GFI #213,
including through notifying the public of changes to approvals,
updating the list of affected applications on CVM's Web site, and
providing periodic progress reports on a 6-month basis. The Agency
issued its first progress report on June 30, 2014. FDA's progress
reports will summarize current and pending actions taken by sponsors to
align with the guidance, including the type of action (e.g.,
withdrawal, change in marketing status) and, when possible without
revealing confidential business information, the type of animal for
which the drug is approved for use and the type of application
(pioneer, generic, combination).
FDA has received confirmation in writing from all 26 affected
sponsors of their commitment to implement the changes. In addition to
the summary information FDA has already released concerning the
affected drug sponsors' responses, the Agency will continue to monitor
the progress of GFI #213 implementation and provide further updates.
FDA intends to notify the public of completed changes to affected
products that are implemented through approvals of supplemental new
animal drug applications. Some sponsors may opt to voluntarily withdraw
their approved applications for certain animal drugs, and the Agency is
also currently notifying the public of these withdrawal actions.
In addition to tracking completion of the changes, FDA recognizes
that it is important to identify ways to assess the effect of these
measures over time. FDA is currently enhancing data sources in a number
of ways to help monitor the effect of GFI #213. Currently, the Agency
collects data on antimicrobial resistance among foodborne pathogens as
part of the National Antimicrobial Resistance Monitoring System
(NARMS), as well as data on the sale and distribution of antimicrobial
drugs intended for use in food-producing animals, which FDA collects
and reports annually under section 105 of the 2008 Animal Drug User Fee
Amendments (ADUFA 105). The U.S. Department of Agriculture (USDA) also
periodically collects antimicrobial use data on livestock and poultry
operations as part of the National Animal Health Monitoring System.
Recent enhancements to the NARMS program make the data more useful
for measuring the effect of GFI #213, particularly a new USDA Food
Safety Inspection Service slaughter sampling program, launched in March
2013, which increases national representativeness of the animal
samples. In addition, FDA is working with four State partners to
perform whole-genome sequencing on NARMS samples. The data will provide
unprecedented details on changes in resistance genes from animals and
animal-derived foods.
Based on broad public input, FDA has enhanced the format of the
ADUFA 105 annual summary reports to better describe data on the annual
sales and distribution of antimicrobials intended for use in food-
producing animals using a more detailed format that will allow the
public to better understand the changes that occur as GFI #213 is
implemented. On October 2, 2014, FDA released the summary report for
2012, using this new format, and provided updated annual reports from
previous years to include the new data tables. The changes expanded the
format of reporting sales and distribution data by antimicrobial class
to include information on the importance of the drug in human medicine.
These changes also provide aggregate data on the approved route of
administration of antimicrobial drugs sold or distributed for use in
food-producing animals, whether such drugs are available over the
counter or require veterinary oversight, and whether they are approved
for therapeutic indications, or both therapeutic and production
indications.
You may be interested to know that the Agency is also developing a
proposed regulation to enhance the existing requirements related to the
collection of antimicrobial drug sales and distribution data for
antimicrobial drugs intended for use in food-producing animals. New
requirements being considered include the collection of additional drug
sales and distribution data, including reporting sales and distribution
data by species.
FDA is working with USDA and the Centers for Disease Control and
Prevention (CDC) to identify possible approaches for further enhancing
current data collection efforts, focused on actual use (exposure) on
the farm. This will help identify meaningful metrics for assessing the
effectiveness of GFI #213 in reducing the public health risk of
antibiotic resistance. The Agency intends to seek further public input
on this issue in early 2015.
In addition, as part of this collaborative effort it was determined
that there is currently no appropriate method to analyze associations
between changes in antimicrobial use and shifts in resistance patterns
on a national level, as is needed to assess the public health impact of
interventions such as GFI #213. Therefore, FDA and USDA are
collaborating with a Cornell University researcher and submitted a
National Institute of Mathematical and Biological Synthesis (NIMBioS)
proposal to create a working group to develop a new mathematical
modeling methodology that would inform the approach to monitoring and
assessing the impacts of GFI #213. This will allow the collaborating
Federal agencies to efficiently allocate limited resources by targeting
data which are most valuable. The proposal was accepted and the first
meeting of the working group occurred in September 2014.
catfish inspection
The Health, Education, Labor, and Pensions Committee has overseen
the FDA for decades, including FDA's inspection and regulation
responsibilities for seafood. My home State of Washington is home to
thousands who make a living in the fishing industry, from recreational
guides, to salesmen, to reel manufacturers, commercial fishermen,
processors, and more. In fact, 2009 data from the National Oceanic and
Atmospheric Administration shows that the seafood industry, including
commercial harvesters, primary dealers and processors, secondary
seafood wholesalers and distributers, grocers, and restaurants) had a
sales impact of more than $7.3 billion and supported more than 57,000
jobs in Washington alone.
As you may know, the 2008 and 2014 Farm bills included provisions
regarding catfish inspection, and the USDA is currently engaged in a
rulemaking process to begin their statutorily required catfish
inspection. I have been a strong supporter of repealing the USDA
catfish inspection program because it could have a negative impact on
the vibrant seafood economy in Washington, and because the Government
Accountability Office identified the USDA catfish inspection office as
duplicative and a waste of taxpayer dollars. The USDA, the agency now
tasked with inspecting only one of many seafood products inspected by
the U.S. Government each year, has identified catfish as a low-risk
food.
Question 4. Can you explain where catfish ranks in terms of risk to
human health?
Answer 4. Seafood in general carries some unique risks, and that is
why FDA established the Hazard Analysis and Critical Control Points
(HACCP) program in 1997. We also have import alerts in place that
provide for increased review and testing of imported seafood that may
pose particular risks. Those programs have been very successful in
mitigating the safety issues inherent in seafood production.
It is also fair to say that, generally speaking, catfish are
generally less risky than certain other types of fish. Catfish are
generally not eaten raw or packaged in ready to eat form.
Question 5. Can you explain how the FDA regulates seafood under its
current regime?
Answer 5. FDA operates a mandatory safety program for all fish and
fishery products under the provisions of the FD&C Act, the Public
Health Service Act, and related regulations. The FDA program includes
research, inspection, compliance, enforcement, outreach, and the
development of regulations and industry guidance.
All seafood processors are required to adhere to HACCP regulations.
Under HACCP, processers of fish and fishery products must identify
hazards that are reasonably likely to occur for their products and
formulate control strategies. Seafood HACCP requirements have been in
place for years and serve as the foundation of the proposed hazard
analysis and risk-based preventive control requirements found in FSMA
proposed rules for all food products.
FDA regularly conducts inspections of domestic and foreign food
facilities in an effort to ensure that seafood processors are adhering
to seafood HACCP regulations. FDA screens all import entries
electronically prior to the products' entering the country, and a
subset of those are physically inspected at varying rates depending on
the potential risk associated with them. The Agency has implemented an
automated screening system, the Predictive Risk-based Evaluation for
Dynamic Import Compliance Targeting (PREDICT) system, which
significantly improves FDA's risk-based targeting of imported food.
When there are concerns about a particular product, including fish,
being imported into the United States, FDA may place foreign processors
who manufacture products that appear to be adulterated or misbranded on
import alert, which notifies FDA field personnel that FDA has
sufficient evidence to refuse admission of future shipments of the
products. To obtain entry of such product, the importer would need to
provide sufficient evidence to FDA that the product is not adulterated
and/or misbranded. The Agency has a number of import alerts for seafood
products for various reasons, including the appearance of the foreign
processors not being in compliance with seafood HACCP, the presence of
unapproved new drugs, the presence of methyl mercury at unsafe levels,
and the products not being labeled correctly or being misbranded.
FDA has also invested in significant technical improvements to
enhance its ability to identify seafood species using state-of-the-art
DNA sequencing. DNA sequencing has greatly improved FDA's ability to
identify misbranded seafood products in interstate commerce.
In addition, FDA can use the new enforcement tools provided by FSMA
to keep unsafe seafood from reaching consumers. For example, under
certain circumstances the Agency can administratively detain seafood,
order a mandatory recall, and refuse entry into the United States of
imported seafood if the facility refuses to allow an inspection.
Senator Sanders
Question. During its consideration of the Food Safety Modernization
Act, Congress emphasized the importance of a regulatory framework that
worked for the broad diversity of farming systems in America. Congress
specifically required the Food and Drug Administration not to include
any requirements that conflict with or duplicate the requirements of
the National Organic Program for certified organic production. Despite
this mandate, the proposed produce safety rule released last year
contained requirements around the use of biological soil amendments of
animal origin that conflicted with the use of manure and compost on
certified organic farms and that are part of sustainable production. I
have heard from many farmers in Vermont that the intervals between
application and harvest were too long. This would severely restrict the
use of manure, impede the use of compost on their farms, disrupt
management practices and increase costs of production. How does the
agency intend to address these issues in the rulemaking process?
Answer. FDA's intent in developing the proposed produce safety rule
is to reduce risk associated with the consumption of produce. We
received many comments on our proposed 9-month, pre-harvest interval
for raw manure that may contact the produce after application, which
differs from the 120-day interval required by the U.S. Department of
Agriculture's (USDA) National Organic Program (NOP) standards for
organic certification. FDA's proposed interval was based on the best
available science and FDA's judgment at the time of the proposal
regarding an interval that would be sufficient to protect food safety
in a wide range of growing conditions across the country.
On September 19, 2014, FDA released proposed revisions to the
proposed rule on produce safety that are more flexible and less
burdensome in key areas. Specifically, FDA is removing the 9-month
proposed minimum-time interval between the application of untreated
biological soil amendments of animal origin (including raw manure) and
crop harvesting. The Agency is deferring its decision on an appropriate
time interval until it pursues certain actions. These include
conducting a risk assessment and extensive research to strengthen
scientific support for any future proposal, working with USDA and other
stakeholders. In addition, at this time, FDA does not intend to take
exception to farmers complying with the USDA's NOP standards, which
call for a 120-day interval between the application of raw manure for
crops in contact with the soil and 90 days for crops not in contact
with the soil.
The Agency is also proposing to eliminate the previously proposed
45-day minimum application interval for compost (also known as humus),
including composted manures. Properly treated and handled compost is
safer than raw manure from a public health standpoint and this change
to the proposal would help facilitate its use while still providing an
appropriate level of public health protection.
