[Code of Federal Regulations]
[Title 9, Volume 1]
[Revised as of January 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 9CFR113.69]

[Page 652-653]
 
                  TITLE 9--ANIMALS AND ANIMAL PRODUCTS
 
  CHAPTER I--ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF 
                               AGRICULTURE
 
PART 113_STANDARD REQUIREMENTS--Table of Contents
 
Sec. 113.69  Pasteurella Multocida Vaccine, Bovine.

    Pasteurella Multocida Vaccine, Bovine, shall be prepared as a 
desiccated live culture bacterial vaccine of an avirulent or modified 
strain of Pasteurella multocida, of bovine origin. Only Master Seed 
which has been established as pure, safe, and immunogenic shall be used 
for vaccine production. All serials of vaccine shall be prepared from 
the first through the fifth passage from the Master Seed.
    (a) The Master Seed shall meet the applicable general requirements 
prescribed in Sec. 113.64 and the requirements in this section.
    (b) Each lot of Master Seed used for vaccine production shall be 
tested for immunogenicity. The immunogenicity of a selected bacterial 
count from the lot of Master Seed shall be established as follows:
    (1) Fifteen Pasteurella multocida susceptible calves shall be used 
as test animals (10 vaccinates and 5 controls) for each route of 
administration recommended on the label.
    (2) An arithmetic mean count of the colony forming units from 
vaccine produced from the highest passage of the Master Seed shall be 
established before the immunogenicity test is conducted. The 10 calves 
to be used as vaccinates shall be injected as recommended on the label 
with a predetermined quantity of vaccine bacteria. The five control 
calves shall be held separately from the vaccinates. To confirm the 
dosage calculation, arithmetic mean count shall be established by 
conducting five replicate titrations on a sample of the bacterial 
vaccine used. Only plates containing between 30 and 300 colonies shall 
be considered a valid test.
    (3) The vaccinates and controls shall be examined and their average 
body temperature determined prior to challenge. Fourteen to twenty-one 
days post vaccination, the vaccinates and controls shall each be 
challenged by the respiratory route with a (virulent) pneumonia 
producing Pasteurella multocida culture and observed for 4 to 10 days. 
The challenge culture and instructions for preparation for use shall be 
furnished or approved by the Animal and Plant Health Inspection Service.
    (4) A satisfactory challenge shall be evidenced in the controls by 
progression of clinical signs consistent with respiratory system 
infection following challenge, including but not limited to acute 
illness with higher body temperature and respiration rate, lacrimation, 
mucoid nasal exudate, expiratory dyspnea, tachypnea, pulmonary rales, 
and cough, possibly terminating in death; moribundity, depression with 
anorexia; diarrhea with substantial weight loss; or any combination of 
these symptoms.
    (5) Lung lesion response to challenge will be assessed in all 
calves. Lung lesions will be assessed at necropsy in calves that succumb 
to challenge. Surviving calves will be euthanized on day 4 to 10 
following challenge and lung lesions assessed at necropsy. Lung lesion 
scores will be used in the assessment of the response to challenge 
exposure. If a significant difference in lung lesion scores cannot be 
demonstrated between vaccinates and controls using a scoring system 
approved by the Animal and Plant Health Inspection Service, the Master 
Seed is unsatisfactory.
    (6) The Master Seed shall be retested for immunogenicity in 3 years 
unless use of the lot previously tested is discontinued. Only five 
vaccinates and five controls need to be used in the retest: Provided, 
that, at least four of five vaccinates and four of five controls shall 
meet the criteria prescribed in paragraphs (b)(4) and (b)(5) of this 
section.
    (7) An Outline of Production change must be made before authority 
for use of a new lot of Master Seed is granted by the Animal and Plant 
Health Inspection Service.
    (c) Test requirements for release. Each serial and subserial shall 
meet the applicable general requirements prescribed in Sec. Sec. 113.8 
and 113.64 and the requirements in this paragraph. Any serial or 
subserial found unsatisfactory

[[Page 653]]

by a prescribed test shall not be released.
    (1) Safety Test. Samples of completed product from each serial or 
first subserial shall be tested for safety in calves as provided in 
Sec. Sec. 113.41(a) and 113.41(b), except that the equivalent of two 
doses of vaccine shall be used and administered in the manner 
recommended on the label.
    (2) Bacterial count requirements. Final container samples of 
completed product shall be tested for bacterial count using the method 
used in paragraph (b)(2) of this section. Two replicate titrations shall 
be conducted on each serial and subserial. Each sample shall be 
rehydrated with accompanying sterile diluent to the volume indicated on 
the label. To be eligible for release, each serial and subserial shall 
have a bacterial count sufficiently greater than that of the vaccine 
used in the immunogenicity test count per dose established to assure 
that, when tested at any time within the expiration period, each serial 
and subserial shall have a bacterial count at least two times greater 
than that used in the immunogenicity test.

[55 FR 35560, Aug. 31, 1990]