The FDA signaled a policy shift by saying it will generally require randomized controlled trials (RCTs) to support approvals of CAR‑T cell therapies, except in narrowly defined circumstances such as very rare or multiply relapsed populations. CBER Director Vinay Prasad and other agency officials outlined the change in a JAMA article and agency briefings, citing experience with single‑arm approvals and the need for comparative evidence. Agency officials noted seven prior CAR‑T biologics were approved on single‑arm data with response‑rate endpoints; moving to RCTs will prioritize survival or clinically meaningful time‑to‑event endpoints. The change raises the bar for sponsors planning registrational paths and could extend development timelines and costs while aiming to produce clearer evidence of benefit versus standard care. Companies with programs in development will need to reassess trial designs, enrollment strategies and global site selection; regulators emphasized exceptions for rare diseases and heavily pretreated cohorts. Observers expect the shift to reshape investment, partnering and go‑to‑market strategies for next‑generation cell therapies.