FDA CRL - AcelRx Pharmaceuticals, Inc.

AcelRx Pharmaceuticals, Inc. received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA 209128) for DSUVIA (sufentanil sublingual tablet), submitted under section 505(b)(2) on December 12, 2016. The FDA determined the application could not be approved in its current form due to several deficiencies. Key issues included insufficient safety data. The agency noted that while the patient count was adequate, there was a lack of data for patients dosed at the maximum amount described in the proposed labeling, which is crucial given the increased drug exposure at steady state. AcelRx is required to collect additional safety data from at least 50 patients with postoperative pain, covering the period following maximum proposed dosing. Significant human factors issues were also identified. The FDA found that the human factors validation study did not adequately demonstrate safe and effective product use by intended users. Specifically, the risk of dropped sufentanil tablets, which could lead to accidental exposure, improper dosing, or diversion, was deemed unacceptable, with no mitigation strategies initially proposed. To address this, AcelRx must develop and validate mitigation strategies for dropped tablets through a new human factors study. Recommended user interface changes include revising the Directions for Use (DFU) to clarify tablet delivery and confirmation, enhancing anatomical labeling in figures, and integrating the complete DFU onto the foil pouch to prevent its separation. Additionally, the FDA reiterated that a Risk Evaluation and Mitigation Strategy (REMS) is necessary for DSUVIA to ensure the benefits outweigh the risk of respiratory depression from accidental exposure. A comprehensive safety update, detailing any new findings, updated adverse event data, and worldwide safety experience, is also required. Comments on prescribing information and labeling are reserved pending resolution of these core deficiencies.