On December 31, 2012, FDA issued two guidance documents detailing the agency’s approach to reviewing the completeness of medical device applications reviewed by the Center for Devices and Radiological Health (CDRH). The two guidance documents cover PMA submissions, Acceptance and Filing Reviews for Premarket Approval PMAs) (“PMA Guidance”), and 510(k) submissions, Refuse to Accept Policy for 510(k)s (“510(k) Guidance”). Both of these documents superseded previous FDA guidance on evaluating whether medical device applications were complete for filing.

Generally, these guidance documents provide a framework describing the necessary criteria for FDA personnel to accept and file submissions for substantive review. These guidance documents were issued by FDA to improve efficiency of the medical device submission process by communicating requirements for an adequately complete application or submission. This goal was particularly emphasized in the 510(k) Guidance, where the agency noted a large number of incomplete and inadequate submissions consumed FDA resources and slowed general review times.

PMA Guidance

The PMA Guidance is generally similar to the agency’s previous guidance on PMA submissions that detail when FDA personnel should make a “Refuse to Accept” (RTA) determination. It provides a detailed checklist in its Appendix to assist in the evaluation of PMA submissions. Some key changes include the following:

  • Applicants must submit a manufacturing section for a complete PMA application. Previously, this section could be submitted within 90 days of the original application submission.
  • FDA has a 15 calendar day objective to review and determine if an application is ready for substantive review.
  • Applicants must provide an electronic copy (eCopy) with their PMA applications.
  • FDA removed the explicit requirement for a PMA application to be “sufficiently organized.”
  • FDA will allow nonclinical data located in other submissions to be referenced and not included in the application.
  • Applicants must include associated NCT Numbers (clinicaltrial.gov numbers) in their applications.
  • Applicants must submit pediatric use information for a complete PMA application.

The PMA Guidance also modifies the previous guidance with additional information and new explanations for FDA’s review policies. Notably, in the nonclinical and clinical information criteria, “key issues” are defined as those specifically identified by FDA as part of the documented regulatory process and thus capable of a RTA determination. The previous guidance had granted FDA personnel more discretion in their RTA determination with this element. Additionally, the PMA guidance makes it clearer that combination device products are covered under its scope.

510(k) Guidance

The 510(k) Guidance is significantly more expansive than its predecessor guidances, although similar to the PMA Guidance. Generally speaking, the 510(k) Guidance addresses specific content requirements for a complete 510(k) submission. The 510(k) Guidance contains an Appendix with separate checklists for traditional, abbreviated and special 510(k) submissions (the previous guidance only had one general checklist). Similar to the PMA Guidance, the 510(k) guidance also has a 15 calendar day objective for an acceptance review determination, as well as requirement for an eCopy to be submitted with an application.

The following are the general RTA Principles and Preliminary Questions for 510(k) submissions that have been added by the 510(k) Guidance (note: these are also applicable to PMA submissions, but are not noted above because these were included in previous PMA guidance):

  • Acceptance review should not be based on a substantive review of the information provided in the 510(k) notification. The review to accept an application should be based on whether the submission contains all required elements and not on the weight of evidence to support a finding of substantial equivalence and other substantive criteria.
  • Staff should determine whether the submitter provided a justification for any alternative approach to the information requirements in a 510(k) submission. Missing elements of an application can be satisfied by providing an acceptable rationale as to why the information requested is not applicable.
  • Is the application with the appropriate Center? FDA will review a 510(k) submission to determine whether the application should be reviewed by another Center or if it is a combination product for which a different Center should take the lead in reviewing.
  • If a Request for Designation (RFD) was submitted for the device or combination product with a device constituent part and assigned to your center, identify the RFD number and confirm the following:
    • Is the device or combination product the same (e.g., design, formulation) as that presented in the RFD submission?
    • Are the indications for use for the device or combination product identified in the 510(k) the same as those identified in the RFD submission?
  • Is there a pending PMA for the same device with the same indications for use?
  • If clinical studies have been submitted, is the submitter the subject of the Application Integrity Policy (AIP)?

The checklists are more expansive and detailed than in the predecessor guidances. Given FDA’s statement noting the inconsistent quality of 510(k) submissions it is receiving, it would be advisable to follow the 510(k) Guidance closely. Please let us know if you have any questions.