You may be interested to know that FDA has provided approximately
$1 million to sponsor research at USDA's Agricultural Research Service
and to develop a produce safety rule research network at the Western
Center for Food Safety at the University of California, Davis. We
intend for these collaborative efforts to result in the collection of
data that may help resolve questions that have arisen during the public
comment period about the necessary time between application of raw
manure, or water that does not meet the relevant quality standard, and
safe harvest of produce in key agro-ecological growing conditions and
for key crops. Our goal is for this research to result in suggested
protocols that farms could follow in compliance with a final produce
safety rule, and for this process to be duplicated for other crops and
regions as further funding is secured. This FDA-sponsored research was
initiated to demonstrate the commitment of Federal agencies to address
the needs of farmers, to provide data to finalize study protocols for
further research, and to attract matching funds from industry.
Senator Casey
restaurant menu labeling
Question 1. FDA may soon release a final rule on menu labeling
requirements for chain restaurants. I think it's important for
consumers to have nutrition information for what they're eating. But
there are some differences between convenience stores and chain
restaurants. I encourage FDA to consider excluding pre-packaged foods,
which are already labeled, from revenues and include fuel sales in
overall sales calculations. Will FDA make this consideration in its
final rule for menu labeling?
Answer 1. Determining which entities are covered by the term
``restaurants and similar retail food establishments'' has proven to be
complex, with strongly held opinions being expressed by those who
advocate for either a more expansive or restrictive scope of coverage.
Since the proposed rules were published in April 2011, FDA has reviewed
approximately 900 comments that were submitted and considered a number
of issues raised, including the menu labeling rule's applicability to
various establishments. Please be assured that we are working
diligently to complete the final rules as quickly as possible.
food safety modernization act
Question 2. One of the greatest concerns some Pennsylvania farmers
have is about the frequency and character of on-farm inspections that
will occur with FDA's new authority under the Food Safety Modernization
Act. There have been several on-farm inspections occurring on
Pennsylvania farms in the past year that have not gone well. I've been
told some of these inspections include incidents of inspectors arguing
with each other about why they were there at all, an inspector who
forced a farmer to come home from vacation for an inspection and then
missed the appointment himself, and a high-profile inspection that was
described as a non-inspection, even in the inspection report that was
later filed. I am concerned about the direction that these inspections
have taken and that the focus of limited resources is shifting away
from high-risk activities and facilities. Can you please discuss why
the agency is conducting these inspections, how the agency plans to
train inspectors so that they are familiar with farming systems, and
how the agency intends to target limited inspection resources to high-
risk operations once the regulations go into effect?
Answer 2. FDA is tasked with ensuring compliance with the
provisions outlined in the produce safety proposed rule which would
establish science-based minimum standards for the safe growing,
harvesting, packing, and holding of produce on farms. To that end, the
rule proposes new standards in the following major areas:
Worker Training and Health and Hygiene
Agricultural Water
Biological Soil Amendments of Animal Origin
Domesticated and Wild Animals
Equipment, Tools, and Buildings
Sprouts
While the Agency currently conducts a limited number of farm
inspections under existing regulations and has existing training
modules related to some farm activities and continues to leverage those
activities internally and with our State counterparts, we are also
assessing existing training and new training opportunities that can be
leveraged moving forward with FSMA implementation. As new rules are
finalized and implemented, FDA intends to work with State and industry
partners in developing and delivering training prior to conducting farm
inspections under the new FSMA authorities. Such training will focus on
regulatory requirements, inspection procedures, and better
understanding of the farming environment.
For example, the Produce Safety Alliance (PSA) is led by Cornell
University, and involves FDA, the U.S. Department of Agriculture
(USDA), State food and agriculture departments, and two national
industry trade associations. The PSA will produce a standard on-farm
training manual and curriculum and plans to offer courses to deliver
the training. The PSA is developing a training protocol with State and
Federal regulators to help ensure uniformity in inspections. It will
also be a repository for up-to-date scientific and technical
information, including a compendium of produce hazards. The training
will be finalized shortly after the publication of the final rule on
produce safety. The Alliance and others will conduct training that will
begin during the period that precedes the compliance dates.
Further, we expect to collaborate with State regulatory partners
under the Partnership for Food Protection (PFP) umbrella, which
includes representatives from the Association of Food and Drug
Officials (AFDO) and the National Association of State Departments of
Agriculture (NASDA), to develop training and tools targeted for use by
regulators when performing inspections and other types of oversight
activities to ensure industry compliance with the new prevention-
oriented standards.
We acknowledge there have been some instances of on-farm activities
in which additional guidance would have been beneficial for both
regulated industry and FDA staff. For example, some farms have
registered unnecessarily with FDA as a facility when they did not need
to do so. Farms are generally exempt from the registration requirement
unless they are a mixed-type facility. A farm mixed-type facility is an
establishment that grows and harvests crops or raises animals and may
conduct other activities within the farm definition but also conducts
activities that require the farm to be registered as a facility.
Facilities required to register with FDA would be subject to the
preventive controls for human food rule and are covered by FDA's FSMA
inspection mandate for food facilities. FSMA requires facility
inspections to be based on risk and the frequency of inspections of
food facilities to increase. It calls for all high-risk domestic food
facilities to be inspected within 5 years of the bill's signing and
then at least once every 3 years after that. Further, all other
domestic food facilities are to be inspected within 7 years of the
bill's signing and then at least once every 5 years thereafter.
We received many comments related to activities conducted on a farm
that are considered part of farming by farmers yet trigger the
requirement for a farm to register with FDA as a facility. On September
19, 2014, FDA released proposed revisions to the proposed rule on
produce safety that are more flexible and less burdensome in key areas.
The proposed revisions include the definition of ``farm''--a farm would
no longer be required to register as a food facility merely because it
packs or holds raw agricultural commodities grown on another farm under
a different ownership. FDA is proposing that such activities would be
subject to the produce safety rule (as applicable) rather than the
preventive controls rule for human food. FDA is seeking comment on the
supplemental notice of proposed rulemaking until December 15, 2014.
The Agency is committed to developing a final rule on produce
safety that prevents illnesses but is also practical and adaptable to a
wide diversity of growing conditions and practices. We also are looking
to working with our Federal and State counterparts who have worked with
the produce community for many years to assist us in our efforts.
Question 3. Additionally, on the food manufacturer side, FDA
inspectors and investigators will need to understand and evaluate the
effectiveness of a facility's food system in order to properly audit
food safety systems. Can you provide a timeline for FDA's
implementation of a comprehensive training program for FDA inspectors,
including State and local partners?
Answer 3. FDA recognizes the need to establish training programs
for Federal and State regulators who will oversee compliance with the
new FSMA regulations, when finalized, to ensure consistency in the
performance and quality of inspections regardless of the regulatory
entity that performs such inspections. To implement FSMA, FDA will need
to work closely with State agencies and other partners to oversee
compliance with the new requirements. FDA has funded the creation of
three private-public university-based alliances--the Produce Safety
Alliance (PSA), the Food Safety Preventive Controls Alliance (FSPCA),
and the Sprouts Safety Alliance (SSA). These alliances are responsible
for providing standardized curricula and establishing mechanisms to
train industry and regulators on the requirements of the produce safety
and preventive controls rules for human and animal food. This will help
promote widespread industry compliance with the rules and provide for
consistent regulatory inspections by State and Federal officials. More
information about the alliances is available on the Internet at http://
www.fda.gov/Food/GuidanceRegulation/FSMA/ucm293423.htm.
Further, we expect to collaborate with State regulatory partners
under the Partnership for Food Protection (PFP) umbrella, which
includes representatives from the Association of Food and Drug
Officials (AFDO) and the National Association of State Departments of
Agriculture (NASDA), to develop training and tools targeted for use by
regulators when performing inspections and other types of oversight
activities to ensure industry compliance with the new prevention-
oriented standards.
Finally, FDA's Office of Regulatory Affairs University (ORAU)
offers an extensive course catalog of instruction, both traditional in
classroom and distance-learning formats. We envision collaborating with
our State regulatory partners to develop and deliver FSMA-related
training targeted specifically for regulators by using the alliances'
standardized curricula and ORAU regulator training. We also envision
that Federal and State regulators will be trained together using
qualified trainers to ultimately establish a cadre of investigators who
will conduct inspections to assess compliance with FSMA rules on the
farm and in food facilities. We expect the Alliances and others to
begin conducting training before the compliance dates of the final
regulations.
Question 4. In Pennsylvania, we have many mid-sized family farms
that are involved in dairy and other production. We also have a high
and increasing demand for local, fresh fruits and vegetables. Many
dairy and commodity farmers are responding to that market demand and
diversifying their operations. This is especially true with younger
generations getting started on well-established family farms. However,
FDA's proposed regulations might discourage those operations from
taking advantage of those market opportunities because those farmers
will not be eligible for the less burdensome requirements due to their
sales from other commodities, and will be faced with the full
compliance costs of meeting the full set of requirements. This is due
to the fact that eligibility for those modified requirements and the
$25,000 de minimus exemption from the produce safety regulations is
based on the value of ``all food'' and not just the value of regulated
food. So in other words, if the value of milk shipped to a processor is
above $25,000 per year (almost all cases) or even $500,000 per year
(most cases), the very first tomato grown and sold off the farm will
have to meet the highest level of requirements contained in FSMA.
Congress in FSMA gave FDA broad authority to develop scale-appropriate
regulations applicable to different practices, sizes, and systems of
production. Given this authority and the flexibility it provides, can
you discuss how you intend to address this issue, especially in light
of the ``all food'' definition?
Answer 4. FDA recognizes the tremendous diversity of the produce
farming industry, not just in terms of the size of farming operations,
but also in the types of commodities produced, crops grown, and growing
methods used. The Agency shares your concern that the new safety
standards must be flexible enough to account for this diversity. FSMA
and the proposed produce safety rule provide various exemptions and
limitations on the rule's coverage. For example, the proposed produce
safety rule excludes certain produce commodities that constitute the
lowest risk, with respect to biological hazards. The proposed produce
safety rule also would not apply to produce for personal or on-farm
consumption.
Regarding calculation of the gross dollar amount of food sold at a
farm or facility, you indicate that the rules should specify that only
food potentially subject to the new regulations ought to count toward
the $25,000 threshold for coverage in the proposed produce safety rule
and for the $500,000 annual gross sales limit for the modified
requirements for a farm or facility in both rules. We are pleased to
inform you that, on September 19, 2014, FDA released proposed revisions
to the proposed rule on produce safety that are more flexible and less
burdensome in key areas. Specifically, FDA is proposing that farms or
farm mixed-type facilities with an average annual monetary value of
produce sales of $25,000 or less will not be covered. The original
proposed rule defined that monetary threshold in terms of all food
sales. The Agency is also proposing corresponding changes to the
definitions of ``very small business'' and ``small business'' to base
those monetary thresholds on produce sales rather than food sales. The
monetary threshold for the qualified exemption with modified
requirements, however, would not change because that exemption is
defined by statute. FDA is seeking comment on the supplemental notice
of proposed rulemaking until December 15, 2014.
