The FDA’s biologics chief signaled a policy shift requiring many oncology CAR‑T programs to demonstrate superiority against existing therapies rather than rely on single‑arm or non‑comparative registrational strategies. The agency emphasized randomized superiority trials for certain CAR‑T indications in a public guidance and commentary. The new expectation raises development costs and trial complexity for smaller CAR‑T developers and may delay timelines for approvals unless companies design head‑to‑head programs. The FDA’s stance reflects a regulatory tightening intended to ensure new cell therapies deliver clear patient benefits over standard of care. Sponsors will need to reassess trial design, endpoints and investment strategies in response to the agency’s updated expectations.