[Federal Register Volume 76, Number 246 (Thursday, December 22, 2011)]
[Notices]
[Pages 79697-79701]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-32775]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-1977-N-0019 (formerly 1977N-0230), FDA-1977-N-0014 
(formerly 977N-0231), FDA-1977-N-0022 (formerly 1977N-0316), and FDA-
1977-N-0224 (formerly 1977N-0317)]


Withdrawal of Notices of Opportunity for a Hearing; Penicillin 
and Tetracycline Used in Animal Feed

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
withdrawing two 1977 notices of opportunity for a hearing (NOOH), which 
proposed to withdraw certain approved uses of penicillin and 
tetracyclines intended for use in feeds for food-producing animals 
based in part on microbial food safety concerns.\1\ (Refs. 1 and 2) FDA 
is taking this action, and closing the corresponding dockets, because: 
FDA is engaging in other ongoing regulatory strategies developed since 
the publication of the 1977 NOOHs with respect to addressing microbial 
food safety issues; FDA would update the NOOHs to reflect current data, 
information, and policies if, in the future, it decides to move forward 
with withdrawal of the approved uses of the new animal drugs described 
in the NOOHs; and FDA would need to prioritize any withdrawal 
proceedings (for example, take into account which withdrawal(s) would 
likely have the most significant impact on the public health) if, in 
the future, it decides to seek withdrawal of the approved uses of any 
new animal drug or class of drugs. FDA is also withdrawing the 
companion proposed rules to these NOOHs. (Refs. 3 and 4)
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    \1\ FDA's approval to withdraw the approved uses of the drugs 
was based on three statutory grounds: (1) The drugs are not shown to 
be safe (21 U.S.C. 360b(e)(1)(B)); (2) lack of substantial evidence 
of effectiveness (21 U.S.C. 360b(e)(1)(C)); and (3) failure to 
submit required reports (21 U.S.C. 360b(e)(2)(A)).

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DATES: This notice is effective December 22, 2011.

ADDRESSES: Submit electronic comments to http://www.regulations.gov. 
Submit written comments to the Division of Dockets Management (HFV-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: William Flynn, Center for Veterinary 
Medicine (HFV-1), Food and Drug Administration, 7519 Standish Pl., 
Rockville, MD 20855, (240) 276-9000, email: [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Questions regarding the use of antimicrobial drugs in food-
producing animals have been raised and debated for many years. (Ref. 5) 
\2\ Following a report that was issued by the British government in 
1969 on the use of antibiotics in veterinary medicine and animal 
husbandry, known as the ``Swann Report,'' the Commissioner of Food and 
Drugs established a task force to review the use of antibiotic drugs in 
animal feeds. The task force, established in 1970, included specialists 
on infectious diseases and animal science from FDA, the National 
Institutes of Health, the U.S. Department of Agriculture, and the 
Centers for Disease Control and Prevention, as well as representatives 
from universities and industry. The task force identified three primary 
areas of concern (human health hazard, animal health hazard, and 
antibiotic effectiveness) and guidelines were established to show 
whether the use of any antibiotic or antibacterial agent in animal feed 
presents a hazard to human and animal health. (Refs. 1 and 6) The task 
force also made certain recommendations concerning restrictions on the 
use of antibiotic drugs in animal feeds at growth promotion and 
subtherapeutic levels. (Ref. 6)
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    \2\ The term ``antimicrobial'' refers broadly to drugs with 
activity against a variety of microorganisms including: Bacteria, 
viruses, fungi, and parasites. Antimicrobial drugs that have 
specific activity against bacteria are referred to as antibacterial 
or antibiotic drugs. However, the broader term ``antimicrobial,'' 
commonly used in reference to drugs with activity against bacteria, 
is used in this document interchangeably with the terms 
antibacterial or antibiotic. Antimicrobial resistance is the ability 
of bacteria or other microbes to resist the effects of a drug. 
Antimicrobial resistance, as it relates to bacterial organisms, 
occurs when bacteria change in some way that reduces or eliminates 
the effectiveness of drugs, chemicals, or other agents designed to 
treat bacterial infections. (Ref. 5)
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    In 1972, FDA published the conclusions and recommendations of that 
task force and proposed to require sponsors to submit specific data for 
antibiotic drugs in animal feeds intended for subtherapeutic or growth 
promotion use when such drugs are also used in human clinical medicine. 
(Ref. 6) In 1973, FDA finalized this proposal in 21 CFR 135.109 (re-
codified at 21 CFR 558.15 in 1974).\3\ (Refs. 7, 8, and 9) This section 
provided that FDA would propose to revoke approved uses in animal feed 
of antibiotic and sulfonamide drugs unless certain data were submitted 
which satisfactorily addressed the outstanding safety and effectiveness 
issues.
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    \3\ Since that time, portions of 21 CFR 558.15 have been removed 
because those portions of the regulation were determined to be 
redundant or obsolete. (See 75 FR 16001, March 31, 2010.)
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    By 1974, FDA had begun to review the data submitted by the sponsors 
of the antibiotic products and requested that the National Advisory 
Food and Drug Committee (NAFDC) review the data and make 
recommendations on the subtherapeutic uses of penicillin and 
tetracyclines. A subcommittee (the Antibiotics in Animal Feeds 
subcommittee) was appointed to work in conjunction with expert 
consultants to address these issues. With respect to the penicillin-
containing drugs, the subcommittee recommended FDA immediately withdraw 
approval of the subtherapeutic uses of penicillin. The

