FDA Provides Update on GMP Inspections
Janet Woodcock, Acting Commissioner of the FDA, provides an update on the FDA’s inspection activity during the COVID-19 pandemic, including what new tools the agency has used for inspections, which has included a mix of mission-critical, on-site inspections and remote record reviews. What does she recommend as the next steps in returning to more normal inspection operations?
FDA inspections during the pandemic
The COVID-19 pandemic has brought change, including to the manner in which regulatory oversight in the form of inspections is conducted. Limiting on-site inspections to those characterized as “mission-critical,” the US Food and Drug Administration (FDA) has used various tools and practices to continue inspections during the COVID-19 pandemic. Janet Woodcock, M.D., Acting FDA Commissioner, and Judy McMeekin, Pharm. D., Associate Commissioner for Regulatory Affairs, FDA, outlined the risk-based approach to inspections that the FDA has taken over the past year and how the agency is preparing to return to a more normal inspection process, in a recent update on FDA Voices, the FDA’s blog in a March 18, 2021 posting.
During the pandemic, the FDA has prioritized inspections by identifying those that are “mission-critical” on a case-by-case basis. “Mission-critical” means the inspection was key to the agency’s public health mission and that the activity could not be accomplished in any other way. This evaluation involved many factors, including whether products: (1) have received breakthrough therapy or regenerative medicine advanced therapy designations; (2) are used to diagnose, treat, or prevent a serious disease or medical condition for which there is no other appropriate substitute; (3) require follow-up due to recalls, or there is evidence of serious adverse events or outbreaks, including human or animal food safety concerns; and (4) are related to the COVID-19 response (e.g., drug shortages).
Beginning last July (July 2020), prioritized domestic surveillance inspections resumed using a rating system that the FDA developed to assist in determining when and where it is safest to conduct prioritized domestic inspections. The COVID-19 Advisory Rating System uses real-time data to qualitatively assess the number of COVID-19 cases in a local area based on state and national data. The resumption of prioritized domestic inspections is based upon location and COVID risk, not upon product type.
To extend its reach during the pandemic, the FDA created and implemented other approaches to facility oversight when entering facilities for inspections was not feasible or advisable. These tools have included the following:
- Compliance history reviews of facilities, including recalls and product complaints, to assist with prioritization;
- Information sharing with state, local, and foreign regulatory partners through mutual recognition and confidentiality agreements;
- Remote assessments for individual program areas to evaluate facility records;
- Review of records and information requests to facilities in advance or in lieu of drug and biological product inspections, and/or to support regulatory decisions and actions;
- Use of sampling and analytical testing of FDA-regulated products both domestically and at the border; and
- Refusing entry of unsafe imported products into the US.
Results thus far
Woodcock and McMeekin said that the FDA continues to assess the agency’s ongoing efforts to execute regulatory oversight. One important measure is how the FDA has performed with respect to its performance commitments under user-fees programs. These statutory programs authorize the FDA to assess and collect fees from companies that produce certain medical products, including drugs and biological products. The FDA has generally committed to reviewing 90% of applications for specified drug and biological products within the timeframes that it has agreed to in user-fee negotiations with the industry. According to the FDA, an analysis of user-fee metrics across prescription drug and generic drug programs during the pandemic showed that the FDA has been able to take on-time actions to evaluate and close out drug applications more than 90% of the time, which meet its review program performance commitments.
The FDA continues to use a risk-based approach to identify the need for pre-approval inspections (PAIs), in which manufacturing facilities are inspected prior to the approval of new products (new drug applications or biologics license applications) and for generics (abbreviated new drug applications). While continuing to conduct mission-critical and prioritized inspections, due to practical constraints, such as travel limitations, quarantine and social distancing requirements, or lockdowns, the FDA has increasingly relied on alternative approaches to inspections. These approaches have included: (1) reviewing the inspection history of facilities to assess feasibility of relying on records or partner inspections; (2) using information shared by trusted foreign regulatory partners; and (3) requesting records directly from facilities in lieu of drug and biological product inspections. As a result of using these alternative approaches, the FDA’s Center for Drug Evaluation and Research (CDER) completed facility assessments to meet time targets under user-fee acts (Prescription Drug User Fee Act, Generic Drug User Fee Amendments, and Biosimilar User Fee Act) by reducing the need to conduct PAIs as follows: (1) 48% of the time in the third quarter of fiscal year (FY) 2020 (April 1 to June 30, 2020); (2) 60% of the time in the fourth quarter of FY 2020 (July 1 to September 30, 2020); and (3) 52% of the time in the first quarter of FY 2021 (October 1 to December 31, 2020).
When the FDA will be able to resume normal inspection activity is still to be determined and is a function of the COVID-19 situation. “As we look to the future, the FDA will continue to leverage and maximize every available tool and resource to meet our inspectional responsibilities while achieving optimal public health outcomes,” said Woodcock and McMeekin in their March 18, 2021 blog post. “We will continue to study how to incorporate additional data sets and insights, and new technologies and tools for facility oversight, including the further use of remote interactive evaluations (e.g., remote livestreaming video of operations, teleconferences or screen sharing), and will work with industry to expand their use. In concert with these efforts, we are pursuing agency-wide preparedness efforts for resuming a more normal state of operations, which will factor in how best to address inspectional activities that were paused due to the pandemic.”