Federal Register Vol. 54, No. 75
Thursday, April 20, 1989
AGENCY: DEPARTMENT OF HEALTH AND HUMAN SERVICES; Food and Drug
Administration; Food and Drug Administration.
DOC TYPE: Rules and Regulations
CFR: 21 CFR Part 58
NUMBER: Docket No. 89N-0054
Effective May 22, 1989; written comments by May 22, 1989.
CONTACT: Paul D. Lepore, Division of Compliance Policy (HFC-230),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD
20857, 301-443-2390.
Written comments to the Dockets Management Branch (HFA-305), Food
and Drug Administration, Rm. 4-62, 5600 Fishers Lane, Rockville,
MD 20857.
Final rule.
The Food and Drug Administration (FDA) is amending its regulations
on good laboratory practice (GLP) for nonclinical laboratory
studies to confirm the FDA policy that testing facilities are to
use humane procedures for animal identification and
experimentation. The agency has determined that toe clipping for
animal identification is a potentially painful procedure and its
use in animal studies should be discouraged. The amendment will
not affect the intent of the regulatory requirements, which is to
assure that animals used in nonclinical laboratory studies are
appropriately identified.
In the Federal Register of December 22, 1978 (43 FR 59986), FDA
published final regulations regarding GLP for nonclinical
laboratory studies. These regulations, codified at 21 CFR Part 58,
prescribe GLP for conducting nonclinical laboratory studies that
support or are intended to support applications for research or
marketing permits for products regulated by FDA, including food
and color additives, animal food additives, human and animal
drugs, medical devices for human use, biological products, and
electronic products. Compliance with these regulations is
intended to assure the quality and integrity of the safety data
filed under provisions of the Federal Food, Drug, and Cosmetic Act
and the Public Health Service Act. (See 21 CFR 58.1(a).) The GLP
regulations were amended in a final rule published on September 4,
1987 (52 FR 33768).
Section 58.90(d) of the GLP regulations provides, in
pertinent part, that ''Warm-blooded animals, excluding suckling
rodents, used in laboratory procedures * * * shall receive
appropriate identification (e.g., tattoo, toe clip, color code,
ear tag, ear punch, etc.) * * *.''
The need for requiring appropriate identification of the
animals was discussed in the preamble to the proposed rule
(November 19, 1976; 41 FR 51206 at 51214) and in the preamble to
the final rule (December 22, 1978; 43 FR 59986 at 60004, par.
157). FDA has determined that appropriate identification is
necessary to preclude animal mixups during a study. Such mixups in
test animal identification could affect the validity of the study
results. Paragraph 157 of the preamble to the final rule advised
that, because of the varied nature of the tests and the test
systems that could be used in a study, the precise manner of
animal identification is left to the discretion of the test
facility.
Elsewhere in the preamble to the final rule (par. 150), the
agency stated that the humane care of test animals is a recognized
and accepted scientific and ethical responsibility that is
encouraged by various agency guidelines and the Animal Welfare
Act. The agency also stated that the promulgation of the GLP
regulations should foster the humane treatment of animals used in
nonclinical laboratory studies.
In light of the foregoing, FDA listed in Sec. 58.90(d)
examples of methods of animal identification which were considered
to be appropriate and humane. At that time, toe clipping was
considered to be appropriate and humane. Since then, an
increasing number of veterinarians for laboratory
animals have determined that toe clipping is potentially painful
and that its use should be discouraged.
As a result, the Interagency Research Animal Committee, a
group consisting of representatives from Federal agencies involved
in the care, use, and conservation of animals used in biomedical
research and testing, has recommended that a scientist wishing to
use toe clipping of animals as a method of animal identification
should obtain the approval of each facility's institutional
animal care and use committee (the committee).
Before giving its consent, the committee should be convinced that
no other method of identifying the animals would be appropriate.
The committee should also be convinced that anesthesia and
antisepsis would be used so that the toe clipping procedure would
be humane and conform to accepted veterinary procedures. The
Interagency Research Animal Committee did not recommend
prohibiting the use of toe clipping entirely, but did recommend
restricting its use to situations where this method of
identification is necessary. The interagency committee also
recommended procedures for performing toe clipping if it is to be
done.
FDA accepts the recommendations of the Interagency Research
Animal Committee and believes that the use of toe clipping of
animals in nonclinical laboratory studies should be discouraged in
accordance with that group's recommendations. Accordingly, FDA is
removing the words ''toe clip'' from the second parenthetical
expression in Sec. 58.90(d). The amendment will eliminate the
impression given by the current regulation that toe clipping is
an approved and humane method of animal identification. The
amendment will not affect the responsibility of testing facilities
to use appropriate and humane methods of animal identification.
Under section 553(b) of the Administrative Procedure Act (5
U.S.C. 553(b) and FDA's administrative practices and procedures
regulations (21 CFR 10.40(e)), the Commissioner finds that notice
and public procedure for amending 21 CFR 58.90(d) are unnecessary
and contrary to the public interest. FDA believes that this
amendment will help to promote the humane treatment of laboratory
animals. However, by removing one example from the
list of examples of methods of identification given
parenthetically in Sec.58.90(d), the agency is neither adding nor
removing a regulatory requirement. That is, the substantive
requirements of the GLP regulations are unchanged by this
amendment. Therefore, the Commissioner finds good cause to proceed
directly to a final rule.
Although the agency is publishing this final rule without an
opportunity for prior notice and comment as a proposed rule, FDA
is providing for comment on this final rule in accordance with
Sec. 10.40(e)(1) of the agency's regulations (21 CFR 10.40(e)(1)).
Economic Impact
In accordance with Executive Order 12291, FDA has analyzed
the potential economic effects of this final rule. The agency has
determined that the rule is not a major rule as defined by the
Order.
Environmental Impact
The agency has determined under 21 CFR 25.24(a)(10) 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.
Comments
Interested persons may, on or before May 22, 1989, submit to
the Dockets Management Branch (address above) written comments
regarding this proposal. Two copies of any comments are to be
submitted, except that individuals may submit one 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
office above between 9 a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 58 Laboratories, Reporting and
Recordkeeping requirements.
Therefore, under the Public Health Service Act as amended by
the Radiation Control for Health and Safety Act of 1968 and under
the Federal Food, Drug, and Cosmetic Act and under authority
delegated to the Commissioner of Food and Drugs, Part 58 is
amended to read as follows:
PART 58-GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY
STUDIES
1. The authority citation for 21 CFR Part 58 is revised to
read as follows:
Authority: Secs. 306, 402(a), 406, 408, 409, 502, 503, 505,
506, 507, 510, 512-516, 518-520, 701(a), 706, 801, Pub. L. 717, 52
Stat. 1045-1046 as amended, 1049-1053 as amended, 1055, 1058 as
amended, 55 Stat. 851 as amended, 59 Stat. 463 as amended, 68
Stat. 511-517 as amended, 72 Stat. 1785-1788 as amended, 76 Stat.
794 as amended, 82 Stat. 343-351, 90 Stat. 539-574 (21 U.S.C. 336,
342(a), 346, 346a, 348, 352, 353, 355, 356, 357, 360, 360b-360f,
360h-360j, 371(a), 376, 381); secs. 215, 351, 354-360F, Pub. L.
410, 58 Stat. 690, 702 as amended, 82 Stat. 1173-1186 as amended
(42 U.S.C. 216, 262, 263b-263n); 21 CFR 5.11.
Sec. 58.90 Amended
2. Section 58.90 Animal care is amended in paragraph (d) by
removing the words ''toe clip,'' from the second parenthetical
expression.