[[Page 79698]]

NAFDC accepted the subcommittee's recommendation and recommended to FDA 
that it ``immediately withdraw approval for the subtherapeutic uses of 
penicillin, i.e., growth promotion/feed efficiency, and disease 
control.'' \4\ (Ref. 1) FDA accepted these recommendations. (Ref. 1)
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    \4\ Generally, FDA no longer considers disease control or 
prevention to be subtherapeutic uses.
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    With respect to the tetracycline-containing drugs, the subcommittee 
recommended that FDA: (1) Discontinue use for growth promotion and/or 
feed efficiency in all animal species for which effective substitutes 
are available; (2) permit their use for disease control where effective 
alternate drugs are unavailable; and (3) control the distribution of 
the tetracyclines to restrict their use. NAFDC did not accept the 
subcommittee's first two recommendations, and instead recommended that 
FDA make no changes in the permitted use of chlortetracycline and 
oxytetracycline in animal feed. (Ref. 2) The NAFDC did adopt the 
subcommittee's third recommendation that the addition of the 
tetracycline in feeds be restricted. (Ref. 2) FDA considered these 
recommendations and decided to propose withdrawal of approval of 
subtherapeutic uses of tetracyclines in animal feeds except for those 
conditions of use for which there are no safe and effective 
substitutes. (Ref. 2)
    This process culminated in the 1977 publication of two NOOHs in the 
Federal Register on proposals by the Bureau of Veterinary Medicine (now 
Center for Veterinary Medicine) to withdraw all uses of penicillin in 
animal feed, and all subtherapeutic uses of tetracycline in animal feed 
except for: (1) Oxytetracyline, as an aid in the control of fowl 
cholera caused by Pasteurella multocida in chickens and infectious 
synovitis caused by Mycoplama synoviae in chickens and turkeys; and (2) 
chlortetracycline (a) as an aid in the maintenance of weight gains in 
the presence of respiratory diseases, such as shipping fever, in 
combination with sulfamethazine in beef cattle, (b) as an aid in the 
control of infectious synovitis caused by M. pasteurella in chickens 
and turkeys, (c) for the control of active infections of anaplasmosis 
in beef cattle, and (d) as an aid in reducing the incidence of 
virbrionic abortion in breeding sheep. (Ref. 1 and 2) \5\ These NOOHs 
were published on August 30, 1977 (penicillin) and October 21, 1977 
(tetracycline).
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    \5\ These matters were assigned Docket Numbers 77N-0230 and 77N-
0316, respectively. Since the original dockets were opened, FDA 
started using a different numbering convention. Docket Number 77N-
0230 is now Docket Number FDA-1977-N-0019, and Docket Number 77N-
0316 is now Docket Number FDA-1977-N-0022.
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    At the same time, FDA also published two companion proposed rules 
proposing to amend the regulations to delete those provisions 
referencing the approved penicillin and tetracycline uses that would be 
affected by a withdrawal. (Refs. 3 and 4) FDA did not withdraw any 
approved use of penicillin or tetracyclines intended for use in feeds 
for food-producing animals as a result of these NOOHs, or finalize the 
proposed companion rules, and some new animal drug approvals for the 
use of these new animal drugs in feeds for food-producing animals 
remain in effect.
    Although FDA initially granted some hearing requests to provide 
sponsors with the opportunity to present evidence on the safety of the 
NOOH products, Congress intervened before any hearing was held, 
directing FDA to hold in abeyance the implementation of its proposed 
withdrawal actions pending the outcome of further research related to 
the use of antibiotics in animal feed. (Refs. 10, 11, and 12)

