蒸汽灭菌和冻干工艺的验证及风险分析.pptxVIP

蒸汽灭菌和冻干工艺的验证及风险分析第1页/共132页 CONTENTRegulatory aspectsMoist Heat SterilizationChoosing the right processValidating a sterilization processCalibration of instrumentsChamber leak test“Utilities”Validation – Physical issuesValidation – Microbiological issuesValidating a lyophilization processProcess ControllerRisk Analysis第2页/共132页 GMP VALIDATION1972 DEVENPORT INCIDENT (UK)Infusional solutions, produced at the Devemport Hospital, caused three patient deceases.The ROSENHEIM Report found the causes in a not correct sterilization treatment. 第3页/共132页 Extracted from the ROSENHEIM ReportThe AIR was not properly removed from the chamberThe drain of the chamber was blocked by pieces of glassesThe lower section of the load did not reach the sterilization temperatureThe temperature recorder showed this anomaly but people thought it was not working properlySterility tests were carried out only on the upper layers of the loadGMP VALIDATION第4页/共132页 ValidationMain concepts Personnel Equipment Process/Products InstrumentsDocuments and SOPQualified, trainedTo be qualified (IQ, OQ, PQ)To be validatedSuitable, calibration has to be planned and documentedUp-to date, distributed, maintained under control第5页/共132页 Terminal Moist-Heat SterilizationEngineering – Equipment ImplicationsChapter 3 of EU-GMP (Premises and Equipment)21 CFR part 211.63, 211.65, 211.67 (Equipment)Annex 11 – UE GMP (Computerised systems) 21 CFR part 211.68 (Automatic, mechanical and electronic equipment)21 CFR part 11 (Electronic records – Electronic Signatures)GAMP (Good Automated Manufacturing Practice)第6页/共132页 Validation21 CFR parts 210-211 (211.100, 211.110, 211.213)21 CFR part 820 (820.75)EU – GMP (Cap. 5.21 – 5.24) EU – GMP Annex 15: (Qualification and Validation)Compliance Policy Guide Sec. 490.100 (Process Validation Requirements for Drug Products Subject to Pre-Market Approval)Terminal Moist-Heat Sterilization第7页/共132页 CONTENTRegulatory aspectsMoist Heat SterilizationChoosing the right processVali