Senator Bennet
regulation of brewers' spent grain
Question. Dr. Hamburg, I have a question on the regulation of
brewers' spent grain. I represent one of the leading beer producing
States in the United States, with large and small craft brewers. If the
FDA moves forward with its proposed rule, ``Current Good Manufacturing
Practice and Hazard Analysis and Risk-Based Preventive Controls for
Food for Animals,'' some brewers have expressed concern that they may
be unable to absorb the cost of compliance and may have no choice but
to dispose of their spent grain in landfills, which could cost millions
in landfill fees. Has the FDA conducted an environmental impact
analysis on the implications of landfilling large quantities of spent
grains into landfills? If so, when can we expect the analysis to be
completed?
Answer. You express concerns that we also heard from many in the
brewing community regarding the potential impact of the proposed rule
on the long-standing practice of beer brewers providing the ``spent
grains,'' resulting from the brewing process, to farmers to use as
animal food.
Breweries making products for human consumption are already subject
to human food Current Good Manufacturing Practice (CGMP) regulations.
FDA's current understanding is that the potential hazards associated
with spent grains from brewers and distillers of human beverages are
minimal, provided the food manufacturer takes common-sense steps, such
as minimizing the possibility of physical or chemical hazards being
inadvertently introduced into a container of spent grains. In addition,
we agree that there are substantial efficiency and sustainability
benefits from the recycling of human food by-products--such as spent
grains--to animal food, and it is not our intention to disrupt this
practice.
We are pleased to inform you that, on September 19, 2014, FDA
proposed a number of revisions to its proposed rule on preventive
controls for animal food that are more flexible and less burdensome in
key areas. Specifically, the Agency has proposed that, in general,
human food processors already subject to and complying with FDA human
food safety requirements, such as brewers, would not need to implement
additional preventive controls or CGMP regulations when supplying a by-
product (e.g., wet spent grains, fruit or vegetable peels, liquid whey)
for animal food, except for proposed CGMPs to prevent physical and
chemical contamination when holding and distributing the by-product
(e.g., ensuring the by-product isn't co-mingled with garbage).
Please be assured that we are working to develop regulations that
are responsive to the concerns expressed, practical for businesses, and
that also help ensure that food for animals is safe and will not cause
injury to animals or humans. FDA is seeking comment on the supplemental
notice of proposed rulemaking until December 15, 2014. We hope to
continue our active dialog with stakeholders, including the brewing
community, about how we can achieve our food safety goals in the most
practical way.
Senator Baldwin
Question. In Wisconsin we have two proud beverage traditions: we
produce a large volume of milk and also have many breweries across our
State. These two industries come together in an interesting way related
to animal feed, and have raised concerns with the FDA's proposed rule,
``Current Good Manufacturing Practice and Hazard Analysis and Risk-
Based Preventive Controls for Food for Animals.''
Many breweries provide spent grains to our dairy and livestock
farmers as a source of animal feed. Under the new rule, breweries could
incur very large compliance costs, which would likely cause them to
divert the grains away from this productive second use into a waste
stream. It is unclear whether the compliance proposed in the rule
addresses a substantial threat to human or animal health, or whether
compliance would result in measureable improvements in safety.
Brewers' spent grains are an indispensable feed source for the
dairy industry in Wisconsin. Can you please describe how the FDA will
review this portion of the proposed rule, consider the input provided
by industry voices that have expressed concern about this provision,
and review options to update this section accordingly?
Answer. You express concerns that we also heard from many in the
brewing community regarding the potential impact of the proposed rule
on the long-standing practice of beer brewers providing the ``spent
grains,'' resulting from the brewing process, to farmers to use as
animal food.
Breweries making products for human consumption are already subject
to human food Current Good Manufacturing Practice (CGMP) regulations.
FDA's current understanding is that the potential hazards associated
with spent grains from brewers and distillers of human beverages are
minimal, provided the food manufacturer takes common-sense steps, such
as minimizing the possibility of physical or chemical hazards being
inadvertently introduced into a container of spent grains. In addition,
we agree that there are substantial efficiency and sustainability
benefits from the recycling of human food by-products--such as spent
grains--to animal food, and it is not our intention to disrupt this
practice.
We are pleased to inform you that, on September 19, 2014, FDA
proposed a number of revisions to its proposed rule on preventive
controls for animal food that are more flexible and less burdensome in
key areas. Specifically, the Agency has proposed that, in general,
human food processors already subject to and complying with FDA human
food safety requirements, such as brewers, would not need to implement
additional preventive controls or CGMP regulations when supplying a by-
product (e.g., wet spent grains, fruit or vegetable peels, liquid whey)
for animal food, except for proposed CGMPs to prevent physical and
chemical contamination when holding and distributing the by-product
(e.g., ensuring the by-product isn't co-mingled with garbage).
Please be assured that we are working to develop regulations that
are responsive to the concerns expressed, practical for businesses, and
that also help ensure that food for animals is safe and will not cause
injury to animals or humans. FDA is seeking comment on the supplemental
notice of proposed rulemaking until December 15, 2014. We hope to
continue our active dialog with stakeholders, including the brewing
community, about how we can achieve our food safety goals in the most
practical way.
Senator Warren
Recently the FDA released two guidance documents, GFI #209 and
#213, and a proposed rule for Veterinary Feed Directives. These
measures will make the use of all antibiotics in animal feed subject to
VFD and eventually eliminate the use of antibiotics for production
purposes. The FDA hopes that these measures will curb the overuse of
antibiotics in animal agriculture.
Question 1a. How do you intend to measure whether the non-judicious
use of antibiotics in animal agriculture declines, or simply stays the
same but under the guise of disease prevention?
Answer 1a. Regarding the concern that medically antimicrobial drugs
will continue to be used under the guise of disease prevention, once
production uses are removed from affected medicated feed products, such
products can only legally be used for prevention purposes if the
labeling of the product includes an FDA-approved prevention indication.
If a medicated feed product were to be used for an unapproved disease
prevention purpose, FDA could initiate action on the grounds that such
use caused the drug to be unsafe under section 512(a) of the Federal
Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 360b(a) and
adulterated within the meaning of section 501(a)(5) of the FD&C Act, 21
U.S.C. 351(a)(5).
In addition, acknowledging the importance of this concept, GFI #213
outlines several important factors that veterinarians should consider
when determining the appropriateness of a preventive use. These factors
include whether: (a) there is evidence of effectiveness, (b) such a
preventive use is consistent with accepted veterinary practice, (c) the
use is linked to a specific etiologic agent, (d) the use is
appropriately targeted to animals at risk of developing a specific
disease, and (e) no reasonable alternatives for intervention exist.
The Agency believes veterinary oversight of these products is a
critical element for ensuring that the above factors are considered in
determining the specific situations where prevention use is necessary
and appropriate. FDA intends to work with veterinary and animal
producer organizations to reinforce the importance of these principles.
The Agency recognizes that it is important to identify ways to
assess the effect of these measures over time. FDA is currently
enhancing data sources in a number of ways to help monitor the effect
of GFI #213. Currently, the Agency collects data on antimicrobial
resistance among foodborne pathogens as part of the National
Antimicrobial Resistance Monitoring System (NARMS), as well as data on
the sale and distribution of antimicrobial drugs intended for use in
food-producing animals, which FDA collects and reports annually under
section 105 of the 2008 Animal Drug User Fee Amendments (ADUFA 105).
The U.S. Department of Agriculture (USDA) also periodically collects
antimicrobial use data on livestock and poultry operations as part of
the National Animal Health Monitoring System.
Recent enhancements to the NARMS program make the data more useful
for measuring the effect of GFI #213, particularly a new USDA Food
Safety Inspection Service slaughter sampling program, launched in March
2013, which increases national representativeness of the animal
samples. In addition, FDA is working with four State partners to
perform whole-genome sequencing on NARMS samples. The data will provide
unprecedented details on changes in resistance genes from animals and
animal-derived foods.
Based on broad public input, FDA has enhanced the format of the
ADUFA 105 annual summary reports to better describe data on the annual
sales and distribution of antimicrobials intended for use in food-
producing animals using a more detailed format that will allow the
public to better understand the changes that occur as GFI #213 is
implemented. On October 2, 2014, FDA released the summary report for
2012, using this new format, and provided updated annual reports from
previous years to include the new data tables. The changes expanded the
format of reporting sales and distribution data by antimicrobial class
to include information on the importance of the drug in human medicine.
These changes also provide aggregate data on the approved route of
administration of antimicrobial drugs sold or distributed for use in
food-producing animals, whether such drugs are available over the
counter or require veterinary oversight, and whether they are approved
for therapeutic indications, or both therapeutic and production
indications.
You may be interested to know that the Agency is also developing a
proposed regulation to enhance the existing requirements related to the
collection of antimicrobial drug sales and distribution data for
antimicrobial drugs intended for use in food-producing animals. New
requirements being considered include the collection of additional drug
sales and distribution data, including reporting sales and distribution
data by species.
FDA is working with USDA and the Centers for Disease Control and
Prevention (CDC) to identify possible approaches for further enhancing
current data collection efforts, focused on actual use (exposure) on
the farm. This will help identify meaningful metrics for assessing the
effectiveness of GFI #213 in reducing the public health risk of
antibiotic resistance. The Agency intends to seek further public input
on this issue in early 2015.
In addition, as part of this collaborative effort it was determined
that there is currently no appropriate method to analyze associations
between changes in antimicrobial use and shifts in resistance patterns
on a national level, as is needed to assess the public health impact of
interventions such as GFI #213. Therefore, FDA and USDA are
collaborating with a Cornell University researcher and submitted a
National Institute of Mathematical and Biological Synthesis (NIMBioS)
proposal to create a working group to develop a new mathematical
modeling methodology that would inform the approach to monitoring and
assessing the impacts of GFI #213. This will allow the collaborating
Federal agencies to efficiently allocate limited resources by targeting
data which are most valuable. The proposal was accepted and the first
meeting of the working group occurred in September 2014.
Under the Veterinary Feed Directive proposed rule, all of the
Nation's 1,366 medicated feed distributors will have two largely
expanded roles--making sure that medicated feed is sold only with a
valid veterinary feed directive and that the feed labeling reflects
appropriate uses. This presents an important opportunity to obtain more
data on what's going on. Right now, our understanding of how these
drugs are used is basically a black box--we know what antibiotics are
being used and how much they are being used, but we don't have a clear
picture of what animals they are going into, how they are being
administered, or for what purpose.
