Abstract
Biohazard assessment of biodefense vaccine candidates forms the basis for a facility- and activity-specific risk assessment performed to determine the biosafety levels and general safety standards required for biological product development. As part of our support to the U.S. biodefense vaccine development program, the author performed a systematic biohazard assessment of potential vaccine candidates with the primary objectives to: (a) identify and characterize hazard elements associated with the wild-type and vaccine strains; (b) provide biohazard information on the vaccine candidate to assist Phase 1 clinical trial facility sites; (c) provide a baseline agent and facility-specific risk assessment at clinical trial facilities interested in performing Phase 1 clinical trials; (d) provide comparative hazard profiles of the vaccine candidates with Material Safety Data Sheet (MSDS) for wild-type to identify and establish appropriate protective biosafety levels; and (e) support a determination of the personal protective equipment as required under the OSHA guidelines. This paper describes the biohazard analysis of two vaccine candidates, Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella tularensis LVS, a viral and bacterial agent, respectively. As part of the biohazard assessment, we performed a thorough review of published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental data on the etiologic agent subtypes and the vaccine candidates.
Using standard analytical procedures, the data were then analyzed relative to two intrinsic hazard parameters–health hazard and environmental hazard. Using a Weight-of-Evidence (WoE) approach, the potential hazards of etiologic agent wild-subtypes and vaccine candidates were ranked under three main categories: Public Health Hazard; Environmental Hazard; and Overall Hazard. A WoE scoring system allows for both a determination of the intrinsic hazard of each vaccine and also allows for a comparison of values between vaccines. The information in this hazard assessment, and the WoE scores in particular, provided a systematic analytical framework to begin facility-specific risk assessments for follow on manufacturing and Phase 1 clinical trials.