On Wednesday, August 19, the U.S. Food and Drug Administration (FDA) issued guidance providing some additional insight into how the agency will determine what drug and biologic inspections may take place during the COVID-19 pandemic because they are viewed as "mission critical." As we have previously discussed, the agency temporarily halted most inspections in March 2020 due to the COVID-19 pandemic and announced that the agency would evaluate “mission critical” inspections on a case-by-case basis. In July 2020, the agency announced that it would work toward resuming “prioritized” domestic inspections, where safe to do so. This new guidance document provides additional insight into FDA’s current thinking on prioritized and mission critical inspections and also explains steps to ensure the safety during domestic inspections, including pre-announced inspections. Foreign pre-approval and for-cause inspection assignments that are not deemed mission-critical remain temporarily postponed, and it remains unclear whether FDA will be doing.

The draft guidance, titled “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency Questions and Answers,” provides additional insight into FDA’s thinking on how the agency will perform inspections during the COVID-19 pandemic. This includes:

-More clearly defining “mission critical” to include whether the products have received breakthrough therapy designation or regenerative medicine advanced therapy designation, or are products used to diagnose, treat, or prevent a serious disease or medical condition for which there is no other appropriate substitute. FDA also explained that the criteria for determining “mission-critical” status will be the same for both domestic and foreign facilities. 

-Restating FDA’s intention to use non-inspectional tools and approaches, where possible, to evaluate a site’s compliance status. This includes requesting existing inspection reports from other trusted foreign regulatory partners through mutual recognition and confidentiality agreements, requesting information from applicants, and requesting records and other information directly from facilities and other inspected entities. 

-Clarifying the agency’s approach to pre-approval inspections for pending applications. Specifically, sponsors will not automatically receive a complete response letter if FDA cannot conduct an inspection, and decisions regarding applications will be based on the totality of the information available to FDA. If, based on a benefit-risk assessment of the product and available information about the facility or site, it is determined that an inspection is needed before approval of an application, FDA will communicate this to the applicant by either issuing a complete response letter — where FDA determines that an inspection is necessary; or by deferring action on the application — where FDA cannot make a compliance determination based on the available information. The guidance document also discusses the impact to changes filed with the agency to approved applications. 

The guidance document explains that FDA is willing to consider requests from applicants to submit certain changes using a lower reporting category based on documented rationale for the change and risk-mitigation information for drug applications or BLAs that are related to the treatment or prevention of COVID-19 or drugs/biologics in shortage. 

As the coronavirus pandemic response evolves, we will continue to monitor FDA’s foreign and domestic drug inspection programs, related pharmaceutical supply chain issues, and the agency’s response to the COVID-19 outbreak more broadly. Please contact us if you have any questions.   

Authored by Jim Johnson, Daniel Roberts, Scott Kaplan, and Chris Fanelli