The final guidance describes the methods by which combination product sponsors can obtain FDA feedback on scientific and regulatory issues and further outlines best practices for agency-sponsor interactions on combination products. Included in this draft guidance is specific information about CPAMs, a new pre-submission meeting mechanism, specifically intended to provide a means for sponsors of combination products to obtain certainty on issues related to marketing authorization requirements and standards, as well as requirements for postmarket modifications to combination products. CPAMs were established by the 21st Century Cures Act of 2016, and we recently analyzed this FDA feedback mechanism online here. The guidance provides a framework for how CPAMs relate to the other methods for interacting with FDA, what information should be submitted in CPAM requests, and the form and content of agreements reached through a CPAM.
The primary difference between the draft and final versions of the guidance is that FDA added into the final guidance a section on when CPAM requests are appropriate, writing: “The Agency encourages combination product sponsors to interact through application-based mechanisms to provide FDA an opportunity to evaluate technical data or engage in scientific discussion before considering a CPAM.” While “[a]pplication-based mechanisms are generally appropriate for requesting feedback on scientific issues, study design, testing approaches, or application preparation considerations for combination products or clarifying topics for which FDA has already published technical guidance,” CPAMs “may be appropriate for seeking agreement from FDA on an approach if previous feedback under an application-based mechanism has not provided sufficient certainty.” In this new section in the guidance, FDA notes that “more information and data may be needed in a CPAM request, as compared to an application-based mechanism submission, to increase the likelihood of reaching an agreement.” (emphasis added).
Separately in the final guidance, FDA also clearly states the purpose for a CPAM: “to address the standards and requirements for marketing authorization of a combination product and other issues relevant to a combination product, such as requirements related to postmarket modification of the product or CGMPs.” In contrast, the dispute resolution and appeals process through the lead FDA Center is appropriate to address disagreement or disputes over constituent part or combination product issues identified as part of an FDA action, the final guidance adds. These disputes may include disagreements over determinations that a product cannot be marketed, complete response actions, clinical holds, or refusal to receive.
In March, we had summarized how comments on the draft version of the guidance asserted FDA should clarify the timeline for CPAM requests, and add in parameters for how long the agency has to respond. Seemingly in response to these comments, FDA added into the final guidance that “[i]f the sponsor requests a face-to-face meeting or teleconference, FDA intends to provide the sponsor preliminary responses to the CPAM request no later than 5 calendar days before the meeting/teleconference,” and “[i]f the sponsor then determines that a meeting/teleconference is not needed or is needed to discuss only certain issues…FDA’s preliminary response will represent the Agency’s final written feedback (on all or the resolved issues) on a CPAM.” In addition, if the meeting/teleconference is held, “FDA intends to provide final written feedback to the sponsor within 30 calendar days following the meeting,” the final guidance states.
While adding this new timeline recommendation for FDA actions, the final guidance also poses a new parameter for CPAM sponsors, stating that after a sponsor receives a preliminary response from the agency, the sponsor “should notify the FDA no later than 3 calendar days following receipt that a face-to-face meeting or teleconference is not needed or identifying the issues which the sponsor wants to further discuss at the meeting/teleconference.”
Authored by Randy Prebula, Dave Fox, and Heidi Gertner
