Natural Resources Defense Council, Inc. et al v. United States Food and Drug Administration et al
Filing
86
DECLARATION of William T. Flynn in Support re: 85 Memorandum of Law,. Document filed by Center for Veterinary Medicine, Bernadette Dunham, Margaret Hamburg, Kathleen Sebelius, United States Department of Health and Human Services, United States Food and Drug Administration. (London, Ellen)
UNITED STATES DISTRICT COURT
SOUTHERN DISTRICT OF NEW YORK
NATURAL RESOURCES DEFENSE
COUNCIL, INC., et al.
Plaintiffs,
v.
11 Civ. 3562 (THK)
ECF Case
UNITED STATES FOOD AND DRUG
ADMINISTRATION, etaZ. ,
Defendants.
DECLARATION OF WILLIAM T. FLYNN, D.V.M., M.S.
I, William T. Flynn, D.V.M., M.S., declare as follows:
1.
I am the Deputy Director for Science Policy for FDA's Center for Veterinary
Medicine ("CVM"). I have held this position since February 2011. Previously, I was the Senior
Advisor for Science Policy at CVM from July 2008 through January 2011 , and Director of
CVM's Policy and Regulations Staff from 2003 through 2008. From 2001 to 2003, I served as a
special assistant to the CVM Deputy Center Director. I also served from 1993 to 2001 in various
capacities in CVM's Office of New Animal Drug Evaluation, including as a drug application
reviewer and acting Team Leader. Prior to joining FDA, I was in private veterinary practice in
Maryland from 1991 to 1993.
2.
In my capacity as Deputy Director for Science Policy, I am responsible for
advising CVM's Center Director on science and policy issues related to CVM's mission, which
is to protect human and animal health. CVM accomplishes its mission by, among other things,
approving safe and effective products for animals and by enforcing applicable provisions of,
among other laws, the Federal Food, Drug, and Cosmetic Act (the "Act").
3.
I received the degrees of Doctor of Veterinary Medicine in 1991, and Master of
Science in Veterinary Preventative Medicine in 1987 from the Ohio State University. I am a
member of the American Veterinary Medical Association.
4.
I am familiar with FDA's regulation and enforcement program for animal drugs,
and with the procedures for approving new animal drugs and withdrawing such approvals. The
statements in this declaration are based on my personal knowledge and belief, and on my
background, training, education, and experience as an FDA official.
FDA's Proposed Schedule For Penicillin and Tetracycline Withdrawal Proceedings
5.
I am aware of this Court's order that FDA re-initiate withdrawal proceedings
("Withdrawal Proceedings") for the approximately 73 penicillin and tetracycline drug products
currently approved for use in animal feed for growth promotion and feed efficiency indications
(the "NOOH Products"). FDA had originally proposed to withdraw the NOOH Products
pursuant to two NOOHs issued in 1977 (the " 1977 NOOHs") because of concerns about
antimicrobial resistance. Following the issuance of the 1977 NOOHs, various manufacturers of
the NOOH Products (often called "sponsors") requested hearings, as permitted by the Act, 21
U.S.C. § 360b(e)(1). The Commissioner of Food and Drugs ("Commissioner") granted these
requests, but the Agency did not hold the hearings after Congress requested that FDA study this
issue further. Because the hearings were requested by the sponsors, but never held, FDA could
not, under the Act, withdraw approvals for the NOOH Products. Moreover, before this Court's
recent ruling, FDA did not consider itself to be under any legal obligation to proceed to hearings
under the 1977 NOOHs.
6.
