FDA 483 - Cosma SPA - January 15, 2016

An FDA inspection of Cosma SpA, an Active Pharmaceutical Ingredient (API) manufacturer in Ciserano, Italy, conducted from January 11-15, 2016, resulted in thirteen observations documented on a Form FDA 483. The inspection highlighted significant deficiencies in the company's adherence to Good Manufacturing Practices. Key issues identified primarily concerned data integrity, where systems used for analytical testing (HPLCs, GCs, FTIRs) lacked audit trails, password protection, or procedures for audit trail review, allowing data to be overwritten or deleted. Furthermore, historical electronic chromatographic data was incomplete. Repeat observations from a 2013 inspection included inadequate monitoring of water systems for objectionable organisms and insufficient microbiological/endotoxin testing in specifications and cleaning validations for APIs intended for sterile drug products. Other critical findings involved a deficient quality system, with issues such as system suitability not being performed prior to testing, uncontrolled cleaning logs, and stability testing methods not proven stability-indicating. Additionally, raw data was not consistently retained (e.g., during weighing and calibration), maintenance and calibration schedules lacked change control, and employee training was not adequately detailed or documented for specific operations and procedure revisions. Cleaning procedures were also found to be inconsistent and poorly documented. Finally, API product labels lacked essential information like retest dates and manufacturer details when transferred externally. Cosma SpA is required to implement comprehensive corrective actions to address these serious compliance issues.