The FDA issued draft guidance recommending circumstances where developers can reduce or omit nonhuman primate testing for certain monoclonal antibodies, formalizing an approach to rely on alternative nonclinical data in some cases. The agency framed the move as a science- and risk-based pathway to lower animal use while maintaining safety assessments ahead of human dosing. Separately, agency documents expand on how sponsors can use in vitro, rodent, and mechanistic data to de-risk first-in-human studies for some antibody programs. Regulators cited advances in predictive models and the global regulatory environment as drivers for the change. Industry sees the guidance as lowering preclinical cost and timing barriers that can disadvantage U.S. developers; it also raises expectations for sponsors to justify non-primate packages with robust analytical and mechanistic evidence.