Establishment of batch 4 of the Biological Reference Preparation (BRP) for rabies vaccine (inactivated) for veterinary use.

Abstract

9 laboratories from 7 countries including both laboratories from the public and private sector participated in a collaborative study organised under the aegis of the European Directorate for the Quality of Medicines Biological Standardisation Programme in order to establish batch 4 of the European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccine (inactivated) for veterinary use. Establishment of Ph. Eur. BRP batch 4 was necessary in order to replace Ph. Eur. BRP batch 3, the stocks of which were dwindling. 8 laboratories provided results. Ph. Eur. BRP batch 4 was calibrated against the 5th International Standard for inactivated rabies vaccine in International Units (IU) using the vaccination challenge method of the Ph. Eur. monograph 0451. The International Standard (IS), Ph. Eur. BRP batch 4 and batch 3 are all freeze-dried vaccines prepared by beta-propiolactone inactivation of the Pitman Moore strain of rabies. Based on the results of the study, a potency of 11 IU/vial was assigned to Ph. Eur. BRP batch 4 for rabies vaccine (inactivated) for veterinary use. Nevertheless, it was noted that the vaccination challenge assay used as the "golden standard" for potency determination of inactivated rabies vaccines for veterinary use is a crude assay requiring the use of a large number of animals. Evidence from this study and from the collaborative study to establish Ph. Eur. BRP batch 3 suggests that the assay is difficult to perform and provides highly variable results. The validation of a suitable in vitro alternative is therefore highly recommended, as is the possible improvement of the in vivo assay, which will most likely remain the "golden" standard.