FDA Seeks Increased Efficiency of Review Process

The Food and Drug Administration (FDA) has issued Draft Guidance for Industry and Food and Drug Administration Staff regarding the types of Communication During the Review of Medical Device Submissions.  The FDA is seeking feedback on the proposed guidance rules.  This guidance updates the Agency's approach to Interactive Review.  It now reflects the FDA's implementation of the Medical Device User Fee Act of 2007 (MDUFA II) Commitment Letters and of undertakings agreed in connection with the Medical Device User Fee Amendments of 2012 (MDUFA III). It also incorporates additional types of communication, all of which are designed to increase the efficiency of the review process. (Download PDF)

The concept of the Interactive Review was discussed in detail as part of the Medical Device User Fee Act (MDUFA) II of 2007.  The process was further described in the guidance “Interactive Review for Medical Device Submissions: 510(k)s, Original PMAs, PMA Supplements, Original BLAs, and BLA Supplements.”  (Download PDF)

Additional funds obtained from user fees will enable the FDA, with the cooperation of industry, to improve the device review process.  The FDA seeks to implement improvements for the medical device review process that will provide further transparency into the review process.  Improvements include new communication commitments.  These additional communications are in the context of:  acceptance review; substantive interactions; and, if applicable, missed MDUFA goals.

This guidance describes four types of communication during the review of a medical device submission:

1. Acceptance Review Communication for premarket notification submissions (510(k)s), original premarket approval applications (Original PMAs), and Panel-Track PMA Supplements
2. Substantive Interaction for 510(k)s, Original PMAs, Panel-Track PMA Supplements, and 180-Day PMA Supplements;
3. Interactive Review for 510(k)s, Original PMAs, PMA Supplements, original Biologics License Applications (Original BLAs), and BLA Supplements
4. Missed MDUFA Decision Communication for 510(k)s, Original PMAs, and Panel-Track PMA Supplements

Through the Interactive Review process the FDA seeks to facilitate efficient and timely review of premarket submissions.  Increased informal interaction between FDA and applicants will include the exchange of scientific and regulatory information.

The Interactive Review process is designed to help accomplish the following:

1. Improve the interaction between the FDA review staff and the applicant during the review process;
2. Prevent unnecessary delays in the completion of the review, thus reducing the overall time to market;
3. Ensure that FDA’s concerns are clearly communicated to the applicant during the review process, as appropriate;
4. Minimize the number of review cycles;
5. Minimize the number of review questions conveyed through deficiency letters; and
6. Ensure timely responses from applicants.
7. Interactive Review has no start/stop impact on the review clock.

Types of Deficiencies Appropriate for Interactive Review

More significant than “minor,” but that can likely be addressed by the applicant in a time frame that would allow FDA review of the response prior to the MDUFA performance goal for that submission type without placing the submission on hold.

Examples include, but are not limited to:

1. Requests for limited additional short-term laboratory bench or biocompatibility testing
2. Further justification for the omission of a test
3. Additional statistical analysis of the clinical data not related to the primary safety or effectiveness endpoint

Timing of Interactive Review

Interactive Review After Substantive Interaction for 510(k)s, Original PMAs, Panel-Track PMA Supplements, and 180-Day PMA Supplements

Any new deficiencies (i.e., deficiencies not raised as part of the Substantive Interaction) should be limited to issues raised by the information provided by the applicant in its response, unless the reviewer concludes (and received supervisory concurrence) that the initial deficiencies identified do not adequately address important issues materially relevant to a decision of substantial equivalence (510(k)) or safety and effectiveness (PMA).19  For example, following the communication of deficiencies in a 510(k) AI letter, FDA might become aware of a heightened potential for device failure through a series of recalls on other devices with a similar feature.  If these recalls indicate that the particular bench test performed by the applicant to evaluate this feature is not predictive of clinical performance, an FDA reviewer, with appropriate supervisory concurrence, might request additional testing to address the safety of this feature to determine substantial equivalence.  As the end of the review cycle approaches, FDA intends to send a communication that lists the remaining issues, limiting the applicant’s response timeframe to a maximum of 7 calendar days and allowing time for FDA to review the response, so that a timely MDUFA decision can be made.

In limited circumstances, a second AI letter for a 510(k) may be appropriate.  One example of such a circumstance would be when a first AI letter indicates that FDA believes no predicate device exists, but the submitter is able to identify a predicate.  A subsequent review of the comparison of the subject device to the newly identified predicate could raise questions appropriate for a second AI request.  Other instances in which a second AI request could be issued should be limited and occur only with concurrence of Division-level management.

Additional Interactive Review

The FDA also encourages the use of Interactive Review at other points in the review process to facilitate the efficient and timely review of a submission.  At FDA’s discretion, Interactive Review can be used:

• Prior to Substantive Interaction for 510(k)s, Original PMAs, Panel-Track PMA Supplements, and 180-Day PMA Supplements; and
• As needed for BLAs, BLA supplements, Humanitarian Device Exemptions (HDEs), and Product Development Protocols (PDPs).

FDA should determine an acceptable timeframe for the applicant to provide a response to the deficiencies based on MDUFA, Office, or Center timelines.  The established timeframe should be based on the impending review deadline, the estimated time that the applicant should need to respond, and the estimated time that FDA should need to review the response.

When final, this document will supersede "Interactive Review for Medical Device Submissions: 510(k)s, Original PMAs, PMA Supplements, Original BLAs, and BLA Supplements" dated February 28, 2008.  If interested in providing comments regarding this draft they can be submitted HERE