[Federal Register Volume 68, Number 153 (Friday, August 8, 2003)]
[Proposed Rules]
[Pages 47272-47277]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-20244]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 510 and 558
[Docket No. 2003N-0324]
New Animal Drugs; Removal of Obsolete and Redundant Regulations
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing removal of
regulations that exempted certain new animal drugs administered in feed
from batch certification requirements. FDA is also proposing removal of
regulations that required sponsors to submit data regarding the
subtherapeutic use of certain antibiotic, nitrofuran, and sulfonamide
drugs administered in animal feed. The intended effect of this proposed
rule is to remove regulations that are obsolete or redundant. Some of
the products and combination uses subject to the listings in these
regulations are subject to a notice of findings of effectiveness and an
opportunity for hearing published elsewhere in this issue of the
Federal Register. One approved product subject to the regulations
proposed for removal is being codified elsewhere in this issue of the
Federal Register.
DATES: Submit written comments on the proposed rule by November 6,
2003.
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Submit electronic comments to: http://www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT: Andrew J. Beaulieu, Center for
Veterinary Medicine (HFV-1), 7519 Standish Pl., Rockville, MD 20855,
301-827-2954, e-mail: [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Elsewhere in this issue of the Federal Register, the agency is
announcing the effective conditions of use for some of the products or
use combinations subject to the listings in parts 510 and 558 (21 CFR
part 510 and 558), specifically, Sec. Sec. 510.515 and/or 558.15, and
the agency is proposing to withdraw the new animal drug applications
(NADAs) for those products or use combinations lacking substantial
evidence of effectiveness following a 90-day opportunity to supplement
the NADAs with labeling conforming to the relevant findings of
effectiveness. One approved product subject to Sec. 558.15 is being
codified in part 558, subpart B in a final rule published elsewhere in
this issue of the Federal Register. Concurrent with that announcement
and final rule, the agency is proposing to remove these two sections of
the Code of Federal Regulations (Sec. Sec. 510.515 and 558.15) for the
reasons described in sections II and III of this document.
II. Part 510, Subpart F Animal Use Exemptions From Certification and
Labeling Requirements and Sec. 510.515 Animal Feeds Bearing or
Containing New Animal Drugs Subject to the Provisions of Section 512(n)
of the Act
A. History of Part 510, Subpart F and Sec. 510.515
In 1945, Congress added section 507 to the Federal Food, Drug, and
Cosmetic Act (the act) (21 U.S.C. 357) requiring the agency to provide
for the certification of batches of drugs composed wholly or partly of
any kind of penicillin (Public Law 79-139, 59 Stat. 463). No
distinction was made
[[Page 47273]]
between the use of the drugs in man or other animals. Section 507 of
the act was subsequently amended several times to include streptomycin,
chlortetracycline, bacitracin, chloramphenicol, and their derivatives.
The law allowed the agency to issue regulations exempting drugs or
classes of drugs from the batch certification requirements. Over the
years, FDA issued exemption regulations for a number of antibiotics
used in animal feeds, provided the involved products were in compliance
with certain provisions. The exemptions are currently contained in
Sec. 510.515.
The Animal Drug Amendments of 1968 consolidated provisions of the
act relating to new animal drugs (including antibiotics in section 507
of the act) into new section 512 (21 U.S.C. 360b). The agency
established procedural regulations under parts 510 and 514 (21 CFR part
514) to implement this provision of the act.
Subsequent to the establishment of the exemption provisions in
Sec. 510.515, the agency came to the conclusion that batch-by-batch
certification was no longer required under any circumstances to assure
the safety of antibiotics. In the Federal Register of September 7, 1982
(47 FR 39155), the agency published regulations exempting all classes
of human and animal use antibiotics from batch certification
requirements based upon a finding of extremely low rejection rates for
the certifiable antibiotics.
