Current State of NHP Use Supporting Fertility Risk Assessment (S11-3)

Clinical drug candidates for non-cancer indications are expected to be tested for effects on fertility and early embryonic development (characterizing risk from premating to conception, and conception to implantation within reproductive life cycle) in routine test species (mostly rodents), however, for many biologics and some small molecules routine test species are not pharmacologically relevant or feasible. For those pharmaceuticals for which NHPs are the only relevant species, use of NHPs is “impractical” for use in mating studies. Guidance suggests that acceptable alternative approaches include: evaluation sexually mature NHP in a repeat dose study of at least 3 months duration with added fertility endpoints as necessary, non-routine species with relevant pharmacology, humanized animal models, or surrogate antibodies. We will describe key considerations when designing sexually mature NHP studies, and present examples of when alternatives were used. There will be discussion around successful use of alternatives, and how subject matter expertise can better be leveraged when employing these alternatives to increase the likelihood of success, overall reducing the use of sexually mature NHP.