[Federal Register Volume 72, Number 20 (Wednesday, January 31, 2007)]
[Proposed Rules]
[Pages 4470-4472]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-1531]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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 http://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 http://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]
BILLING CODE 3410-34-P