FDA CRL - HQ Specialty Pharma

The FDA issued a Complete Response Letter (CRL) to HQ Specialty Pharma Corporation regarding its New Drug Application (NDA 215212) for Meropenem for Injection 2 g/vial, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The application, received November 16, 2020, cannot be approved in its current form due to significant nonclinical and product quality deficiencies. A primary issue is the inadequate safety qualification of leachables from the drug product’s container closure system. The FDA found the company's risk assessment insufficient, noting discrepancies with acceptable intake thresholds for non-genotoxic leachables and the inappropriate application of modified Haber’s rule and QSAR analysis for general toxicity. To address this, HQ Specialty Pharma must complete and submit a planned 14-day repeat dose toxicity study in Beagle dogs. Furthermore, the proposed overfill amount for the drug product vials exceeds USP General Chapter <1151> recommendations. The company is required to conduct a study justifying the overfill and demonstrating consistent withdrawal of the labeled drug amount. The FDA also reserved comments on the proposed prescribing information and carton/container labeling, indicating they are not adequate until other deficiencies are resolved. Upon resubmission, a comprehensive safety update, as mandated by 21 CFR 314.50(d)(5)(vi)(b), is required. This update must include new clinical and nonclinical safety data, comparative analyses of adverse events, updated exposure information, and a summary of worldwide safety experience, along with English translations of foreign labeling.