Insufficient Safety Data at Maximum Dosing
Severity: criticalThe safety database, while suitable in patient number, lacked sufficient patients dosed at the maximum amount described in the proposed labeling to adequately assess the safety of Dsuvia, especially considering the nearly 4-fold increase in exposure and more than 2-fold increase in maximum concentration at steady state.
Recommended response: Collect additional safety data in at least 50 patients with postoperative pain sufficient to evaluate the safety of Dsuvia for a period following the maximum dosing proposed.
Inadequate Human Factors Validation and Risk Mitigation
Severity: criticalThe human factors validation study data did not demonstrate that the user interface supports safe and effective use. Failures resulting in dropped sufentanil tablets pose risks for accidental exposure, improper dosing, and diversion, which were deemed unacceptable without proposed additional mitigation measures.
Recommended response: Develop mitigation strategies to address the risk of dropped sufentanil tablets. Conduct another HF validation study to demonstrate the effectiveness of recommended mitigation strategies and ensure no new risks. Incorporate specific changes to the Directions for Use (DFU) and Pouch Package design.
Prescribing Information Not Finalized
Severity: majorFinal comments on the proposed labeling are reserved until the application is otherwise adequate. The applicant is encouraged to review PLR requirements and use the SRPI checklist to ensure conformity with format items in regulations and guidances.
Recommended response: Update content of labeling in structured product labeling (SPL) format, ensuring compliance with PLR requirements and the SRPI checklist.
Cited: 21 CFR 314.50(l)(1)(i)
Proprietary Name Resubmission Required
Severity: minorThe proposed proprietary name DSUVIA was found acceptable pending approval of the application in the current review cycle. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name with the complete response to the application deficiencies.
REMS Discussion Pending Complete Response
Severity: majorA Risk Evaluation and Mitigation Strategy (REMS) will be necessary for DSUVIA, if approved, to ensure benefits outweigh the risk of respiratory depression from accidental exposure. Further discussion of the proposed REMS will occur after the complete response to this action letter has been submitted.
Recommended response: Submit a complete response to the deficiencies to allow for continued discussion and finalization of the proposed REMS.
Cited: Section 505-1 of the FDCA
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), is required with the response. This includes data from all nonclinical and clinical studies, significant changes in safety profile, updated adverse event tabulations, and worldwide experience.
Recommended response: Include a safety update as described in 21 CFR 314.50(d)(5)(vi)(b) when responding to the deficiencies.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Container Label and Carton Labeling Comments
Severity: minorFinal comments on proposed container and carton labeling are reserved until the application is otherwise adequate. Specific recommendations were provided for the single dose applicator container label (e.g., including all required information, expiration date), pouch labeling (readability, adding patient instructions), and carton labeling (readability).
Recommended response: Incorporate recommended changes to container and carton labeling for improved readability and completeness, ensuring all required information is present.
Cited: 21 CFR 201.10(i)
