FDA May Delay Approval of Drugs Where Necessary Inspection Is Not Feasible

FDA announced in July that it planned to resume “prioritized domestic inspections” for certain regulated products that had been put on hold by COVID-19 since March. The agency also would continue to conduct “mission critical” inspections, utilizing methods to ensure the safety of all involved personnel. But it was unclear to biopharma companies from the July 10, 2020 press release which products and situations would warrant on-site visits and how the agency would respond where the pandemic made an inspection unsafe or unfeasible.

Now a new guidance from FDA, published on August 19, 2020, provides answers to such questions about when the agency will seek to visit a site and how it will respond when a needed inspection cannot be conducted safely. FDA explains that it may delay approval of new products in situations where travel restrictions and other concerns block a preapproval inspection that the agency considers necessary.

Breakthrough therapies and regenerative medicine advanced therapies may gain approval even without a desired inspection. This policy also applies to other “mission critical” therapies used to diagnose, treat, or prevent a serious disease where no treatment alternative is available.

However, if an application involves a less critical medicine, and FDA has concerns about the adequacy of the facility but cannot conduct a site visit before the application’s “action date,” then FDA will issue a complete response letter that explains the reasons for delaying approval.

The agency will try to avoid such situations by utilizing other methods to access needed information on a manufacturing operation without an actual site visit. FDA will review earlier inspection reports, request records and information from the applicant and from the facility, and seek to obtain inspection reports from other trusted foreign regulatory partners. And for drugs made overseas where inspections continue to remain on hold, the agency will review product quality through sampling and testing at border control sites.

Similar assessments will apply to bioresearch monitoring (BIMO) surveillance of research sites, conducted to ensure that investigators follow policies to protect research subjects and to ensure the accuracy of clinical trial data. Here, FDA will continue to follow risk-based approaches that consider the nature of the application and site-specific factors.

The new guidance also provides flexibility for manufacturers looking to make changes in a facility or production process for an approved product affected by supply chain disruptions due to the pandemic. FDA will expedite such requests for drugs and biologics used in treating COVID-19 patients and for critical products in shortage situations. This will involve weighing the impact of postapproval changes and a firm’s efforts to mitigate the risk to product quality associated with a change. For critical products, FDA may permit a manufacturer to use a lower reporting category to facilitate the change and avoid pre-approval review and inspection of the changes. In such situations, firms should consult relevant FDA review offices on the most appropriate way to proceed.

The guidance on Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency is temporary, in effect only for the duration of the current health emergency. However, it goes into effect immediately, without the usual delay for stakeholder comment.