FDA CRL - Xellia Pharmaceuticals ApS

The FDA issued a Complete Response Letter (CRL) to Xellia Pharmaceuticals, ApS, regarding their New Drug Application (NDA 213895) for Vancomycin Injection, 5 g/100 mL. Submitted on September 20, 2019, the application was deemed unapprovable in its current form. No inspection dates were provided in the document.

The main issues identified were related to Product Quality and Nonclinical Toxicology. Xellia Pharmaceuticals must fully qualify all applicable leachables from the proposed drug product. Additionally, a comprehensive toxicological risk assessment is required for any leachable exceeding 5 mcg/day. This assessment needs to cover local and systemic toxicity, mutagenicity, carcinogenicity, and reproductive toxicity, and should be based on long-term stability samples, including any secondary container closure systems. The FDA referenced established guidelines, such as those from PQRI and ICH M7, for evaluating genotoxic potential.

Required actions for Xellia Pharmaceuticals include addressing these leachables deficiencies and submitting a safety update. This update must detail any significant changes in the drug's safety profile and any information suggesting a substantial change in the incidence of common adverse events, as per 21 CFR 314.50(d)(5)(vi)(b). While labeling comments were reserved, the FDA encouraged reviewing relevant regulations for Prescribing Information. Xellia must resubmit a complete response addressing all identified deficiencies within one year, as outlined under 21 CFR 314.110, or risk the withdrawal of the application. The company may also request a meeting with the FDA to discuss the necessary steps for approval.