II. Discussion

    At this time, FDA is withdrawing the 1977 NOOHs because: (1) FDA is 
engaging in other ongoing regulatory strategies developed since the 
publication of the 1977 NOOHs with respect to addressing microbial food 
safety issues; (2) FDA would update the NOOHs to reflect current data, 
information, and policies if, in the future, it decides to move forward 
with withdrawal of the approved uses of the new animal drugs described 
in the NOOHs; and (3) FDA would need to prioritize any withdrawal 
proceedings (for example, take into account which withdrawal(s) would 
likely have the most significant impact on the public health) if, in 
the future, it decides to seek withdrawal of the approved uses of any 
new animal drug or class of drugs.
    Although FDA is withdrawing the 1977 NOOHs, FDA remains concerned 
about the issue of antimicrobial resistance. Today's action should not 
be interpreted as a sign that FDA no longer has safety concerns or that 
FDA will not consider re-proposing withdrawal proceedings in the 
future, if necessary. FDA has not ruled out the prospect of future 
regulatory action, either with respect to the antimicrobial new animal 
drugs covered by the 1977 NOOHs or any others. However, as discussed 
further in this document, FDA intends to focus its efforts for now on 
the potential for voluntary reform and the promotion of the judicious 
use of antimicrobials in the interest of public health. Importantly, 
this strategy leaves open the possibility of pursuing withdrawal 
proceedings at a later time if FDA's proposed strategy does not yield 
satisfactory results.

1. FDA Is Engaging in Other Ongoing Regulatory Strategies Developed 
Since the Publication of the 1977 NOOHs With Respect to Addressing 
Microbial Food Safety Issues

    Since the 1977 NOOHs published, FDA has continued to investigate 
the safety concerns associated with subtherapeutic uses of antibiotics 
intended for use in feeds for food-producing animals. As mentioned 
previously, Congress directed FDA to hold proceedings with respect to 
the 1977 NOOHs in abeyance and instead to conduct more research on the 
issues in question. (Ref. 10, 11, and 12) In response, FDA contracted 
with the National Academy of Sciences (NAS) to conduct a study of the 
safety issues related to the use of antibiotics in animal feed. (Refs. 
5 and 13) In particular, FDA asked the NAS to: (1) Study the human 
health effects of the subtherapeutic use of penicillin and tetracycline 
in animal feed; (2) review and analyze published and unpublished 
epidemiological and other data necessary to assess human health 
consequences of such use; (3) assess the scientific feasibility of 
additional epidemiological studies; and (4) make recommendations about 
additional research needed. (Refs. 5 and 9)
    The NAS issued its report in 1980, concluding that a very limited 
amount of epidemiological research had been completed on either the 
subtherapeutic or therapeutic use of antimicrobials in animal feeds and 
that existing data could neither prove nor disprove the postulated 
hazards to human health from subtherapeutic antimicrobial use in animal 
feed. (Refs. 5 and 9) The report stated that ``[t]he lack of data 
linking human illness with subtherapeutic levels of antimicrobials must 
not be equated with proof that the proposed hazards do not exist. The 
research necessary to establish and measure a definitive risk has not 
been conducted and, indeed, may not be possible.'' (Refs. 5 and 13)
    In 1984, FDA contracted with the Seattle-King County Health 
Department to complete a study intended to provide additional 
information regarding potential public health concerns regarding the 
use of antimicrobial drugs in animal feed. The study focused on

