The U.S. Food and Drug Administration released draft guidance formalizing the "plausible mechanism" framework to support approvals of individualized cell and gene therapies when randomized trials are impractical. The guidance outlines evidence expectations for safety, efficacy, and manufacturing quality for bespoke medicines targeting ultrarare genetic conditions. The draft clarifies data standards, preclinical considerations, and manufacturing controls that sponsors must meet to pursue approvals based on mechanistic rationale and limited clinical experience. Agency officials and stakeholders framed the move as enabling gene‑editing and personalized therapies previously advanced under ad hoc approaches. Regulatory analysts say the guidance could accelerate submissions for single‑patient or small‑cohort programs, while raising questions about post‑market evidence requirements and scalability of individualized manufacturing. The FDA invited public comment as it finalizes the pathway.