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. FY95 activities: 1. Completed approximately 25 potency tests to assess the stability following reconstitution of US Standard Pertussis Vaccine, Lot 11 and used these data to support extension of the dating period from 24 hours to 14 days following reconstitution. 2. Approximately 2500 ampoules of lyophilized mouse serum with antibodies to PT, FHA, pertactin, and fimbriae were designated as US Standard Pertussis Antiserum (mouse), Lot 1. The serum will serve as a primary standard serum for the mouse immunogenicity test for licensed acellular vaccines. Using defined reagents and methods, a final validation study for the mouse immunogenicity test was conducted that will be used to determine intra-laboratory reproducibility and define assay validity criteria. Continued collaborative studies to assess the inter-laboratory reproducibility of the proposed standard assay. 3. 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. Completed a validation study in which ten independent assays were performed in each of three mouse strains. Data from this study are being used to assess intra-laboratory reproducibility and define assay validity criteria for this test. 4. Continued 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. 5. Continued development of software for randomization and for profit and Wilson-Worcester analysis of bioassay data. 6. Assisted in writing a technical report of an international collaborative study of test systems to assess toxicity of whole-cell pertussis vaccines. 7. Participated in development of a protocol for international collaborative study of a proposed new international standard whole-cell pertussis vaccine.
