The Food and Drug Administration announced on Mar. 10 that it has set expectations for the scope of meetings aimed at reducing drug approval rejections due to manufacturing issues, agreeing with some industry proposals while rejecting others.
This move comes as a response to a series of complete response letters tied to problems at drug manufacturing facilities, which have made pre-approval inspections a key focus in ongoing negotiations for the Prescription Drug User Fee Act (PDUFA) reauthorization. Recently, Incyte's planned expansion of its PD-1 blocker Zynyz for non-small cell lung cancer was rejected because of manufacturing issues at a former Catalent site now owned by Novo Nordisk.
In November, the FDA proposed giving applicants more opportunities to engage with its staff in order to reduce risks during reviews. The agency identified fewer facility-related complete response letters as a goal for upcoming meetings. Industry representatives later shared a list of topics they hoped could be discussed during pre-submission facility meetings. According to recently published minutes from a February meeting, the FDA agreed that these meetings could cover prior production site inspections and novel or unique process elements relevant to making the drug candidate. The agency also said discussions could include strategies to reduce risks and groups of facilities—referred to as “supply chain nodes”—that may support future applications.
However, the FDA told industry representatives that other proposed topics—including alternative tools for assessing facility information, inspection scheduling, and overall novel or unique manufacturing processes—should remain outside the scope of these meetings. The agency said applicants should use existing types of regulatory meetings for discussions about process development, validation, manufacturing schedules, and data submission.
While excluding certain topics from pre-submission meetings, the FDA noted that manufacturers "may provide awareness of manufacturing schedules." Last year, companies used PreCheck program meetings to inform the FDA that aligning schedules with pre-approval inspections can force them to keep production suites idle and delay submissions.
The decision reflects the agency’s plan to keep talks "focused on facility needs in the context of strategy discussion, as relevant to a specific application." As both sides continue refining details following their February PDUFA session, there is general agreement about what pre-submission facility meetings should address. This consensus forms the basis for including such meetings in PDUFA VIII—the next agreement between industry and the FDA—which will apply from 2028 through 2032 when PDUFA VII expires in September 2027.
