FDA CRL - Par Sterile Products, LLC

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Par Sterile Products, LLC, for their New Drug Application (NDA 212156) for Micafungin for Injection, 50 mg/vial and 100 mg/vial. The application, filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, cannot be approved in its current form due to several product quality, nonclinical, and labeling deficiencies.

Key issues identified include: Product Quality: Compatibility studies showed critically low assay values for the drug product in 5% dextrose, raising concerns about efficacy. The proposed acceptance criteria for several specified and unspecified impurities were significantly above ICH Q3B qualification thresholds, requiring tighter limits or comprehensive toxicological justification. Nonclinical: A revised leachables assessment with toxicological data was pending. Additionally, the high impurity limits necessitated further characterization and toxicological evaluation, potentially requiring new nonclinical studies if adequate safety data is not provided. Labeling: The proposed Prescribing Information and carton/container labeling did not conform to FDA regulations (21 CFR 201.56, 201.57) and required revision to align with FDA's proposed changes and be submitted in Structured Product Labeling (SPL) format.

Required actions for Par Sterile Products, LLC include conducting a root cause analysis and re-testing for the low assay values, tightening impurity limits or providing robust toxicological data, submitting a revised leachables assessment, and ensuring all labeling adheres to regulatory standards. Furthermore, a comprehensive safety update (per 21 CFR 314.50) is mandated, detailing new safety data, adverse event comparisons, and worldwide experience. Finally, a facility inspection is required before the application can be reconsidered for approval.