[[Page 79699]]

the relationship between the occurrence of Salmonella spp. (Salmonella) 
and Campylobacter jejuni (C. jejuni) in foods of animal origin and the 
occurrence of human illness caused by those two organisms. The study 
report indicated that the bacteria obtained from human cases and those 
obtained from retail poultry had similar antibiotic susceptibility 
patterns, including similar levels of resistance to tetracycline. 
(Refs. 5 and 14)
    In 1987, FDA asked the Institute of Medicine to conduct an 
independent review of the human health risks associated with the 
subtherapeutic uses of penicillin and tetracycline in animal feed. 
(Refs. 5 and 15) The IOM established a committee which developed a 
risk-analysis model using data on Salmonella infections that resulted 
in human death. (Refs. 5 and 15) The Committee did not find a 
substantial body of direct evidence establishing conclusively the 
presence of a human health hazard resulting from the use of 
subtherapeutic concentrations of penicillin and the tetracyclines in 
animal feeds. (Refs. 5 and 15) Nonetheless, the Committee found a 
considerable body of indirect evidence implicating both the 
subtherapeutic and therapeutic use of antimicrobials as a potential 
human health hazard, and made recommendations for further study of the 
issue.\6\ (Refs. 5 and 15)
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    \6\ FDA's draft guidance titled ``The Judicious Use of Medically 
Important Antimicrobial Drugs in Food-Producing Animals'' (Draft GFI 
209) contains information on additional key studies 
relevant to this issue. For example, in 1997, the World Health 
Organization (WHO) issued a report which concluded that all uses of 
antimicrobials lead to the selection of resistant forms of bacteria 
and that ``low-level, long-term exposure to antimicrobials may have 
greater selective potential than short-term, full-dose therapeutic 
use.'' (Ref. 17) The WHO report contained several recommendations, 
including a recommendation that the use of antimicrobial drugs for 
growth promotion in animals be terminated if these drugs are also 
prescribed for use as anti-infective agents in human medicine or if 
they are known to induce cross-resistance to antimicrobials used for 
human medical therapy. (Ref. 17) It also recommended that national 
practices of antimicrobial use in animals be reviewed, and policies 
be developed to reduce the risks of selection and dissemination of 
antimicrobial resistance. (Ref. 17) Further, in 1999 the National 
Research Council issued a report that, among other things, 
recommended that further development and use of antibiotics in both 
human and animal medicine have oversight by an interdisciplinary 
panel of experts. (Ref. 18)
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    During the 1990's, FDA continued to investigate the potential risks 
associated with the use of antibiotic drugs intended for use in feeds 
for food-producing animals and how to mitigate risks associated with 
such use. In 1999, FDA published a concept paper titled, ``Proposed 
Framework For Evaluating and Assuring the Human Safety of the Microbial 
Effects of Antimicrobial New Animal Drugs Intended for Use in Food-
Producing Animals'' (``Framework Document''). (Ref. 19) Among other 
things, the Framework Document called for revisions to the pre-approval 
safety assessment for antimicrobial new animal drugs, and the 
categorization of antimicrobial drugs based on their importance to 
human medicine. (Ref. 19)
    In 2003, FDA published a final guidance for industry (GFI 
152), outlining an approach for conducting a qualitative risk 
assessment to evaluate human food safety with respect to the potential 
microbiological effects of antimicrobial new animal drugs on food-borne 
bacteria of human health concern. (Ref. 20) The importance of a drug 
for human medical therapy is a key factor to be considered in the 
evaluation. (Ref. 20) Since 2003, FDA has applied the principles 
contained in GFI 152 when assessing antimicrobial resistance 
risks for antimicrobial drugs as part of the new animal drug approval 
process. In some cases, this has had the effect of limiting the claims 
for which such drugs are approved while still protecting animal and 
human health.
    Recognizing that already-approved antimicrobial new animal drugs 
also have antimicrobial resistance risks associated with their use, FDA 
began to look at the safety of some of these already approved drugs. 
However, because the process of reviewing safety information for 
antimicrobial drugs approved before 2003 (and pursuing withdrawal 
proceedings if appropriate in some cases) would take many years and 
would impose significant resource demands on the Agency, FDA began 
thinking about alternate approaches to address safety concerns. As a 
result, 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 for industry titled ``The Judicious Use of 
Medically Important Antimicrobial Drugs in Food-Producing Animals'' 
(draft GFI 209). (Ref. 5) 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 described in the draft guidance 
is that the use of medically important antimicrobial drugs in food-
producing animals should be limited to those uses that are considered 
necessary for assuring animal health. (Ref. 5) 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 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). (Ref. 5) 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. (Ref. 5) This principle speaks to the need for the 
scientific and clinical training of licensed veterinarians to assure 
that medically important antimicrobials are used in a judicious manner.
    Based on feedback the Agency 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 accomplish 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 achieve an orderly transition of 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) on March 29, 2010 (75 FR 15387), 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. (Ref. 21) FDA received numerous public 
comments in response to the ANPRM and is taking those comments into 
account in considering possible revisions to this regulation.
    FDA believes that the strategy set out in draft GFI 209 
represents another pathway to achieving the same goals contemplated by 
the 1977 NOOHs, i.e., the judicious use of medically important 
antimicrobial drugs. FDA believes that by implementing this strategy 
and proceeding in part under the statutory authority provided under the 
Animal

