FDA 483 - Merck Serono SA - June 08, 2022

During an FDA inspection from June 30 to July 8, 2022, Merck Serono S.A. (MS-Aubonne), a drug product manufacturer in Aubonne, Switzerland, received a Form FDA 483 outlining significant observations related to current Good Manufacturing Practices (cGMP) for sterile products. The primary issues centered on inadequate procedures for preventing microbiological contamination. This included aseptic process simulations that weren't representative of commercial operations, such as unsupported use of alternate sterilization equipment and insufficient evaluation of interventions. Inspectors also noted critical deficiencies during aseptic setup, including operator contact with sterile surfaces without subsequent sanitization, improper goggle use, and blocking of critical airflow. Environmental monitoring in aseptic areas was found lacking, with insufficient surface monitoring in high-risk zones and inadequate airflow pattern (smoke) studies failing to account for dynamic conditions or operator interaction. Cleaning and disinfection processes were also deficient, with unvalidated decontamination procedures and disinfectant efficacy studies that excluded representative surfaces. Further concerns involved inadequate cleaning validation to prevent cross-contamination due to erroneous acceptance limits and unvalidated swab recovery procedures. Deviation investigations were insufficient, particularly regarding unaddressed HEPA filter leak test failures and misreported out-of-specification results. Critical utilities like sterilization processes were not adequately qualified, and electronic data acquisition systems lacked validated controls for user rights, data integrity, and audit trail reviews. Finally, Quality Assurance oversight was deemed inadequate, failing to conduct necessary risk assessments and re-qualify critical methods on-site. The firm must address these observations to ensure regulatory compliance.