FDA 483 - Novartis Pharma Stein AG - December 06, 2022

An FDA inspection of Novartis Pharma Stein AG, a drug product manufacturer, was conducted from November 28 to December 6, 2022. The inspection resulted in several observations documented on a Form FDA 483, highlighting critical deficiencies in current Good Manufacturing Practice (cGMP). Key issues included inadequate procedures to prevent microbiological contamination of sterile drug products, such as an unacceptable practice of wiping sterile equipment. Equipment design was found inappropriate, exemplified by a failed aseptic process simulation where system risks were not fully evaluated. The aseptic simulation process itself was deficient, lacking assessment of product hold steps. Furthermore, the firm failed to adhere to its written production and process control procedures, specifically regarding audit trail reviews for computerized systems, protocols for glass breakage events on filling lines, and standardized parameters for bacterial endotoxins testing, leading to potential data integrity and process variability concerns. Facility maintenance was also cited, with observations of dust accumulation and external access points like doors lacking proper seals at the GMP warehouse. Novartis is expected to respond with comprehensive corrective actions to address these regulatory findings.