Pursuant to the Court's order, CVM conducted an analysis to estimate the time
and resources that would be required to complete the Withdrawal Proceedings. Because CVM
2
anticipates issuing 2 NOOHs and 73 individual drug products are at stake, these proceedings are
likely to be more time-intensive and procedurally complex than any prior CVM drug withdrawal
proceeding. As discussed below, CVM's best proj ection at this time is that the Withdrawal
Proceedings, including one hearing, would take approximately five and a half years, and would
require the involvement of more than one dozen FDA employees, many of whom would need to
devote substantial effort on this project, taking them away from other duties, including drug
review, scientific research, policy and guidance development, antimicrobial resistance
surveillance activities, and post-approval monitoring activities. To the best of my knowledge,
CVM has never convened hearings to withdraw so many animal drug products at a single time,
and therefore these estimates are highly speculative. Moreover, to the extent that multiple
hearings are required, CVM estimates that substantially more time will be required.
7.
Even for the involuntary withdrawal of a single animal drug product, it is
impossible to predict with certainty how long the proceedings will take. This is because CVM
does not know whether the drug sponsor will request a hearing, whether the request for a hearing
will have merit and be granted, or the complexity of the scientific and legal issues that the
sponsor may raise. Moreover, to the extent that a drug sponsor requests and is granted a hearing
on a proposed withdrawal, the schedule for such hearings will not be determined by CVM, but
rather will be controlled primarily by the Presiding Officer (most likely an Administrative Law
Judge ("ALJ")).
Timeline For Re-Issuance of NOOHs For Penicillins and Tetracyclines
8.
The first step in the Withdrawal Proceedings would be to update and re-issue the
1977 NOOHs. The 1977 NOOHs must be updated because the FDA is legally required to
provide drug sponsors with notice of the bases for a proposed withdrawal prior to a hearing. 21
3
C.F.R. § 12.21(b). Because the scientific knowledge surrounding antimicrobial resistance has
evolved over the past 35 years, CVM believes that it is obligated to consider the more recent
science since the 1977 NOOHs were originally published.
9.
To update the scientific evidence would involve conducting a thorough analysis
of the available evidence to determine whether any new information has emerged over the past
35 years that could bear on FDA's original analysis. Failing to update the 1977 NOOHs to take
into account the current state of scientific understanding would result in presentations in the
Withdrawal Proceedings that would be incomplete, lack scientific rigor, and would be subject to
challenge.
10.
According to precedent, CVM must first satisfy the initial burden of producing
evidence that provides a legally sufficient basis for initiating withdrawal proceedings before the
burden shifts to the drug sponsor to show that its product is safe. Given the significance of this
initial showing by the Agency, it is critically important that the evidence presented in the NOOH
be complete and scientifically rigorous. It would be imprudent for CVM to issue an NOOH that
did not include an examination of the scientific developments of the past 35 years, as this could
obviously put the Agency at greater risk of not meeting its burden of proof at a hearing.
11.
CVM has attempted to identify the specific tasks required to re-issue the NOOHs,
and has estimated the time and personnel commitments associated with each of these tasks. As
noted above, because these proceedings could be substantially more complex than any in CVM' s
history, these projections are speculative. First, CVM will need to search its official files for
relevant information. Under 21 C.F.R. § l2.85(a)(2), prior to a hearing, CVM is required to
provide "all documents in the director's files containing factual information, whether favorable
or unfavorable to the director' s position, which relate to the issues involved in the hearing."
4
CVM would collect all such documents at the outset so they are available to prepare for an
NOOH and an administrative hearing. Because antimicrobial resistance has been the subject of
research and concern for more than 40 years, this search for documents will be a substantial
undertaking. CVM estimates that the search will take a team of 10 to 14 Agency employees (3
to 5 from CVM's Office of New Animal Drug Evaluation, 3 to 5 from CVM's Office of
Research, 2 from CVM's Office of the Director, and 2 from CVM's Office of Surveillance and
Compliance) approximately 60 days, although more time may be required depending on the
location and condition of FDA's older files. These employees would need to devote substantial
time to this document search, taking them away from their day-to-day public health protection
activities, including pre-approval drug safety review, policy and guidance development, postapproval monitoring activities, and enforcement efforts.
12.
