FDA 483 - GlaxoSmithKline Biologicals SA - June 24, 2019

An FDA inspection conducted at GlaxoSmithKline Biologicals SA, a vaccine manufacturer in Rixensart, Belgium, from June 3 to June 24, 2019, resulted in a Form FDA 483. The inspection revealed several significant observations related to manufacturing controls and quality systems. Deficiencies were noted in laboratory controls, specifically regarding the establishment of appropriate specifications for in-process materials, including microbial purity, bioburden, and endotoxin monitoring for bulk vaccine products like Shingrix. The firm failed to thoroughly investigate bacterial contamination in the Water for Injection (WFI) system used for sterile bulk manufacturing, including root cause analysis and a review of relevant product complaints. Furthermore, previous corrective actions for contamination issues were found deficient, lacking adequate assessment of automated systems and incomplete cleaning validations. Observations also included inadequate process validation practices, where critical ranges were not fully assessed, and a lack of approved documentation by the Quality Unit for operations conducted outside standard procedures. Equipment maintenance issues were identified in manufacturing areas, including material build-up, leaks, and dripping substances. These observations indicate potential deviations from Current Good Manufacturing Practices (cGMP), which are essential for assuring the quality and safety of pharmaceutical products. GlaxoSmithKline is expected to address these findings and provide a comprehensive response detailing their proposed corrective and preventive actions to ensure compliance with regulatory standards.