In 1988, Congress removed from the act all antibiotic certification
provisions for animal drugs when it enacted the Generic Animal Drug and
Patent Term Restoration Act (GADPTRA). Subsequently, the agency
published a final rule on May 26, 1989 (54 FR 22741), which removed all
of the certifiable antibiotic procedural regulations that then appeared
in parts 510 and 514. That rule indicated that removal of the technical
regulations concerning specific antibiotic drugs, such as Sec.
510.515, which contained information about their conditions of use,
would be the subject of future regulations.
Since that time, FDA has removed many drug uses and use
combinations from Sec. 510.515. The agency did this when it withdrew
approval of products subject to the regulation, or when it published
approval regulations for them, in part 558, subpart B, after completing
their Drug Efficacy Study Implementation (DESI) finalization (see,
e.g., 61 FR 35949, July 9, 1996). Consequently, a regulation that at
one time contained dozens of batch certification exemption provisions
now lists only a few products and use combinations.
B. Removal of Sec. 510.515
The purpose of Sec. 510.515, which was to provide exemption from
batch certification of certain drugs intended for use in animal feed,
was rendered obsolete with the enactment of GADPTRA. Because the
regulation is out dated relative to its intended purpose, the agency is
proposing to remove it.
This action is not intended to have a substantive effect on any
approved new animal drugs. As noted in section II.A of this document,
some of the drug uses and use combinations currently listed in Sec.
510.515 have approvals that are codified in part 558 subpart B.
Therefore, these uses will not be substantively affected by removal of
listings in this regulation. Other drug use combinations currently
listed in Sec. 510.515 are also listed in Sec. 558.15, but their
approvals, if any, have not been codified in part 558 subpart B. As
discussed in section II.B of this document, and in the notice appearing
elsewhere in this issue of the Federal Register, the use combinations
that have been approved will be codified in part 558 subpart B. In
regard to the only other listed drug (para-aminobenzoic acid), the
agency is unaware of any company that currently holds approval for it,
or markets it, and believes it is no longer used in the practice of
veterinary medicine. If a person wishes to market a drug or drug
combination being removed under this proposal and believes that it
holds a valid approval for it that is not already codified in part 558
subpart B or subject to the final rule or notice published elsewhere in
this issue of the Federal Register, the person should present evidence
supporting approval to avoid facing potential regulatory action in the
event of future marketing.
III. Section 558.15 Antibiotic, Nitrofuran, and Sulfonamide Drugs in
the Feed of Animals
A. History of Sec. 558.15
In the mid-1960s, FDA became concerned about the safety to man and
animals of long-term antibiotic use in animals, and for several years
the agency studied the effects of low-level feeding of antibiotics to
animals. In April 1970, the Commissioner of Food and Drugs
(Commissioner) established a task force of scientists from government,
industry, and academia to comprehensively review the use of antibiotics
in animal feed. In the Federal Register of February 1, 1972 (37 FR
2444), the agency published the conclusions of that task force and
proposed to require sponsors to submit specific data for antibacterial
drugs intended for subtherapeutic or growth promotion use. The task
force identified areas in which data were needed and established
criteria for studies intended to show whether use of antimicrobials in
animal feed presents a hazard to human or animal health. The criteria
reflected four basic issues with respect to which data were needed: (1)
The potential to increase the frequency of bacteria carrying
transferable drug resistance; (2) the potential to increase the
antibiotic resistance of, or the shedding of, Salmonella spp.; (3) the
potential to enhance bacterial pathogenicity; and (4) the potential for
drug residues to cause an increase in pathogenic bacteria resistant to
human antibiotics drugs or to cause human hypersensitivity reactions.
The 1972 proposal also stated that all then-approved subtherapeutic
and/or growth promoting uses in animal feeds of antibiotics and
sulfonamides that are also used in humans would be revoked unless data
identified by the task force were submitted to FDA.
In the Federal Register of April 20, 1973 (38 FR 9811), the agency
published the final rule which established 21 CFR 135.109 Antibiotic
and sulfonamide drugs in the feed of animals (redesignated as Sec.
