CSL Behring LLC: CSL312

Please refer to your biologics license application (BLA) dated October 13, 2023, received October 13, 2023, and your amendments, submitted under section 351(a) of the Public Health Service Act for CSL312 (garadacimab).

We also acknowledge receipt of your amendment dated August 9, 2024, which was not reviewed for this action.

1. Following pre-license inspection of CSL Behring GmbH, Emil-von-BehringStrasse 76, Marburg, Hesse, Germany (FEI 3003098680), listed in this application, the FDA conveyed the deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

2. The manufacturing process for CSL312 semi-finished product (SFP) is not designed to minimize potential contamination of the sterile drug product.

A process performance qualification (PPQ) protocol and the results of the first)" PPQ batch were provided in the amendment received July 12, 2024; however, additional process validation and other supporting data are needed to support the process change.

The amendment received August 9, 2024, was submitted late in the review cycle and was not reviewed.

Include © and sufficient stability data to support consistency, stability and proposed shelf life of the CSL312 SFP.

The process validation data for CSL312 drug product manufacturing are insufficient to demonstrate consistent process performance.

The amendment received June 11, 2024, noted that a new plunger movement study will be conducted using 15 filled syringes with plunger stopper positions manipulated manually to create a |{jmm air bubble.

In the information request response dated June 3, 2024, you agreed to commit to perform a real-time/real-condition shipping validation study and to submit the data in a future annual report.

The FDA also requested testing for a total of 3 batches of the subject autoinjector (Al) to include dose accuracy, injection time, activation force, extended needle length, and lockout force to demonstrate that the device will perform as intended to the end of its proposed shelf-life of 36 months.