Question 1b. Does the FDA currently have the authority and capacity
not only to inspect the facilities to make sure that VFDs are complete
and being used appropriately, but also to collect data from the VFDs
about how antibiotics are being used in animal agriculture?
Answer 1b. FDA believes that the VFD regulation, when finalized,
will establish a clear set of requirements governing the sale or
distribution of VFD drugs. This includes specifying the type of
information that veterinarians must include on the VFD authorizations
they issue as well as the type of records that need to be maintained.
Veterinarians, feed mills, and producers are required to maintain
copies of VFDs and to make them available to FDA upon request during
inspections or other investigations.
FDA currently has the authority to collect data from VFDs during
inspection. We anticipate, as part of the implementation of GFI #213, a
large number of over-the-counter products transitioning to a new VFD
status when the VFD proposed rule is finalized. FDA intends to continue
to conduct inspections in order to ensure that veterinarians, feed
mills, and producers understand the new VFD requirements, once
established, and are in compliance with them.
Question 1c. If not, what resources and authority do you need to
capture the information?
Answer 1c. As noted above, FDA has the authority to collect data
from VFDs during inspection.
Question 1d. If the FDA was able to compile the data associated
with veterinary feed directives, would the agency be able to better
track how exactly antibiotics are being used in different types of food
animals?
Answer 1d. FDA does not consider VFDs to be a comprehensive source
of drug use information because they are limited to medicated feeds and
do not capture all antibiotics, such as those for use in water and
injectable products. In addition, VFDs do not necessarily accurately
represent the amount that is actually administered by the end-user.
However, the Agency is considering all options for collecting
additional data that would enhance our assessment of the impacts of our
efforts to address antimicrobial resistance.
As noted in the response to question 1(a) above, the Agency is
currently developing a proposed regulation to enhance the existing
requirements related to the collection of antimicrobial drug sales and
distribution data for antimicrobial drugs intended for use in food-
producing animals.
In addition, as we explain in greater detail above, FDA is working
with USDA and CDC to identify possible approaches for further enhancing
current data collection efforts, focused on actual use (exposure) on
the farm, which will help identify meaningful metrics for assessing the
effectiveness of GFI #213 in reducing the public health risk of
antibiotic resistance.
Senator Alexander
In the Food Safety and Modernization Act, Congress directed FDA to
concentrate produce safety rulemaking on commodities or commodity
groups with the highest risk profile. However, FDA appears to have
rejected that approach.
Question 1a. Why did FDA choose to broadly regulate commodities
that have not been associated with human foodborne illness, when the
law specifically asked the FDA to focus on highest risk produce?
Answer 1a. The law directed FDA to ``establish science-based
minimum standards for the safe production and harvesting of those types
of fruits and vegetables . . . for which the Secretary has determined
that such standards minimize the risk of serious adverse health
consequences or death'' (Federal Food, Drug, and Cosmetic Act (FD&C
Act) 419(a)(1)(A)). We specifically solicited comment on our approach
in the proposed produce rule and will be considering those comments
carefully as we move forward to finalize the rule. FDA initially
considered covering only those produce commodities or commodity groups
that had been associated with foodborne illness outbreaks. However,
because only a small percentage of outbreaks are both reported and
attributed to a specific food vehicle, outbreak data may not provide a
complete picture of the commodities upon which we need to focus to
minimize current and future risk of illness. The food vehicle
responsible for an outbreak is not identified in about half of all
outbreaks. Identifying the vehicle of an outbreak in which the vehicle
is contained in a multi-ingredient food (e.g., salsa, salads) is
particularly challenging. As our ability to detect outbreaks and to
identify food vehicles responsible for an outbreak improves, it is
likely that previously unrecognized outbreak vehicles will be
identified. A further complication to the use of outbreak data as an
indication of commodity risk is that, until a food is identified as a
vehicle in an outbreak, public health officials may not be likely to
include questions about that commodity when investigating an outbreak,
making the attribution of outbreaks to commodities with no outbreak
history more difficult.
In addition, as discussed in the draft Qualitative Assessment of
Risk that the Agency issued along with the proposed rule, our data show
that the patterns of outbreaks associated with produce commodities
change over time. On the one hand, some commodities, such as tomatoes
and leafy greens, have a continuing and repeated pattern of association
with outbreaks, over multiple years. On the other hand, occasionally a
produce commodity is associated with an outbreak that had not been
previously linked to foodborne illness. For example, papayas had not
been associated with outbreaks prior to an outbreak that occurred in
2011. Therefore, a regulatory approach that relied on a static list of
commodities prepared solely from a history of outbreaks would not be
able to prevent future outbreaks in commodities not previously
associated with an outbreak.
FDA tentatively elected not to take a commodity-specific approach,
in part, because we do not believe that the past history of outbreaks
can be fully predictive of future outbreaks. We also reviewed the
relative risk of different commodities using other data sources, such
as commodity characteristics and pathogen surveillance data. Our
analysis shows that each data source presents certain gaps that make it
challenging to develop a commodity-specific approach that would
adequately minimize the risk of serious adverse health consequences or
death. [Please note that the only commodity-specific requirements
proposed in this rule are those designated for sprouts, which have
unique growing procedures (i.e., warm, moist nutrient-rich environment
for an extended period of time that supports pathogen growth in
addition to sprouting) and, therefore, present a unique risk profile.
For this reason, we tentatively concluded that a specific set of safety
standards for this produce commodity is warranted.] However, as we
mentioned earlier, we have specifically solicited comment on this
determination and on whether there are commodity-specific approaches
that would adequately minimize the risk of serious adverse health
consequences or death and whether such approaches would sufficiently
move us toward the prevention-based food safety system envisioned by
FSMA.
Question 1b. Did FDA consider the risks and benefits associated
with regulating individual commodities? How were those cost-benefit
results different for leafy grains as compared to citrus, for example?
Answer 1b. FDA did explore the option of excluding commodities not
associated with any recorded outbreaks in Option 2, under Section D.
Regulatory Options (found on page 43 of the preliminary regulatory
impact analysis). However, for the numerous reasons listed there and in
Section IV.C of the proposed rule, we tentatively concluded that this
was not the most appropriate option. We specifically solicited comment
on this topic in the preliminary regulatory impact analysis and will be
considering those comments carefully as we move forward to finalize the
rule.
We tentatively concluded that an integrated approach that focuses
on the likelihood of contamination of produce posed by the agricultural
practices applied to the crop, while exempting the lowest-risk produce,
would provide the most appropriate balance between public health
protection, flexibility, and appropriate management of different levels
of risk. We also tentatively concluded that we should use a regulatory
framework based on practices, procedures, and processes associated with
growing, harvesting, packing, and holding of all covered produce. We
considered and tentatively rejected the option to develop a framework
that (based solely on a history of outbreaks or illnesses associated
with the commodity) would be applicable to individual commodities or
classes of commodities. Procedures, processes, and practices in each of
the on-farm routes of contamination outlined in the proposed rule have
the potential to introduce biological hazards into or onto any covered
produce.
Question 2. Do you commit to providing a flexible approach to
getting consumers the nutrition information that they need without
unnecessarily adding cost and complexity without scientific evidence it
will produce a benefit?
Answer 2. FDA's recently proposed update to the Nutrition Facts
label reflects the latest scientific information, including the link
between diet and chronic diseases such as obesity and heart disease.
FDA is proposing to replace out-of-date serving size requirements to
better align with how much people really eat and require labels that
feature a fresh design to highlight key parts of the label such as
calories and serving sizes. These changes would provide information to
help consumers make better-informed food choices to support a healthy
diet.
The estimated benefits of these changes would far outweigh the
costs. FDA is proposing that manufacturers have 2 years after the
effective date of the final rule to comply with any new requirements.
Senator Burr
Question 1. I have heard concerns from my constituents that the
final rule may establish costly testing requirements that divert
resources away from the most critical food safety activities. The Food
Safety Modernization Act was intentionally designed to be flexible and
risk-based, based on the circumstances of products and manufacturing
operations. FDA was not supposed to impose a one-size-fits-all approach
to food safety. Do you agree that pathogen testing should be based on
the risk of the product, process, and hygienic status of the production
environment, as well as the risk information provided from verification
activities?
Answer 1. In our proposed rule, ``Current Good Manufacturing
Practice and Hazard Analysis and Risk-Based Preventive Controls for
Human Food,'' we did not include specific requirements for
environmental monitoring but we acknowledged that such programs, when
implemented appropriately in particular facilities, could be used to
verify the effectiveness of preventive controls when contamination of
food with an environmental pathogen is reasonably likely to occur. On
September 19, 2014, FDA released proposed revisions to its proposed
rule on preventive controls for human food that are more flexible and
less burdensome in key areas. With regard to product testing and
environmental monitoring, the Agency is now providing an opportunity
for input on specific language and seeking comment on whether to
include it in the final rule. Specifically, FDA is seeking comment on
whether the preventive controls for human food should require a
facility, as appropriate to the facility, the food, and the nature of
the preventive control, to conduct product testing or environmental
monitoring to verify implementation and effectiveness of preventive
controls if contamination of a ready-to-eat food with an environmental
pathogen is a significant hazard. FDA is seeking comment on the
supplemental notice of proposed rulemaking until December 15, 2014.
Question 2. Why has the agency failed to amend the definition of
``retail food establishment'' as required by the Food Safety
Modernization Act to clarify that the sale of food directly to
consumers includes the sale of food through community-
supported agriculture programs, farmers markets, and other direct-
consumer venues? Without this required clarification, these entities
could be subject to regulation that is not consistent with
congressional intent. Does the agency plan to include this important
clarification in the re-proposal of the regulations later this year? If
not, please explain the agency's path forward for carrying this
statutory clarification.
Answer 2. We learned a great deal during our conversations with
farmers, including information about the diversity of these operations,
and through other outreach engagements, in addition to numerous
comments received to the docket. FDA recognizes the importance of
crafting food safety standards that are practical to implement for the
diverse industry. Section 102 of FSMA requires that FDA clarify the
definition of ``retail food establishment'' relative to certain direct-
to-consumer platforms. FDA intends to address this clarification in an
upcoming rulemaking that addresses this issue and other provisions of
FSMA Section 102.
Question 3. Why has the agency proposed significantly increasing
the types of studies and clinical research for certain foods through
IND submissions? Is the intent of this final guidance to make certain
foods adhere to pharmaceutical drug standards?
