While a new facility setup program aimed at encouraging onshoring received a positive reception at a recent meeting, industry representatives said the current rules on existing production plants are the main regulatory issues facing manufacturing teams.
The FDA’s proposed PreCheck program to encourage the onshoring of drug production has received a broadly positive reception from groups working across the supply chain. Yet while attendees at a meeting to discuss the program found things to like in the FDA’s proposal, members of the industry made the case that there are barriers to scaling domestic manufacturing that are outside the scope of the current policy.
Responding to an executive order on promoting domestic production of critical medicines, the FDA shared plans in August to accelerate the establishment of high-priority new manufacturing plants in the U.S. Its PreCheck proposal has two parts. First, selected manufacturers will receive early technical advice from the FDA before a facility is operational. Second, the FDA will hold pre-submission meetings to resolve issues and expedite assessments of quality information.
The agency held a full-day meeting to discuss the proposal at the end of September, opening the floor to manufacturers of finished products and producers of active pharmaceutical ingredients. Michael Kopcha, director of the FDA’s Office of Pharmaceutical Quality (OPQ), set out the FDA’s vision for a new way of working that “prioritizes proactive collaboration over reactive oversight.”
“We want to have a resilient, secure domestic supply chain, where FDA and industry are able to work together from site design all the way through to production,” Kopcha said at the PreCheck meeting. “This drives towards a new paradigm of pharmaceutical regulation, one we’ve long strived for in OPQ. It’s taken us a little bit of time to get here, but we are finally here.”
But while representatives of companies including AbbVie, Amgen, Eli Lilly and Sanofi expressed upbeat opinions on the FDA’s proposals, many attendees also said that the FDA must go beyond the current scope of the PreCheck program to fix the most significant regulatory hurdles drug manufacturers are facing in the U.S. today.
“FDA PreCheck program is a promising step forward in strengthening U.S.-based pharmaceutical manufacturing,” a spokesperson for the API Innovation Center told BioSpace via email. “Discussions also surfaced practical industry hurdles,” including the timing of inspections and the process for authorizing post-approval changes. Those issues, the spokesperson said, “will need to be addressed for the program to reach its full promise.”
The Industry’s Wishlist
Christopher Shilling, chief regulatory officer at gene therapy service provider Forge Biologics, was among the industry representatives who attended the meeting in person and shared feedback with the FDA. Talking to BioSpace shortly after the meeting, Shilling said there is “a lot of enthusiasm” for PreCheck and a belief that the program offers “good intentions and good opportunities for the field.”
Representatives of multiple companies flagged the FDA’s current approaches to pre-approval inspections and post-approval changes as two of the key challenges they face. While PreCheck may help selected newly built facilities prepare for pre-approval inspections, the current proposals offer no relief for the problems faced by existing production plants.
Shilling said chemistry, manufacturing and controls (CMC) inspection issues “continue to plague” some biologic approval applications. The FDA has issued CMC-related rejections to companies including Scholar Rock and Ultragenyx in recent months.
Shilling, hitting a point made repeatedly at the meeting, is encouraging the FDA to consider decoupling the timing of pre-approval inspections and authorization applications. Currently, inspections take place as the clock is ticking down to the deadline for FDA’s decision on whether to approve a drug. Attendees proposed various ways to assess facilities outside of drug approval cycles in order to accelerate or waive pre-approval inspections, thereby relieving time pressure and avoiding CMC-based rejections.
Attendees named post-approval changes as another major headache, telling the FDA that the current system is inflexible and imposes overly burdensome requirements on the addition of new manufacturing lines at existing facilities.
The FDA’s current target is to review and act on 90% of manufacturing changes that it deems to be major within four months of receiving the application for branded drugs and within six months for generics. The deadline extends to up to 10 months when an inspection is needed. Simon Hotchin, vice president for regulatory affairs at Amgen, was among the attendees to ask whether some changes could be processed under a pathway that allows companies to ship the affected products 30 days after contacting the FDA.
Reassessing post-approval change requirements could accelerate onshoring by cutting the time it takes companies to scale up production at existing facilities, attendees told the FDA.
Next Steps
Overall, feedback at the meeting indicated that while the industry would welcome a more collaborative approach to setting up new facilities, some of the current rules on existing production plants are the main regulatory issues facing manufacturing teams. Mahesh Ramanadham, deputy director at the FDA’s OPQ, addressed the disconnect between the scope of PreCheck and this feedback.
Responding to the calls for the agency to rethink tasks such as pre-approval inspections, Ramanadham said, “PreCheck may not be built to handle everything.” Rather, the initiative may need to be connected to other FDA programs and tools to address the problems facing drug manufacturers in the U.S. today, he said.
Industry representatives now have another opportunity to put their views to the FDA as part of a call for written comment that is scheduled to close on Oct. 30. The feedback will inform the FDA’s plans for the PreCheck program and broader considerations of how the agency can facilitate onshoring.