[[Page 79700]]

Drug Availability Act of 1996 (ADAA) \7\ to designate drugs as VFD 
drugs (authority which was not available in 1977), it will achieve its 
goal of promoting the judicious use of antimicrobial drugs in a more 
timely and resource-efficient manner than could be accomplished 
otherwise.\8\
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    \7\ ADAA (Pub. L. 104-250), which was signed into law on October 
9, 1996, introduced several amendments to the Federal Food, Drug, 
and Cosmetic Act that provided FDA with more flexibility in how it 
regulates animal drugs and animal feeds. One such amendment made by 
the law was to add a new ``veterinary feed directive'' category of 
new animal drugs to allow the approval and use of drugs in animal 
feed on a veterinarian's order while incorporating safeguards to 
help ensure the safe use of the drug.
    \8\ FDA's experience with contested, formal withdrawal 
proceedings is that the process can consume extensive periods of 
time and significant amounts of Agency resources. For example, when 
FDA withdrew a class of animal drugs called nitrofurans in 1991, the 
proceedings took nearly 20 years. In another proceeding, the 
withdrawal of diethylstilbestrol (``DES'') in animals became final 
in 1979, 7 years after issuance of an NOOH. More recently, the 
withdrawal of enrofloxacin for use in poultry took almost 5 years 
and cost FDA approximately $3.3 million.
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2. FDA Would Update the NOOHs To Reflect Current Data, Information and 
Policies If, in the Future, it Decides To Move Forward With the 
Withdrawal of the Approved Uses of the New Animal Drugs Described in 
the NOOHs

    Although FDA is optimistic that its proposed strategy to achieve 
the judicious use of all medically important antimicrobials, as set out 
in draft GFI 209, will be successful, it has not foreclosed 
the possibility of using the withdrawal provisions in the Federal Food, 
Drug, and Cosmetic Act, if necessary, in the future. This applies not 
only to the classes of antimicrobial drugs covered by the 1977 NOOHs, 
but also any other production use claims (i.e., growth promotion/feed 
efficiency uses) for a medically important antimicrobial new animal 
drug or class of drugs intended for use in food-producing animals. 
However, if FDA were to pursue withdrawal of approval of any production 
use claims, it would first publish a notice in the Federal Register 
giving the sponsor(s) of the affected new animal drug(s) notice of the 
proposed withdrawal(s) and an opportunity for a hearing.
    If, at some future time, FDA decides to proceed with the withdrawal 
of the production uses of penicillins and tetracyclines intended for 
use in feeds for food-producing animals that were the subject of the 
1977 NOOHs, it would publish a new Federal Register notice giving 
sponsors an opportunity for a hearing on the matter. A new notice would 
be appropriate for many reasons. First, more than three decades have 
passed since the original notice appeared in the Federal Register. FDA 
would publish a new Federal Register notice to ensure all current 
sponsors of the approved new animal drugs are properly notified and 
have an opportunity to request a hearing.
    Second, not all uses proposed to be withdrawn in the 1977 NOOHs are 
still approved. The 1977 NOOH which proposed withdrawal of all 
penicillin-containing premixes intended for use in animal feed also 
included the then-approved therapeutic uses of penicillin in feed. The 
stated grounds for proposing to withdraw approval of the therapeutic 
uses of the penicillin-containing premixes were that there was not 
substantial evidence of effectiveness of these products for the claimed 
therapeutic uses. However, there are no currently approved therapeutic 
uses of penicillins in animal feed.
    Third, the body of scientific information relevant to the use of 
penicillins and tetracyclines in animal feeds has grown since 1977. If 
the Agency were to pursue the NOOHs, FDA would need to provide notice 
to the sponsors that the information available since 1977 would be used 
to support the proposal to withdraw the approved uses of the drugs.
    For example, in the early 1990's FDA began collaborating with other 
government agencies to track antibiotic resistance in foodborne 
bacteria through a national public health surveillance system, known as 
the National Antimicrobial Resistance Monitoring System or ``NARMS,'' 
established to monitor antimicrobial susceptibility among enteric 
bacteria from humans, retail meats, and food animals. (Ref. 22) Also, 
since the 1977 NOOHs published, there have been numerous reports, 
including those by the National Academy of Sciences (Ref. 13), the 
Institute of Medicine (Ref. 15), the World Health Organization (Ref. 
17), and the National Research Council (Ref. 18), that have reviewed 
available information and made recommendations. In addition, there have 
been advances in our understanding of the genetics of resistance (e.g., 
ways in which bacteria accumulate multiple resistance genes).
    Fourth, FDA would need to provide notice regarding which approved 
uses were the subject of the NOOH. In the past, FDA has referred to 
``subtherapeutic'' uses at various times to include: (1) ``Increased 
rate of gain, disease prevention, etc.'' (Ref. 7); (2) ``any use of an 
antibacterial drug continuously in feed for longer than 14 days'' (Ref. 
23); and (3) ``lower levels than therapeutic levels needed to cure 
disease.'' (Refs. 1 and 2) FDA's thinking on this issue has evolved 
over the last three decades, and FDA now generally considers disease 
control and prevention claims to be judicious uses (in other words, 
therapeutic uses), especially when the drug is administered at the 
direction and under the oversight of a licensed veterinarian. (Ref. 5)

