FDA CRL - Corium, Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Corium, Inc. regarding its New Drug Application (NDA 212304) for ADLARITY (donepezil transdermal system), submitted under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The agency determined the application could not be approved in its current form due to significant product quality, stability, and manufacturing concerns, alongside deficiencies observed during a recent inspection of a manufacturing facility.Key issues include the transdermal system's susceptibility to easy separation by hand, which poses safety and quality risks. Corium must redesign the product to prevent this. Additionally, the drug product demonstrated instability during long-term storage, showing reduced in vitro drug release and unclear changes in the donepezil salt:base ratio. The company is required to conduct a bioequivalence study comparing product at the beginning and end of shelf-life, or develop a more stable formulation.Furthermore, major differences were identified between the intended commercial manufacturing process and the process used for the pivotal clinical batch. The submitted data was insufficient to bridge these differences, necessitating a new bioequivalence study with oral Aricept using the proposed commercial product and manufacturing process. Finally, satisfactory resolution of the manufacturing facility inspection deficiencies is mandatory for approval.