When FDA Can Accept Greater Premarket Uncertainty for Medical Devices
The Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration (FDA) finalized guidance on Thursday that explains when agency review staff may be able to accept greater premarket uncertainty about a device’s benefit-risk profile.Revisions to the September 2018 draft version of the 22-page guidance document offer additional clarifications, reflecting recommendations industry offered during the public comment period. The guidance informs industry of the process FDA follows for considering acceptable levels of uncertainty about a device in making benefit-risk determinations for premarket applications, de novo classification requests or humanitarian device exemption applications.
Per AdvaMed’s request, revisions reduce the use of the term “appropriate” as the group had argued that the term “appropriate” is “problematic because what is ‘appropriate’ is subjective and is neither well understood nor well established in FDA regulatory practice.” The final guidance makes additional use of the term “reasonable” instead, as AdvaMed suggested.
Other recommendations from AdvaMed led to clarifying that the agency “generally expects to hold an advisory committee meeting,” rather than “intends,” and new details relating to small patient populations. The guidance details an approach on devices for small patient populations that “would be applied on a case by case basis, taking into account the factors described in Section IV and the relevant non-clinical and/or clinical information about the device. Sponsors may submit a Q-submission to discuss with the appropriate review team,” CDRH now adds.
Updates to the draft guidance clarify that it is intended to be used as complementary to other guidances. This includes final guidance on the factors FDA considers when making benefit-risk determinations, an updated version of which was issued Thursday in conjunction with that of uncertainty. References to FDA guidances on such factors, either for considering uncertainty or making benefit-risk determinations, comes after the Bringing Real-world Insight for Device Governance and Evaluation Coalition urged the agency to make such revisions for clarification.
The updated guidance on factors to consider for benefit-risk determinations adds a worksheet for agency staff to make such assessments. “The revised worksheet provides structure to guide and organize the benefit-risk factors and to support consistent decision-making,” CDRH said.
Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions: Guidance for Industry and Food and Drug Administration Staff
Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications: Guidance for Industry and Food and Drug Administration Staff