Answer 3. This question refers to final guidance issued by FDA on
September 10, 2013, entitled ``Guidance for Industry: Investigational
New Drug Applications (INDs)--Determining Whether Human Research
Studies can be Conducted without an IND.'' The guidance was initially
published in draft for public comment in 2010. Although largely
addressing pharmaceutical issues, both the 2010 draft and the 2013
final guidance also addressed circumstances when dietary supplements
are studied for drug uses and therefore the study requires an IND.
Because several comments on the draft guidance recommended that the
dietary supplement section should be expanded and clarified and that
other categories of foods should also be discussed, the final guidance
included a more detailed section on dietary supplements and added a
section on conventional foods. At both the draft and final stages, the
guidance as it relates to dietary supplements and other foods was
intended to clarify when an IND is required under the Federal Food,
Drug, and Cosmetic Act. Because the final guidance generated
significantly more interest and concern from industry than did the 2010
draft, FDA reopened the comment period on the portion of the final
guidance relating to foods, as well as the portion relating to
cosmetics. That additional comment period has closed, and FDA is in the
process of reviewing the comments.
Senator Burr and Senator Isakson
Question. It is essential that FDA have a good working relationship
with the Agricultural Community as the agency proceeds with
implementation of FSMA. Therefore, it is particularly concerning to
hear that the relationship between farms and the FDA is strained due to
the manner in which the agency has engaged in inspection and compliance
activities. Please outline how the FDA plans to ensure a good working
relationship with the Agricultural Community moving forward, including
ensuring inspectors are consistently complying with the agency's
compliance standards and strategies? How will the agency ensure that
regulated entities, including product growers, are afforded due process
in the issuance, revision, appeal, and adjudication of 483s, including
with respect to disagreement over ``significant findings,'' in order to
ensure adequate resolution of 483s in the future?
Answer. FDA appreciates and takes very seriously the extensive
input we have received from produce farmers and others in the
agricultural sector on the proposed FSMA rules on produce safety and
preventive controls for human food. Our discussions with farmers have
reiterated the importance of taking a collaborative approach to
implementing the rules. This entails working with our State,
territorial, and tribal partners; extension services; and industry to
provide education, training, and technical assistance to help farmers
and facilities comply with the rules, once finalized, and move toward
the shared goals of food safety and consumer confidence in the safety
of the food supply.
FDA is developing outreach materials in cooperation with State,
industry, and consumer groups to ensure there is uniformity in the
information and education activities related to the new requirements
under FSMA. In addition, FDA will be providing training programs for
inspectors to ensure that inspections to determine compliance with the
new requirements will be uniform. The Produce Safety Alliance (PSA) is
led by Cornell University, and involves FDA, the U.S. Department of
Agriculture (USDA), State food and agriculture departments, and two
national industry trade associations. The PSA will produce a standard
on-farm training manual and curriculum and plans to offer courses to
deliver the training. It will develop and disseminate science- and
risk-based training and education programs to provide produce farms
with fundamental food safety knowledge, starting in advance of the
proposed produce safety rule and continuing after the final rule is
promulgated. In addition, the PSA is developing a training protocol
with State and Federal regulators to help ensure uniformity in
inspections. It will also be a repository for up-to-date scientific and
technical information, including a compendium of produce hazards. The
training will be finalized shortly after the publication of the final
rule on produce safety. The Alliance and others will conduct training
that will begin during the period that precedes the compliance dates.
Regarding potential disagreements in the future between the Agency
and regulated entities, FDA's Office of Regulatory Affairs (ORA) has
analyzed the need and is initiating the process to establish an
Ombudsman position and associated processes, whereby issues or
establishment concerns raised in these inspectional communications may
be escalated by the establishment or by FDA in a manner consistent with
how disputes are processed by other FDA centers and offices. As part of
the FSMA implementation effort, FDA and ORA have acknowledged
industry's request to consider dispute resolution processes that
provide for confidentiality as well as for enhanced consistency across
all regions and commodities and an improved global approach in light of
the increased formal foreign presence. The possible ORA Ombudsman would
address these goals as well as offer a process for resolving issues
that arise outside of an inspection.
Senator Burr, Senator Enzi, and Senator Isakson
Question. The Food Safety Modernization Act adopted a ``reasonably
foreseeable'' standard with respect to preventive controls. In
legislating FSMA Congress debated whether to follow the HACCP model,
but definitively decided not to use HACCP in the bill, instead
establishing preventive controls with a different standard. Why is FDA
proposing a standard different than what was enacted in FSMA in the
proposed regulations?
Answer. In the proposed rule, ``Current Good Manufacturing Practice
and Hazard Analysis and Risk-Based Preventive Controls for Human
Food,'' we proposed that the application of preventive controls would
be required in cases where facilities determine that hazards are
reasonably likely to occur. We received many comments related to the
use of the term ``reasonably likely to occur.'' Comments expressed
concern that if we use this term as the basis for determining the need
for preventive controls, then either all preventive controls will need
critical control points (CCPs) or people will be confused by the term
being different in this rule from the seafood and juice Hazard Analysis
and Critical Control Points (HACCP) rules. In the proposed revisions to
the proposed rule on preventive controls for human food that we
released on September 19, 2014, we indicated that we are proposing to
eliminate the term ``hazard reasonably likely to occur'' throughout the
proposed requirements to reduce the potential for a misinterpretation
that all necessary preventive controls must be established at CCPs. The
revised regulations would use a new term (``significant hazard'') in
its place. The defined term ``significant hazard'' would be linked to
the facility's hazard analysis, which addresses risk (i.e., both the
severity of a potential hazard and the probability that the hazard will
occur). Thus, this term would reflect the risk-based nature of the
requirements. FDA is seeking comment on the supplemental notice of
proposed rulemaking until December 15, 2014.
Senator Enzi
Question 1. I have heard concerns from rural veterinarians and
livestock producers about the onerous burdens placed on the livestock
industry by the FDA's food animal antibiotic use guidance and proposed
Veterinary Feed Directive. Many rural areas, including most parts of
Wyoming, are underserved by large animal veterinarians and it is
already difficult for these professionals to service remote areas where
livestock are raised. Could you please tell me how FDA provided
accommodations in its proposal for the concerns these individuals
raised in the rulemaking process?
Answer 1. With the publication of GFI #213 on December 12, 2013,
FDA began the 3-year implementation of its strategy to promote the
judicious use of medically important antimicrobial drugs in food-
producing animals. The goal of the strategy is to work with animal drug
sponsors to voluntarily phaseout the use of medically important
antimicrobials in food animals for production purposes (e.g., to
enhance growth or improve feed efficiency) and to bring the therapeutic
uses of such drugs (e.g., to treat, control, or prevent specific
diseases) under the oversight of licensed veterinarians. In order to
help phase in veterinary oversight of those drugs covered by the
guidance that are intended for medically appropriate uses in feed, FDA
also issued a proposed rule to update the existing regulations relating
to VFD drugs.
Because of the complex scientific and regulatory issues involved
and the potential impact that changes to the VFD regulations may have
on stakeholders, FDA sought stakeholder input via multiple
opportunities for public comment, including an advance notice of
proposed rulemaking (ANPRM) (75 FR 15387, March 29, 2010) and draft
text of proposed amendments to the current VFD regulations (77 FR
22247, April 13, 2012). FDA also announced its plans for a series of
five meetings (78 FR 14801, March 7, 2013) which were held around the
country in 2013 to provide the public with opportunities to discuss and
provide critical feedback on the challenges faced by livestock
producers and veterinarians as FDA phases in veterinary oversight of
the therapeutic use of certain medically important antimicrobials. The
meetings were jointly sponsored by FDA and the U.S. Department of
Agriculture's (USDA) Animal and Plant Health Inspection Service and
were intended to provide a forum to discuss potential challenges faced
by animal producers in areas of the country that may lack access to
adequate veterinary services and to explore possible options for
minimizing adverse impacts.
Based on the input the Agency received, the proposed VFD regulation
includes several provisions that could allow veterinarians to more
effectively provide services to food animal producers in remote
geographical areas where veterinary professional resources are limited
and distances are great. For example, one major proposed change is to
replace the explicit veterinary-client-patient relationship (VCPR)
provision with the requirement that veterinarians ordering the use of
VFD drugs do so only ``in animals under his or her supervision or
oversight in the course of his or her professional practice, and in
compliance with all applicable veterinary licensing and practice
requirements.'' The purpose of this revision is to defer to the
individual States and the veterinary profession for the specific
criteria for acceptable veterinary professional conduct, rather than
relying on a more rigid, one-size-fits-all, Federal standard. From a
practical standpoint, this enables the veterinary profession and
individual States to adjust the specific criteria for a VCPR to
appropriately align with current veterinary practice standards,
technological and medical advances, and other regional considerations.
Other examples that are intended to help accommodate concerns
regarding veterinary access are connected to a number of proposed
changes to the information required on a VFD order. These include
establishing a ``default'' maximum expiration date of 6 months,
allowing veterinarians to estimate the approximate number of animals
instead of the exact quantity of feed, and allowing veterinarians the
option to identify premises where the animals are located instead of
more detailed individual animal identification. While the existing
process requires VFD orders to be written for a specific amount of
medicated feed to be delivered to specifically identified animals,
these proposed revisions would allow veterinarians to opt for this
level of specificity or to exercise their professional judgment to
issue a broader ``standing order'' for up to 6 months and for a
specified approximate number of animals.
FDA has worked with many stakeholder groups and USDA to develop a
strategy that it believes will be successful in reducing antimicrobial
resistance while minimizing adverse impacts on animal health and
disruption to the animal agricultural industry. In order to help
minimize these impacts while still ensuring that VFD drugs are used in
a manner that affords adequate protection for human and animal health,
FDA has proposed amendments to the existing VFD regulations to improve
the efficiency of the VFD program. The comment period for the proposed
VFD regulation closed March 12, 2014, and the Agency is currently
reviewing all comments received. As part of the effort to finalize and
implement updated VFD regulations, FDA will continue to work with
affected stakeholders in the veterinary and livestock industries to
ensure the needed outreach and education is provided to support the
implementation of these significant changes to how antimicrobials are
used in food-producing animals.
Question 2. What is the status of implementation of the ``Tester
Amendment'' to the Food Safety Modernization Act (FSMA) which provides
specific accommodations to the preventive controls in the law for small
farmers and producers?
Answer 2. FDA has included provisions implementing the ``Tester
Amendment'' in its proposed rules implementing sections 103 (preventive
controls) and 105 (produce safety) of FSMA.
