The FDA proposed a “Plausible Mechanism Framework” as an alternative evidence pathway for individualized and disease-targeted therapies when standard randomized trials may be impractical. BIO said it supports the initiative but called for clearer scope, operational detail, and modality-agnostic implementation. BIO urged extending the framework beyond strictly individualized products, providing definitions and references to existing FDA guidance, and aligning CMC expectations with feasibility constraints early in development. BIO also pushed for explicit incorporation of prior knowledge and platform technologies across the product lifecycle—attempting to reduce uncertainty for sponsors developing rare-disease or precision therapies.