FDA CRL - Teva Pharmaceuticals, Inc.

On May 27, 2016, the FDA issued a Complete Response Letter to Teva Pharmaceuticals, Inc. regarding its New Drug Application for Austedo (deutetrabenazine), submitted under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The FDA determined the application could not be approved due to several unresolved issues. Primary concerns involved clinical pharmacology, specifically that Teva had not identified all major human metabolites, which is necessary to justify the drug's safety profile relative to its reference drug, Xenazine. Furthermore, the FDA identified a potential 'rebound effect'—the worsening of symptoms after discontinuing the medication—necessitating a formal evaluation of clinical dependence. Product quality deficiencies were also noted, including the need for a more comprehensive stability testing protocol for the first commercial batches and a required test for drug substances that was submitted too late for review in the initial cycle. To address these issues, Teva must provide a detailed safety update, conduct systematic evaluations of patient withdrawal using specific medical rating scales, and update its manufacturing stability commitments and container labeling to prevent medication errors. While the document does not list specific facility inspection violations, it requires a full resubmission addressing these clinical and quality gaps within one year.