9 C.F.R. § 113.317   Parvovirus Vaccine (Canine).
Title 9 - Animals and Animal Products

Title 9: Animals and Animal Products
PART 113—STANDARD REQUIREMENTS
Live Virus Vaccines

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§ 113.317   Parvovirus Vaccine (Canine).

Parvovirus Vaccine recommended for use in dogs shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds 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 §113.300 and the requirements in this section.

(b) The Master Seed shall be tested for reversion to virulence in dogs using a method acceptable to Animal and Plant Health Inspection Service. If a significant increase in virulence is seen within five backpassages, the Master Seed is unsatisfactory.

(c) Each lot of Master Seed shall be tested for immunogenicity. The selected virus dose shall be established as follows:

(1) Twenty-five canine parvovirus susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood samples drawn from each dog shall be individually tested for neutralizing antibody against canine parvovirus to determine susceptibility. Dogs shall be considered susceptible if there is no neutralization at a 1:2 final serum dilution in a constant virus-varying serum neutralization test in cell culture using 50 to 300 TCID₅₀ of canine parvovirus.

(2) A geometric mean titer of the vaccine produced at the highest passage from the Master Seed shall be established before the immunogenicity test is conducted. The 20 dogs used as vaccinates shall be administered a predetermined quantity of vaccine virus by the method recommended on the label. To confirm the dosage calculations, five replicate virus titrations shall be conducted on a sample of the vaccine virus dilution used. If two doses are used, five replicate confirming titrations shall be conducted on each dose.

(3) Fourteen days or more after the final dose of vaccine the vaccinates and the controls shall be challenged with virulent canine parvovirus furnished or approved by Animal and Plant Health Inspection Service and the dogs observed each day for 14 days. Rectal temperature, blood lymphocyte count, and feces for viral detection shall be taken from each dog each day for at least 10 days postchallenge and the presence or absence of clinical signs noted and recorded each day.

(i) The immunogenicity of the Master Seed shall be evaluated on the following criteria of infection: temperature ≥103.4 ° F; lymphopenia of ≥50 percent of prechallenge normal; clinical signs such as diarrhea, mucus in feces, or blood in feces; and viral hemagglutinins at a level of ≥1:64 in a 1:5 dilution of feces or a test of equal sensitivity. If at least 80 percent of the controls do not show at least three of the four criteria of infection during the observation period, the test is inconclusive and may be repeated.

(ii) If at least 19 of the 20 vaccinates do not survive the observation period without showing more than one criterion of infection described in paragraph (c)(3)(i), of this section, the Master Seed is unsatisfactory.

(4) The Master Seed shall be retested for immunogenicity in 3 years unless use of the lot previously tested is discontinued. Five susceptible dogs (four vaccinates and one control) may be used in the retest. Susceptibility shall be determined in the manner provided in paragraph (c)(1) of this section.

(i) Each vaccinate shall be administered a predetermined quantity of vaccine virus as provided in paragraph (c)(2) of this section.

(ii) Fourteen to 21 days after the last vaccination, a second serum sample shall be drawn from each dog and tested for neutralizing antibody to canine parvovirus in the same manner used to determine susceptibility.

(iii) If the control has not remained seronegative at 1:2, the test is inconclusive and may be repeated.

(iv) If three of the four vaccinates in a valid test do not develop titers of at least 1:16 final serum dilution, and the remaining vaccinate does not develop a titer of at least 1:8, the Master Seed is unsatisfactory, except as provided in paragraph (c)(4)(v) of this section.

(v) If the results of a valid SN test are unsatisfactory, the vaccinates and the control may be challenged as provided in paragraph (c)(3) of this section. If at least three of the four criteria of infection are not shown in the control dog, the test is inconclusive and may be repeated, except that if any of the vaccinates show more than one criterion of infection, the Master Seed is unsatisfactory.

(5) An Outline of Production change shall be made before authority for use of a new lot of Master Seed shall be granted by Animal and Plant Health Inspection Service.

(d) Test requirements for release. Each serial and subserial shall meet the applicable general requirements prescribed in §113.300 and the requirements in this paragraph. Any serial or subserial found unsatisfactory by a prescribed test shall not be released.

(1) Virus titer requirements. Final container samples of completed product shall be tested for virus titer using the titration method used in paragraph (c)(2) of this section. To be eligible for release, each serial and each subserial shall have a virus titer sufficiently greater than the titer of vaccine used in the immunogenicity test in paragraph (c) of this section to assure that, when tested at any time within the expiration period, each serial and subserial shall have a virus titer of 10^0.7 greater than that used in the immunogenicity test, but not less than 10^2.5 ID₅₀ per dose.

[50 FR 436, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991]