Second, CVM would need to conduct an in-depth search for publicly available
literature and other information (e.g.. scientific reports) on the scientific topics that would be
addressed at the hearings. In addition to requiring submission of all documents in the Director's
files, FDA regulations require CVM to submit "[a]ll other documentary data and information
relied upon." 21 C.F.R. § 12.85(a)(3). Because CVM has a large amount of information in hand
already, and given that CVM should be able to assign multiple research teams to cover separate
subjects simultaneously, CVM estimates that a team of six to ten Agency employees (3 to 5 from
CVM's Office of New Animal Drug Evaluation, and 3 to 5 from CVM's Office of Research)
will be able to complete the necessary literature search in 90 days.
13.
Third, as the information in CVM's files and the publicly-available information
and literature is compiled, CVM estimates that it will require a team of six to ten Agency
employees (3 to 5 from CVM's Office of New Animal Drug Evaluation, and 3 to 5 from CVM's
5
Office of Research), including several senior scientists spending substantial amounts oftime,
approximately six months to review the information and determine the Agency's current
scientific position with regard to the microbial food safety of the NOOH Products. This task
involves reviewing the documents retrieved in CVM's files and through a literature search of
publicly available information, analyzing the materials, understanding how the materials relate to
each other, and evaluating the reliability and accuracy of the information. After the information
and literature has been fully reviewed, CVM estimates that it will take a team of eight to twelve
Agency employees (3 to 5 from CVM's Office of New Animal Drug Evaluation, 3 to 5 from
CVM's Office of Research, 1 from CVM' s Office of the Director, and 1 from the Office of Chief
Counsel), including several senior scientists spending substantial amounts of time, approximately
60 days to identify whether the available scientific data supports the withdrawal of the NOOH
Products, and to frame the legal and scientific arguments that may be included in re-issued
NOOHs.
14.
Fourth, CVM expects that it will take a team often to fourteen Agency
employees (3 to 5 from CVM's Office of New Animal Drug Evaluation, 3 to 5 from CVM's
Office of Research, 2 from CVM's Office of the Director, and 2 from the Office of Chief
Counsel) approximately 60 days to draft the revised NOOHs.
15.
Fifth, CVM anticipates that it will take approximately 60 days for senior Agency
management and FDA's Office of Chief Counsel to review and clear the revised NOOHs, and
for the revised NOOHs to be edited and published in the Federal Register.
16.
Altogether, CVM estimates that it will take approximately 17 months from the
beginning of the process to the final publication of the revised NOOHs, although this represents
only CVM's best current estimate. To the extent that CVM is able to conduct certain of the
6
above tasks simultaneously, or ifthe tasks take less time than expected, it is possible that the
revised NOOHs could be published in as few as 11 months; at this point, CVM believes that the
17 month projection is more realistic. It is also important to note that, in addition to the tasks
identified above, there is other work that CVM will need to accomplish during this time period.
For instance, in preparation for sUbmitting documents to the hearing docket in accordance with
21 C.F.R. § 12.85, it will likely take 2 CVM employees about 30 days to develop an index of
files and other relevant documents to be submitted. 21 C.F.R. § 12.85. Because documents in
the record will be available to the public, 21 C.F.R. § 12.105, FDA would have to redact the
documents to remove confidential commercial and trade secret information that FDA is obligated
by law to protect. It would likely take 2 Agency employees (1 from CVM's Office of the
Director, and 1 from the Office of Chief Counsel) about 60 days to redact these documents.
Likewise, as is often done in cases involving complex and disputed scientific issues, CVM would
interview and retain outside expert witnesses to testify on its behalf at a hearing. Although CVM
could proceed to a hearing using only witnesses who are FDA employees, FDA believes that the
use of independent outside experts may be warranted depending on the issues identified for
hearing.
Timeline for Hearings
17.