558.15 in 1974). The section was subsequently amended on September 5,
1973, to include the nitrofurans (38 FR 23942). In the Federal Register
of February 25, 1976 (41 FR 8282), the agency withdrew approvals for
those antimicrobial drugs not in compliance with the data submission
requirements of Sec. 558.15. The same document added paragraphs (g)(1)
and (g)(2) to Sec. 558.15. These paragraphs listed the medicated
premixes and drug combinations, respectively, which had submitted the
required data for agency review. These are known as the interim
marketing provisions.
B. Approval Status of Products and Use Combinations Subject to the
Listings in Sec. 558.15
The preamble to the final rule that added the Sec. 558.15 interim
marketing provisions stated that all products and combination uses
subject to the listings in the regulation were the subject of approved
applications (41 FR 8282 and 8285, February 25, 1976). However, a
number of years after this regulation was issued, it became apparent
that the administrative record associated with 15 products was
incomplete, calling into question their approval status.
[[Page 47274]]
One cause of this problem relates to the Animal Drug Amendments of
1968. Under Section 108 of this law, any product that had been approved
before 1968 by a new drug application, food additive petition,
certifiable antibiotic application, or master file would be considered
to be the subject of an approved new animal drug application under the
new section 512. Because Sec. 558.15 dealt with antimicrobials used in
animal feed, the products listed in Sec. 558.15 were considered food
additives before the 1968 animal drug amendments. In addition, a number
of them contained certifiable antibiotics. The approval processes for
these products before the 1968 amendments were complex, redundant, and
involved the acceptance of secondary manufacturers/distributors,
sometimes based on a demonstration of equivalence of their products to
primary sponsor products and sometimes not. Unlike the current new
animal drug application process under section 512 of the act, this was
generally not an orderly process. As a result, the agency's and
sponsors' ability to document the pre-1968 approvals has been hampered.
Because their administrative records were incomplete, in 1998 the
agency undertook to determine whether any of the 15 products were
unapproved and, therefore, erroneously listed in Sec. 558.15. In this
regard, the agency asked sponsors to identify the involved product,
attach associated labeling, and certify its approval status.
Certification was forthcoming for 10 of the 15 applications. The agency
informed the involved parties by letter that their certifications would
be used as part of the administrative record of approval and that it
planned to codify these approvals as soon as possible, very likely in
concert with the removal of Sec. 558.15. Because the agency was unable
to verify that the remaining five products were approved, the agency
believes they were erroneously listed in Sec. 558.15.
C. Reasons for Removal of Sec. 558.15
The agency is proposing to remove Sec. 558.15 because it long ago
fulfilled its stated purpose of requiring sponsors to submit data
regarding the subtherapeutic use of antibiotics on the market at the
time of its publication. The safety studies required to be conducted on
the products listed at the time the section was issued were completed
long ago. In addition, as discussed in section III.D of this document,
the agency has a new strategy and concept for assessing the safety of
antimicrobial new animal drugs, including subtherapeutic use of
antimicrobials in animal feed, with regard to their microbiological
effects on bacteria of human health concern. Therefore, the removal of
Sec. 558.15 does not mean that studies will no longer be required to
assess the consequences of the use of antimicrobials in food-producing
animals.
D. The Antibiotic Resistance Issue After Publication of Sec. 558.15
While, at the time of its publication, Sec. 558.15 accurately
reflected FDA's basis for assessing the safety of subtherapeutic uses
of antibiotics in feed, based on new information and considerable
experience, over time FDA developed a new strategy and concept to deal
with the issue of antimicrobial resistance. Accordingly, it is useful
to review the history of the antimicrobial resistance issue from the
time Sec. 558.15 was issued to the present relative to the
significance of the removal of Sec. 558.15 on FDA's ability to deal
with the issue.
As discussed in section III.A of this document, under Sec. 558.15,
FDA received data addressing the subtherapeutic use of antibiotics in
animal feed. To assist FDA in assessing the data, the Commissioner
asked the agency's National Advisory Food and Drug Committee (NAFDC) to
review the data and issues involved and to make recommendations to him
on the future use of subtherapeutic antibiotics in animal feeds.
