FDA EIR - CSL Behring GmbH - March 04, 2022

The FDA conducted a cGMP surveillance inspection of CSL Behring GmbH in Marburg, Germany, from February 21 to March 4, 2022. The inspection, focusing on biological drug products and substances, identified several significant deficiencies across quality, production, facilities, and equipment systems, leading to a six-item Form FDA-483.

Key violations included inadequate investigations into unexplained discrepancies, such as mold contamination in bulk drug lots and brown residue in vials without proper evaluation of washing cycles. Product Technical Complaint records lacked sufficient rationale for not investigating retention samples, particularly concerning atypical characteristics and particles in various licensed products. Manufacturing buildings were not consistently maintained in sanitary conditions, evidenced by recurrent insect infestations from 2018-2021, with investigations lacking comprehensive follow-up across campus facilities. Procedures to prevent microbiological contamination of sterile drug products were deemed insufficient, specifically regarding the cleaning validation of lyophilizers where sterilization was conducted before confirming cleaning effectiveness. Lastly, significant issues with loose crimp caps on sterile drug product vials, resulting in over 50 complaints and 15 deviations since 2017, indicated inadequate crimping procedures, materials, and equipment.

Although initially classified as Official Action Indicated, the inspection status was downgraded to Voluntary Action Indicated. CSL Behring is required to implement voluntary corrective actions to address these serious findings and ensure compliance with cGMP regulations, including enhancing investigation completeness, improving rationale for sample retention, strengthening pest control, validating cleaning processes, and rectifying vial crimping issues. The firm acknowledged the observations during the closeout.