[Federal Register Volume 72, Number 245 (Friday, December 21, 2007)]
[Rules and Regulations]
[Pages 72563-72564]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-24649]



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  Federal Register / Vol. 72, No. 245 / Friday, December 21, 2007 / 
Rules and Regulations  

[[Page 72563]]



DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 113

[Docket No. APHIS-2006-0079]
RIN 0579-AC30


Viruses, Serums, Toxins, and Analogous Products; Standard 
Requirements for Live Vaccines

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 
certain live bacterial and viral vaccines by removing the requirement 
to retest the Master Seeds for immunogenicity 3 years after the initial 
qualifying immunogenicity test. In addition, we are amending the 
requirement concerning mouse safety tests prescribed for a biological 
product recommended for animals other than poultry. These changes 
update the standard requirements by eliminating unnecessary testing of 
Master Seed bacteria and viruses and other forms of bulk or completed 
biological product.

DATES: Effective Date: January 22, 2008.

FOR FURTHER INFORMATION CONTACT: Dr. Albert P. Morgan, Chief Staff 
Officer, Operational Support Section, Center for Veterinary Biologics, 
Policy, Evaluation, and Licensing, APHIS, USDA, 4700 River Road, Unit 
148, Riverdale, MD 20737-1228; (301) 734-8245.

SUPPLEMENTARY INFORMATION:

Background

    The Virus-Serum-Toxin Act regulations in 9 CFR part 113 (referred 
to below as the regulations) contain standard procedures and 
requirements that are used to establish the purity, safety, potency, 
and efficacy of veterinary biological products. Current standard 
requirements for certain live bacterial and viral vaccines require that 
each Master Seed be retested for immunogenicity 3 years after the 
initial immunogenicity test.
    The requirement to confirm the immunogenicity of a Master Seed at 3 
years has been in place since the master seed concept for vaccine 
production was established, and had been considered necessary until 
such time that an accumulation of data derived from such confirmatory 
testing established the antigenic stability of Master Seed bacteria and 
viruses over extended periods of storage. Data accumulated by 
veterinary biologics licensees over several years have shown that the 
immunogenicity of the Master Seed is not adversely affected over 
extended periods of storage.
    On January 31, 2007, we published in the Federal Register (72 FR 
4470-4472, Docket No. APHIS-2006-0079) a proposal\1\ to amend the 
Virus-Serum-Toxin Act regulations for certain live bacterial and viral 
vaccines by removing the requirement to retest the Master Seeds for 
immunogenicity 3 years after the initial qualifying immunogenicity 
test. We also proposed to amend the requirement concerning mouse safety 
tests prescribed for biological products recommended for animals other 
than poultry.
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    \1\ To view the proposed rule and the comments we received, go 
to http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=APHIS-2006-0079.
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    We solicited comments concerning our proposal for 60 days ending 
April 2, 2007. We received two comments by that date, from a trade 
association representing veterinary biologics manufacturers and a 
representative of a State animal health commission.
    One commenter supported the elimination of unnecessary testing/
retesting from the regulations and noted that such action would 
decrease duplicative testing in animals. With regard to using the 
subcutaneous route of inoculation when conducting the mouse safety 
test, that same commenter recommended that proposed Sec.  113.33(a)(1) 
should provide the option to split the injection volume among more than 
one injection site. The commenter pointed out that this recommendation 
was consistent with the ``good practice'' guidelines for subcutaneous 
injections recommended by the Association for Assessment and 
Accreditation of Laboratory Animal Care.
    We agree with the commenter's recommendation and have amended Sec.  
113.33(a)(1) in this final rule to allow the option of dividing the 0.5 
mL inoculation volume among more than one injection site.
    The second commenter expressed concern that adverse local reactions 
may be missed if intraperitoneal inoculation is the only route used for 
the mouse safety test, and suggested that such test be conducted by 
inoculating mice using both the subcutaneous and intraperitoneal routes 
instead of by only one route as had been proposed.
    In response to the commenter's concern that adverse local reactions 
may be missed if only one route is used, we wish to point out that 
Sec.  113.300(b) of the regulations requires final container samples 
from each serial of product to be tested for safety in at least one 
species for which the vaccine is intended; the purpose of such test is 
to ensure freedom from undue adverse local reactions. Accordingly, we 
are not making any changes in this final rule in response to the 
comment.
    Therefore, for the reasons given in the proposed rule and in this 
document, we are adopting the proposed rule as a final rule, with the 
changes discussed in this document.

Executive Order 12866 and Regulatory Flexibility Act

    This proposed 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 regulations for certain live bacterial and 
viral vaccines to eliminate the requirement to retest the Master Seed 
for immunogenicity 3 years after the initial qualifying immunogenicity 
test. In addition, this amendment updates the regulations concerning 
mouse safety tests by requiring either intraperitoneal or subcutaneous 
inoculation of mice, but not both, in such tests. The primary effect of 
this rule will be to update the standard requirements by eliminating 
unnecessary testing of Master Seed bacteria and viruses and other forms 
of bulk or completed product in animals.

