Natural Resources Defense Council, Inc. et al v. United States Food and Drug Administration et al

Filing 59

DECLARATION of Mitchell S. Bernard in Support re: 56 MOTION for Summary Judgment on Plaintiffs Third Claim for Relief.. Document filed by Center For Science In The Public Interest, Food Animal Concerns Trust, Natural Resources Defense Council, Inc., Public Citizen, Inc., Union Of Concerned Scientists, Inc.. (Attachments: # 1 Exhibit A, # 2 Exhibit B, # 3 Exhibit C, # 4 Exhibit D, # 5 Exhibit E)(Bernard, Mitchell)

EXHIBIT A
TO THE DECLARATION OF MITCHELL S. BERNARD

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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NOV 7 2011

Food and Drug Administration
Rockville MD 20857

Ms. Sarah Klein, Esq.
Food Safety Program
Center for Science in the Public Interest
1875 Connecticut Avenue, NW
Suite 300
Washington, DC 20009
Re: Original Docket No. 99P-0485/CP
New Docket No. FDA-1999-P-1286
Dear Ms. Klein:
This is the final response from the Food and Drug Administration ("FDA" or the
"Agency") to Citizen Petition (Original Docket No. 99P-0485/CP; New Docket No.
FDA-1999-P-1286) submitted on March 9, 1999, on behalf of the Center for Science in
the Public Interest, Environmental Defense Fund, Food Animal Concerns Trust, Public
Citizen’s Health Research Group, and Union of Concerned Scientists. Your petition
requests that FDA rescind already-approved subtherapeutic uses of medically important
antibiotics in livestock feed. The petition alleges the drugs are unsafe under the Federal
Food, Drug, and Cosmetic Act ("FD&C Act") when used for subtherapeutic purposes in
animal agriculture because such use can drive the selection and transfer of antibiotic
resistance in human pathogens, thereby compromising the effectiveness of antibiotics for
treating infections in humans.
FDA’s Center for Veterinary Medicine ("Center" or "CVM") has already issued two
tentative responses to this Citizen Petition. CVM’ s first tentative response, dated August
19, 1999, explained that due to the complex nature of the action requested, FDA needed
additional time to issue a final response. On February 28, 2001, CVM issued a second
tentative response explaining that comments had been received from more than 38,000
people concerning the petition and that the comments and other relevant data and
information needed to be evaluated by the Agency before action would be taken. The
letter further stated that a final response granting or denying the petition would not be
issued until FDA makes a decision about whether to withdraw the drug approvals listed
in the petition.
We have reviewed the issues raised in your petition. Although we share your concern
about the use of medically important antimicrobial drugs in food-producing animals for
growth promotion and feed efficiency indications (i.e., production uses), in accordance
with 21 CFR 10.30(e)(1)(ii), FDA is denying your petition. The reasons for this decision
1

We understand that petitioners use the term "subtherapeutic uses" to include growth promotion, improved
feed efficiency, and disease prevention indications. However, FDA does not generally consider disease
prevention to be a subtherapeutic use. See FDA’s draft guidance entitled, "The Judicious Use of Medically
Important Antimicrobial Drugs in Food-Producing Animals," draft Guidance for Industry 9209, at 16.

are discussed below.
In your citizen petition, you call upon this Agency to withdraw "subtherapeutic uses" of
certain antibiotics in livestock feed. Specifically, the petition requests the FDA
Commissioner to "rescind approvals for subtherapeutic uses in livestock of any antibiotic
used in (or related to those used in) human medicine" (footnote omitted). 2 The petition
further states that the Agency "should take action now to rescind approvals for
subtherapeutic uses in livestock of any antibiotic used in (or related to those used in)
human medicine." It is not entirely clear to us whether the action you are requesting is
for the FDA Commissioner to issue an order now withdrawing approval or whether you
instead are asking that formal withdrawal proceedings be initiated. Because it is unclear
which of these two alternative interpretations is intended, we will address them both.
ISSUANCE OF WITHDRAWAL ORDER
To the extent the petition is seeking the immediate issuance by the FDA Commissioner of
an order withdrawing the approvals of subtherapeutic uses of medically important
antimicrobials in livestock feed, we must deny your petition because there is a formal
evidentiary process that must be followed before new animal drug approvals may be
withdrawn. In order to withdraw a new animal drug’s approval, FDA must follow a
number of statutory requirements, such as providing the sponsor of the new animal drug
with notice that the Agency proposes to withdraw approval of the drug and an
opportunity for a formal evidentiary hearing on the matter. FDA cannot withdraw
approval of a new animal drug until the legally-mandated process is complete.
Prior to initiating formal proceedings to withdraw approval of a new animal drug, CVM
makes a determination about whether such action is warranted after analyzing the
relevant data and information. The Center’s determination about whether to initiate
action to withdraw approval of a new animal drug is primarily an internal process,
although participation by drug sponsors and the public may be requested. This process
may include, among other things, an in-depth review and evaluation of available data and
information related to the particular drug, collection of additional data if needed, and in
some instances a risk assessment. This process will be used to determine whether
statutory grounds may exist to support a withdrawal action. If the Center concludes that
grounds exist to withdraw a new animal drug approval, before moving forward to
withdraw under section 5 12(e) of the FD&C Act, FDA must provide the drug’s sponsor
with notice and an opportunity for a formal administrative hearing ("NO OH").
Issuance of NOOHs and requests for a hearing are governed by the federal regulations
dealing with formal evidentiary hearings. A sponsor who requests a formal hearing is
required to submit detailed data to justify the request. The sponsor’s request and
supporting documentation will be reviewed and, if the Commissioner determines that a
hearing is justified, the Commissioner will issue a notice of hearing. If the Commissioner
2

The petition also states that the "ban should include subtherapeutic applications of such medically
important antibiotics as penicillin, tetracyclines, erythromycin, lincomycin, tylosin, and virginiamycin, as
well as other antibiotics used in (or related to those used in) human medicine for growth promotion,
improved feed efficiency, and disease prevention."

