FDA CRL - NOBELPHARMA CO LTD

The U.S. FDA issued a Complete Response Letter (CRL) to Nobelpharma Co., Ltd. regarding their New Drug Application (NDA 213478) for sirolimus topical gel, 0.2%, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The application cannot be approved in its current form due to several outstanding issues. Key deficiencies include product quality concerns, specifically regarding active pharmaceutical ingredient (API) assay results and the need to revise manufacturing process parameters with robust supporting data and scalability discussions. A critical unresolved issue is the mandatory facility inspection of TOYO PHARMACEUTICAL CO. LTD. in Osaka, Japan (FEI 3016419927) to assess compliance with Current Good Manufacturing Practices (CGMP). This inspection was delayed due to travel restrictions and must be completed before the application can be approved, irrespective of other deficiencies being addressed. Additionally, Nobelpharma is required to provide a comprehensive safety update encompassing all nonclinical and clinical studies, detailing significant changes in the safety profile, presenting combined new and original safety data, and including narratives for serious adverse events. Updates on exposure, worldwide safety experience, and translated foreign labeling are also necessary. Comments on proposed prescribing information are reserved until other issues are resolved, emphasizing conformity with labeling regulations. While the proposed proprietary name, Hyftor, was found acceptable, it must be resubmitted with the complete response. Nobelpharma must address all deficiencies and resubmit the application within one year. Approval is contingent upon satisfactory resolution of all issues, particularly the successful completion of the facility inspection.