FDA CRL - United Therapeutics Corporation

The FDA issued a Complete Response Letter (CRL) on October 7, 2016, to United Therapeutics Corporation for its New Drug Application (NDA 208276) for the Remodulin (treprostinil) Implantable System, originally submitted on December 16, 2015. The agency determined the application could not be approved in its current form, citing significant deficiencies under the Federal Food, Drug, and Cosmetic Act.

The primary issue relates to the device component of this drug-device combination product. The proposed implantable pump device, submitted under a separate Premarket Approval Application (PMA), received a "Not Approvable" letter from the FDA on March 11, 2016. Consequently, the drug NDA cannot be approved until the device component is deemed approvable.

Additionally, product quality concerns were identified due to insufficient data to evaluate the risk of patient exposure to microbial contaminants. The application lacked evidence demonstrating the catheter tip maintains a "closed system" against microbial ingress, questioning the efficacy of the drug product's preservative in this context. Other requirements include updating prescribing information, resubmitting the proprietary name, and providing a comprehensive safety update with new and existing clinical data. United Therapeutics Corporation must address these deficiencies within one year for potential resubmission.