In 1977, the NAFDC made its findings known to FDA. The FDA
carefully considered the recommendations made by the NAFDC. On August
30, 1977 (42 FR 43770), the Director of the Center for Veterinary
Medicine (Director) proposed to revoke all regulations providing for
the subtherapeutic use of penicillin alone and in combination with
other drugs in animal feeds. Because the National Academy of Sciences
National Research Council (NAS/NRC) DESI review concluded that no
therapeutic uses of penicillin in animal feed were supported by
adequate evidence of effectiveness, he also proposed to revoke all
regulations providing for the therapeutic use of penicillin in animal
feed. Also, in the Federal Register of August 30, 1977 (42 FR 43772),
the Director issued a notice of opportunity for hearing (NOOH) on a
proposal to withdraw approval of NADAs for all penicillin-containing
premixes intended for use in animal feeds. The NOOH was issued, under
section 512(e) of the act (21 U.S.C. 360b(e)), on the grounds that
evidence showed that such products have not been shown to be safe, that
the applicants failed to establish and maintain records and make
reports as required, and that there was a lack of substantial evidence
that such products were effective for certain uses.
Subsequently, in the Federal Register of October 21, 1977 (42 FR
56254), the Director proposed to revoke regulations providing for the
subtherapeutic use of tetracyclines in animal feed except for those
specific conditions of use for which there were no safe and effective
substitutes at that time. Also in the Federal Register of October 21,
1977 (42 FR 56264), the Director issued an NOOH on a proposal to
withdraw approval of NADAs for certain subtherapeutic uses of
tetracyclines (chlortetracycline and oxytetracycline) in animal feeds.
In 1978, after FDA proposed to withdraw approval of various uses of
penicillin and tetracyclines in animal feeds, Congress directed FDA to
conduct further studies related to the use of antibiotics in animal
feed and to hold in abeyance implementation of its proposed withdrawal
actions pending the outcome of the studies (see H.R. Rept. 95-1290 at
p. 99 (June 13, 1978)). As directed, FDA spent $1.5 million of its
appropriations for a study of the safety issues relating to the use of
antibiotics in animal feeds. The study entitled ``The Effects on Human
Health of Subtherapeutic Use of Antimicrobials in Animal Feeds,''
conducted by the NAS/NRC, was published in 1980 (Ref. 1). It concluded
that existing data could neither prove nor disprove the postulated
hazards to human health from subtherapeutic antimicrobial use in animal
feeds.
On November 20, 1984, the Natural Resources Defense Council, Inc.
(NRDC), petitioned the Secretary of Health and Human Services
(Secretary) to immediately suspend approval of the subtherapeutic use
of penicillin and tetracyclines in animal feeds (Ref. 2). NRDC's
petition requested that the Secretary invoke the imminent hazard
provision of the act (21 U.S.C. 360b(e)(1)) which authorizes the
Secretary to suspend approval of an application for the use of a new
animal drug if an imminent hazard exists to the health of man or to the
animals for which the drug is intended. Soon after the filing of the
petition, there was a congressional hearing in December 1984 before the
House of Representatives Committee on Science and Technology,
Subcommittee on Investigations and Oversight, as well as an informal
hearing before the Commissioner of FDA on January 25, 1985.
On November 13, 1985, the Secretary denied the NRDC petition on the
basis that an ``imminent hazard'' had not been demonstrated (Ref. 3).
This decision was based on an analysis of the evidence cited by the
NRDC as well as scientific
[[Page 47275]]
evidence, information, and opinions coming out of the January 25, 1985,
public hearing and other relevant data collected and analyzed by FDA.
Subsequently, the Commissioner directed the agency to contract with
the NAS, Institute of Medicine (IOM), to conduct a risk assessment of
the potential risk to human health associated with the practice of
feeding subtherapeutic levels of penicillin and the tetracyclines to
animals for growth promotion, feed efficiency, and disease prevention.