3. FDA Would Need To Prioritize Any Withdrawal Proceedings (for 
Example, Take Into Account Which Withdrawal(s) Would Likely Have the 
Most Significant Impact on the Public Health) if, in the Future, It 
Decides To Seek Withdrawal of the Approved Uses of Any New Animal Drug 
or Class of Drugs

    To the extent that FDA decides to move forward with withdrawal 
proceedings for any medically important antimicrobial drugs intended 
for use in feeds for food-producing animals, it would need to 
prioritize which withdrawal(s) to propose first based on various 
considerations, including which withdrawal(s) would have the most 
significant impact on the public health. It is possible that FDA would 
conclude that its judicious use goals would better be achieved by first 
pursuing withdrawals of drugs other than penicillins and tetracyclines. 
FDA notes that it would need to conduct such an evaluation regardless 
of the statutory grounds contemplated for the withdrawal action.

III. Conclusion

    At this time, FDA is withdrawing the 1977 NOOHs because: (1) FDA is 
engaging in other ongoing regulatory strategies developed since the 
publication of the 1977 NOOHs with respect to addressing microbial food 
safety issues; (2) FDA would update the NOOHs to reflect current data, 
information, and policies if, in the future, it decides to move forward 
with withdrawal of the approved uses of the new animal drugs described 
in the NOOHs; and (3) FDA would need to prioritize any withdrawal 
proceedings (for example, take into account which withdrawal(s) would 
likely have the most significant impact on the public health) if, in 
the future, it decides to seek withdrawal of the approved uses of any 
new animal drug or class of drugs.
    Although FDA is withdrawing the 1977 NOOHs, FDA continues to view 
antimicrobial resistance as a significant public health issue. Today's 
action should not be interpreted as a sign that FDA no longer has 
safety concerns about the use of medically important antibiotics in 
food producing animals or

[[Page 79701]]

that FDA will not consider re-proposing withdrawal proceedings in the 
future, if necessary. FDA has not ruled out the prospect of future 
regulatory action, either with respect to the antimicrobial new animal 
drugs covered by the 1977 NOOHs or any others. However, for now, FDA's 
efforts will focus on promoting voluntary reform and the judicious use 
of antimicrobials in the interest of best using the agency's overall 
resources to protect the public health. Importantly, this strategy 
leaves open the possibility of pursuing withdrawal proceedings at a 
later time if FDA's proposed strategy does not yield satisfactory 
results.
    As indicated previously, as part of the withdrawal of the two 1977 
NOOHs, the Agency will close their corresponding dockets. However, we 
encourage interested persons to submit comments to the docket 
established in connection with draft GFI 209. The docket 
number associated with draft GFI 209 is FDA-2010-D-0094.

