CSL Behring GmbH – FDA 483, May 17, 2018

During an inspection from April 30 to May 17, 2018, the FDA identified significant manufacturing deficiencies at CSL Behring GmbH, a biological drug manufacturer in Marburg, Germany. The inspection, conducted under the Federal Food, Drug, and Cosmetic Act and Good Manufacturing Practice (GMP) regulations, resulted in thirteen observations documented on an FDA Form 483. Key issues included a pervasive failure to thoroughly investigate unexplained discrepancies, such as foreign matter in Berinert vials, product ineffectiveness, blocked filters, and microbial contamination events. Investigations often lacked scientific evidence, health hazard evaluations, or robust corrective actions. Laboratory controls were deemed deficient, with unsuitable assays and inadequate specifications for cell culture media, coupled with non-contemporaneous documentation of production activities. The stability program was found lacking, with unaddressed Out-of-Expectation results and inadequate sampling. Sterilization process validation was insufficient, particularly with smoke studies that did not reflect actual operations. The firm also failed to ensure proper equipment calibration, minimize contamination risks during processing, and submit timely biological product deviation reports, including one related to cleaning failures affecting distributed product. Packaging changes, which led to broken vials and a Class II recall, lacked appropriate robustness testing and quality unit oversight. Further observations cited insufficient equipment maintenance, inadequate employee training for critical tasks like microbial counting and visual inspection, and uncontrolled air pressure in a manufacturing area. Finally, the company distributed products based on unapproved process changes. CSL Behring GmbH is required to implement comprehensive corrective and preventive actions to address these systemic issues and ensure compliance.