The U.S. Food and Drug Administration issued a refusal-to-file (RTF) for Moderna’s mRNA influenza application, prompting immediate pushback from the company and alarm across the vaccine sector. Moderna said the agency’s letter cited procedural issues, not safety or efficacy, and described the decision as inconsistent with prior guidance given during development. The dispute has centered on trial comparators and whether the phase 3 design met the agency’s expectations. Regulatory sources and industry leaders warned the move could chill investment in new vaccine platforms if it signals a higher bar or abrupt policy shifts at CBER. Analysts noted staff-level reviewers appeared prepared to accept the submission while the office director signed the RTF, a sequence that market commentators view as a sign of internal agency tension. Moderna has requested a Type A meeting to clarify next steps and is pursuing regulatory review in other jurisdictions that have accepted its file. For companies developing next-generation vaccines, the episode underscores risk around agency communication and the importance of pre-submission alignment on comparators and endpoints. Biotech executives and investors are watching whether the decision triggers legal challenges, revised trial designs, or changes to regulatory engagement best practices.