FDA 483 - Merck Serono S.p.A. - May 10, 2023

During an FDA inspection conducted from May 2 to May 10, 2023, the drug product manufacturer Merck Serono S.p.A. (MS-Bari) in Modugno, Italy, received a Form FDA 483. This document outlined significant observations related to deficiencies in Current Good Manufacturing Practice (CGMP) for drug products. Key issues identified included concerns with aseptic processing, where the design of a filling machine necessitated manual interventions that could compromise sterility. Control strategies for product-contact excipients were deemed inadequate, with an excipient repeatedly exposed to the atmosphere, potentially leading to degradation and product quality issues. Furthermore, critical components were added to drug product batches before endotoxin test results were finalized, risking contamination. The inspection also highlighted that the sterilization process for certain equipment was not fully validated, failing to demonstrate adequate sterilization of internal surfaces. Maintenance programs for equipment used in cleaning and sterilization were found to be insufficient, with discoloration and process wear-and-tear issues lacking proper mitigation or remediation. Lastly, the cleaning and disinfection of aseptic processing areas were inadequate, as non-product contact surfaces in the filling area were not consistently disinfected with a sporicidal agent after every drug product batch. Merck Serono S.p.A. is required to address these observations by developing and implementing comprehensive corrective and preventive actions.