[Federal Register Volume 64, Number 161 (Friday, August 20, 1999)]
[Rules and Regulations]
[Pages 45419-45421]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-21595]



DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 113

[Docket No. 97-103-2]


Viruses, Serums, Toxins, and Analogous Products; Update of 
Incorporation by Reference for Rabies Vaccine

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: We are amending the regulations pertaining to the standard 
requirements for rabies vaccine, killed virus, so that they incorporate 
the latest edition of a guide to laboratory techniques. The regulations 
currently refer to the previous edition of that guide, which was 
published in 1973. This action will ensure that the latest edition of 
the guide is incorporated by reference and used in conducting potency 
tests during the production of inactivated (killed) veterinary rabies 
vaccines.

EFFECTIVE DATES: September 20, 1999. The incorporation by reference 
provided for by this rule is approved by the Director of the Federal 
Register as of September 20, 1999.

FOR FURTHER INFORMATION CONTACT: Dr. David A. Espeseth, Special 
Assistant to the Deputy Administrator, Veterinary Services, Center for 
Veterinary Biologics, Licensing and Policy Development, VS, APHIS, 4700 
River Road Unit 148, Riverdale, MD 20737-1231; (301) 734-8245.

SUPPLEMENTARY INFORMATION:

Background

    The regulations in 9 CFR part 113 pertain to standard requirements 
for the preparation of veterinary biological products. A standard 
requirement consists of test methods, procedures, and criteria 
established by the Animal and Plant Health Inspection Service (APHIS) 
to determine that a veterinary biological product is pure, safe, 
potent, and efficacious and not worthless, dangerous, contaminated, or 
harmful.
    ``Laboratory Techniques in Rabies,'' which is a guide to laboratory

[[Page 45420]]

techniques for rabies research and diagnosis and for the production of 
vaccine and immunoglobulin and which is published by the World Health 
Organization (WHO), is incorporated by reference into the Code of 
Federal Regulations at 9 CFR 113.209(b)(1). In 1996, the WHO published 
a fourth edition of ``Laboratory Techniques in Rabies'' (edited by F.X. 
Meslin, M.M. Kaplan, and H. Koprowski), but the incorporation by 
reference in Sec. 113.209(b)(1) still refers to the 1973 third edition 
of that guide.
    On March 4, 1999, we published in the Federal Register (64 FR 
10400-10402, Docket No. 97-103-1) a proposed rule to amend the 
regulations in Sec. 113.209(b)(1) so that they refer to the fourth 
edition of ``Laboratory Techniques in Rabies'' in order for the latest 
version to be incorporated by reference and used. In that document, we 
also proposed to update several provisions of the regulations to make 
them consistent with the guidelines contained in the fourth edition and 
to ensure that the regulations met the requirements of the Office of 
the Federal Register regarding the proper language of incorporation.
    We solicited comments concerning our proposal for 60 days ending 
May 3, 1999. We did not receive any comments. Therefore, for the 
reasons given in the proposed rule, we are adopting the proposed rule 
as a final rule, without change.

Executive Order 12866 and Regulatory Flexibility Act

    This rule has been reviewed under Executive Order 12866. The rule 
has been determined to be not significant for the purposes of Executive 
Order 12866 and, therefore, has not been reviewed by the Office of 
Management and Budget.
    In accordance with the Regulatory Flexibility Act, we have 
considered the potential effects of this action on small entities. We 
have identified four producers of rabies vaccine as the entities 
potentially affected by this rule. Those producers fall into one of two 
standard industrial classification (SIC) categories, either SIC 2836 
(Biological Products, Except Diagnostic Substances) or SIC 2834 
(Pharmaceutical Preparations). According to Small Business 
Administration (SBA) criteria, a business in SIC 2836 is considered to 
be a small entity if it has 500 or fewer employees, and a business in 
SIC 2834 is considered to be a small entity if it has 750 or fewer 
employees. Under those criteria, none of the four producers identified 
are small entities.
    ``Laboratory Techniques in Rabies'' is a guide to laboratory 
techniques for rabies research and diagnosis and for the production of 
vaccine and immunoglobulin that is incorporated by reference into the 
standard requirements regulations in 9 CFR 113.209(b)(1). This rule 
amends those regulations so that the language used in the guide's 
incorporation by reference is correct and ensures that the current 
edition of the guide is incorporated by reference and used.
    The testing required under Sec. 113.209(b)(1) will remain the same. 
However, some retesting may be required due to change in the 
international standard for the LD50 of the challenge dose. 
We expect that the cost of a retest, which is estimated to be 
approximately $2,400 for the mice and animal care, will have minimal 
economic effect on the producers of rabies vaccines, none of which are 
small entities under SBA criteria.
    Under these circumstances, the Administrator of the Animal and 
Plant Health Inspection Service has determined that this action will 
not have a significant economic impact on a substantial number of small 
entities.

