FDA 483 - Chiesi Farmaceutici S.p.A. - March 28, 2025

During an FDA inspection conducted from March 21-28, 2025, at Chiesi Farmaceutici S.p.A., a drug substance and drug product manufacturer located in Parma, Italy, several significant observations were noted regarding their manufacturing controls and quality systems. The inspection highlighted deficiencies that could impact product quality and safety. Specifically, the firm's visual inspection procedures and operator qualification processes were found to be inadequate for identifying atypical defective products. The relevant Standard Operating Procedure lacked definitions for critical, major, and minor defects, as well as classifications for inherent, intrinsic, or extrinsic particles. Furthermore, the test sets used for operator qualification were insufficient, potentially leading to rejection bias and failing to adequately train operators. Another critical finding concerned the biological indicators used to validate the sterilization cycle for DPA stoppers. The established acceptance criteria were deemed insufficient to ensure the required sterility assurance level. Finally, droplets were observed on a valve during the manufacturing of a specific drug product lot, raising concerns about the integrity of the manufacturing system and an increased risk of microbial contamination. Chiesi Farmaceutici S.p.A. is expected to address these observations to ensure compliance with good manufacturing practices.