Moderna Flu Vaccine Letter Shows How FDA's Refuse-to-File Decisions Work

Moderna said on February 10 that the Food and Drug Administration's Center for Biologics Evaluation and Research will not begin reviewing its biologics license application for mRNA-1010, an investigational seasonal influenza vaccine, and has issued a refusal-to-file letter. According to the company's release, the letter, signed by center director Vinayak Prasad, identified the choice of a licensed standard-dose flu vaccine as the comparator in a Phase 3 study as "the sole reason for the refusal." Moderna said the letter cited the lack of an "adequate and well-controlled" study and did not identify specific safety or efficacy concerns. The company said the decision was inconsistent with CBER's earlier written feedback and that it had requested a Type A meeting.

BioPharma Dive reported that the letter was dated February 3 and that Moderna had posted it publicly. The company had used a priority review voucher for the application.

A threshold check before review

Every application to market a new drug or biologic goes through a filing decision before review begins. For new drug applications, 21 CFR 314.101 says FDA will decide within 60 days of receipt whether the application may be filed, and defines filing as "a threshold determination that the NDA is sufficiently complete to permit a substantive review." The date of filing starts the 180-day period in the statute that the regulation calls the "filing clock."

The regulation lists grounds for refusal, including a missing application form, an application that "does not on its face contain information required" by law, missing English translations and missing statements that clinical studies complied with ethics-board and informed-consent rules. For biologics, 21 CFR 601.2 says a license application "shall not be considered as filed until all pertinent information and data have been received" by FDA.

How CBER applies it

CBER's internal procedure on refusals, SOPP 8404, version 12, effective December 15, 2025, says refusals rest on findings such as administrative incompleteness, scientific incompleteness, including omission of critical data or analyses, and content so poorly presented that meaningful review is precluded. It says CBER will try to fix easily correctable deficiencies, and that before a final decision, a recommended refusal is discussed with senior leadership including the center director. The procedure calls for the letter to reach the applicant within 60 days of CBER's receipt date.

The document also draws a line between two kinds of FDA letters. A refusal to file "is not a final determination concerning potential approvability or the scientific/medical merits of the application," it says, but an early signal that omissions or inadequacies are severe enough to make the application incomplete on its face or to impede a prompt review. Complete response deficiencies, by contrast, come after a full review of a filed application and can involve issues such as the balance of risks and benefits, the size of a clinical effect or "nuances of study design."

What an applicant can do next

The SOPP says an RTF letter must list the deficiencies and tell the applicant it can protest and ask CBER to file and review the application over protest. The NDA rule sets out a similar path: an applicant may request an informal conference within 30 days and, if it still wants the application filed, FDA will file it over protest and review it. An applicant can also correct the gaps and submit a complete new application.

Moderna said mRNA-1010 has been accepted for review in the European Union, Canada and Australia, and that it does not expect the letter to affect its 2026 financial guidance.