The FDA released draft guidance frameworks aimed at accelerating development of personalized and ultrarare therapies. The 'plausible mechanism' concept would let developers advance individualized genomic and RNA‑based treatments for ultrarare conditions with limited trial populations, provided they supply robust mechanistic and target engagement evidence. Agency centers CDER and CBER emphasized genomic editing and RNA therapies in the proposals. Separately, the agency outlined an expedited framework to tailor regulatory expectations for individualized treatments where randomized controlled trials are infeasible. Industry responses seek clearer evidentiary standards and operational guidance, noting the tension between flexibility and the need for predictable approval pathways. If finalized, these frameworks could lower barriers for one‑patient or very small‑cohort programs while raising questions about post‑approval evidence collection and long‑term safety surveillance.