Table 3: Potency testing of inactivated rabies vaccines: the NIH test and its variants

Number of tests required Mice to be used Number of animals/ dilution Number of dilutions Diluent to be used Number of vaccinationsa Interval between vaccinations (days) Interval between vaccination and challenge (days) Challenge dose (LD50)b Observation period after challenge (days) Criteria for evaluation
Ph. Eur. for human use (38) - Female ± 4 weeks 11-15g Suitablec 3 n.s. 2 7 7 after second ~50 5-14 Death or signs of rabies
WHO (4) 2 13-16g >16 5 (>3) PBS 2 7 14 after first 12 < 25 < 50 > 5-14 Death
Ph. Eur. for veterinary use (33) - Female > 4 weeks > 10 > 3 n.s. 1 n.a. 14 ~50 5-14 Signs of rabies
SAM0308.01 (15) 1 (3, when repeated) Female CF-1 13-15g 16 5 PBS 2 7 ± 1 14 ± 1 after first 12-50 6-14 Death or signs of rabies
OIE (5) - 3-4 weeks > 10 n.s. n.s. 1 or 2 7 if applicable 14 days later > 10 n.s. n.s.
9CFR 113.209 (7) 2 13-16g > 16 5 (> 3) PBS 2 7 14 after first 12 < 25 < 50 > 5-14 Death
Simplified single-dilution test (12) - Female 10 1 - 1 n.a. 14 ? 14 > 80% survival

aInjection volume: 0.5ml; injection route: intraperitoneal.
bChallenge virus: CVS27; challenge route: intracerebral; injection volume: 0.03ml.
cA suitable number of animals should be used to meet the statistical requirements for a valid test.

n.a. = not applicable; n.s. = not specified; PBS = phosphate-buffered saline.

9CFR = US Code of Federal Regulations, Title 9; NIH = National Institutes of Health; OIE = Office International des Epizooties; Ph. Eur. = European Pharmacopoeia; SAM = Supplemental Assay Method; WHO = World Health Organization.