FDA Issues Long-Awaited Final Rule on Combo Product Postmarket Safety

Regulatory NewsRegulatory News | 19 December 2016 |  By 

More than the seven years after it was first proposed, the US Food and Drug Administration (FDA) on Monday finalized new postmarket safety reporting requirements for combination products.

The final rule, first proposed in 2009, which is the first time the agency has issued specific recommendations for combo products, is part of FDA’s efforts to ensure more consistent postmarketing safety reporting for these drug/device, biologic/device, biologic/drug or drug/biologic/device products, while enabling companies to be as efficient as possible with their reporting.

“These regulations for drugs, devices, and biological products share many similarities; however, each set of regulations has certain unique reporting requirements, standards, and timeframes based in part on the characteristics of the type of product,” FDA said in explaining the need for the final regulations. “These variations among the regulations and lack of clarity on how to apply these requirements to combination products can result in inconsistent and incomplete postmarketing safety reporting for combination products and their constituent parts.”

The final rule comes as FDA in August said it is beginning a new pilot project linked to its intercenter consult request (ICCR) process for combination products of drugs, medical devices and/or biologics.


The agency said it received 16 sets of comments on the proposed rule, with commenters seeking clarification of the scope of the proposed rule, among other issues.

"After considering the comments received on the proposed rule, the Agency has made clarifications and other revisions in the final rule to, among other things: (1) Clarify that the final rule applies only to combination product and constituent part applicants; (2) clarify when a single report may suffice to comply with more than one reporting requirement; and (3) incorporate biological product deviation reporting and device correction and removal reporting requirements applicable to combination product applicants," FDA said.


In addition to the application type-based reporting requirements (depending on if parts of the combo product were approved under a new drug application (NDA) or biologics license application (BLA), etc.), the final rule requires combination product applicants to submit additional reports based on the constituent parts included in the combination product (e.g., malfunction reports if the combination product includes a device, field alert reports if it includes a drug and biological product deviation reports if it includes a biologic).

The 83-page final rule also requires constituent part applicants (those who have approved parts of the combo product) to share certain postmarketing safety information they receive with one another. And it specifies how combination product and constituent part applicants must submit postmarketing safety reporting data to FDA and what records they must maintain.

In terms of changes between the proposed and final rule, FDA has:

  • eliminated the requirement to comply with blood fatality reporting requirements for combination products that received marketing authorization under an NDA or abbreviated new drug application (ANDA) as “facilities at which such events occur are currently required to make blood fatality reports irrespective of the type of application”
  • revised the requirement for all combination product applicants to submit 15-day reports to permit these reports to be submitted within 30 days rather than 15 days for combination products that received marketing authorization under a device application (to “enable better alignment of reporting for device-led combination products because this timing would be consistent with the timing for submission of medical device reports,” FDA said)
  • incorporated Biological Product Deviation Reporting (BPDR) and correction and removal reporting requirements for combination product applicants to ensure that the issues addressed by these reporting requirements, for biological products and devices, respectively, are also addressed for combination products that include these types of constituent parts
  • clarified that all applicants must comply with the applicable postmarket surveillance review (PMSR) requirements with respect to their product
  • made clear that the duties to share information within 5 calendar days apply only to constituent part applicants and that they must share only information they receive regarding events that involve a death or serious injury
  • clarified and simplified the recordkeeping requirements associated with PMSR obligations for combo product applicants and constituent part applicants.

Furthermore, in terms of efficiency for sponsors, FDA notes that “if the applicant has submitted one type of report and that report: includes all of the information that would also be required in another type of report; is required to be submitted in the same manner under this rule as that other report; and is submitted within applicable deadlines, the submission of the single report will be considered to satisfy both reporting obligations.”

Final Rule: Postmarketing Safety Reporting for Combination Products


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