Objectives: Appropriately designed and adequately controlled quality control tests are a cornerstone of the pertussis vaccine regulatory program. Whole-cell pertussis vaccines have been adequately controlled by potency and toxicity tests defined by Federal Regulation; the Laboratory is responsible for maintenance of Standards for these tests. Acellular pertussis vaccines, on the other hand, represent a new product class for which there are no standardized and internationally-accepted methods for assessment of product potency and safety. With respect to quality control of pertussis vaccines, the Laboratory: a) Prepares and maintains standard materials for the control testing of pertussis vaccines. b) Standardizes the toxicity and immunogenicity tests employed for currently licensed acellular pertussis vaccines. c) Develops and evaluates new tests to assess the safety, purity, and potency of acellular pertussis vaccines. FY94 activities: 1. Completed an international collaborative study that assessed that potency and reproducibility of the proposed new US Standard. Data was used to assign potency to this vaccine that was designated as US Standard Pertussis Vaccine, Lot 11. 2. Completed approximately 20 potency assays to assess the stability following reconstitution of Lot 11 Standard and initiated statistical anlaysis of these data. 3. Undertook an historical review of CBER and manufacturer potency testing data of lots of whole-cell pertussis vaccines submitted for release. Data are undergoing analysis to evaluate inter-laboratory reproducibility and to examine for temporal trends. 4. Lyophilized about 3000 ampoules of mouse serum with antibodies to PT, FHA, pertactin, and fimbriae that is a proposed reference serum for the mouse immunogenicity test for licensed acellular vaccines. Defined reagents and methods for the immunogenicity test and initated a final validation study that will be used to detemine intra-laboratory reproducibility and define assay validity criteria. Continued collaborative studies to assess the inter-laboratory reproducibility of the proposed standard assay. 5. Continued development of software for randomization and for probit and Wilson- Worcester analysis of bioassay data. 6. Continued the evaluation of the characteristics of several mouse strains in the histamine sensitivity test that will be used as the final bulk toxicity test for acellular pertussis vaccines. Began a validation study in which ten independent assays will be performed in each of three mouse strains. Data from this study will be used to assess intra-laboratory reproducibility and define assay validity criteria for this test.