Executive Order 12372

    This program/activity is listed in the Catalog of Federal Domestic 
Assistance under No. 10.025 and is subject to Executive Order 12372, 
which requires intergovernmental consultation with State and local 
officials. (See 7 CFR part 3015, subpart V.)

Executive Order 12988

    This final rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule will not preempt any State or local laws, regulations, or 
policies, unless they present an irreconcilable conflict with this 
rule. The Virus-Serum-Toxin Act does not provide administrative 
procedures which must be exhausted prior to a judicial challenge to the 
provisions of this rule.

Paperwork Reduction Act

    This rule contains no new information collection or recordkeeping 
requirements under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 
et seq.).

List of Subjects in 9 CFR Part 113

    Animal biologics, Exports, Imports, Incorporation by reference, 
Reporting and recordkeeping requirements.
    Accordingly, we are amending 9 CFR part 113 as follows:

PART 113--STANDARD REQUIREMENTS

    1. The authority citation for part 113 continues to read as 
follows:

    Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.2(d).

    2. In Sec. 113.209, paragraphs (b)(1) and (d)(3) are revised to 
read as follows:


Sec. 113.209  Rabies Vaccine, Killed Virus.

* * * * *
    (b) * * *
    (1) The preinactivation virus titer must be established as soon as 
possible after harvest by at least five separate virus titrations. A 
mean relative potency value of the vaccine to be used in the host 
animal potency test must be established by at least five replicate 
potency tests conducted in accordance with the standard NIH test for 
potency in chapter 37 of ``Laboratory Techniques in Rabies,'' Fourth 
Edition (1996), edited by F.X. Meslin, M.M. Kaplan, and H. Koprowski, 
World Health Organization, Geneva, Switzerland (ISBN 92 4 154479 1). 
The provisions of chapter 37 of ``Laboratory Techniques in Rabies,'' 
Fourth Edition (1996), are the minimum standards for achieving 
compliance with this section and are incorporated by reference. These 
provisions state that the challenge virus standard to be used as the 
challenge in the NIH test and the reference vaccine for the test are 
available from the national control authority. In the United States, 
that authority is the Animal and Plant Health Inspection Service's 
Center for Veterinary Biologics Laboratory, located at 1800 Dayton 
Avenue, P.O. Box 844, Ames, IA 50010; phone (515) 239-8331; fax (515) 
239-8673. This incorporation by reference was approved by the Director 
of the Federal Register in accordance with 5 U.S.C. 552(a) and 1 CFR 
part 51. Copies may be obtained from the World Health Organization 
Publications Center USA, 49 Sheridan Avenue, Albany, NY 12210. Copies 
may be inspected at the Animal and Plant Health Inspection Service, 
Center for Veterinary Biologics, Licensing and Policy Development, 4700 
River Road, Riverdale, MD, or at the Office of the Federal Register, 
800 North Capitol Street, NW., suite 700, Washington, DC.
* * * * *
    (d) * * *
    (3) Potency test. Bulk or final container samples of completed 
product from each serial must be tested for potency by tests conducted 
in accordance with the standard NIH test for potency in Chapter 37 of 
``Laboratory Techniques in Rabies,'' Fourth Edition

[[Page 45421]]

(1996), which is incorporated by reference at paragraph (b)(1) of this 
section. The relative potency of each serial must be at least equal to 
that used in an approved host animal immunogenicity test.

    Done in Washington, DC, this 13th day of August, 1999.
Bobby R. Acord,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 99-21595 Filed 8-19-99; 8:45 am]
BILLING CODE 3410-34-P