[Federal Register Volume 68, Number 114 (Friday, June 13, 2003)]
[Rules and Regulations]
[Pages 35282-35283]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-14957]


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DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 113

[Docket No. 01-091-2]


Viruses, Serums, Toxins, and Analogous Products; Standard 
Requirements for Determination of Residual Free Formaldehyde Content of 
Biological Products

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: We are amending the Virus-Serum-Toxin Act regulations for the 
determination of residual free formaldehyde in veterinary biologics to 
specify that such determinations be made using the ferric chloride 
method, and that the residual free formaldehyde content be measured in 
grams per liter. The ferric chloride method has been adopted as an 
international standard by scientific experts and regulatory authorities 
in the United States, Canada, Japan, and the European Union. The effect 
of this rule will be to reduce the differences in technical 
requirements for veterinary biologics among regulatory agencies in 
different countries and further ensure the safety and shelf life of 
veterinary biologics by adopting a method that has been standardized 
and accepted internationally.

EFFECTIVE DATE: July 14, 2003.

FOR FURTHER INFORMATION CONTACT: Dr. Albert P. Morgan, Chief Staff 
Officer, Operational Support Section, 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 Virus-Serum-Toxin Act regulations in 9 CFR part 113 (referred 
to below as the regulations) prescribe standard requirements for the 
preparation and testing of veterinary biological products. Standard 
requirements consist of test methods, procedures, and criteria that 
define the standards for purity, safety, potency, and efficacy for a 
given type of veterinary biological product. When a standard procedure 
for testing veterinary biological products is validated and approved by 
the Animal and Plant Health Inspection Service (APHIS) for general use, 
it is proposed for codification in the regulations. Sections 113.100 
and 113.200 of the regulations prescribe the requirement for 
determination of residual free formaldehyde content in inactivated 
bacterial products and killed virus vaccines, respectively.
    On April 5, 2002, we published in the Federal Register (67 FR 
16327-16329, Docket No. 01-091-1) a proposal to amend to amend the 
regulations for determination of residual free formaldehyde content in 
inactivated bacterial products and killed virus vaccines to specify 
that such determinations be made using the ferric chloride method, and 
that the residual free formaldehyde content be measured in grams per 
liter. The proposed rule was intended to reduce the differences in 
technical requirements for veterinary biologics among regulatory 
agencies in different countries and further ensure the safety and shelf 
life of veterinary biologics by adopting a method which has been 
standardized and accepted internationally.
    We solicited comments concerning our proposal for 60 days ending on 
June 4, 2002. We received one comment by that date, from a national 
trade association representing veterinary biologics manufacturers. The 
commenter expressed support for the efforts of APHIS and the 
International Cooperation on Harmonization of Technical Requirements 
for the Registration of Veterinary Medicinal Products (VICH) to 
harmonize the technical requirements for product registration among the 
participating regions and recommended that APHIS adopt the provisions 
of the proposed rule.
    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.
    We are amending the Virus-Serum-Toxin Act regulations for 
determination of residual free formaldehyde content in biological 
products to require that such free formaldehyde determinations be made 
using the ferric chloride method, which determines residual free 
formaldehyde content by measuring the quantity of coloring matter in 
solution by the quantity of light absorbed in passing through the 
solution. In addition, this rule provides that the maximum allowable 
residual free formaldehyde content of veterinary

[[Page 35283]]

biologics be measured in grams per liter, rather than equivalent 
percent or parts per million. The effect of this action will be to 
provide a standardized method that has been shown to be more accurate 
than the basic fuchsin method and that has been standardized and 
adopted internationally.
    This rule will affect all licensed manufacturers of veterinary 
biologics that test inactivated bacterial products and killed virus 
vaccines for free formaldehyde content. Currently, there are 
approximately 135 veterinary biologics establishments, including 
permittees. According to the standards of the Small Business 
Administration, most veterinary biologics establishments would be 
classified as small entities.
    We do not expect that this rule will impose any additional testing 
or economic burden on these manufacturers because manufacturers 
currently test their products for free formaldehyde content using the 
basic fuchsin and other methods, and the reagents and equipment 
necessary to perform the ferric chloride test for free formaldehyde 
content that will be required under this rule are expected to be 
comparable in cost.
    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 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 final rule contains no new information 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, Reporting and recordkeeping 
requirements.

0
Accordingly, we are amending 9 CFR part 113 as follows:

PART 113--STANDARD REQUIREMENTS

0
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 371.4.


0
2. In Sec.  113.100, paragraph (f) is revised to read as follows:


Sec.  113.100  General requirements for inactivated bacterial products.

* * * * *
    (f) If formaldehyde is used as the inactivating agent, and the 
serial has not been found satisfactory by the viricidal activity test, 
bulk or final container samples of completed product from each serial 
must be tested for residual free formaldehyde content using the ferric 
chloride test.\2\ Firms currently using tests for residual free 
formaldehyde content other than the ferric chloride test have until 
July 14, 2004 to update their Outline of Production to be in compliance 
with this requirement.
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    \2\ The procedures for performing the ferric chloride test for 
residual free formaldehyde may be obtained from USDA, APHIS, Center 
for Veterinary Biologics-Laboratory, 1800 Dayton Road, P.O. Box 844, 
Ames, IA 50010.
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    (1) The residual free formaldehyde content of biological products 
containing clostridial antigens must not exceed 1.85 grams per liter 
(g/L).
    (2) The residual free formaldehyde content of bacterins, bacterin-
toxoids, and toxoids, other than those containing clostridial antigens, 
must not exceed 0.74 grams per liter (g/L).

0
3. In Sec.  113.200, paragraph (f) is revised to read as follows:


Sec.  113.200  General requirements for killed virus vaccines.

* * * * *
    (f) Formaldehyde content. If formaldehyde is used as the killing 
agent, the residual free formaldehyde content must not exceed 0.74 
grams per liter (g/L) as determined using the ferric chloride test.\3\ 
Firms currently using tests for residual free formaldehyde content 
other than the ferric chloride test have until July 14, 2004 to update 
their Outline of Production to be in compliance with this requirement.
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    \3\ The procedures for performing the ferric chloride test for 
residual free formaldehyde may be obtained from USDA, APHIS, Center 
for Veterinary Biologics-Laboratory, 1800 Dayton Road, P.O. Box 844, 
Ames, IA 50010.

    Done in Washington, DC, this 10th day of June 2003.
Peter Fernandez,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 03-14957 Filed 6-12-03; 8:45 am]
BILLING CODE 3410-34-P