The goal of the project is to advance the FDA's mission to protect consumers by providing scientifically sound criteria to assure the safety and potency of vaccines and immune globulins, to prevent the transmission of viruses by blood, and to assess the risks associated with transmissible spongiform encephalopathies and regulated products. The project is intended to provide CBER and other Centers in the FDA with valid methods and statistical approaches that bridge the fields of biostatistics and laboratory-based experimental microbiology and immunology. Earlier research on vaccine test development resulted in development of statistical test-validity criteria and decision (lot release) criteria that were accepted by WHO Working Parties and the WHO Expert Committee on Biological Standards for two alternate tests for the safety of Poliovirus Vaccine Live Oral (OPV): 1) Mutant Analysis by PCR and Restriction Endonuclease Cleavage (MAPREC-see bibliography), and 2) the Transgenic Mouse Neurovirulence test (v.i.). In addition an innovative test was developed for the potency of inactivated poliovirus vaccine based on protection of transgenic mice susceptible to polioviruses against lethal challenge with wild-type viruses. Other more recent collaborative efforts involving nine CBER laboratories in OBRR, OTRR, and OVRR include the following: 1. development of the statistical basis for a test to predict the neurovirulence of mumps vaccines; 2. an assessment of inhibition of immune response to inactivated polioviruses by other components of combined vaccines; 3. research on the modulation of susceptibility of macrophages to infection with HIV and apoptosis in infected monocytes and cell lines; 4. development of accessible statistically sound models for validation and analysis of data generated by oligonucleotide microarrays to discriminate viral subtypes and for improved immunoassays that may offer more sensitive screening of blood donors infected with human T-cell lymphotropic viruses; 5. provided guidance for development of a new national reference standard for Rho(D) immune globulin; 6. provided guidance on preparing quantitative risk analyses for transmissible spongiform encephalopathies based on the most current statistically sound principles (based on advanced training in quantitative risk assessment techniques received from the Harvard School of Public Health and Palisades Corp.); 7. produced risk models and sensitivity analyses for Creutzfeldt-Jakob disease (CJD) in CBER-regulated transplanted tissues; 8. with CDRH scientists, development of an analytical approach suitable for addressing the risk of transmitting CJD by FDA-regulated surgical instruments and implanted devices. 9. developed statistical methods for evaluation of a novel vaccinia neutralization assay based on a reporter gene expression; 10. provided guidance on statistical approaches for the development and validation of pre-clinical toxicity assays for vaccinia-based smallpox vaccines.
