Major pharmaceutical companies have urged the U.S. Food and Drug Administration (FDA) to change its inspection process for drug manufacturing facilities, citing challenges that arise when inspections are tied directly to new drug approval applications.
During consultations with the FDA as part of the development of its PreCheck program, companies such as AbbVie, Eli Lilly, Johnson & Johnson, Merck, Sanofi, and Forge Biologics expressed concerns about pre-approval inspections (PAIs). The current process requires a facility to be inspected by the FDA when it is used to manufacture a medicine submitted for approval. Industry representatives say this timing creates pressure and can result in complete response letters (CRLs), which delay or block drug approvals due to unresolved issues found during inspections.
Kevin Fitzpatrick, senior vice president for quality assurance at AbbVie, described the difficulties: “We brought on a new U.S. manufacturing facility two years ago and the PAI for that facility was weeks prior to our PDUFA date. At that point, we’re under a lot of pressure. Any questions or comments or observations that come up [during the PAI] are very difficult to resolve in that time frame.”
Miguelina Matthews, head of quality intelligence, advocacy and pharmacopoeia affairs at Sanofi, told the FDA that unpredictable inspection schedules can lead to CRLs. These concerns were echoed in both verbal testimony and written feedback submitted to the agency.
Many industry responses proposed decoupling inspections from drug approval application reviews. They suggested that inspecting sites before authorization applications are filed would give companies more time to address compliance issues before they impact approval decisions.
The PreCheck program was initially designed by the FDA to support construction of new facilities in the United States. However, drugmakers have called for its scope to extend support to existing plants as well. Representatives from Sanofi and Forge Biologics highlighted how PreCheck could help activate idle production capacity and assist ongoing facility projects.
Guggenheim Securities analysts noted that clearer inspection timelines could benefit manufacturers by providing advance notice needed for scheduling production runs during FDA visits. Karen Wolfrom, global head of regulatory affairs at Lonza, explained how contract manufacturers face particular challenges aligning their varied production schedules with inspection dates: “In the meantime, we have other important medicines that are coming into the suite. Do we delay them going into the suite so that we can keep it open and idle to do an inspection for this particular product? There’s that dance,” she said at an FDA meeting in September. “It’s terrible to have a submission delayed because we have to be in active manufacturing at the time.”
Manufacturers producing small quantities—such as those targeting rare diseases—face additional difficulties synchronizing batch production with inspection requirements. Christopher Shilling, chief regulatory officer at Forge Biologics, told BioSpace that gene therapy clients may only need a few batches produced: “jumping through hoops” is required to align inspections with these limited runs.
The Alliance for Regenerative Medicine (ARM), representing cell and gene therapy companies including Forge Biologics, recommended phased or modular inspections—checking parts of a facility like vector suites or cleanrooms as they become ready instead of waiting until an entire plant is operational—to help identify issues earlier in the process. Johnson & Johnson also supported this approach in its feedback.
Generic drugmakers face their own set of inspection-related burdens. According to a spokesperson from the Association for Accessible Medicines—which represents generic and biosimilar manufacturers—these companies must host both federal FDA inspectors and state-level authorities separately, increasing workload demands on staff who manage document requests during each visit. The spokesperson suggested improved cooperation between federal and state agencies could reduce redundancy; mutual recognition agreements already allow FDA reliance on some overseas regulatory agency inspections as a potential model for domestic collaboration.
The FDA closed its window for written feedback on PreCheck in late October after receiving 74 submissions alongside hours of oral testimony. The agency has not yet issued a public response or finalized details about implementation of the PreCheck program.
