FDA Post-Approval Studies Guidance Applies Tighter Timelines

The new FDA final guidance for post-approval studies (PAS) accelerates some of the timelines in the previous version, and introduces some new deadlines to this policy. These changes are the same as they were in the May 2021 draft guidance, but manufacturers should assume that these new deadlines are now in force for PAS studies required for PMA devices.

The FDA’s Center for Devices and Radiological Health released this final guidance Oct. 6, the same date on which the new final guidance for Section 522 studies was published. The PAS guidance is part of the FDA’s approach to allowing some devices onto the market even when the device’s benefit-risk profile is not entirely clear. These studies may be required as a condition of approval for PMA devices, and the protocol should include information on how the manufacturer intends to deal with issues such as potential losses to study subject follow-up. The guidance also provides insights into the FDA’s expectations on study enrollment and the timing of study reports, but also reminds manufacturers that the status of their studies will be listed in a publicly accessible database.

The most important feature of this guidance may be the requirements for enrollment of a PAS, which are now quite rigorous, such as that the first subject must be enrolled within six months of the date of the FDA’s approval of the protocol. Additionally, 20% of subjects must be enrolled within 12 months, and 50% must be enrolled within 18 months. All subjects should be enrolled by 24 months of the FDA approval of the study. These requirements were listed in the draft guidance as well.

The FDA prefers to have a PAS protocol already in place as of the date of device approval, and will work interactively with the sponsor toward that end. If the agency and the manufacturer have not come to agreement on the protocol by that date, the manufacturer has 30 days after device approval to submit the protocol. In this case, the protocol would be submitted as a PMA supplement, but the manufacturer will have to file multiple PAS protocols separately if more than one study is needed, each as PMA supplements.

The guidance stated that the FDA will attempt to conclude its review of the study protocol within 60 calendar days of its approval of the device, with an interim review time of 30 calendar days. However, the agency’s ability to meet that 60-day turn-around time is contingent upon the manufacturer’s prompt response to any queries the agency may have about the protocol at 30 days. A failure on the part of the manufacturer in this set of timelines will result in the protocol being classified as overdue.

The manufacturer can apply for an amendment of the protocol, but the FDA is unlikely to allow any amendments to timelines due to enrollment problems, as such issues should have been addressed during interactions between the manufacturer and the agency. However, the FDA may allow changes to enrollment timelines if it becomes evident that the enrollment targets were already impracticable as of the date the device was approved. In that instance, the enrollment target deadlines would be adjusted accordingly.

These studies come with reporting requirements, such as enrollment status reports, which are required for each enrollment deadline. An overall PAS progress report can include enrollment status report information if the reporting requirements for each report type coincide, but progress reports are typically required every six months until the study has reached full enrollment, and annually thereafter. The final status report is due three months after the last follow-up date for the last study subject unless the sponsor and the FDA have agreed upon a different timeline.

The FDA has limited authority to respond to a failure to complete the PAS, but the guidance states that the agency could respond by issuing an order for a Section 522 postmarket surveillance study. A failure to complete a Section 522 study could result in the device being deemed misbranded, in which case the agency may respond with injunction, seizure, and civil monetary penalties.