In FY 99 LMD continued to lead the WHO Collaborative Study of TgPVR mice and to coordinate results and analyses by participating consultants from CBER, NIBSC, and Canadian regulatory authorities. In June 1998 a WHO Consultation entitled Regulatory Model in Transgenic Mice (TgPVR 21) for Neurovirulence Tests of Oral Poliovirus Vaccine was convened by the WHO Global Programme for Vaccines and Immunization and hosted by LMD at CBER. Documentation prepared by the group was evaluated by the WHO Expert Committee on Biological Standardization (ECBS) in October 1998. In response to recommendations from ECBS in the framework of Phase 4 of the WHO Collaborative Study, the number of tests of type 3 vaccine lots that had failed or passed the monkey neurovirulence test was increased. A statistical model developed earlier by LMD for regulatory decision on acceptance or rejection of type-3 poliovirus vaccine lots underwent an additional validation in Phase 4 as well. Additional experiments in transgenic mice were performed with type-1 and type-2 OPV preparations. Appropriate infectivity doses of vaccine to be tested have been investigated. The same statistical model developed for type-3 OPV will be validated in several laboratories at the beginning of FY'00. The WHO Consultation Group met again in June 1999 to update documentation for presentation to the WHO ECBS Meeting in October 1999. The decision was made to recommend that the ECBS include the Tg mouse neurovirulence test in the WHO Requirements for OPV as alternative to the monkey test. The next step should be implementation--introduction of the mouse test into manufacturing practice and by national regulatory authorities wishing to use it. The WHO Consultation Group asked LMD to serve as a center for training of and consulting with all interested parties.