As discussed above, to the extent that drug sponsors request and are granted
hearings, the subsequent schedule will be largely controlled by the ALJ, and it is impossible to
predict with certainty or confidence how long the hearings would take. However, based upon
prior experience with other hearings to withdraw approval of new animal drug applications, most
recently emofloxacin in poultry, CVM's estimate of the time and personnel needed for the
hearing is as follows.
7
18.
First, following the publication of revised NOOHs, drug sponsors would be given
30 days to respond and request hearings. See 21 C.F.R. § 12.22(b)(l); 21 C.F.R.
§ 514.200(a)(I). As part of their submissions, the sponsors would be required to submit specific
data and information to support the continued approval of their products. 21 C.F.R.
§ 514.200(c).
19.
Second, any requests for hearings would need to be reviewed carefully by the
Agency. We would expect such review to take approximately 90 days, and CVM estimates that
it would involve from between nine and thirteen Agency employees (2 from CVM's Office of
the Director, 3 to 5 from CVM's Office of Research, 3 to 5 from CVM' s Office of New Animal
Drug Evaluation, and 1 from the Office of Chief Counsel).
20.
Third, a team of four Agency employees (2 from CVM, 1 from the Office of
Chief Counsel, and 1 from the Office of Foods) would need approximately 60 days to develop a
recommendation to the Commissioner on whether to grant a hearing, or instead grant summary
determination in favor of CVM (i. e., withdrawing the drugs without a hearing).
21.
Fourth, if the Commissioner does not grant summary determinations in favor of
CVM, the Commissioner would decide which disputed issues need to be resolved through a
hearing and, as required by 21 C.F.R. § 12.35, publish a Federal Register notice announcing
hearings and describing the issues in dispute. We anticipate this would occur within
approximately 60 days from the recommendation to the Commissioner on whether to grant a
hearing. In sum, we anticipate that a notice of hearing in the Federal Register would be
published approximately 8 months after the publication of the NOOHs.
22.
Although the Commissioner has the authority to serve as the presiding officer at a
withdrawal hearing, the Commissioner has historically designated an ALJ as the hearing officer.
8
See 21 C.F.R. § 12.60. Once designated, the ALI would have substantial control over the timing
and nature of the remaining proceedings, and scheduling issues would be largely left to his or her
discretion. 21 C.F.R. § 12.70.
23.
Based on prior experience in the recent withdrawal of enrofloxacin for use in
poultry, CVM estimates a hearing schedule as follows. This estimate is for one hearing, and
assumes that it would involve a limited number of sponsors. If a significant number of sponsors
request hearings, or if two or more separate hearings are required to be held, substantially more
time and personnel may be required to complete the hearings. Also, this projection assumes that
approximately 11 to 15 Agency employees will be substantially committed to supporting the
Withdrawal Proceedings.
•
Submission ofInformation by CVM CVM must submit relevant documents to the
docket, along with a statement on the factual issues in the Notice of Hearing and the
type of supporting evidence the Center Director intends to introduce at the hearing.
21 C.F.R. § 12.85(a) This information must be submitted before publication of the
Notice of Hearing.
•
Notice ofParticipation. Notices of participation would need to be filed within 30
days after publication of the Notice of Hearing.
•
Motions to ModifY Issues for Hearing. Motions to modify the issues for hearing
would be due approximately three weeks after the Notices of Participation are filed.
Responses to such motions would be due approximately one week later.
•
Sponsors/Review by CVM Drug sponsors normally have 60 days to submit materials
that they intend to rely upon at the hearing. 21 C.F.R. § 12.85(b).
•
Exchange of Witness Lists, Curriculum Vitae, and Prior Written Statements by All
Experts on Witness List. Although 21 C.F.R. § 12.92 anticipates that participants in a
hearing will bring their witness lists (along with CV s and prior written statements) to
the prehearing conference, in practice, the ALI may set a schedule that allows CVM
and the other hearing participants to exchange witness lists, CV s, and all prior written
statements by any of the proposed witnesses after the prehearing conference, or the
ALJ may issue a scheduling order without having a prehearing conference. CVM
anticipates the participants would have to exchange witness lists, CV s and prior
9
written statements approximately 30 days after the sponsor submits materials they
intend to rely on at the hearing.
