FDA CRL - Aft Pharmaceuticals Ltd

The U.S. FDA issued a Complete Response Letter (CRL) to AFT Pharmaceuticals Ltd. for its New Drug Application (NDA 215320) for Combogesic (acetaminophen/ibuprofen) solution for injection, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. Following its review of the August 31, 2021 submission, the FDA determined that the application cannot be approved in its current form due to significant nonclinical and labeling deficiencies. The primary nonclinical concern centers on inadequate toxicological risk assessments for leachables exceeding the 5 mcg/day qualification threshold. The FDA found the company's reliance on a genotoxicity-focused threshold (ICH M7) insufficient for general toxicity and noted that recent submissions for tentatively identified compounds lacked confirmed structural identification and quantification using validated methods. AFT Pharmaceuticals is required to submit a revised toxicological risk assessment based on confirmed and quantified leachables from long-term stability data, supported by robust scientific principles and original study reports. Additionally, the FDA mandates revisions to the prescribing information and carton/container labeling to ensure compliance with regulatory standards, including submission in Structured Product Labeling (SPL) format and adding a specific Medication Guide statement. The company must also resubmit the proprietary name, Combogesic IV, and provide a comprehensive safety update when responding to these deficiencies.