In 1988, the NAS/IOM reviewed the information concerning the
antibiotic resistance issue available at the time. An expert committee
was convened to determine the human health risks associated with the
practice of feeding subtherapeutic levels of penicillin and
tetracyclines to animals for growth promotion, feed efficiency, and
disease prevention. In the report entitled ``Human Health Risks with
the Subtherapeutic Use of Penicillin or Tetracyclines in Animal Feed''
the committee developed a risk-analysis model, using data only on
Salmonella infections that resulted in human death (Ref. 4). The
committee found a considerable amount of indirect evidence implicating
both subtherapeutic and therapeutic use of antimicrobials as a
potential human health hazard. The committee did not find data
demonstrating that use of subtherapeutic penicillin or tetracycline
directly caused humans to die from salmonellosis. The committee noted
that it was not possible to separate the public health effects of
therapeutic and subtherapeutic uses and strongly recommended further
study of the issue.
Based upon the report and other relevant information, the agency:
(1) Concluded that the risks were neither proved nor disproved, (2) did
not deny there was some degree of risk, and (3) did not conclude that
the continued subtherapeutic use of penicillin and the tetracycylines
in animal feed is safe. The notices of opportunity for hearing
published in the Federal Registers of August 30 and October 21, 1977,
remain pending.
The American Society of Microbiology issued a report in 1995 that
cited grave concerns about both human and animal antibiotic use and the
rise in antimicrobial resistance (Ref. 5). The report advocated: A
significant increase in resistance monitoring in the United States,
more education about the use and risks of antimicrobials, and more
basic research designed to develop new antimicrobials and vaccines and
disease prevention measures. The report criticized overuse of
antibacterials in human medicine, but also pointed out the extensive
use of antibacterials in food production, which was partly attributed
to the consolidation of farms to facilities with large numbers of
confined animals. The report made it clear that the antibiotic
resistance problem is global and was a precursor to involvement by the
United Nation's World Health Organization (WHO). The meetings of the
WHO in 1997 and 1998 led to the development of a number of
recommendations regarding the use of antimicrobial drugs in food-
producing animals (Refs. 6 and 7).
In 1999, FDA issued ``Guidance for Industry: Consideration of the
Human Health Impact of the Microbial Effects of Antimicrobial New
Animal Drugs Intended for Use in Food-Producing Animals'' ([numsign]78)
(64 FR 70715, Dec. 17, 1999). In this guidance, FDA reaffirmed its
statutory authority to evaluate the safety of new animal drugs with
respect to their microbiological effects on bacteria of human health
concern. FDA asserted that this consideration applies to all
antimicrobial new animal drugs intended for use in food-producing
animals including both therapeutic use and use at subtherapeutic levels
for production purposes. Subsequently, the agency released a concept
paper, which has come to be known as the Framework Document, which
described a possible approach that the FDA could take in regulating
antimicrobial new animal drugs intended for use in food-producing
animals (Ref. 8).
Since the publication of the Framework Document, FDA has held a
number of public meetings as well as two meetings of its Veterinary
Medical Advisory Committee to obtain input on the concepts outlined in
the Framework Document. Based on this input, FDA drafted a guidance for
industry (GFI) to implement several of the key strategies and concepts
discussed in the Framework Document. The draft guidance for industry
entitled ``Draft Guidance for Industry: Evaluating the Safety of
Antimicrobial New Animal Drugs With Regard to Their Microbiological
Effects on Bacteria of Human Health Concern'' ([numsign]152) (67 FR
58058, Sept. 13, 2002) outlines a risk analysis process for evaluating
the safety of antimicrobial new animal drugs. This guidance, subject to
public comment, represents the Center for Veterinary Medicine's current
best thinking on how to assure the safety of antimicrobial new animal
drugs intended for use in food-producing animals.
