Viruses, Serums, Toxins, and Analogous Products; Standard Requirements for Live Vaccines, 4470-4472 [E7-1531]

Agencies

• DEPARTMENT OF AGRICULTURE
• Animal and Plant Health Inspection Service

[Federal Register Volume 72, Number 20 (Wednesday, January 31, 2007)]
[Proposed Rules]
[Pages 4470-4472]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-1531]


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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: Proposed rule.

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SUMMARY: We are proposing 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. In addition, we are 
proposing to amend the requirement concerning mouse safety tests 
prescribed for a biological product recommended for animals other than 
poultry. These proposed changes would update the standard requirements 
by eliminating unnecessary testing of Master Seed bacteria and viruses 
and other forms of bulk or completed biological product.

DATES: We will consider all comments that we receive on or before April 
2, 2007.

ADDRESSES: You may submit comments by either of the following methods:
     Federal eRulemaking Portal: Go to https://
www.regulations.gov, select ``Animal and Plant Health Inspection 
Service'' from the agency drop-down menu, then click ``Submit.'' In the 
Docket ID column, select APHIS-2006-0079 to submit or view public 
comments and to view supporting and related materials available 
electronically. Information on using Regulations.gov, including 
instructions for accessing documents, submitting comments, and viewing 
the docket after the close of the comment period, is available through 
the site's ``User Tips'' link.
     Postal Mail/Commercial Delivery: Please send four copies 
of your comment (an original and three copies) to Docket No. APHIS-
2006-0079, Regulatory Analysis and Development, PPD, APHIS, Station 3A-
03.8, 4700 River Road Unit 118, Riverdale, MD 20737-1238. Please state 
that your comment refers to Docket No. APHIS-2006-0079.
    Reading Room: You may read any comments that we receive on this 
docket in our reading room. The reading room is located in room 1141 of 
the USDA South Building, 14th Street and Independence Avenue, SW., 
Washington, DC. Normal reading room hours are 8 a.m. to 4:30 p.m., 
Monday through Friday, except holidays. To be sure someone is there to 
help you, please call (202) 690-2817 before coming.
    Other Information: Additional information about APHIS and its 
programs is available on the Internet at https://www.aphis.usda.gov.

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

[[Page 4471]]

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 in the regulations for certain live bacterial and viral 
vaccines require each lot of Master Seed virus or bacteria used for 
vaccine production to be tested for the ability to provoke an immune 
response (immunogenicity) prior to licensure. In addition, the 
regulations require such Master Seed virus and bacteria to be retested 
3 years after completion of the initial immunogenicity test to confirm 
persistence of the ability to provoke an immune response.
    The requirement to periodically confirm the immunogenicity of a 
Master Seed has been in place since the adoption of the master seed 
concept for vaccine production; and had been considered necessary by 
APHIS 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. APHIS' analysis 
of data submitted by veterinary biologics licensees over several years 
has shown that the immunogenicity of the Master Seed is not adversely 
affected over extended periods of storage. Therefore, the requirement 
to retest Master Seed bacteria and viruses for immunogenicity 3 years 
after completion of the initial immunogenicity test is no longer 
considered necessary and would be removed. The elimination of such 
testing would result in a reduction in testing costs for veterinary 
biologics licensees and permittees.

Mouse Safety Tests

    Safety tests are conducted to ensure that veterinary biologicals 
are free from properties causing undue local or systemic reactions. 
When the mouse safety test is prescribed in a standard requirement or 
filed Outline of Production for veterinary biologicals, the current 
regulations in Sec.  113.33 specify that vaccine must be tested by 
inoculating one group of eight mice intracerebrally with 0.03 mL of 
vaccine and a second group of eight mice intraperitoneally with 0.5 mL 
of vaccine. Recent data, however, show that inoculating mice 
subcutaneously with 0.5 mL of vaccine is as effective as intracerebral 
inoculation with 0.03 mL. Therefore, we are proposing to amend the 
regulations regarding the mouse safety test by removing the reference 
to intracerebral inoculation with 0.03 mL of vaccine and replacing it 
with a reference to subcutaneous inoculation with 0.5 mL of vaccine. 
The subcutaneous and intraperitoneal routes of inoculation are 
considered equally sensitive for the purposes of the mouse safety test. 
Therefore, we are also proposing to amend the regulations to provide 
that only one route of inoculation--either the subcutaneous route or 
intraperitoneal route--be used in the test, rather than two routes as 
is currently required, and that the test be performed on a single group 
of eight mice, rather than the two groups of eight currently required. 
Although this proposed change would reduce the level of testing 
required by the regulations, we do not anticipate that the reduction in 
the number of mice used in the safety test would result in an increased 
number of vaccine-associated local or systemic reactions.
    These proposed amendments would update the standard requirements 
for veterinary biological products by eliminating test procedures which 
are no longer necessary to ensure the safety of veterinary biologics.

