FDA 483 - Grifols Therapeutics LLC - December 13, 2018

An FDA inspection of Grifols Therapeutics LLC, a plasma fractionator located in Clayton, NC, conducted from December 5-13, 2018, revealed significant observations detailed in a Form FDA 483. The findings indicate deficiencies in various aspects of the company's quality and manufacturing control systems, suggesting non-compliance with current Good Manufacturing Practices.

Key issues included a failure to thoroughly investigate unexplained discrepancies, specifically regarding unexpected adverse event trends for products like Gamunex, where investigations were either delayed or not initiated appropriately. The inspection also identified critical shortcomings in the visual inspection program: seven out of seven personnel requalification records showed failing test results that were not detected or remediated, leading to no subsequent training or product impact assessment. Furthermore, visual inspection training itself was inadequate, with acceptance limits allowing for critical defects to be missed.

Additional observations noted deficiencies in environmental monitoring systems within aseptic processing areas, including improperly positioned air and particle probes and insufficient supporting studies. Smoke studies for filling lines were incomplete, failing to demonstrate adequate airflow. The quality review process was deemed inadequate, lacking comprehensive review of media fill records. Lastly, growth promotion testing of media used for environmental monitoring and bioburden testing was insufficient, not reflecting actual usage conditions. Grifols Therapeutics LLC is required to implement and document comprehensive corrective actions in response to these observations.