FDA灭菌工艺验证申报资料指南(中英文)

GuidanceforIndustryfortheSubmissionDocumentationforSterilizationProcessValidationinApplicationsforHumanandVeterinaryDrugProducts人药和兽药无菌工艺验证申报资料的工业指南CenterforDrugEvaluationandResearch(CDER)CenterforVeterinaryMedicine(CVM)November1994CMC2FDA药品评价与研究中心（CDER）FDA兽药中心（CVM）1994年11月TABLEOFCONTENTSI.INTRODUCTION.....................................................................................................................1A.Purpose.......................................................................................................................1B.DocumentingSterilizationProcessValidation.....................................................2C.Remarks..............................................................................................................2II.INFORMATIONFORTERMINALMOISTHEATSTERILIZATIONPROCESSES.................................................................................................................3A.DescriptionoftheProcessandProduct........................…………………………….....31.TheDrugProductandContainer-ClosureSystem..................................32.TheSterilizationProcess.........................................................................33.TheAutoclaveProcessandPerformanceSpecifications........................44.AutoclaveLoadingPatterns.....................................................................45.MethodsandControlstoMonitorProductionCycles...............................46.RequalificationofProductionAutoclaves..................................................47.Reprocessing...........................................................................................4B.ThermalQualificationoftheCycle.............................................................................41.HeatDistributionandPenetrationStudies...............................................42.ThermalMonitors.....................................................................................53.TheEffectsofLoadingonThermalInput.................................................54.InformationIncludedintheBatchRecord............................................5C.MicrobiologicalEfficacyoftheCycle..........................................................................51.IdentificationandCharacterizationofBioburdenOrganisms…………….62.SpecificationsforBioburden....................................................................63.Identification,Resistance,andStabilityofBiologicalIndicators..............................................................................................................64.TheResistanceoftheBiologicalIndicatorRelativetoThatofBioburden..................................................................................................65.MicrobiologicalChallengeStudies...........................................................7D.MicrobiologicalMonitoringoftheEnvironment..........................................................7E.Container-ClosureandPackageIntegrity...................................................................71.SimulationoftheStressesFromProcessing............................................72.DemonstrateIntegrityFollowingtheMaximumExposure........................83.MultipleBarriers.......................................................................................84.TheSensitivityoftheTest........................................................................85.IntegrityOvertheProductShelfLife........................................................8F.BacterialEndotoxinsTestandMethod...............................................................8G.SterilityTestingMethodsandReleaseCriteria....................................................8H.EvidenceofFormal,WrittenProcedures............................................................9III.OTHERTERMINALSTERILIZATIONPROCESSES.....................................................9A.EthyleneOxide..........................................................................................................91.DescriptionoftheSterilizer.....................................................................92.CycleParameters...................................................................................103.MicrobiologicalMethods........................................................................104.Stability...................................................................................................10B.Radiation............................................................................................................101.TheFacilityandtheProcess..................................................................102.ThePackagingoftheProduct...............................................................103.Multiple-DoseMappingStudies.............................................................104.MicrobiologicalMethodsandControls...................................................115.MonitoringStability..................................................................................11IV.INFORMATIONFORASEPTICFILLMANUFAC