FDA CRL - Fidelity BioPharma Co.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Fidelity BioPharma Co. on March 29, 2024, for their New Drug Application (NDA 216190) for Ontralfy (tizanidine) oral solution, 2 mg/5 mL, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The application cannot be approved due to product quality and nonclinical deficiencies.

Key concerns include drug substance impurity assessment, where the company's conclusion lacked proper application of guidance, necessitating alternative methods to establish an acceptable intake (AI) limit. Working with the drug master file (DMF) holder to set an AI limit is recommended. Additionally, nonclinical data failed to support a proposed impurity specification exceeding the ICH Q3B(R2) qualification threshold; this requires either lowering the specification or providing more data.

Labeling comments were reserved until resolution, and the conditionally acceptable proprietary name, Ontralfy, must be resubmitted. Required actions involve a comprehensive safety update, detailing profile changes, presenting new and combined safety data, providing updated exposure information, and summarizing worldwide experience. Fidelity BioPharma must fully address all deficiencies and resubmit within one year to avoid potential withdrawal. The product cannot be legally marketed until approved.