FDA 483 - Laboratorios Farmaceuticos Rovi S. A. - May 19, 2023

On May 19, 2023, the FDA issued a Form 483 to Laboratorios Farmaceuticos Rovi S. A., a sterile drug manufacturer located in Madrid, Spain, following an inspection from May 11-19, 2023. The inspection revealed six observations concerning deficiencies in their manufacturing processes and quality control for sterile drug products.

**Observation 1** cited inadequate procedures to prevent microbiological contamination. This included continued use of gloves with pinholes, lack of procedures and documented training for using a "tool" during filling, inadequate storage and disinfection of sterilized equipment, untracked rejects during aseptic filling, and unreviewed/unretained glove integrity testing data.

**Observation 2** noted that procedures for preventing microbiological contamination lacked adequate validation of aseptic and sterilization processes. Media fills were not representative of routine production regarding critical interventions, fill length, and maximum personnel. Non-viable monitoring excursions were not always investigated. Sterilization cycle validation for equipment and stoppers was inadequate, with biological indicators not placed in worst-case positions. Smoke studies were insufficient, not demonstrating unidirectional airflow for all activities.

**Observation 3** indicated a lack of control procedures to monitor and validate manufacturing processes, specifically regarding visual inspection of embedded particles in stoppers. No procedure existed for this inspection, training was undocumented, raw data was not retained, and the method's ability to differentiate particle types was unproven.

**Observation 4