Question 3. Despite last year's sequester, FDA received from
Congress an increase of $96 million over the amount provided in fiscal
year 2013 and $3 million above the agency's budget request. In the most
recent FSMA implementation progress report, you announced that you are
doing more inspections and working hard to meet court ordered deadlines
to release pending regulations. This has been done with appropriated
funds, and without the imposition of new regulatory taxes. Could you
explain then why FDA needs these user fees? Have you hired or trained
new inspectors, retrained current inspectors? How have you done so in
the absence of final regulations?
Answer 3. FDA is committed to fully implementing FSMA and is
working diligently to prioritize new and existing resources toward this
effort. We have adequate resources to issue the required regulations
and conduct the mandated number of domestic inspections, and we will
continue efforts to make the best use of the resources we have.
However, FDA cannot fully implement FSMA and achieve the benefits of a
safer food supply without a significant increase in resources.
As you know, the President's fiscal year 2015 budget request
affirms the need for additional resources to implement FSMA by
requesting that Congress provide $253 million in additional funding via
a combination of added appropriations and new user fees. These
resources are needed to adequately implement FSMA, including resources
needed to retrain FDA and State inspectors, provide grants to States to
build the capacity to conduct inspections and coordinate with FDA, and
implement the new import safety system mandated by Congress.
The urgency of receiving adequate funding in 2015 and 2016 is that
FDA is under court-ordered deadlines to issue key final rules in late
2015 and early 2016, which means FDA must be equipped to begin sound
inspection and other oversight activities to ensure smooth and
effective implementation in late 2016 and 2017. Without immediate
investment in the advance preparation that is essential for sound
implementation of the FSMA rules, implementation will be disrupted and
delayed to the detriment of public health, consumers, and the food
industry.
For example, with regard to your question about inspectors, FDA
inspectors are currently trained to inspect food manufacturers using a
compliance model focused on finding evidence of hazards. The new food
safety paradigm will be focused on preventing food contamination
through a system-based approach and on ensuring consistency among all
inspections. This new paradigm involves a major reorientation and
retraining of almost 1,700 inspectors, compliance officers, and other
staff involved in food safety activities in fundamentally different
approaches to food safety inspection and compliance. To accomplish this
in time, training in the new prevention and systems approach must begin
in 2015, with further technical training continuing into 2016 and
beyond after the FSMA rules are finalized.
In addition, the States are projected to conduct over half of the
domestic facility inspections required by FSMA. Building State capacity
to coordinate effectively with FDA is a central tenet of FSMA and is
needed to ensure that States are prepared to conduct these inspections
using the same standards and methodologies as FDA inspectors. States
will need inspector training, greater information sharing capacity with
FDA and other States, State laboratory coordination, and inspector
certification programs. Like FDA's own retraining effort, those
processes, which will be carried out mostly via FDA grants to 40 or
more States, must begin in 2015 if the States are to be prepared when
industry becomes obligated to comply with the new prevention standards
starting in 2016.
Question 4. It is my understanding that not all FSMA rules have
been issued. As a result, we do not yet know the entire cost of
implementation. Will you be asking for more and more fees to regulate
these businesses as these rules come out?
Answer 4. FDA does not currently anticipate proposing new user fees
to support FSMA implementation beyond those identified in the fiscal
year 2015 request.
Question 5. What research have you done in relation to alternatives
to the use of partially hydrogenated oils (PHOs) in food production,
such as saturated fat or palm oil? What are the potential consequences
to using these alternatives, which are the only options available at
this time? Was a cost-benefit analysis conducted prior to the FDA rule
banning trans fats?
Answer 5. Since FDA's trans fat labeling rule took effect in 2006,
FDA has observed that the food industry has significantly reduced the
amount of partially hydrogenated oils (PHOs) used in their products. We
have also observed that in all product categories the food industry now
offers at least some products that do not contain PHOs. To reduce the
risk of coronary heart disease, ideally PHOs should be replaced with
healthier oils (e.g., polyunsaturated or monounsaturated oils) rather
than oils high in saturated fat. While PHOs may be replaced with oils
high in saturated fats for some products, a 2010 review article showed
that major brand-name reformulations generally reduced the trans fat
content substantially without making equivalent increases in saturated
fat. The notice FDA issued about PHOs in 2013 was not a rule banning
trans fats; rather, it was a tentative determination that PHOs are not
generally recognized as safe (GRAS) for any use in food. In response to
this notice, FDA has received a number of comments about alternatives
to PHOs, including comments from the soybean industry that they have
developed high oleic soybean varieties (a healthier alternative to
PHOs) which may be used as an alternative to PHOs.
In 2013, FDA conducted an estimate of the potential costs and
benefits associated with removing PHOs from the food supply. FDA
estimates that monetizing the lives saved, along with the value of the
nonfatal illnesses and medical expenses prevented, yields an estimated
20-year value of benefits from this proposal of about $117 billion. The
estimated cost of removing PHOs from the food supply over 20 years (at
a 7 percent discount rate) is $12 billion.
Question 6. There is bipartisan support to eliminate duplicative
programs and reduce government waste. The Government Accountability
Office (GAO) has concluded on numerous occasions that the USDA catfish
program would duplicate FDA's seafood Hazard Analysis Critical Control
Points (HACCP) program. The most recent GAO report in April 2013
concluded that repealing the USDA catfish program ``would avoid
duplication of Federal programs and could save taxpayers millions of
dollars annually without affecting the safety of catfish intended for
human consumption.'' FDA has the government's preeminent seafood
experts and if implemented the USDA catfish program would require two
separate seafood regulators with two very different regulatory
frameworks depending on the species of fish. Based on FDA's evaluation
of the science, is there any food safety basis that would justify
duplicative regulation of seafood products by USDA treating catfish any
differently than any other seafood that FDA regulates?
Answer 6. FDA operates a mandatory safety program for all fish and
fishery products under the provisions of the Federal Food, Drug, and
Cosmetic Act (FD&C Act), the Public Health Service Act, and related
regulations. The FDA program includes research, inspection, compliance,
enforcement, outreach, and the development of regulations and industry
guidance.
Seafood in general carries some unique risks, and that is why FDA
established the Hazard Analysis and Critical Control Points (HACCP)
program in 1997. Currently, all seafood processors are required to
adhere to HACCP regulations. Under HACCP, processers of fish and
fishery products must identify hazards that are reasonably likely to
occur for their products and formulate control strategies. Seafood
HACCP requirements have been in place for years and serve as the
foundation of the proposed hazard analysis and risk-based preventive
control requirements found in the FSMA proposed rules for all food
products.
FDA also has import alerts in place that provide for increased
review and testing of imported seafood that may pose particular risks.
These programs have been very successful in mitigating the safety
issues inherent in seafood production.
With regard to catfish specifically, catfish are generally less
risky than some other types of fish. Catfish are generally not eaten
raw or packaged in ready to eat form.
Question 7. Section 12106 of the 2014 Farm bill, the Agriculture
Act of 2014, includes new language that was inserted for the first time
during the Farm bill conference process that requires USDA to issue a
final rulemaking taking jurisdiction of ``catfish'' from FDA. Unless
Congress acts to repeal the USDA catfish program, this would mean FDA
would maintain primary jurisdiction over all seafood except
``catfish,'' which USDA would regulate. Under Section 12106(b)(4) of
the Agriculture Act, FDA and USDA are directed to enter into a
memorandum of understanding (MOU) regarding the inspection of seafood.
Given that FDA has primary jurisdiction over seafood and employs the
government's seafood experts, can you confirm that in any MOU signed by
FDA in relation to the USDA catfish program, FDA will insist that FDA
inspectors will have primary jurisdiction over seafood other than
catfish even if USDA is in the same facility to inspect catfish?
Answer 7. On April 30, 2014, FDA and USDA signed an MOU to address
fish of the order Siluriformes, which includes catfish, as required by
the Agriculture Act of 2014. The MOU reflects FDA's intention to
continue to exercise its current regulatory oversight over seafood
other than Siluriformes.
Senator Murkowski
Question 1. I continue to strongly oppose FDA approval of
genetically engineered salmon. I do not believe that FDA has adequately
studied the environmental effects, the economic impacts on wild salmon
and seafood markets that would result from approval, let alone the
potential human health impacts. Given these concerns Commissioner
Hamburg, can you assure me that FDA is prepared to deny approval of the
sale of GE salmon to consumers if your agency determines that it cannot
guarantee that it is safe to eat?
Answer 1. FDA will not approve the application related to
AquAdvantage Salmon unless it determines that food derived from
AquAdvantage Salmon meets the standard of a ``reasonable certainty of
no harm.'' FDA regulates genetically engineered (GE) animals under the
new animal drug review provisions of the Federal Food, Drug, and
Cosmetic Act (FD&C Act). The recombinant DNA (rDNA) construct used to
introduce the fast growing trait into AquAdvantage Salmon meets the
definition of a drug because it is intended to affect the structure or
function of the animal. The new animal drug approval process provides
the most rigorous review for such products that the U.S. Government has
in place. This regulatory pathway prohibits the introduction of
AquAdvantage Salmon, or food derived from AquAdvantage Salmon, into
U.S. commerce without a specific FDA approval, which would include an
evaluation of food safety. The Agency will not approve the application
related to AquAdvantage Salmon until it has completed its science-based
review of animal health and food safety, determined that the rDNA
construct is safe to the animal, that food derived from AquAdvantage is
safe to eat, and met its requirements under the National Environmental
Policy Act.
Question 2. If FDA were to approve GE salmon for sale to consumers,
what steps will the agency take to require clear labeling to ensure
consumers know what they are buying?
Answer 2. FDA regulates the labeling of food derived from GE
animals under the FD&C Act. Under the FD&C Act, FDA may require special
labeling for a GE food when the food differs materially from other
foods, for example, where the food differs in nutritional profile or
functionality. The Agency is looking carefully at this issue with
respect to food derived from AquAdvantage Salmon. We recognize that
many consumers are interested in knowing whether the foods they
purchase are produced using genetic engineering. Currently, food
manufacturers may indicate through voluntary labeling whether foods
have or have not been developed through genetic engineering, provided
that such labeling is truthful and not misleading. FDA is supportive of
such voluntary labeling. The Agency has issued draft guidance for
industry on voluntary labeling of plant-based foods to indicate whether
such foods have or have not been derived from GE plants to assist firms
that wish to provide such labeling. We are working to finalize this
guidance.
Question 3. Does FDA have existing authority to require labeling of
GE salmon?
