FDA CRL - Proximagen, LLC

The FDA issued a Complete Response Letter (CRL) to Proximagen, LLC, for its New Drug Application (NDA 211321) of Nayzilam (midazolam) nasal spray. The application was deemed unapprovable due to significant deficiencies primarily related to the Quality System for this combination product, specifically regarding the integration and responsibilities of UCB BioPharma SPRL (UCB), which has acquired the NDA.

The main violations include inadequate demonstration of compliance with the Quality System Regulation (21 CFR Part 820). Proximagen failed to sufficiently detail management responsibilities (21 CFR 820.20), design controls (21 CFR 820.30), purchasing controls (21 CFR 820.50), and corrective and preventive actions (21 CFR 820.100), particularly concerning UCB's involvement and established procedures. The FDA also noted the absence of a production flow diagram clarifying facility responsibilities and an insufficient explanation of UCB's integration into manufacturing control processes. Additionally, the proposed prescribing information did not conform to regulatory content and format requirements (21 CFR 201.56/201.57), and unresolved manufacturing facility inspection deficiencies at UCB require satisfactory resolution.

To achieve approval, Proximagen must resubmit the NDA within one year. The resubmission needs to comprehensively address all identified issues, providing detailed documentation on UCB's role and procedures within the Quality System, revising all labeling materials, and resolving all outstanding manufacturing facility observations.