[Federal Register: October 6, 2003 (Volume 68, Number 193)]
[Proposed Rules]
[Page 57638-57639]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06oc03-15]
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Proposed Rules
Federal Register
________________________________________________________________________
This section of the FEDERAL REGISTER contains notices to the public of
the proposed issuance of rules and regulations. The purpose of these
notices is to give interested persons an opportunity to participate in
the rule making prior to the adoption of the final rules.
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[[Page 57638]]
DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service
9 CFR Part 113
[Docket No. 03-054-1]
Viruses, Serums, Toxins, and Analogous Products; Standard
Requirements for Bovine Virus Diarrhea and Bovine Rhinotracheitis
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 concerning Standard Requirements for Bovine Virus Diarrhea
Vaccine, Killed Virus, and Bovine Rhinotracheitis Vaccine, Killed
Virus, to require that those vaccines elicit specific antibody titer
that is at least 80 percent of the geometric mean antibody titer
obtained in the vaccinates in the host animal protection study to pass
the potency test. We are proposing these changes based on data showing
that the 1:8 minimum antibody titer for vaccinates specified in the
current standard requirement potency tests may not be adequate to
protect animals challenged with virulent virus. The effect of the
proposed changes would be to establish potency test requirements for
these vaccines that are based on the host animal protection study
performed by the licensee.
DATES: We will consider all comments that we receive on or before
December 5, 2003.
ADDRESSES: You may submit comments by postal mail/commercial delivery
or by e-mail. If you use postal mail/commercial delivery, please send
four copies of your comment (an original and three copies) to: Docket
No. 03-054-1, Regulatory Analysis and Development, PPD, APHIS, Station
3C71, 4700 River Road Unit 118, Riverdale, MD 20737-1238. Please state
that your comment refers to Docket No. 03-054-1. If you use e-mail, address your comment to regulations@aphis.usda.gov. Your comment must
be contained in the body of your message; do not send attached files.
Please include your name and address in your message and ``Docket No.
03-054-1'' on the subject line.
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.
APHIS documents published in the Federal Register, and related
information, including the names of organizations and individuals who
have commented on APHIS dockets, are available on the Internet at
http://www.aphis.usda.gov/ppd/rad/webrepor.html.
FOR FURTHER INFORMATION CONTACT: Dr. Albert P. Morgan, Chief of
Operational Support, 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. A standard
requirement consists of test methods, procedures, and criteria
established by the Animal and Plant Health Inspection Service (APHIS)
to help ensure that veterinary biological products are pure, safe,
potent, and efficacious. The requirements in Sec. 113.215 for Bovine
Virus Diarrhea Vaccine, Killed Virus, and in Sec. 113.216 for Bovine
Rhinotracheitis Vaccine, Killed Virus, specify minimum potency
requirements for those products. Under those regulations, a serial of
vaccine must induce antibody titers of at least 1:8 in calves.
The current standard requirements state that four of the five
calves vaccinated with bovine virus diarrhea vaccine or bovine
rhinotracheitis vaccine in a valid potency test must respond with
minimum antibody titers of at least 1:8 or greater for a satisfactory
serial, but do not specify that the titers must have been shown to be
protective in a host animal protection study. Post-vaccinal antibody
titers of 1:8 were once considered to be the minimal index of
protection for bovine virus diarrhea vaccines and bovine
rhinotracheitis vaccines, but more recent data suggest that while some
bovine virus diarrhea vaccines and bovine rhinotracheitis vaccines may
induce antibody titers of 1:8, those titers may not be indicative of
protection in all cases.
We are proposing to amend the standard requirements in Sec. Sec.
113.215 and 113.216 by changing the minimum specific antibody titers
that must be obtained in calves in a satisfactory potency test from at
least 1:8 to at least 80 percent of the geometric mean antibody titer
elicited in vaccinates challenged successfully in the manufacturer's
host animal protection study. We believe that a minimum antibody titer
that is based on the protective titer determined in the host animal
protection study will be more indicative of an efficacious product than
the 1:8 titer currently specified in the standard requirements.
We are proposing to establish minimum potency requirements for
Bovine Virus Diarrhea Vaccine, Killed Virus, and Bovine Rhinotracheitis
Vaccine, Killed Virus, that are specific to the products that each
manufacturer has shown to be efficacious in a host animal protection
study. We would set 80 percent of the geometric mean antibody titer
elicited in vaccinates used in the host animal protection study as the
minimum specific antibody titer that each vaccine must induce to pass
the potency test. We have determined that vaccines that induce titers
similar to the titers elicited in the efficacy study are more likely to
protect cattle against disease.
