无菌制剂工艺验证方案

PHARMACEUTICALINSPECTIONCONVENTIONPHARMACEUTICALINSPECTIONCO-OPERATIONSCHEME1July2004PI007-2PI007-21July2004RECOMMENDATIONONTHEVALIDATIONOFASEPTICPROCESSES©PIC/SJuly2004Reproductionprohibitedforcommercialpurposes.Reproductionforinternaluseisauthorised,providedthatthesourceisacknowledged.Editor:PIC/SSecretariatP.O.Box5695CH-1211Geneva11e-mail:[e-mail]:(Lyophilised)Products..............................................................54.6Semi-SolidProducts(e.g.sterileointments)..................................................64.7ClinicalTrialsMaterialsandSmallBatchSizeProducts...............................64.8BiologicalandBiotechnologyProducts..........................................................64.9SterileBulkPharmaceuticals..........................................................................65.PROCESSSIMULATIONTESTCONDITIONS..........................................75.1TestPerformance...........................................................................................75.2SelectionofGrowthMedium...........................................................................75.3IncubationConditions......................................................................................85.4ReadingoftheTest.........................................................................................85.5TestFrequency...............................................................................................86.INTERPRETATIONOFDATA......................................................................97.ENVIRONMENTALANDPERSONNELMONITORING...........................117.1AirBorneMicrobialandNon-ViableParticleMonitoring................................117.2Non-viablemonitoring...................................................................................117.3MicrobialMonitoring.......................................................................................117.4InterventionMonitoring..................................................................................128.STAFFTRAINING........................................................................................12PagePI007-2-ii-1July20049.IMPORTANTFACTORSINVALIDATIONOFASEPTICMANUFACTURING.....................................................................................139.1Container/ClosureIntegrityTesting..............................................................139.2Container/ClosureSterilisation.....................................................................139.3EquipmentCleaningandSterilisation...........................................................139.4Disinfection...................................................................................................149.5FilterValidation..............................................................................................149.6VentFilters....................................................................................................159.7EquipmentMaintenanceandTesting...........................................................159.8BlowFillSeal/FormFillSeal.........................................................................159.9SterilityTest..................................................................................................1610.REVISIONHISTORY...................................................................................16_______________1July2004Page1of16PI007-21.DOCUMENTHISTORYAdoptionbythePIC/SCommittee7September1999EntryintoforceofversionPR1/991January2000EntryintoforceofversionPI007-11September20012.INTRODUCTION2.1Purpose2.1.1Theaimofthisdocumentistoprovideguidancetothecurrentpracticeinthisfieldbygivingrecommendationsforthevalidationofasepticprocesses.Inparticular,thedocumentshouldprovideguidanceforGMPins