On August 19, FDA announced the availability of a temporary guidance for industry entitled, “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency Questions and Answers.” FDA issued the guidance to address frequently-asked questions from industry regarding the impacts of the COVID-19 public health emergency on drug development programs, ongoing manufacturing operations and FDA’s ability to conduct inspections. The guidance provides information related to inspections for facilities manufacturing pharmaceutical products and sites involved in the conduct of clinical, analytical and nonclinical studies.
Prioritization and “Mission-Critical” Inspections
This guidance confirms that FDA has resumed prioritized domestic inspections, which generally include pre-approval and surveillance inspections, and that it is conducting certain other “mission-critical” domestic inspections on a case-by-case basis. FDA also states that foreign pre-approval and for-cause inspection assignments that are not deemed mission-critical remain temporarily postponed, although those deemed mission-critical will still be evaluated on a case-by-case basis.
FDA considers a number of factors in determining whether a given inspection is “mission-critical,” including whether the product being inspected is subject to breakthrough therapy or regenerative medicine advanced therapy designation, or whether the products are intended to diagnose, treat, or prevent a serious disease or medical condition for which there is no other appropriate substitute. Both for-cause and pre-approval inspections may be deemed mission-critical, and FDA also considers issues such as the safety of investigators, site personnel, and trial participants and other patients at clinical study sites.
Impact on Applications
Recognizing that sponsors and applicants are concerned about how limited inspection activity may affect FDA’s review of pending submissions, FDA states that it is continuing normal assessment operations for all disciplines. This includes risk-based evaluations regarding the need for both manufacturing establishment and BIMO inspections. As it has previously stated, FDA is also continuing to rely on additional tools in making decisions about inspections, such as reviewing compliance history, sharing information through mutual recognition and confidentiality agreements, and requesting records “in advance of or in lieu of” facility inspections as authorized by section 704(a)(4) of the Food, Drug, and Cosmetic Act.
With respect to communicating with applicants regarding pre-approval/pre-license inspections that cannot be conducted because of travel restrictions, FDA says in the guidance that it does not plan to automatically issue complete response letters if FDA cannot conduct an inspection at a facility listed in an application. Instead, FDA will rely on the totality of the information available to FDA to evaluate whether an inspection is needed. If FDA determines that it needs to conduct an inspection because available information raises concerns about the site, and if travel restrictions may prevent FDA from conducting the inspection before the action date, FDA intends to notify applicants about these circumstances as soon as possible during the review cycle. If the inspection of a facility that raises such concerns has not been completed by the action date, FDA intends to issue a complete response. If FDA does not have adequate information to reach a determination on the acceptability of a facility, the FDA project manager will contact the applicant to notify the applicant that FDA may defer action on the application until an inspection can be completed.
Finally, the guidance provides information about changes to applications related to COVID-19, such as adding or changing facilities and manufacturing process changes, and discusses FDA’s approach to accelerating review and approval of certain post-approval changes. In particular, the Agency is willing to consider certain changes under lower reporting categories based on risk-mitigation information for drug applications or BLAs related to the treatment or prevention of COVID-19 or drugs/biologics in shortage. FDA may also implement flexible assessment practices, such as risk-based adjustments to data submissions and determinations regarding the need for inspections.
if you have any questions concerning the material discussed in this client alert, please contact the following members of our Food, Drugs, and Devices practice.
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