[Federal Register Volume 68, Number 193 (Monday, October 6, 2003)]
[Proposed Rules]
[Pages 57638-57639]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-25252]


 ========================================================================
 Proposed Rules
                                                 Federal Register
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 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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  Federal Register / Vol. 68, No. 193 / Monday, October 6, 2003 / 
Proposed Rules  

[[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 [email protected]. 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