On October 30, CDRH issued the Final Guidance “De Novo Classification Process (Evaluation of Automatic Class III Designation)” (the “De Novo Guidance”). This is a final version of the 2014 draft by the same name (see our earlier blog post here). On the same day, CDRH also issued the draft guidance “Acceptance Review for De Novo Classification Requests” (the “De Novo RTA Guidance”). Subsequently, on November 21, FDA held a webinar regarding the guidances. During the webinar, FDA explained the key provisions of both guidances and emphasized that the De Novo RTA Draft Guidance is not yet in effect. FDA will be posting a transcript, audio recording and slides here.
The final De Novo guidance is virtually unchanged from its 2014 draft. One new addition of note – which the Agency also highlighted during last week’s webinar – has to do with what happens if there is more than one de novo submission pending for a new type of device. The final guidance indicates that if there is more than one de novo submission for the same type of device, CDRH will review both simultaneously. When the first submission is granted, the Agency will notify the sponsor of the second submission (the second sponsor). The second sponsor will have the opportunity to withdraw their de novo and then submit a 510(k) establishing substantial equivalence to the first de novo (appropriately referencing information in its original de novo). While the guidance says it does not anticipate such a situation will arise, it will be a difficult situation for the second sponsor because it will lose its significant de novo submission user fee (currently $93,229). Even though the second sponsor will be able to reference the data in the de novo application, marketing authorization will be delayed while a 510(k) submission is prepared and a new review clock is initiated.
The Agency raised a few additional interesting points regarding the De Novo Guidance during the webinar. First, CDRH clarified that unlike 510(k)s which are cleared and PMAs which are approved, de novo requests are “granted.” This may be an important promotional point for companies after their de novo is granted, and a helpful semantic distinction. Second, a webinar participant asked how to determine if a de novo or a PMA is the appropriate regulatory pathway. We expected the Agency to refer the caller to the 513(g) process, a response that we have had several clients receive. Instead, however, CDRH indicated that it is up to the company to determine if its product fits within the definitions of Class I, II, or III, and it will also depend on the company’s business strategy. While it was somewhat surprising to hear CDRH defer to the company’s judgement and preference regarding classification when it directly affects the regulatory pathway, we are certain FDA would provide guidance if requested through the appropriate pathway (e.g., the 513(g) process).
The draft De Novo RTA Guidance is also unremarkable. The draft guidance contains checklists and looks very similar to the 510(k) RTA. Like the 510(k) RTA process, the de novo administrative review will occur in the first 15 days after receipt of a submission. In addition, the draft guidance gives the CDRH reviewer discretion to determine if missing items can be addressed interactively instead of refusing a submission.
Unlike the 510(k) RTA checklist, the De Novo RTA Guidance contains two checklists: a high-level checklist of required items; and a more detailed checklist of recommended items. If the submission contains the items on the second checklist, the guidance recommends including a completed copy of the second checklist. There is some duplication between the two checklists, e.g., both lists include a classification summary. In addition, the second list appears to include information that one would expect to see in a de novo submission. For example, the second list includes labeling and full tests reports. These are items that are typically required in a premarket submission; they are not optional. According to the guidance, a de novo request should only be refused if items on the first checklist are missing. Because of the duplication and the appearance of apparently required items on the option list, we expect that it may be administratively difficult to implement the two-checklist approach.
CDRH is accepting comments on the draft guidance through December 29. Once a final version of the guidance is issued, according to the draft, there will be a 60-day delay on implementation meaning that de novo submissions received in the first 60 days after issuances of the final guidance will not be refused for failure to include all required items. This will be important for companies with de novo submissions in process of being drafted to allow them time to comply. Although the De Novo RTA Guidance is not yet final, sponsors would be wise to begin reviewing and operationalizing the checklists now to ensure that their submissions contain the appropriate content for review.