FDA CRL - CSL Behring LLC

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for CSL Behring LLC's Biologics License Application (BLA 761367) for CSL312 (garadacimab). The FDA determined the application could not be approved in its current form, citing several deficiencies related to manufacturing and regulatory submissions under the Public Health Service Act.

Key issues identified during a pre-license inspection of CSL Behring GmbH in Marburg, Germany, necessitate satisfactory resolution. The company must provide responses to the FDA 483 observations, and a re-inspection may be required.

Microbiology concerns were raised regarding the manufacturing process for the semi-finished product (SFP), which was deemed insufficient to minimize potential contamination. Further process validation data, stability data for a new process, and sterilization validation summaries are required.

Product quality deficiencies include an insufficient control strategy for the drug product manufacturing process, particularly concerning consistent filling weight/volume for individual syringes. The FDA requests robust process control strategies supported by relevant data, along with comprehensive process validation data derived from adequate sampling of production batches.

Additionally, the FDA requires revised prescribing information to comply with content and format regulations, including specific updates outlined in prior communications. The proposed proprietary name "Andembry" must be resubmitted after all other deficiencies are addressed. Finally, a comprehensive safety update, incorporating all new nonclinical and clinical data, is mandatory for the resubmission. CSL Behring must address all these points for potential approval.