•
Objections to Witness Lists Based on Qualifications. Objections would be due
approximately 30 days after witness lists are exchanged.
•
Discovery. Discovery, which could include, e.g., written interrogatories and requests
for admissions, would begin after witness lists are exchanged and would take
approximately 90 days to conduct.
•
Exchange 0/Proposed Stipulations. An exchange of proposed stipulations would
take place approximately 10 days after the completion of discovery.
•
Joint Stipulations. Joint stipulations would be due approximately 7 days after the
exchange of Proposed Stipulations.
•
Submission a/Written Testimony and Exhibits. Written testimony and exhibits would
be due approximately 90 days after submission of Joint Stipulations.
•
Motions to Strike Testimony and Exhibits and Permission to Conduct CrossExamination. Motions to Strike Testimony and Exhibits and Permission to Conduct
Cross-Examination would be due approximately 45 days after submission of written
testimony and exhibits.
•
Responses to Motions to Strike Testimony/Exhibits and Permission to Conduct CrossExamination. Responses to Motions to Strike TestimonylExhibits and Permission to
Conduct Cross-Examination would be due approximately 14 days after the Motions
to Strike and Motions to Conduct Cross-Examination are submitted.
•
Submission 0/ Proposed Findings 0/ Facts and Conclusions 0/Law. Proposed
Findings of Fact, with record references, would be due approximately 30 to 45 days
after the Responses to Motions to Strike TestimonylExhibits and Permission to
Conduct Cross-Examination are submitted.
•
Submission a/Critiques a/Other Parties' Proposed Findings o/Fact. Critiques of
each party' s Proposed Findings of Fact would be due approximately 30 days after the
Proposed Findings were submitted.
•
Cross-Examination a/Witnesses. Cross-examination of witnesses during a public
hearing would take place as scheduled by the ALJ.
•
Submission 0/ Briefs. The ALJ will set a schedule for the filing of briefs promptly
after the taking of evidence is completed. Ordinarily, briefs are to be filed within 45
days of the close of the hearing. 21 C.F.R. § 12.96(a).
10
24.
Following the completion of post-hearing briefing, the ALJ's initial decision
would not likely occur in less than 6 months. The initial decision becomes the final decision of
the Commissioner by operation of law unless a participant files exceptions with the Division of
Dockets Management under 21 C.F.R. § 12.125(a) or the Commissioner files a notice of review
under 21 C.F.R. § 12.125(f). See 21 C.F.R. § 12.120(e). In the event the Commissioner reviews
the initial decision, we would expect a final decision within 6 to 12 months after the ALJ issues
his or her decision.
25.
Altogether, the hearing process described above would take approximately 41
months in total. As discussed above, it is impossible to predict exactly how long the hearing
process will take. Hearings could take more or less time, depending on factors that are largely
out of CVM' s control. Assuming the 41-month projection bears out, and if, for instance, CVM
were to begin the process ofre-issuing the NOOHs on June 1,2012, CVM's best estimate is that,
if a hearing is requested and granted, and if an initial ALJ decision is appealed to the
Commissioner, the withdrawal process would not be completed until between June, 2017, and
December, 2017. This projection assumes, as discussed above, that the NOOHs will take
approximately 11 to 17 months to republish (see
~
16), and that a notice of hearing would be
published in the Federal Register about 8 months after the NOOHs are published (see
~
21). This
projection does not account for any post-hearing appeals to the federal courts. The NOOH
Products would remain on the market pending a final decision of the Commissioner.
The Diversion of Resources From Other Programs
26.