Executive Order 12866 and Regulatory Flexibility Act

    This proposed 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 proposing to amend 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 proposed amendment would update 
the regulations concerning mouse safety tests by requiring either 
intraperitoneal or subcutaneous inoculation of mice in place of the 
current requirement to inoculate mice intracerebrally and 
intraperitoneally. These proposed amendments, if adopted, would remove 
test procedures that do not provide additional assurance that such 
products are not worthless, contaminated, dangerous, or harmful.
    This proposed rule would affect veterinary biologics licensees and 
permittees producing live bacterial and viral vaccines and/or 
conducting the mouse safety test. According to the 2006 Current 
Veterinary Biologics Product Catalog, there are approximately 122 
licensed and 21 permittee veterinary biologics establishments. The 
majority of these establishments produce veterinary products and would 
be affected by this proposal. The entities are classified under North 
American Industrial Classification System (NAICS) code 325414, 
Biological Product Manufacturing, and NAICS code 541710, Research and 
Development in the Physical, Engineering and Life Sciences. The small 
entity size standard for both groups is 500 or fewer employees.
    According to the Small Business Administration, most veterinary 
biologics establishments would be classified as small entities. In 
2002, there were 296 establishments in the Biological Product 
Manufacturing subsector, 96 percent of which had fewer than 500 
employees. However, APHIS does not have the 2006 information on the 
sizes of all potentially affected entities.
    The proposed changes would reduce testing costs for those entities 
by eliminating the requirement to retest the Master Seed for 
immunogenicity 3 years after the initial qualifying immunogenicity 
test. The proposed changes would also reduce, by half, the number of 
mice used in mouse safety tests by requiring either intraperitoneal or 
subcutaneous inoculation of mice in place of the current requirement to 
inoculate mice both intracerebrally and intraperitoneally. By revising 
the mouse safety test, it would only be necessary to test mice by 
requiring inoculation either intraperitoneally or subcutaneously. 
Reducing the number of mice needed for inoculation would therefore 
decrease the total cost of laboratory testing.
    This proposal would not impose any additional economic burden upon 
the establishments because it actually eliminates testing requirements 
for the Master Seed and reduces the number of mice, by half, to be 
tested. The overall effects of this action would be to reduce the costs 
associated with producing and testing veterinary and biological 
products. APHIS has been unable to quantify the potential cost savings, 
and welcomes public comment on the savings that would be afforded by 
the proposed rule. While the overall effect of this action would be to 
reduce the costs associated with producing and testing veterinary 
biological products, we do not expect the amount saved would represent 
a significant percentage of overall costs.
    Under these circumstances, the Administrator of the Animal and 
Plant Health Inspection Service has determined that this action would 
not

[[Page 4472]]

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 proposed rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule would 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 proposed 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.

    Accordingly, we propose to amend 9 CFR part 113 as follows:

PART 113--STANDARD REQUIREMENTS

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

    Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.4.

    2. In Sec.  113.8, paragraph (d) would be amended as follows:
    a. By revising the heading to paragraph (d).
    b. By removing paragraph (d)(1).
    c. By removing the paragraph designation ``(d)(2)''.


Sec.  113.8  In vitro tests for serial release.

* * * * *
    (d) Extending the dating of a reference. * * *
* * * * *
    3. In Sec.  113.33, paragraphs (a)(1) and (a)(2) would be 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, 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]

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


Sec.  113.67  [Amended]

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


Sec.  113.70  [Amended]

    6. In Sec.  113.70, paragraph (b)(5) would be removed.


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

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


Sec.  113.303  [Amended]

    8. In Sec.  113.303, paragraph (c)(6) would be removed.


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

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


Sec.  113.305  [Amended]

    10. In Sec.  113.305, paragraphs (b)(1)(iii) and (b)(2)(iii) would 
be removed and paragraph (b)(2)(iv) would be redesignated as paragraph 
(b)(2)(iii).


Sec. Sec.  113.308 and 113.316  [Amended]

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


Sec.  113.309  [Amended]

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


Sec.  113.310  [Amended]

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


Sec.  113.311  [Amended]

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


Sec.  113.312  [Amended]

    15. In Sec.  113.312, paragraphs (b)(5) and(b)(6) would be removed 
and paragraph (b)(7) would be redesignated as paragraph (b)(5).


Sec. Sec.  113.313 and 113.328  [Amended]

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


Sec. Sec.  113.325 and 113.326  [Amended]

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


Sec.  113.329  [Amended]

    18. In Sec.  113.329, paragraph (c)(5) would be removed and 
paragraphs (c)(6) and (c)(7) would be redesignated as paragraphs (c)(5) 
and (c)(6), respectively.

    Done in Washington, DC, this 25th day of January 2007.
Kevin Shea,
Acting Administrator, Animal and Plant Health Inspection Service.
 [FR Doc. E7-1531 Filed 1-30-07; 8:45 am]
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