The U.S. FDA’s shift toward accepting one adequate, well‑controlled pivotal trial as a default for marketing authorization sparked debate over global consequences. FDA Commissioner Marty Makary and CBER Director Vinay Prasad argued the change could speed development and lower costs; analysts and international stakeholders cautioned it may conflict with global regulatory norms and payer expectations. Separately, the FDA proposed a rapid “plausible mechanism” framework for rare disease drug development intended to streamline approvals for genetically personalized therapies. Industry groups praised the intent but requested clarification on evidentiary standards and implementation to avoid ambiguity in trial design and global harmonization. Regulators, industry and payers will now need to reconcile the new U.S. posture with established requirements elsewhere to ensure that approval pathways remain credible and compatible with reimbursement and international regulatory standards.