Ever since the FDA issued a Refuse-To-File (RTF) letter to Moderna regarding its initial determination not to review the Biologics License Application (BLA) for Moderna’s new mRNA flu vaccine, the buzz in the industry has sounded as loud as a chainsaw cutting through the thick trunk of a giant redwood tree. How could this happen? While the issuance of an RTF letter is not always deadly to a firm’s proposed filing, it is certainly unusual, especially when the firm already thought it had an agreement with the FDA on its approach after multiple meetings with the Agency. Clearly, something had changed, and the Agency’s action sent a shockwave through the BLA world. But not for long.
The FDA’s reversal of its decision, in my opinion, demonstrates that there was some significant disagreement among senior-level Agency management, and the review staff at least, as well as likely members of the firm. Yet, this disagreement seems to have resolved at breakneck speed after a hastily arranged Type A meeting with the FDA. The typical timeline for arranging a Type A meeting belies the speed with not only the occurrence of the meeting itself but its resultant decision to reverse the refusal of the BLA. Typically, after receiving a request for such a meeting, the Agency will decide whether the meeting is warranted within fourteen days. Then, if the meeting is agreed to, the Agency will schedule the meeting within thirty days, and usually it is months longer for the FDA to resolve the issue, yet all of this all occurred within just a few calendar days. To my eye, this means that the FDA got spooked by the general industry reaction and someone within the Agency thought better of the approach to refuse the application.
While Moderna did agree to a revised regulatory approach, as reported by Axios (here), “the new proposal seeks full approval for people age 50 to 64 and accelerated approval for those 65 and older, with a requirement for an additional study in older adults once the vaccine is on the market.” The speed at which the FDA reversed its initial decision is something I’ve never seen in my forty-one years of FDA and industry experience.
Once an RTF letter is issued, typically the firm must resubmit the application with revised information and a new user fee; however, the penalty associated with an RTF letter is forfeiture of 25% of the original user fee. I wonder whether the FDA “revoked” the RTF letter or Moderna had to resubmit its application and take the 25% hit on the user fee. My guess is that there was some middle ground reached, but how this issue was resolved has not been revealed.
The firestorm caused by the initial refusal to file the Moderna BLA certainly played out quickly, and clearly illustrates the impact of the exit of historical knowledge and the brain drain that the FDA has experienced since the DOGE firing disruptions and the resultant staff turnover and senior-level changes.
