Study On The Potency Test By The ELISA For Rabies Vaccine

The rabies vaccine development and manufacture for human has been relied on NIH in vivo animal method to ensure rabies vaccine’s biological efficacy and batch consistency for decades. Even thought NIH in vivo method is well known for result variation, low repeatability, challenging procedure, long assay turn around time, high cost and significant consideration of animal crudity from humane point of view, NIH animal method is still required as final batch release quality control biological activity test for rabies vaccine for human.As a general principle, potency assay for rabies vaccine development is designed to measure the ability of the vaccine to protect the animal(human) against subsequent challenge with the active component responsible for the pathogenicity(ATLA 26, 1998). The vaccine immunogenicity(bioactivity of stimulation) could be critically determined by the key antigen component in the virus. So there is a mechanistically predictable correlation assumption that controlling virus key antigen level could indirectly predict vaccine bioactivity. Beside all the considerations associated to NIH animal method, in last decades, the use of quality control test methods are designed and implemented to fulfill batch consistency rather than ensuring lot effectiveness. Since the beginning of last decade World Health Organization(WHO), European Centre for the Validation of Alternative Methods(ECVAM), FDA and many researchers from academia and vaccine industries have put a lot of effort to push for alternative methods for the potency testing of vaccine manufacture. Among all the potential alternative methodologies, enzyme-linked immunoassay(ELISA) has been under intensive investigation and been used as important potency assays to support biological type drug lot release and even served as final release bioassay for several vaccine manufacture production.The objective of this report is to assess and address the foreseeing feasibility of using ELISA to detect rabies virus G protein level as GMP lot release method to eventually replace NIH animal test at the final product release stage.Different batches final releasing data from both ELISA and NIH animal study has been compared and analyzed in this report and a positive linear correlation between the two methods has been established. Significant advantage of ELISA method, such as assay accuracy, precision, repeatability, ease of the assay procedure, reduction of cost and QCable, has been analyzed out. All the data and referenced result from this report support the feasibility of replacing NIH animal as the GMP release test for rabies human vaccine manufacture with G protein ELISA assay.This report also summarizes the practical process to eventually replace NIH animal test by ELISA. Currently the process is still at the accumulation data stage across all the vaccine manufacturers. Communication and cooperation with FDA and governor regulatory authorities with all the data, finding and clinical experience/data is very crucial. All these efforts will help to make the replacement of NIH animal method with ELISA or another in vitro methodology change from a feasibility test toward a reality implementation for vaccine manufacture eventually.