[[Page 72564]]

    There are approximately 125 veterinary biologics establishments, 
including licensees and permittees that may be affected by this rule. 
According to the standards of the Small Business Administration, most 
veterinary biologics establishments would be classified as small 
entities.
    It is anticipated that no increased recordkeeping burden will be 
added to licensees or permittees since the amended regulations actually 
will mean that fewer tests will be needed and fewer reports required to 
be submitted. We further anticipate that licensees and permittees may 
benefit economically from the cost savings associated with the 
reduction in the amount of required animal testing. The overall effect 
of this amendment will be to reduce the costs associated with producing 
and testing veterinary biological products.
    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 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.


Sec.  113.8  [Amended]

0
2. In Sec.  113.8, paragraph (d) is amended as follows:
0
a. In the heading by removing the words ``Repeat immunogenicity tests'' 
and adding the words ``Extending the dating of a reference'' in their 
place.
0
b. By removing paragraph (d)(1).
0
c. By removing the paragraph designation ``(2)''.

0
3. In Sec.  113.33, paragraphs (a)(1) and (a)(2) are revised to read as 
follows:


Sec.  113.33  Mouse safety tests.

* * * * *
    (a) * * *
    (1) Vaccine prepared for use as recommended on the label shall be 
tested by inoculating eight mice intraperitoneally or subcutaneously 
with 0.5 mL (the inoculation volume may be divided among more than one 
injection site), and the animals observed for 7 days.
    (2) If unfavorable reactions attributable to the product occur in 
any of the mice during the observation period, the serial or subserial 
is unsatisfactory. If unfavorable reactions which are not attributable 
to the product occur, the test shall be declared inconclusive and may 
be repeated: Provided, That, if the test is not repeated, the serial or 
subserial shall be declared unsatisfactory.
* * * * *


Sec. Sec.  113.66, 113.68, and 113.69  [Amended]

0
4. In Sec. Sec.  113.66, 113.68, and 113.69, paragraph (b)(6) is 
removed and paragraph (b)(7) is redesignated as paragraph (b)(6).


Sec.  113.67  [Amended]

0
5. In Sec.  113.67, paragraph (b)(7) is removed and paragraph (b)(8) is 
redesignated as paragraph (b)(7).


Sec.  113.70  [Amended]

0
6. In Sec.  113.70, paragraph (b)(5) is removed.


Sec. Sec.  113.71, 113.306, and 113.318  [Amended]

0
7. In Sec. Sec.  113.71, 113.306, and 113.318, paragraph (b)(4) is 
removed and paragraph (b)(5) is redesignated as paragraph (b)(4).


Sec.  113.303  [Amended]

0
8. In Sec.  113.303, paragraph (c)(6) is removed.


Sec.  113.302, 113.304, 113.314, 113.315, 113.317, 113.327, 113.331, 
and 113.332  [Amended]

0
9. In Sec. Sec.  113.302, 113.304, 113.314, 113.315, 113.317, 113.327, 
113.331, and 113.332, paragraph (c)(4) is removed and paragraph (c)(5) 
is redesignated as paragraph (c)(4).


Sec.  113.305  [Amended]

0
10. In Sec.  113.305, paragraphs (b)(1)(iii) and (b)(2)(iii) are 
removed and paragraph (b)(2)(iv) is redesignated as paragraph 
(b)(2)(iii).


Sec. Sec.  113.308 and 113.316  [Amended]

0
11. In Sec. Sec.  113.308 and 113.316, paragraph (b)(5) is removed and 
paragraph (b)(6) is redesignated as paragraph (b)(5).


Sec.  113.309  [Amended]

0
12. In Sec.  113.309, paragraph (c)(9) is removed and paragraph (c)(10) 
is redesignated as paragraph (c)(9).


Sec.  113.310  [Amended]

0
13. In Sec.  113.310, paragraph (c)(8) is removed and paragraph (c)(9) 
is redesignated as paragraph (c)(8).


Sec.  113.311  [Amended]

0
14. In Sec.  113.311, paragraph (c)(7) is removed and paragraph (c)(8) 
is redesignated as paragraph (c)(7).


Sec.  113.312  [Amended]

0
15. In Sec.  113.312, paragraphs (b)(5) and(b)(6) are removed and 
paragraph (b)(7) is redesignated as paragraph (b)(5).


Sec. Sec.  113.313 and 113.328  [Amended]

0
16. In Sec. Sec.  113.313 and 113.328, paragraph (c)(6) is removed and 
paragraph (c)(7) is redesignated as paragraph (c)(6).


Sec. Sec.  113.325 and 113.326  [Amended]

0
17. In Sec. Sec.  113.325 and 113.326, paragraph (c)(5) is removed and 
paragraph (c)(6) is redesignated as paragraph (c)(5).


Sec.  113.329  [Amended]

0
18. In Sec.  113.329, paragraph (c)(5) is removed and paragraphs (c)(6) 
and (c)(7) are redesignated as paragraphs (c)(5) and (c)(6), 
respectively.

    Done in Washington, DC, this 13th day of December 2007.
Kevin Shea,
Acting Administrator, Animal and Plant Health Inspection Service.
 [FR Doc. E7-24649 Filed 12-20-07; 8:45 am]
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