蒸汽灭菌和冻干工艺的验证及风险分析 - 意大利CTP Giuseppe Ruggirello 2018年注射剂工业大会课件讲义教材.pptVIP

OPERATIONAL QUALIFICATION  8 Verification of documentation 8.1 Standard Operative Procedures 8.2 Calibration certificate of critical instruments 9 Verification of system functionalities 9.1 Input/Output 9.2 Alarms 9.3 Production receipes 9.4 Security and Access 9.5 Back-up Restore 10 Operational verification 10.1 Maximum and minimum temperature of shelfs 10.2 Control loop (for temperature of the shelf) 10.3 Temperature distribution 10.4 Temperature of condenser 10.5 Vacuum system 10.6 Vacuum deep 10.7 Leak Rate of system and lyophilizater chamber 10.9 Cleaning In Place 10.9 Sterilization cycle 10.10 Load lyophilization 10.11 Defrost of condenser Lyophilization Verify that the Ultimate Cooling Temperature and the Ultimate Heating Temperature comply to technical specifications. Maximum and minimum temperature of shelfs Lyophilization: OQ Condenser temperature Verify that the Condenser Cooling Rate and the Ultimate Condenser Cooling Temperature comply to technical specifications. Verification of shelf temperature Shelf Temperature: Verificatin of control loop for the temperature. Usual acceptance criteria: +/- 1.5 °C respect to the set-point. Temperature distribution Verification of temperature distribution in the shelfs Example: 5 TCs by shelf. Test temperature: -40, +20, +40 °C Max temperature diff: 2 °C (between TCs on different shelfs). Lyophilization: OQ Verify that, in the system free of humidity, the Evacuation Rate and the Ultimate Vacuum) comply to the technical specifications. Verification of Vacuum System Verify the performance of control loop for vacuum system. The acceptance criteria should be +/- 5 microbar of the set-point. Verification of Control Loop for Vacuum Lyophilization: OQ Verification of Leak Rate Any leak in to the lyophilizer could introduce a risk of microbiological or chemical contamination. The leak rate test carried out during qualification represents baseline for future maintenance. For a new equipment it is strongly suggest