E. Effect of the Removal of Sec. 558.15
Based on the previous discussion, the removal of Sec. 558.15 will
have no effect on FDA's ability to address the issue of antimicrobial
resistance. Additionally, the removal of Sec. 558.15 is not intended
to have a substantive effect on the products subject to the section's
interim marketing provisions. Most of the products or use combinations
subject to the listings have approvals that are already codified in
part 558 subpart B. The agency's actions on the products and use
combinations whose approval is not already codified in part 558 subpart
B are described elsewhere in this issue of the Federal Register. One
action consists of publishing the agency's findings of effectiveness
for these products and use combinations, under DESI, and, where
relevant, proposing to withdraw approval of applications for
indications lacking substantial evidence of effectiveness and providing
a notice of opportunity for hearing. The other action is the codifying
of one approval in part 558 subpart B. This action is a final rule
since the product is not subject to DESI. As noted in section III.B of
this document, the agency believes that five products subject to the
listings in Sec. 558.15 were erroneously listed there. Because the
regulation could only permit the interim marketing of approved
products, the removal of Sec. 558.15 will not have a substantive
effect on the five unapproved products. Further, the agency is unaware
of any company that currently markets any of these five products. If a
company wishes to market one of these drug products and believes that
it holds a valid approval for it that is not already subject to an
approval reflected in part 558 subpart B, the company should present
evidence supporting approval to avoid facing potential regulatory
action in the event of future marketing.
IV. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
V. Analysis of Economic Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory
[[Page 47276]]
alternatives and, when regulation is necessary, to select regulatory
approaches that maximize net benefits (including potential economic,
environmental, public health and safety, and other advantages;
distributive impacts; and equity). The agency believes that this
proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive order. In addition, the proposed
rule is not a significant regulatory action as defined by the Executive
order and so is not subject to review under the Executive order.
FDA is proposing to revoke Sec. Sec. 510.515 and 558.15 because
they are obsolete. The purpose of Sec. 510.515 was to provide
exemption from certification and labeling requirements of certain drugs
used in animal feeds. FDA has discontinued the practice of certifying
antibiotic animal drugs, thereby rendering the regulation obsolete
relative to its intended purpose. The original purpose of Sec. 558.15,
requiring the submission of the results of studies on the effects of
long-term administration of then-marketed antimicrobial drugs in animal
feed on the occurrence of multiple drug-resistant bacteria associated
with these animals, is also obsolete as FDA has a new strategy and
concept for assessing the safety of antimicrobial new animal drugs,
including subtherapeutic use of antimicrobials in animal feed, with
regard to their microbiological effects on bacteria of human health
concern.
Almost all of the drug product listings contained in Sec. Sec.
510.515 and/or 558.15 are already reflected in approval regulations
published elsewhere in part 558 subpart B. In two documents published
in this issue of the Federal Register, the agency is addressing the
drug product listings whose approvals are not currently reflected in
the approval regulations in part 558 subpart B.
A. Benefits
This proposal is expected to provide clarity and equity in the
regulations for new animal drugs for use in animal feeds by deleting
the obsolete provisions at Sec. Sec. 510.515 and 558.15. We do not
expect this proposed rule to result in a direct human or animal health
benefit. Rather, this proposal would remove unnecessary regulations
that both provided exemptions for certifications that no longer occur,
or required the submission of safety data for approved subtherapeutic
uses of antibiotics, nitrofurans and sulfonamides in the 1970s.
B. Compliance Costs
FDA expects this proposal to result in the loss of marketing
ability for five combination uses listed in Sec. 558.15 as described
in III.B of this document. In an attempt to certify the approval
status, FDA contacted, or attempted to contact, the three sponsors of
these five drug combinations. Attempts with one sponsor indicated that
they did not wish to certify the transitional approvals, and no
response was received from the other sponsors concerning these
transitional approvals. Accordingly, we believe that these products
were erroneously listed in Sec. 558.15 and that these sponsors no
longer market these combination uses as provided for under Sec.
558.15. The revocation of Sec. 558.15 is not expected to have a
substantive effect on any approved new animal drugs, or to cause any
approved new animal drug to lose its marketing ability. Therefore, we
do not expect any loss of sales to result from this provision. We
request public comment on the loss of sales or other effects to any
products or drug combinations that will lose marketing ability due to
this proposed rule.
