Industry and FDA representatives have reached a general agreement on planned pre-submission facility meetings but have expressed different views about the specifics.
The FDA has set expectations for the scope of meetings to reduce rejections of drug approval filings on manufacturing grounds, agreeing with some industry proposals while pushing back against other ideas.
A series of complete response letters (CRLs) tied to problems at drug manufacturing facilities has made pre-approval inspections a focus area for the teams negotiating Prescription Drug User Fee Act (PDUFA) reauthorization. Most recently, Incyte suffered a rejection Monday of its planned expansion of PD-1 blocker Zynyz to treat non-small cell lung cancer due to manufacturing issues at a former Catalent site now owned by Novo Nordisk.
In November, the FDA proposed giving applicants opportunities to engage with its staff to derisk reviews. The agency named fewer facility-related CRLs as a goal of the next meeting.
The two sides developed the idea in subsequent interactions, culminating in industry representatives sharing a list of topics that could fall within the scope of pre-submission facility meetings. The agency recently published minutes from the February meeting at which it reviewed the list of potential topics.
FDA officials agreed pre-submission meetings could cover prior production site inspections and novel or unique process elements of facility operations relevant to making the drug candidate. The agency also agreed meetings could address strategies to reduce risks as well as groups of facilities that may be used to support a future application, which it called “supply chain nodes.”
However, the FDA told industry representatives that other proposed topics—including alternative tools to assess facility information, inspection scheduling and overall novel or unique manufacturing processes—should be outside the scope of the meetings. Applicants should use existing types of regulatory meetings to discuss process development, validation, manufacturing schedules and data submission, the agency said.
While pushing to exclude manufacturing and inspection schedules from the final list of meeting topics, the agency said the industry “may provide awareness of manufacturing schedules.” Manufacturers used meetings about the PreCheck program last year to tell the FDA that aligning schedules with pre-approval inspections can force them to keep production suites idle and delay submissions.
The FDA’s decision to exclude some topics from the pre-submission meetings reflects its plans to keep the talks “focused on facility needs in the context of strategy discussion, as relevant to a specific application.” While industry and the FDA were still refining the details as of the February PDUFA session, the agency said there is general agreement about the focus of pre-submission facility meetings.
That high-level consensus provides the basis for including the meetings in the final terms of PDUFA VIII, an agreement between industry and the FDA that will apply across the agency’s 2028 to 2032 financial years. The current agreement, PDUFA VII, expires in September 2027.