As discussed above, CVM estimates that the Withdrawal Proceedings will require
the efforts of over a dozen of FDA employees and take a minimum of five and one half years to
11
complete. This will inevitably drain resources from other FDA and CVM programs. CVM has
not determined yet precisely how it would reallocate resources in order to hold the hearings, but
resources will be diverted from certain important CVM programs because of the Withdrawal
Proceedings. For instance, CVM's Office of Research ("OR") employees who would need to be
involved in hearing activities work on other important efforts to combat antimicrobial resistance,
such as the National Antimicrobial Resistance Monitoring System ("NARMS"). NARMS is a
national public health surveillance system that tracks antibiotic resistance in foodborne bacteria.
The NARMS program was established in 1996 as a partnership between FDA, the Centers for
Disease Control and Prevention ("CDC"), and the U.S. Department of Agriculture. The primary
objectives ofNARMS are to monitor trends in antimicrobial resistance among foodborne
bacteria from humans, retail meats, and animals; to disseminate timely information on
antimicrobial resistance to promote interventions that reduce resistance among foodborne
bacteria; to conduct research to better understand the emergence, persistence, and spread of
antimicrobial resistance; and to assist the FDA in making decisions related to the approval of
safe and effective antimicrobial drugs for animals.
27.
Likewise, the Office of New Animal Drug Evaluation would be required to
dedicate substantial resources to the Withdrawal Proceedings, which could delay CVM's review
of pending new animal drug applications. Slowed animal drug application reviews would
inevitably delay the approval of important new drug therapies for animals that are currently
under review by the Agency.
28.
In particular, CVM is concerned that the commitment of resources to Withdrawal
Proceedings will detract from FDA's ability to work with drug sponsors that choose to withdraw
their growth promotion claims in accordance with the principles set out in Guidance for Industry
12
(GFI) #209. CVM expects that some drug sponsors, in connection with withdrawing their
approvals for growth promotion indications, will seek approvals for legitimate new therapeutic
indications at the same time. The review of such new applications is expected to require a
substantial amount of effort from the CVM scientists who specialize in microbial food safety. If
the review of new NADAs is delayed because CVM personnel are committed to working on
Withdrawal Proceedings, CVM is concerned that drug sponsors' willingness to engage in the
voluntary process described in GFI #209 and draft GFI #213 will be diminished.
29.
Furthermore, it is important that any schedule for the Withdrawal Proceedings, if
one is imposed at all, be flexible enough that CVM can respond to public health and animal
health crises as they may arise. As an example, FDA is currently monitoring a recall by
Diamond Pet Food of several brands of dry pet food formulas due to Salmonella contamination.
The recall affects products distributed in mUltiple states, Puerto Rico, and Canada. As of May
11, 2012, CDC reports 15 human illnesses linked to this pet food, 5 of which required
hospitalization. Other emerging issues may also need to be investigated and addressed during
the pendency of the Withdrawal Proceedings. For example, in 2007, there was an extensive pet
food recall involving melamine and cyanuric acid-contaminated wheat and rice gluten in pet
food. Beginning in mid-March 2007, with the report of the deaths of dogs and cats, 60 million
individual packages of pet food from approximately 100 companies were recalled. Veterinarians,
toxicologists, pathologists, chemists, and other scientists from CVM and other parts of the
Agency collaborated to identify the source of the contamination and the cause of animal deaths,
and in 2008, CVM' s Office of Research developed a method to detect the melamine and related
analogs in animal feed and in tissues of animals produced for human consumption. This method
was quickly adapted to the testing for these substances in milk and infant formula.
13
Pursuant to 28 U.S.C. § 1746, I declare under penalty ofpeIjury that the foregoing is true
and correct.
11I/'--f_!_~_--->'
__
Executed on _ _ _
2012, in Rockville, Maryland.
wJ1!i:X?1:=
Deputy Director for Science Policy
Center for Veterinary Medicine
United States Food and Drug Administration
14
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