Answer 3. FDA regulates the labeling of food derived from GE
animals under the FD&C Act. The FD&C Act prohibits food labeling that
is false or misleading, and provides, in relevant part, that labeling
is misleading if it fails to reveal ``material'' facts. Accordingly,
and as interpreted by Federal courts, the Agency may require special
labeling for a GE food when the genetic change results in a
``material'' difference in the food, such as a difference in
nutritional content or functionality. However, the fact that a food
comes from a GE source is normally not a material fact within the
meaning of the FD&C Act, and thereby does not, by itself, trigger
required labeling. These courts have further held that consumer desire
to know alone is not sufficient to require such labeling.
Question 4. I am very concerned about the lack of progress to
either lift the ongoing Chinese ban of all shellfish imports from the
West Coast of the United States, or to at least narrow the restrictions
to smaller regions. When I met recently with constituents in Ketchikan,
they shared with me their frustrations with the slow pace of
discussions with the Chinese. These are mostly small, family businesses
that are being hit hard by the ban, with the region losing hundreds of
thousands of dollars a week throughout the winter season. What specific
actions is FDA taking to expedite the resolution of the ban?
Answer 4. As you know, on May 23, 2014, Chinese food safety
officials advised the National Oceanic and Atmospheric Administration
(NOAA) that they were lifting their ban on imports of live shellfish,
including geoduck clams from Alaska and Washington. We understand the
economic impact such a suspension has on local businesses and are
pleased that China has lifted the ban.
In December 2013, near the beginning of the suspension, officials
from FDA's Center for Food Safety and Applied Nutrition and ORA met
with food safety officials in China about this issue. FDA reviewed
evidence from Washington and Alaska health officials and NOAA that
demonstrated the safety of geoduck clams. Based on this evidence, FDA
was confident that geoduck clams, as well as other species of bivalve
molluscan shellfish, were in compliance with State and Federal
regulations and met the rigorous public health standards necessary to
control the safety of shellfish intended for human consumption. FDA
relayed its safety assessment to China's General Administration of
Quality Supervision, Inspection and Quarantine (AQSIQ).
As part of its trade facilitation mission, NOAA's Seafood
Inspection Program issues health certificates for U.S. exporters for
certain commodities, such as the geoducks in question. In this role,
NOAA has coordinated the communication with AQSIQ on this issue. FDA,
as the regulatory authority for seafood, works with NOAA when there are
safety questions. FDA contributed significantly to all of NOAA's
written correspondence to AQSIQ on the issue. Contributions included
providing scientific and technical details on paralytic shellfish
poisoning toxins and arsenic as hazards in seafood and information on
methodologies for detecting these hazards and the National Shellfish
Sanitation Program. FDA staff also engaged in extensive technical
discussions with the NOAA delegation team as they prepared for a
meeting with AQSIQ held on March 21, 2014, in China. FDA was available
to NOAA during the meeting to address any scientific, technical, or
regulatory issues.
FDA will work diligently with NOAA and other U.S. partners on any
followup needed to ensure the continued export of shellfish to China.
Senator Hatch
Question. While further reduction of trans fat in the food supply
is important, I am concerned about the specific course FDA utilized to
meet its goal by tentatively determining PHOs as no longer generally
recognized as safe (GRAS). This appears to be a significant change in
how the GRAS process has been utilized in the past. I understand you
have some data to support this decision, but I am questioning how you
decided to address PHOs through the GRAS process rather than through
other means.
Given the importance of GRAS to the entire industry, including my
constituents in the dietary supplement industry, I am concerned that
this change will have significant effect without adequate discussion.
Can you provide me with assurance that you won't move forward with such
changes in the GRAS process without thorough and adequate discussion
with the industry?
Answer. As you know, on November 8, 2013, FDA announced in the
Federal Register that the Agency has tentatively determined that
partially hydrogenated oils (PHOs), the primary dietary source of
industrially produced trans fatty acids (trans fat), are not generally
recognized as safe (GRAS) for any use in food based on current
scientific evidence establishing the health risks associated with the
consumption of trans fat, and therefore PHOs are food additives. If
finalized, this would mean that PHOs could not be used in food without
prior FDA approval for use as a food additive.
FDA addressed the status of PHOs through this tentative
determination because the uses of these substances by the food industry
have been based on their GRAS status for use in food. For example,
partially hydrogenated soybean oil, cottonseed oil, coconut oil, and
palm oil are considered GRAS based on a history of use prior to 1958,
while the partially hydrogenated versions of low erucic acid rapeseed
oil and menhaden oil, although not commonly used, are affirmed by
regulation as GRAS for use in food.
A substance is GRAS if it is generally recognized, among experts
qualified by scientific training and experience to evaluate its safety,
as having been adequately shown through scientific procedures to be
safe under the conditions of its intended use (or, in the case of a
substance used in food prior to 1958, through either scientific
procedures or experience based on common use in food). However, the
GRAS status of a specific use of a particular substance in food is
time-dependent. That is, as new scientific data and information develop
about a substance or the understanding of the consequences of
consumption of a substance evolves, expert opinion regarding the safety
of a substance for a particular use may change such that there is no
longer a consensus that the specific use is safe. The fact that the
status of a substance may evolve over time is the underlying basis for
FDA's regulation at 21 CFR 170.38, which provides in part that FDA
may, on its own initiative, propose to determine that a substance is
not GRAS.
FDA will certainly consider the views of industry and work with
them to implement, with minimal disruption, any final determination the
Agency may make. FDA extended, until March 8, 2014, the comment period
for the November 2013 Federal Register notice, due to multiple requests
for a 60-day extension. If FDA makes a final determination that PHOs
are not GRAS, the Agency intends to provide adequate time for producers
to reformulate any products as necessary and that would minimize market
disruption. To help address this concern in an appropriate manner, the
Federal Register notice calls for comment on how long it would take the
food industry to phaseout its use of PHOs. Further, we requested
comment specifically on the costs of such a decision to small
businesses and any special considerations that might be made in order
to minimize the burden on these entities.
Senator Isakson
Obesity is a serious public health problem in our country. I
believe there are basically two approaches we can take to confronting
this challenge. One is to educate and empower people to make healthier
diet and exercise choices for themselves and their families, which I
believe is the better and more effective approach. The other
alternative is to tax and regulate and try to use the power of the
government to stop people from making choices that are viewed as
unhealthy, and it seems to me that FDA's decision to issue a
``tentative determination'' that trans fats and partially hydrogenated
oils are unsafe falls into this category. It is my understanding that
the food industry has already been in the process of phasing out the
use of trans fats, but this heavy-handed regulatory approach threatens
to disrupt that process. I am also concerned that by issuing a
tentative determination rather than going through the formal regulatory
process, FDA is avoiding the requirements to respond to public comments
and to estimate the economic impact of this decision.
Question 1. Could you explain why your agency decided to use a
tentative determination notice as opposed to a rulemaking for this
decision? Also, could you clarify what you believe to be the scope of
FDA's existing authority to regulate food products based on concerns
that their long-term use may be one of multiple factors contributing to
obesity, heart disease, or other health problems?
Answer 1. As you know, on November 8, 2013, FDA announced in the
Federal Register that the Agency has tentatively determined that
partially hydrogenated oils (PHOs), the primary dietary source of
industrially produced trans fatty acids (trans fat), are not generally
recognized as safe (GRAS) for any use in food based on current
scientific evidence establishing the health risks associated with the
consumption of trans fat, therefore that PHOs are food additives. If
finalized, this would mean that PHOs could not be used in food without
prior FDA approval for use as a food additive.
FDA addressed the status of PHOs through this tentative
determination because the uses of these substances by the food industry
have been based on their GRAS status for use in food. For example,
partially hydrogenated soybean oil, cottonseed oil, coconut oil, and
palm oil are considered GRAS based on a history of use prior to 1958,
while the partially hydrogenated versions of low erucic acid rapeseed
oil and menhaden oil, although not commonly used, are affirmed by
regulation as GRAS for use in food.
A substance is GRAS if it is generally recognized, among experts
qualified by scientific training and experience to evaluate its safety,
as having been adequately shown through scientific procedures to be
safe under the conditions of its intended use (or, in the case of a
substance used in food prior to 1958, through either scientific
procedures or experience based on common use in food). However, the
GRAS status of a specific use of a particular substance in food is
time-dependent. That is, as new scientific data and information develop
about a substance or the understanding of the consequences of
consumption of a substance evolves, expert opinion regarding the safety
of a substance for a particular use may change such that there is no
longer a consensus that the specific use is safe. The fact that the
status of a substance may evolve over time is the underlying basis for
FDA's regulation at 21 CFR 170.38, which provides in part that FDA
may, on its own initiative, propose to determine that a substance is
not GRAS.
FDA will consider the views of industry and work with them to
implement, with minimal disruption, any final determination the Agency
may make. If FDA makes a final determination that PHOs are not GRAS,
the Agency intends to provide adequate time for producers to
reformulate any products as necessary and that would minimize market
disruption. To help address this concern in an appropriate manner, the
Federal Register notice calls for comment on how long it would take the
food industry to phaseout its use of PHOs. Further, we requested
comment specifically on the costs of such a decision to small
businesses and any special considerations that might be made in order
to minimize the burden on these entities.
Question 2. As you are aware, this committee has expressed concern
about illegal animal drug compounding and has requested a GAO report to
further investigate this issue. I have received reports of entities
characterizing themselves as ``compounding pharmacies'' that are
essentially copying FDA-approved products and mass-marketing them as a
cheaper alternative that is not subject to the safety requirements and
quality controls with which manufacturers must comply. What steps is
your agency currently taking, using existing resources and statutory
authority, to address the problem of entities mass-producing copies of
FDA-approved animal drug products? Additionally, please outline any
efforts FDA has undertaken to work with State pharmacy boards with
respect to animal drug compounding oversight.
Answer 2. FDA is also very concerned about illegal animal drug
compounding, particularly the production of drug products that are
essentially copies of FDA-approved products. Animal drugs were included
in the Agency's inspection initiative last year that targeted high-risk
compounding firms, and followup actions are currently being evaluated.
In addition, FDA continues to collect evidence including product
samples and adverse event reports from various sources and will target
firms whose practices, if deficient, would pose the highest risk to
public health. To aid in this endeavor, FDA has been working closely
with the State boards of pharmacy to identify firms engaged in
deficient or inappropriate practices and, when appropriate, we plan to
take action, including enforcement action, to protect public health.
FDA is also working closely with veterinary associations to ensure that
practitioners have the information they need to distinguish between
approved and unapproved animal drug products to allow them to make
informed decisions when choosing a product for their client.