C. Regulatory Flexibility Analysis
The Regulatory Flexibility Act requires agencies to analyze
regulatory options to minimize any significant impact on a substantial
number of small entities. FDA has determined in section V.B of this
document that this proposed rule would not impose compliance costs on
the sponsors of any products that are currently marketed. Further, it
is not expected to cause any drugs that are currently marketed to lose
their marketing ability. We therefore certify that the proposed rule
would not have a significant economic effect on a substantial number of
small entities. No further analysis is required under the Regulatory
Flexibility Act (as amended).
D. Unfunded Mandates Reform Act
Section 202(a) of the Unfunded Mandates Reform Act of 1995 (Public
Law 104-4) requires that agencies prepare a written statement of
anticipated costs and benefits before proposing any rule that may
result in an expenditure by State, local, and tribal governments, in
the aggregate, or by the private sector, of $100 million or more in any
one year (adjusted annually for inflation).
The Unfunded Mandates Reform Act does not require FDA to prepare a
statement of costs and benefits for the proposed rule because the rule
is not expected to result in any 1-year expenditure that would exceed
$100 million adjusted for inflation. The current inflation-adjusted
statutory threshold is about $110 million.
VI. Paperwork Reduction Act of 1995
FDA tentatively concludes that this proposed rule contains no
collections of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 is not
required.
VII. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. National Academy of Sciences/National Research Council, ``The
Effects on Human Health of Subtherapeutic Use of Antimicrobials in
Animal Feeds,'' 1980.
2. Petition of the Natural Resources Defense Council, Inc., to
Secretary of Health and Human Services, New York, NY, November 20,
1984.
3. Decision of the Secretary Denying Petition, Docket No. 84P-
0399, November 13, 1985.
4. National Academy of Sciences/Institute of Medicine, ``Human
Health Risks With the Subtherapeutic Use of Penicillin or
Tetracyclines in Animal Feed,'' 1989.
5. Report of the American Society for Microbiology Task Force on
Antibiotic Resistance; the American Society for Microbiology, Public
and Scientific Affairs Board; Washington, DC, March 16, 1995.
6. World Health Organization (WHO), ``The Medical Impact of the
Use of Antimicrobials in Food Animals,'' Report of a WHO meeting,
WHO/EMC/ZOO/97.4, Berlin, Germany, October 13 to 17, 1997.
7. WHO, ``Use of Quinolones in Food Animals and Potential Impact
on Human Health,'' Report of a WHO meeting, WHO/EMC/ZDI/98.12,
Geneva, Switzerland, June 2 to 5, 1998.
8. Discussion paper: ``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,''
Center for Veterinary Medicine, Food and Drug Administration, 1999;
Docket 98D-1146 (http://www.fda.gov/cvm/antimicrobial/ar_framework.htm).
VIII. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments to http://www.fda.gov/dockets/ecomments or two paper copies of any written comments, except
that individuals may submit one paper copy. Comments are to be
identified with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division
[[Page 47277]]
of Dockets Management between 9 a.m. and 4 p.m. Monday through Friday.
List of Subjects
21 CFR Part 510
Administrative practice and procedure, Animal drugs, Labeling,
Reporting and recordkeeping requirements.
21 CFR Part 558
Animal drugs, Animal feeds.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR parts 510 and 558 be amended as follows:
PART 510--NEW ANIMAL DRUGS
1. The authority citation for 21 CFR part 510 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.
Subpart F [Removed and Reserved]
2. Subpart F, consisting of Sec. 510.515, is removed and reserved.
PART 558--NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS
3. The authority citation for 21 CFR part 558 continues to read as
follows:
Authority: 21 U.S.C. 360b, 371.
Sec. 558.4 [Amended]
4. Section 558.4 Requirement of a medicated feed mill license is
amended in paragraph (c) by removing ``and in Sec. Sec. 510.515 and
558.15 of this chapter''.
Sec. 558.15 [Removed]
5. Section 558.15 Antibiotic, nitrofuran, and sulfonamide drugs in
the feed of animals is removed.
Dated: August 1, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-20244 Filed 8-5-03; 4:09 pm]
BILLING CODE 4160-01-S