IV. Penicillin and Tetracycline Uses in Animal Feed

    FDA is withdrawing the 1977 NOOHs, and the related companion 
proposed rules, because: (1) FDA is engaging in other ongoing 
regulatory strategies developed since the publication of the 1977 NOOHs 
with respect to addressing microbial food safety issues; (2) FDA would 
update the NOOHs to reflect current data, information, and policies if, 
in the future, it decides to move forward with withdrawal of the 
approved uses of the new animal drugs described in the NOOHs; and (3) 
FDA would need to prioritize any withdrawal proceedings (for example, 
take into account which withdrawal(s) would likely have the most 
significant impact on the public health) if, in the future, it decides 
to seek withdrawal of the approved uses of any new animal drug or class 
of drugs.

V. References

    The following references are on display in the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20857, and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday (except on Federal 
holidays). We have verified all Web site addresses, but we are not 
responsible for any subsequent changes to the Web sites after this 
document publishes in the Federal Register.

    1. 42 FR 43772 (August 30, 1977).
    2. 42 FR 56264 (October 21, 1977).
    3. 42 FR 43770 (August 30, 1977).
    4. 42 FR 56254 (October 21, 1977).
    5. Draft GFI 209, ``The Judicious Use of Medically 
Important Antimicrobial Drugs in Food-Producing Animals,'' June 28, 
2010; http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf.
    6. 37 FR 2444 (February 1, 1972).
    7. 38 FR 9811 (April 20, 1973).
    8. 21 CFR 135.109 (revised as of April 1, 1974).
    9. 21 CFR 558.15 (revised as of April 1, 1975).
    10. H. Rept. 95-1290, ``Agriculture, Rural Development and 
Related Agencies Appropriation Bill, 1979,'' June 13, 1978.
    11. H. Rept. 96-1095, ``Agriculture, Rural Development and 
Related Agencies Appropriation Bill, 1981,'' June 17, 1980.
    12. S. Rept. 97-248, ``Agriculture, Rural Development and 
Related Agencies Appropriation Bill, 1982,'' October 23 (legislative 
day, October 14), 1981.
    13. National Academy of Sciences/National Research Council, 
``The Effects on Human Health of Subtherapeutic Uses of 
Antimicrobials in Animal Feeds,'' 1980, pp. 53-54.
    14. 1984 Seattle-King County Study: ``Surveillance of the Flow 
of Salmonella and Campylobacter in a Community.''
    15. National Academy of Sciences/Institute of Medicine, ``Human 
Health Risks With the Subtherapeutic Use of Penicillin or 
Tetracyclines in Animal Feed,'' 1988.
    16. 68 FR 47272, 47275 (August 8, 2003).
    17. 1997 World Health Organization (WHO) Report, '' The Medical 
Impact of Antimicrobial Use in Food Animals,'' http://whqlibdoc.who.int/hq/1997/WHO_EMC_ZOO_97.4.pdf
    18. 1999 National Research Council (NRC) Report: ``The Use of 
Drugs in Food Animals-Benefits and Risks.''
    19. A Proposed Framework for Evaluating and Assuring the Human 
Safety of the Microbial Effects of Antimicrobial New Animal Drugs 
Intended for Use in Food-Producing Animals, http://www/fda/gov/
AdvisoryCommittees/CommitteesMeetingMaterials/
VeterinaryMedicineAdvisoryCommittee/ucm126607.htm.
    20. Final Guidance for Industry 152, ``Evaluating the 
Safety of Antimicrobial New Animal Drugs With Regard to Their 
Microbiological Effects on Bacteria of Human Health Concern,'' 
October 23, 2003.
    21. 75 FR 15387 (March 29, 2010).
    22. http://www/fda/gov/AnimalVeterinarySafetyHealth/
AntimicrobialResistance/
NationalAntimmicrobialResistanceMonitoringSystem/default.htm.
    23. 41 FR 8282 (February 25, 1976).

    Dated: December 16, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-32775 Filed 12-21-11; 8:45 am]
BILLING CODE 4160-01-P