FDA CRL - ZYDUS WORLDWIDE DMCC

On March 3, 2023, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Zydus Worldwide DMCC regarding their New Drug Application (NDA 211566) for sitagliptin tablets. This action follows a previous letter dated September 2, 2021, and a subsequent company response on January 5, 2023. Operating under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, the FDA determined the application could not be approved in its current form. The primary deficiency identified was product quality issues related to impurities. Zydus is required to submit a comprehensive plan outlining measures to reduce these impurities both at the time of release and throughout the product's shelf-life. Additionally, the FDA mandates a thorough safety update, as detailed under 21 CFR 314.50(d)(5)(vi)(b). This update must include new nonclinical and clinical study data, a detailed analysis of adverse events (including comparisons to original data), justifications for trial discontinuations, case report forms for serious adverse events or deaths, and an overview of the drug's worldwide safety experience and exposure. Revisions to prescribing information, carton, and container labeling are also necessary, along with the resubmission of the proprietary name "Zituvio," once product quality issues are resolved. Zydus must resubmit the application, fully addressing all identified deficiencies, within one year of the CRL date for further review. The drug product cannot be legally marketed until formal approval is granted.