FDA CRL - Mylan Laboratories Limited

Mylan Laboratories Limited received a Complete Response Letter (CRL) from the FDA concerning its New Drug Application (NDA 206610) for Acetaminophen for Injection, 1 g/vial, filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The FDA could not approve the application due to significant nonclinical and safety data deficiencies. The primary nonclinical issues revolved around the assessment of substances that could migrate from the container-closure system into the drug product. Specifically, the FDA identified inconsistencies in the detection and quantification limits between Mylan’s extractable and leachable studies. There was also an inadequate correlation between these studies and the presence of unidentified compounds exceeding safety qualification thresholds. Mylan must clarify these discrepancies, justify their analytical methods, and identify all unknown compounds for a revised toxicological risk assessment, or alternatively, test the final drug product for these substances. Additionally, Mylan is required to provide a comprehensive safety update, as per 21 CFR 314.50(d)(5)(vi)(b). This update mandates new clinical and nonclinical safety data, detailed adverse event reporting, worldwide safety experience, and updated exposure information. Revisions to product labeling are also necessary once these core issues are resolved. Mylan must fully address all deficiencies and resubmit the application within one year.