The new article addresses the aspects related to the evaluation of post-approval study reports. 

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to post-approval studies for medical devices. According to the existing legislation, in certain cases, marketing approval granted by the FDA could be conditional on post-approval studies the medical device in question should undergo after the formal approval is granted. The present guidance provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be taken into consideration by medical device manufacturers, study sponsors, and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Furthermore, it is explicitly stated that an alternative approach could be applied, provided such an approach is in line with the underlying regulations and has been agreed with the authority in advance. 

As explained in previous articles, the reports related to post-approval studies could be interim (generated in the course of a study) and final (prepared upon completion of a study). The present article describes in detail the approach to be applied when evaluating such reports. 


Evaluation of Interim Reports 

First of all, the document describes the way interim post-approval study reports should be evaluated. According to the guidance, FDA intends to review Enrolment Status Reports to assess progress towards the study enrolment milestones identified in the PMA approval order (i.e., comparing study enrolment milestones to actual enrolment). The document further outlines the specific factors the authority will take into consideration when evaluating interim reports – they include, inter alia, the following ones: 

  • The completeness of the report and its content (including with respect to the progress in achieving the endpoints of the study);
  • Compliance with the study protocol and details regarding deviations, if any (all deviations should be explained);
  • The safety and performance of a medical device in question when used for its intended purpose;
  • Achievement of study enrolment milestones;
  • Explanation regarding any delays or failures. 

With respect to the last point, the authority expects the study sponsor facing issues with meeting enrolment milestones to take additional actions and introduce specific measures such as:

  • Current and past enrolment recovery efforts;
  • Evaluation of slow enrolment;
  • Device availability on the market;
  • Measures taken to initiate study sites;
  • Measures taken to incentivize study subjects;
  • Outreach to study investigators and potential subjects; and
  • Plans to remove barriers to site and subject participation. 

The authority also mentions that once a failure to meet a study milestone is identified, a sponsor should assess the situation and provide information regarding grounds for the delay and notify the authority if this could potentially impact the overall study and achieve its goal. 

Under the general rule, it should take 30 calendar days for the authority to review the report (calculation of the term starts from the date the interim report has been received by the FDA). It is also important to mention that the authority may raise additional questions or request additional information, should it will be reasonably necessary for the course of the review. In particular, it is stated that if an interim report includes insufficient data or the sponsor failed to meet enrolment milestones or study timelines, FDA ultimately may take enforcement actions to ensure compliance with PAS requirements, as appropriate; additionally, if the PAS results identify new safety and/or effectiveness concerns for a device, FDA may consider taking actions, which may include issuing a Safety Communication to provide recommendations on patient management, as appropriate. 

Evaluation of a Final Report 

The document also covers the matters related to the evaluation of a final PAS report. According to the guidance, the said report should describe in detail the methodology applied during the study, as well as the results achieved. In the report in question relating to a study that has been completed, it should also demonstrate how the respective requirements set forth by the authority in the PMA approval order are satisfied. At the same time, if the report describes a post-approval study terminated before its completion, it should contain all the data collected in the course of a study before it was terminated. 

As in the case of interim study reports, the authority also outlines the scope of factors to be taken into consideration when evaluating a final PAR report. According to the guidance, these factors include, inter alia, the following ones:

  • The completeness of the report content;
  • Adherence to methodology in the PAS protocol and reasons for deviations from the methodology;
  • Evaluation of data in the report to assess the performance, safety, and effectiveness of the device; and
  • Evaluation of fulfillment of the condition(s) of approval identified in the PMA approval order. 

According to the guidance, it should take up to 60 days for the authority to review a final report – calculation starts from the date it is received by the authority. As in the case with interim reports, the authority may also raise additional questions and request additional information. 

Once the authority determines that the PAS requirements have been fulfilled, the appropriate letter will be provided to the party responsible for the device in question. Upon receipt of such a confirmation, additional reports are not mandatory. At the same time, if the results of the study require the device labeling to be changed, a PMA supplement would probably be required. 

In summary, the present FDA guidance describes in detail the way the authority will review the reports related to post-approval studies. The scope of the guidance covers the aspects related to both interim and final reports. 



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