Amphastar Pharmaceuticals, Inc. – FDA CRL

On February 26, 2024, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to Amphastar Pharmaceuticals, Inc. regarding its Biologics License Application (BLA 761403) for a biosimilar insulin aspart product. The FDA determined it cannot approve the application in its current form due to significant clinical and manufacturing concerns. The primary issue involves the clinical pharmacology study; the FDA identified deficiencies in the bioanalytical methods used for insulin quantitation, rendering the pharmacokinetic data from Study API-I004-CL-B unreliable. This prevents the demonstration of biosimilarity to the reference product, NovoLog. Additionally, a pre-license facility inspection resulted in an FDA Form 483, and the facility has not yet provided satisfactory responses to the identified deficiencies. Under the regulatory framework of 21 CFR 601.3, Amphastar is required to take specific actions for resubmission. These include conducting a new pharmacokinetic study using a validated bioanalytical method and resolving all facility-related inspection issues. The company must also provide a comprehensive safety update featuring global data, adverse event retabulations, and updated clinical exposure information. Amphastar has one year to submit a complete response that addresses all cited deficiencies, including revised labeling and a resubmission of the proposed proprietary name, before a new review cycle can begin.