FDA Releases Final Guidance on Postmarket Safety Reports for Combination Products


Posted July 30, 2019

The Food and Drug Administration (FDA) has issued final guidance that addresses compliance with the agency's 2016 final rule on postmarketing safety reporting requirements (PMSRs) for combination products, which consist of two or more types of medical products (i.e., drug, device, biologic).

The final guidance, Postmarketing Safety Reporting for Combination Products, instructs applicants of combination products on how to submit reports and avoid duplication, providing examples of applicants that are subject to the rule (e.g., a "company that holds an approved NDA for a pre-metered dry powder inhaler copackaged with a filled drug product cartridge”).

The guidance also covers recordkeeping requirements, including examples for both drug- and device-focused products, as well as charts showing the content required for reports and when reports are due to the FDA.

The final guidance "will help applicants better understand how to submit their combination product postmarketing safety reports,” said Amy Abernethy, the FDA’s principal deputy commissioner, in a statement. “This guidance reinforces FDA’s expectations for timely postmarketing safety information about combination products.”

The agency has wrote in a briefing document that it "does not intend to enforce the additional constituent part-based PMSR requirements until July 2020 for most combination products, and until January 2021 for vaccine combination product," in order to give applicants enough time to make necessary adjustments.

In its comments on the draft guidance, AdvaMed, the medical device trade association, indicated its agreement with the FDA's goal of consistency and streamlining in the process by avoiding duplicative requirements for combination products. AdvaMed had sought an extension of the proposed five-day reporting requirement on adverse events to 15 days, as well as detailed tables illustrating requirements, scenarios, and expectations.

With the aim of preventing risk of harm to the public, the final guidance describes scenarios where five-day reporting requirements would apply. One such example provided by the agency is as follows:

“The applicant for a prefilled rescue inhaler approved under an NDA determines that a reportable adverse event was caused by a design flaw that causes the inhaler actuator to fail and the drug to not be delivered. The design flaw is known to be present in the product in the field, and the product in the field can fail in the same manner, likely resulting in life-threatening injury or death (which would pose an unreasonable risk of substantial harm to the public health)."