2

grants a hearing, a formal evidentiary hearing is held. Generally, the Commissioner will
appoint a presiding officer to conduct the hearing and render an initial decision, which
can be appealed to the Commissioner. An order withdrawing the approval of a new
animal drug will issue only after this process is completed and the Commissioner has
found that the cited grounds for withdrawing the drug have been demonstrated. Because
no hearings have been held with respect to the animal drugs at issue in the Citizen
Petition, and because the Commissioner has not made any final determination about
whether grounds for withdrawal under section 5 12(e) of the FD&C Act have been
satisfied, the relief requested in the Citizen Petition cannot be granted at this time. 3
INITIATION OF WITHDRAWAL PROCEEDINGS
If petitioners are asking FDA to immediately institute formal withdrawal proceedings, we
deny your request. As discussed below, for various reasons the Agency has decided not
to institute formal withdrawal proceedings at this time and instead is currently pursuing
other alternatives to address the issue of antimicrobial resistance related to the production
use of antimicrobials in animal agriculture.
The Agency’s experience with contested, formal withdrawal proceedings is that the
process can consume extensive periods of time and Agency resources. For example, the
first NOOHs for withdrawal of nitrofuran approvals were issued in 1971, but the final
rule withdrawing the approvals was not issued until 1991. Withdrawal of
diethylstilbestrol (DES) approvals became final in 1979, seven years after issuance of an
NOOH. More recently, the withdrawal of approved uses of enrofloxacin in poultry took
almost five years and cost FDA approximately $3.3 million.
Recognizing that the process of reviewing safety information for antimicrobial drugs
approved before 2003, and pursuing withdrawal proceedings in some cases, would take
many years and would impose significant resource demands on the Agency, in June
2010, FDA proposed a different strategy to promote the judicious use of medically
important antimicrobials in food-producing animals in a draft guidance entitled, "The
Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals"
draft Guidance for Industry #209 ("draft GFT 9209"). Generally speaking, judicious uses
would be those uses that are appropriate and necessary to maintaining the health of
humans and animals.
Draft GFI #209 proposes two principles aimed at ensuring the judicious use of medically
important antimicrobials in food-producing animals. The first principle set out in the
draft guidance is that the use of medically important antimicrobial drugs in foodproducing animals should be limited to those uses that are considered necessary for
assuring animal health. As set out in the draft guidance, FDA does not consider
production uses of such drugs to be necessary for assuring animal health because, unlike
other uses, production uses are not directed at any specifically identified disease but
Although the Agency did publish two Notices for Opportunity for a Hearing in 1977 on proposals to
withdraw approvals of the new animal drug applications for all uses of penicillin and some uses of
tetracyclines in animal feed, no hearings were held on these proposals and no final findings were made by
the Commissioner.

rather are expressly indicated and used for the purpose of enhancing the production of
animal-derived products (e.g., promoting faster weight gain or improving feed
efficiency). The second principle set out in the draft guidance is that the use of medically
important antimicrobial drugs in food-producing animals should be limited to those uses
that include veterinary oversight or consultation. This principle speaks to the need for the
scientific and clinical training of licensed veterinarians in assuring that medically
important antimicrobials are used in a judicious manner.
Based on feedback this Agency has received following the issuance of draft GFI #209,
FDA believes that the animal pharmaceutical industry is generally responsive to the
prospect of working cooperatively with the Agency to implement the principles
recommended in draft GFI #209. FDA intends to work with sponsors who approach
FDA and are interested in working cooperatively with the Agency to phase out
production uses of medically important antimicrobials and to transition medically
important antimicrobials currently approved for over-the-counter use in food-producing
animals to a marketing status that involves veterinary oversight (i.e., veterinary feed
directive ("VFD") status for feed use drugs and prescription status for drugs approved for
use through other routes of administration).
As part of the proposed strategy, FDA issued an advance notice of proposed rulemaking
("ANPRM") in March 2010 to seek public comment on whether and to what extent
efficiency improvements should be made to the current VFD process as set forth in
FDA’s regulation at 21 CFR 558.6. FDA received numerous public comments in
response to the ANPRM and is taking those comments into consideration in drafting a
revised rule.
FDA believes that the strategy set out in draft guidance #209 is a pathway to achieving
the same goals as those advocated by your organization, i.e., judicious use of medicallyimportant antimicrobials. Additionally, given the considerable amount of Agency
resources that are required to pursue withdrawal proceedings, we believe the current
proposed approach will accomplish these goals in a more timely and resource-efficient
manner than would otherwise be the case. Moreover, this strategy does not foreclose
initiating withdrawal proceedings in the future.
CONCLUSION

For the foregoing reasons, FDA denies your petition. FDA is committed to working with
animal drug sponsors, the veterinary and public health communities, the animal
agriculture community, and all other interested stakeholders in developing a strategy to
address antimicrobial resistance concerns in a manner that is protective of both human
and animal health.

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Acting Assistant Commissioner for Policy
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