As regulatory professionals well know, the approval of a device by the US Food and Drug Administration (FDA) isn't the end of a company's regulatory obligations. Postmarketing studies, adverse event reports, manufacturing compliance and change reports are all part of the regulatory lifecycle after approval.

But so too is something else: the annual report required of devices approved through the premarket approval (PMA) process.

Background

The requirement under 21 CFR 814.82(a) and 84(b), calls for the company to submit a report annually containing the following:

(1) Identify changes described in 814.39(a) and changes required to be reported to FDA under 814.39(b).

(2) Contain a summary and bibliography of the following information not previously submitted as part of the PMA:

(i) Unpublished reports of data from any clinical investigations or nonclinical laboratory studies involving the device or related devices and known to or that reasonably should be known to the applicant.

(ii) Reports in the scientific literature concerning the device and known to or that reasonably should be known to the applicant. If, after reviewing the summary and bibliography, FDA concludes that the agency needs a copy of the unpublished or published reports, FDA will notify the applicant that copies of such reports shall be submitted.

(3) Identify changes made pursuant to an exception or alternative granted under 801.128 or 809.11 of this chapter.

Annual Report as a Tool

With the multitude of important postmarketing requirements, it can be easy to forget about the importance of the annual report. But as FDA explains in a new final guidance, Annual Reports for Approved Premarket Approval Applications, its importance should not be discounted.

"Annual reports are one of the important tools that FDA relies on to gather information about the device in its post-approval setting," it wrote. The annual report often provides what individual reports do not: a macro-level look at the device's performance, manufacturing and safety over the course of an entire year.

As a tool, the annual report's effectiveness is key, FDA said. But the agency said it wants to improve the quality of the annual reports it receives such that it receives "a more complete picture of the post-market safety profile of the device" and the impact of any changes.

"Having the information submitted in this way will help ensure that limited Agency resources are devoted to assessing meaningful information rather than requiring FDA to sift through vast amounts of data that have not been systematically reviewed by the firm," it said.

The Annual Reports: What to Submit

So what do device manufacturers and sponsors need to submit? The guidance notes the basics, including the device's PMA number, the device name, company name, date of report and the reporting period the report covers.

Change identification-that is, the changes made to the device or the manufacturing process-is given extensive consideration in the guidance.

If a change required a PMD supplement or a 30-day notice prior to approval, FDA recommends that the submitter reference the document number assigned to the document by FDA in the annual report. The agency has, after all, already approved the change.

But for smaller changes that have not been approved by FDA, the report must contain a description of the change, the rationale for the change, the scientific and regulatory analysis of the change, and a grouping of all similar changes.

"FDA recommends that the applicant provide separate tables for manufacturing changes, design changes, and labeling changes, and that the applicant identify changes that are associated with each other so it is clear which changes are linked," it wrote, and provided a recommended table format for the changes. Examples of change rationales are also provided in the guidance.

The report should also include a summary of scientific literature addressing the company's device, as well as unpublished data known to the applicant (such as preliminary data from an ongoing study). Each report should be evaluated for its impact on the safety or efficacy profile of the device. FDA may request full copies of the reports, it said.

Further, the reports should contain data on the number of devices shipped or sold during the reporting period.

FDA will review most reports within 90 days of receipt, at which time it will either acknowledge the report, request additional information or find that certain changes contained within the report were not appropriate. In the latter case, the company will need to immediately file a PMA Supplement or 30-day Notice.

 

Annual Reports for Approved Premarket Approval Applications

Federal Register