Scientific Publications by FDA Staff

Procedia Vaccinol 2011;5:47-59

Alternative methods and strategies to reduce, refine, and replace animal use for human vaccine post-licensing safety testing: state of the science and future directions.

Isbrucker R, Levis R, Casey W, McFarland R, Schmitt M, Arciniega J, Descamps J, Finn T, Hendriksen C, Horiuchi Y, Keller J, Kojima H, Sesardic D, Stickings P, Johnson NW, Allen D

NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use (the 3Rs). Six topics were addressed in detail by speakers and workshop participants and are reported in a series of reports. This workshop report, the fifth in the series, addresses methods and strategies for human vaccine post-licensing safety testing that can reduce, refine, and replace animal use. It also provides recommendations for priority research and other activities necessary to advance the development and/or implementation of 3Rs methods for human vaccine post-licensing safety testing. Workshop participants agreed that future 3Rs activities should give highest priority to vaccine safety tests that (1) use the most animals per test and for which many vaccine lots are tested annually, (2) produce high variability and/or require frequent repeat tests, (3) are associated with severe animal pain and distress, and/or (4) involve nonhuman primates. Based on these criteria, safety tests for diphtheria, pertussis, oral polio, and tetanus vaccines were identified as the highest priorities. Recommended priority research, development, and validation activities included (1) expanding use of the transgenic mouse model for oral polio vaccine, and (2) developing alternatives to the monkey neurovirulence test for preclinical safety and lot release neurovirulence testing of mumps vaccines. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for human vaccine post-licensing safety testing that will benefit animal welfare while ensuring continued production of safe human vaccines and protection of human and animal health.