Senator Isakson and Senator Enzi
Question. As you know, the Food Safety Modernization Act explicitly
exempts alcohol production from FDA regulation. I am troubled that the
FDA has indicated an intention to regulate brewers' spent grain through
the proposed rule on animal feed. The premium, high food-grade barley
used to produce beer is the same grain that results in brewers' spent
grain. It makes no sense to us to exclude the handling and distribution
of those grains while the brewery is using it to produce beer, yet deny
that brewery the benefit of the exemption once the grain is spent. We
believe Congress intended to exempt the entire process of manufacturing
beverage alcohol products, including by-products or residue of that
alcohol manufacturing process, even if the by-products or residue have
separate value or potential use as food for animals. Will you
reconsider this issue prior to finalizing the FSMA rules?
Answer. Yes. You express concerns that we also heard from many in
the brewing community regarding the potential impact of the proposed
rule on the long-standing practice of beer brewers providing the
``spent grains,'' resulting from the brewing process, to farmers to use
as animal food.
Breweries making products for human consumption are already subject
to human food Current Good Manufacturing Practice (CGMP) regulations.
FDA's current understanding is that the potential hazards associated
with spent grains from brewers and distillers of human beverages are
minimal, provided the food manufacturer takes common-sense steps, such
as minimizing the possibility of physical or chemical hazards being
inadvertently introduced into a container of spent grains. In addition,
we agree that there are substantial efficiency and sustainability
benefits from the recycling of human food by-products--such as spent
grains--to animal food, and it is not our intention to disrupt this
practice.
We are pleased to inform you that, on September 19, 2014, FDA
proposed a number of revisions to its proposed rule on preventive
controls for animal food that are more flexible and less burdensome in
key areas. Specifically, the Agency has proposed that, in general,
human food processors already subject to and complying with FDA human
food safety requirements, such as brewers, would not need to implement
additional preventive controls or CGMP regulations when supplying a by-
product (e.g., wet spent grains, fruit or vegetable peels, liquid whey)
for animal food, except for proposed CGMPs to prevent physical and
chemical contamination when holding and distributing the by-product
(e.g., ensuring the by-product isn't co-mingled with garbage).
Please be assured that we are working to develop regulations that
are responsive to the concerns expressed, practical for businesses, and
that also help ensure that food for animals is safe and will not cause
injury to animals or humans. FDA is seeking comment on the supplemental
notice of proposed rulemaking until December 15, 2014. We hope to
continue our active dialog with stakeholders, including the brewing
community, about how we can achieve our food safety goals in the most
practical way.
Senator Kirk
Question 1. Data is critical to understanding the use of
antibiotics in animal agriculture. I was glad to see that in September
2013, the FDA proposed improvements to current antibiotic data
reporting under the Animal Drug User Fee Act. However, in order to
properly implement Guidance 213, additional data would help industry
target specific areas where improvement is needed. Dispensing status,
route of administration, drug class and indication would not only
provide better insight, but it would make the process more efficient.
When will the FDA issue the 2012 data report in the proposed new
format? Will the agency followup on the July 2012 ANPR by proposing a
rule to collect additional data?
Answer 1. As you know, FDA sought additional public input in
September 2013 (78 FR 58308 (September 26, 2013)), on proposed
additions to FDA's annual Summary Report of Antimicrobials Sold or
Distributed for Use in Food-producing Animals (ADUFA 105 annual summary
report). Based on broad public input, FDA has enhanced the format of
the ADUFA 105 annual summary reports to better describe data on the
annual sales and distribution of antimicrobials intended for use in
food-producing animals using a more detailed format that will allow the
public to better understand the changes that occur as GFI #213 is
implemented. On October 2, 2014, FDA released the summary report for
2012, using this new format, and provided updated annual reports from
previous years to include the new data tables. The changes expanded the
format of reporting sales and distribution data by antimicrobial class
to include information on the importance of the drug in human medicine.
These changes also provide aggregate data on the approved route of
administration of antimicrobial drugs sold or distributed for use in
food-producing animals, whether such drugs are available over the
counter or require veterinary oversight, and whether they are approved
for therapeutic indications, or both therapeutic and production
indications.
The Agency is also developing a proposed regulation to enhance the
existing requirements related to the collection of antimicrobial drug
sales and distribution data for antimicrobial drugs intended for use in
food-producing animals. New requirements being considered include the
collection of additional drug sales and distribution data, including
reporting sales and distribution data by species.
FDA is working with the U.S. Department of Agriculture (USDA) and
the Centers for Disease Control and Prevention (CDC) to identify
possible approaches for further enhancing current data collection
efforts, focused on actual use (exposure) on the farm. This will help
identify meaningful metrics for assessing the effectiveness of GFI #213
in reducing the public health risk of antibiotic resistance. The Agency
intends to seek further public input on this issue in early 2015.
In addition, as part of this collaborative effort it was determined
that there is currently no appropriate method to analyze associations
between changes in antimicrobial use and shifts in resistance patterns
on a national level, as is needed to assess the public health impact of
interventions such as GFI #213. Therefore, FDA and USDA are
collaborating with a Cornell University researcher and submitted a
National Institute of Mathematical and Biological Synthesis (NIMBioS)
proposal to create a working group to develop a new mathematical
modeling methodology that would inform the approach to monitoring and
assessing the impacts of GFI #213. This will allow the collaborating
Federal agencies to efficiently allocate limited resources by targeting
data which are most valuable. The proposal was accepted and the first
meeting of the working group occurred in September 2014.
Question 2. The Agency recently published guidance seeking to
clarify what constitutes a ``medical food'', and what conditions might
need the use of medical foods. Specifically, the agency is seeking to
clarify the use of certain medical claims on labels, and the guidance
states that diabetes and pregnancy are two types of conditions that do
not warrant the use of medical foods, because they can be treated
through ``diet alone''.
This point of ``treating diabetes through diet alone'' goes beyond
the statutory definition of a ``medical food'', as outlined in the
original Orphan Drug Act. Treating diabetes is not as simple as
monitoring food intake. By disallowing the use of clear labeling to
notify patients of what is contained in certain medical foods, this
guidance has the potential to further negative health outcomes
associated with the disease, increase patient confusion, and limit
patient choice. Does the Commissioner have any comment on the diabetes
portion of the medical foods guidance, which is now through its draft
stage?
Answer 2. FDA recognizes and appreciates the difficulties
associated with managing diabetes. We received a number of comments
during the comment period regarding the diabetes portion of the medical
foods draft guidance and are considering them as we determine how to
proceed with the draft guidance.
Senator Roberts
Question 1. I have heard quite a bit of conversation from our
industry leaders about the implementation of the Food Safety and
Modernization Act. More recently I have been hearing concerns related
to the Preventive Controls for Human Food proposed rule that I believe
is still open for comment. I am specifically hearing feedback that the
proposed rule mentions testing and supplier verification requirements
in the preamble but does not provide the specific requirements in the
rule. I also understand that a version of the rule that was more
prescriptive on these requirements was released but not published. Can
you assure me that you will not finalize the rule with these more
prescriptive testing and supplier verification requirements unless they
go through a full notice and comment period regulatory process,
including the revised economic analysis? Can you also assure me that
this rule will not be issued as an interim final rule?
Answer 1. In our proposed rule, ``Current Good Manufacturing
Practice and Hazard Analysis and Risk-Based Preventive Controls for
Human Food,'' we did not include specific requirements for product
testing, environmental monitoring, and supplier controls, but we
acknowledged that such programs, when implemented appropriately in
particular facilities, could be used to verify the effectiveness of
preventive controls. On September 19, 2014, FDA released proposed
revisions to its proposed rule on preventive controls for human food
that are more flexible and less burdensome in key areas. With regard to
product testing, environmental monitoring, and supplier controls, the
Agency is now providing an opportunity for input on specific language
and seeking comment on whether to include it in the final rule.
Specifically, FDA is seeking comment on whether the preventive
controls for human food should require a facility, as appropriate to
the facility, the food, and the nature of the preventive control, to
conduct product testing to verify implementation and effectiveness of
preventive controls. FDA is also seeking comment on whether the
preventive controls for human food should require a facility, as
appropriate to the facility, the food, and the nature of the preventive
control, to conduct environmental monitoring to verify implementation
and effectiveness of preventive controls if contamination of a ready-
to-eat food with an environmental pathogen is a significant hazard.
The potential provisions would require supplier controls when the
receiving facility's hazard analysis identifies a significant hazard
for a raw material or ingredient and that hazard is controlled before
the facility receives the raw material or ingredient from a supplier.
We have indicated that if these provisions were to be included, the
facility would have flexibility to determine the appropriate
verification activity (such as onsite audit, sampling, and testing)
unless there is a reasonable probability that exposure to the hazard
will result in serious adverse health consequences or death to humans.
In that instance, an annual onsite audit of the supplier would be
required unless the facility can show that other verification
activities and/or less frequent onsite auditing of the supplier provide
adequate assurance that the hazards are controlled.
FDA is seeking comment on this new language until December 15,
2014.
Question 2. The economic impact analyses accompanying the proposed
Produce Rule and proposed Preventive Controls Rule estimated very high
compliance costs for farmers and food facilities. In the analyses, FDA
sought comment on a number of issues and failed to adequately account
for certain costs and realities on farm, including length of growing
season. Given that FDA will be re-proposing major sections of the
rules, including sections that determine scope and impact of the rules,
can you please discuss whether the agency plans to release revised
economic impact analyses for public comment?
Answer 2. The economic analyses for the proposed rules on produce
safety and preventive controls for human food that accompanied the
original proposed rules contain estimates that were based on the best
data available to FDA at the time of publication. We understand that,
due to the limited amount of data, and because the estimates reflect
average costs over broad size categories, the estimates may not
perfectly reflect reality for every individual farm or facility.
Wherever possible, we attempted to capture the variability across size
and category and the uncertainty inherent in this type of estimation.
On September 19, 2014, FDA released proposed revisions to its
proposed rule on preventive controls for human food and its proposed
rule on produce safety that are more flexible and less burdensome in
key areas. The Agency performed additional analyses to examine the
impacts of the amended and new proposed provisions, which can be found
in the corresponding dockets as references to the Federal Register
supplemental notices for the preventive controls for human food
proposed rule and the produce safety proposed rule, and can also be
found on FDA's Web site.\1\ FDA is seeking comment on the new language,
including the additional economic analyses, until December 15, 2014.
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\1\ http://wwwfda.gov/downloads/Food/GuidanceRegulation/FSMA/
UCM415041.pdf; http://www.fda.gov/downloads/Food/GuidanceRegulation/
FSMA/UCM415037.pdf.
[Whereupon, at 11:10 a.m., the hearing was adjourned.]
[all]