FDA CRL - Alvotech USA, Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Alvotech USA, Inc. regarding its Biologics License Application (BLA 761299) for AVT02, submitted under section 351(k) of the Public Health Service Act. The application, seeking approval for a biosimilar product, cannot be approved in its present form due to several identified deficiencies.A primary issue involves unresolved deficiencies observed during an inspection of Alvotech hf's manufacturing facility in Reykjavik, Iceland. Resolution of these facility-related concerns is essential for approval. Additionally, the FDA requires revisions to product labeling, specifically mandating a bolded statement about the Medication Guide on carton and container labeling. While the proprietary name, Simlandi, was found acceptable, it must be resubmitted with the complete response.Crucially, a comprehensive safety update is required. This update must detail any significant changes in the safety profile, include updated nonclinical and clinical safety data, provide analyses of adverse events and study discontinuations, include case reports for serious events, update exposure information, summarize worldwide safety experience, and provide English translations of foreign labeling.Alvotech must address all identified deficiencies and resubmit the application within one year, as the drug product cannot be legally marketed until written approval is granted.