FDA CRL - Aquestive Therapeutics Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to Aquestive Therapeutics Inc. regarding their New Drug Application (NDA 219870) for dibutepinephrine sublingual film. While no specific facility inspection dates were cited in the document, the FDA determined the application cannot be approved in its current form due to significant concerns regarding user safety and drug performance. The primary issues involve critical errors observed during human factors validation studies. Participants struggled to open the packaging, sometimes tearing the film, which could lead to delayed or insufficient dosing during a severe allergic reaction. Additionally, users frequently placed the film incorrectly or chewed it, and pediatric subjects reported localized irritation—such as burning or an unpleasant taste—that led to premature removal of the medication. These errors create uncertainty regarding how the drug is absorbed and its overall clinical effectiveness. Under the regulatory framework of the Federal Food, Drug, and Cosmetic Act, Aquestive must take several corrective actions to resolve these deficiencies. These include redesigning the product's container closure and instructions, conducting a new human factors validation study with a matching placebo, and performing additional clinical pharmacology trials to evaluate the impact of improper administration (such as chewing or incorrect placement) on the drug's concentration levels. The company must also provide a comprehensive safety update upon resubmission.