欧美生物制品制造中的cGMP实践.pptVIP

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Case Studies…(continued) Case Study #2: Lyophilizer Contamination Two different colors of broken glass! Must have come from different products = high potential risk of cross contamination. Cleaning SOP was not being followed. The SOP did specify for operators to raise the shelf stack and clean all visible contaminants before executing CIP cycle. CIP cycle for this lyophilizer was not effective at removing all contaminants (broken glass). * Nov. 12, 2009 Case Studies…(continued) Case Study #3: Undocumented Changes GMP requirement to document all changes that may impact product safety and quality. GMP requirement to evaluate the root cause of process deviations and evaluate the impact of the deviations on production batches. Example: A new hot WFI distribution system was installed during a factory expansion. The system passed all validation testing and was placed into normal service. * Nov. 12, 2009 Case Studies…(continued) Case Study #3: Undocumented Changes After several months in service, routine monitoring indicated repeated microbial failures at several sample locations. At some time (undocumented), the configuration of the valves at the sampling locations was changed and all future samples were clean. An FDA inspection of the facility occurred several years later. * Nov. 12, 2009 Case Studies…(continued) Case Study #3: Undocumented Changes During the inspection, the auditor performed a spot-check of the WFI system drawing to compare it against the actual as-built installation. The auditor discovered several discrepancies between the drawing and the installation. The company had no explanation or change control documentation for the discrepancies. The auditor proceeded to investigate. * Nov. 12, 2009 Case Studies…(continued) Case Study #3: Undocumented Changes Upon inspection of the WFI sampling documentation, it was determined that the