While allowing flexibility for delays in postmarketing adverse event reporting, the guidance states that firms that are unable to fulfill normal adverse event reporting requirements during the pandemic must document the “[h]igh absenteeism and/or other factors (e.g., an increase in adverse event reporting) that is/are preventing the firm from meeting normal adverse event reporting requirements.” In addition, FDA emphasizes that any delayed reports must be submitted within 6 months “after adverse event reporting processes have been restored to the pre-pandemic state.”
Table 1 of the guidance identifies the reports that “may be stored if necessary” during a pandemic and those that must still be submitted in a timely fashion. Products for which reporting obligations remain unchanged include blood and blood components, source plasma, and human cells, tissue, and cellular and tissue-based products (HCT/P) and products with special concerns. With regard to reports that “may be stored if necessary,” FDA will not object if a company maintains newly received information about adverse events, but does not submit reports on the AE in the timeframes mandated by statute or regulation. Reports that “may be stored if necessary” include:
- Periodic safety update reports for all drug products
- 15-day alert reports and follow-up reports for approved NDAs and ANDAs, so long as the product is neither indicated for influenza nor has it been approved within the prior 3 years
- 15-day alert reports for over-the-counter (OTC) drug products marketed without an approved application (OTC drugs marketed pursuant to an OTC drug monograph)
- 15-day alert reports and follow-up reports for prescription drug products marketed without an approved NDA
- 15-day alert reports for dietary supplements
- Medical Device Reports (MDRs) from manufacturers that address nonfatal serious injuries or device malfunctions
The guidance makes a point of stating that FDA’s relaxed policies are not intended to discourage safety reporting by companies that are able to continue their reporting operations during the pandemic. In addition, the guidance specifically states that it is not applicable to monitoring and reporting adverse events for investigational products being studied in clinical trials. FDA has issued separate guidance addressing clinical trials challenges during the COVID-19 pandemic.
If FDA has specified a product as presenting “special concerns,” the sponsor must timely submit required adverse event reports regardless of the more general recommendations. Special concerns could include:
- product-related safety issues such as newly emerging safety issues (e.g., an antihypertensive drug associated with liver failure or a non-pandemic-related vaccine associated with anaphylaxis); or,
- product problems with associated adverse events (e.g., nonfatal serious infections associated with a pre-filled syringe that was recalled due to bacterial contamination).
Order of operations
If a company cannot submit all of its postmarketing adverse event reports by the regular, mandated deadlines, it should prioritize the submission of stored reports, filing reports with 15- or 30-day timeframes before periodic safety reports, for example. An appendix to the guidance outlines the current timeframe requirements for postmarketing safety reports.
Continuity of operations plans required
FDA advises firms to develop and prepare to implement their continuity of operations plan (COOP) “in the event that they are not able to fulfill all adverse event reporting requirements because of pandemic-related high employee absenteeism.” In crafting this COOP, FDA says firms should consider the following types of factors:
- What activities are directly relevant to the processing and submission of mandatory adverse event reports to FDA?
- How would sites based in the U.S. and abroad be differentially affected by a pandemic?
- What are the relative amounts of resources dedicated to mandatory adverse event reporting at each site?
The guidance recommends that, in the event adverse event reporting is impacted, companies maintain documentation surrounding the circumstances, and in particular, (1) the declaration of the pandemic and (2) the reasons why the company is unable to fulfill its reporting obligations.
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Comments on this guidance may be submitted at any time. If you may need assistance developing a continuity of operations plan, or have any questions about postmarketing adverse event reporting during this novel coronavirus outbreak, please contact your Hogan Lovells attorney or any of the authors of this alert.
Authored by Philip Katz, Robert Church, Jim Johnson, Lynn Mehler, Lina Kontos, David Horowitz, and Heidi Gertner