The FDA’s biologics leadership signaled a policy shift requiring many new CAR‑T applications to demonstrate superiority versus existing therapies, the agency’s guidance and commentary show. Regulators expect more randomized, head‑to‑head trials rather than single‑arm approvals based on historical benchmarks, increasing the evidentiary bar for cell therapy developers. Vinay Prasad, the FDA’s biologics chief, and related agency publications framed the change as a move to protect patients and ensure new treatments offer meaningful benefits over approved standards. Developers will need to redesign trial strategies, potentially extending timelines and costs for programs that previously sought accelerated pathways based on single‑arm data. The policy adjustment may slow some near‑term approvals but could also shift investment toward larger, comparative trials that produce clearer value propositions for payers and clinicians.