FDA CRL - InnoPharma Licensing LLC

The FDA issued a Complete Response Letter (CRL) to InnoPharma Licensing LLC for their New Drug Application (NDA 206968) for Acetaminophen Injection, 10 mg/mL, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The letter, issued after reviewing amendments up to June 30, 2020, indicates the application cannot be approved in its current form due to significant nonclinical, product quality, and labeling deficiencies. Key issues include inadequate validated leachable data for the container closure system and an insufficient toxicological risk assessment for detected acetaminophen adducts, requiring either a toxicology study or evidence of adduct instability. Product quality concerns involve the leachable profiling methodology, particularly the Analytical Evaluation Threshold calculation, the use of semi-quantitative methods for later stability time points, and unexplained changes in leachable profiles. The FDA also noted missing accelerated stability data and photostability report details. Required actions include submitting a revised toxicological risk assessment based on validated leachable data, demonstrating comprehensive leachable detection methods with correct AET calculation, reanalyzing stability data with fully validated methods, and providing complete stability study reports. Additionally, the company must update prescribing information to meet current regulatory requirements and revise carton and container labeling to ensure clarity regarding strength presentation, expiration dates, and lot numbers, addressing potential medication errors.