Potency
Under this proposed rule, vaccinates in a valid potency test would
have to develop minimum antibody titers that are at least 80 percent of
the geometric mean antibody titer developed by vaccinates that were
protected against challenge in the manufacturer's host animal
protection study.
[[Page 57639]]
Miscellaneous
The regulations in Sec. Sec. 113.215(c)(2)(vii) and
113.216(c)(2)(vii) provide that prevaccination and postvaccination sera
from a satisfactory potency test shall be submitted to the National
Veterinary Services Laboratories (NVSL) for testing by APHIS. The
testing referred to in those paragraphs is now performed by APHIS'
Center for Veterinary Biologics-Laboratory, and not by NVSL, so we
would amend Sec. Sec. 113.215(c)(2)(vii) and 113.216(c)(2)(vii) to
reflect that change.
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.
Currently, only 7 of the approximately 135 licensed veterinary
biologics manufacturers produce Bovine Virus Diarrhea Vaccine, Killed
Virus, and Bovine Rhinotracheitis Vaccine, Killed Virus, and would thus
be affected by this proposal. According to the standards of the Small
Business Administration, most veterinary biologics establishments would
be classified as small entities.
This proposed rule would amend the standard requirements in Sec.
113.215 for Bovine Virus Diarrhea Vaccine, Killed Virus, and in Sec.
113.216 for Bovine Rhinotracheitis Vaccine, Killed Virus, by specifying
that the effectiveness of the antibody titers based on host animal
studies is the basis for determining the potency of the vaccine. We
believe that the antibody titer elicited in the manufacturer's host
animal protection study would be more indicative of the efficacy of the
vaccine than the titer currently specified in the regulations. This
change would affect all licensed manufacturers of veterinary biologics
producing Bovine Virus Diarrhea Vaccine, Killed Virus, and Bovine
Rhinotracheitis Vaccine, Killed Virus. However, we do not expect that
there would be any increase in costs for the biologics manufacturers
affected by this proposed rule. The changes should actually be cost
neutral for most affected manufacturers because those manufacturers
would not be required to change the way that their products are
manufactured or tested.
Under these circumstances, the Administrator of the Animal and
Plant Health Inspection Service has determined that this action would
not have a significant economic impact on a substantial number of small
entities.
Executive Order 12372
This program/activity is listed in the category 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 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, 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. 113.215, paragraphs (c)(2)(v) and (c)(2)(vii) would be
revised to read as follows.
Sec. 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus.
* * * * *
(c) * * *
(2) * * *
(v) Test interpretation. If the controls have not remained
seronegative at 1:2, the test is a No Test (NT) and may be repeated. If
at least four of the five vaccinates in a valid test have not developed
50 percent endpoint titers that are at least 80 percent of the
geometric mean antibody titer developed in the vaccinates in the host
animal protection study provided for in paragraph (b) of this section,
the serial is unsatisfactory except as provided in paragraph (c)(2)(vi)
of this section.
* * * * *
(vii) The prevaccination and postvaccination sera from a
satisfactory potency test shall be submitted to the Center for
Veterinary Biologics-Laboratory for confirmatory testing.
3. In Sec. 113.216, paragraphs (c)(2)(v) and (c)(2)(vii) would be
revised to read as follows.
Sec. 113.216 Bovine Rhinotracheitis Vaccine, Killed Virus.
* * * * *
(c) * * *
(2) * * *
(v) Test interpretation. If the three controls have not remained
seronegative at 1:2, the test is a No Test (NT), and may be repeated.
If at least four of the five vaccinates in a valid test have not
developed 50 percent endpoint titers that are at least 80 percent of
the geometric mean antibody titer developed in the vaccinates in the
host animal protection study provided for in paragraph (b) of this
section, the serial is unsatisfactory, except as provided in paragraph
(c)(2)(vi) of this section.
* * * * *
(vii) The prevaccination and postvaccination sera from a
satisfactory potency test shall be submitted to the Center for
Veterinary Biologics-Laboratory for testing by the Animal and Plant
Health Inspection Service.
Done in Washington, DC, this 30th day of September 2003.
Kevin Shea,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 03-25252 Filed 10-3-03; 8:45 am]
BILLING CODE 3410-34-P