Sterile processing-无菌工艺设备

1ProcessStages1.DispensingandWeighing2.Compounding3.SterileFiltration4.ContainerPreparation5.StopperPreparation6.FillingandStoppering7.CappingandCrimping8.Inspection9.PackingTypicalProcessSteps2ProcessStagesTypicalProcessFlowforanAsepticallyProcessedVialFormulation3UnpackStoppersCapsTypicalProcessBlockFlowDiagramforanAsepticallyProcessedVialFormulationFormulationRoomLoadStopperFeedStationStopperVialFillVialCapSealFeedStationSealVialwithCapInkCartridgeTrayOffVialsWarehouseWashVialLoadVialsStretchwrapPalletWarehouse(Quarantine)ReleasefromQuarantineDispatchInspectionHeadTankatFillStationUnpackVialsComponentPrepRoomFillingRoomDepyrogenateVialColdStore(20Cto80C)Filter(0.22µm)PrintVialCapCappingRoomInspectionInkjet/TrayOffRoomTransferContainerStopperProcessorTransferContainerWFIGenerationSystemWaterforInjectionWarehouseTransfertoCompoundingRoomPoolintoTankBulkDrugSubstanceNitrogenStorageTankNitrogenFilterthru2x0.22µmfiltersQCTestsVialsShrinkWrappedPalletsVialsWarehouseStoppersCapsCompoundingRoomColdStore(2-80C)ColdStore(2-80C)AirlockAirlockStoreStoreWarehouseCaps(GammaIrradiated)StoppersStoreat20Cto80CColdStoreBackgroundAreaClassificationRequiredByProcessStepExternalUnclassifiedPharmaceuticalGradeGradeD(Pharmaceuticalwithlocalmonitoring)GradeC(ISO8Class100,000)GradeB(ISO7Class10,000)GradeA(ISO5Class100)LaminarFlowZoneOpenProcessingClosedProcessingISLIsolator(Class100)4ProcessStages1.DispensingandWeighingCentralisedDispensing:SolidActivesandExcipientsSmallQuantitiesofLiquidActivesandExcipientsKeyConsiderations:AreaClassificationCrossContaminationPotentialToxicCompoundsDecentralisedDispensing:WaterandSolventsKeyConsideration–DesignofCompoundingRoom(s)wheredispensingperformed5ProcessStages2.Compounding(Formulation)Roomwhereproductcomponents(Active,Excipients,Solventsetc)arebroughttogethertoproducetheformulationthatwillsubsequentlybefilled.E.g.PoolingofpremixedproductSimpleLiquidMixingDissolutionofsolidactiveEmulsificationKeyConsiderationUtilityRequirementsProximitytoFillingPointAreaClassificationCrossContaminationFlowofpeople,cleananddirtyequipment,rawmaterials,product,waste6ProcessStages3.SterileFiltrationProductissterilefilteredthrough0.2mfilter(s)toprovideadefinedreductioninthemicrobiologicalconcentrationpriortofilling.Postfiltrationtheproductisdeemedsterile.KeyConsiderationsSterilisationoffilterinplacePoststerilisationpre-productionintegritytestingPostproductionintegritytesting(insitu)EliminationofAsepticconnectionsFilterLocation7Exercise2CompoundingandFiltrationProductbeingcompounded/formulated,filteredandfilledintomobile300lvessels.Whatdesignfeaturesshouldbeconsideredtomimimiseissuessuchasmanualhandling/contaminationfor:A:FillingAreaB:Vessel8Exercise-AnswerFillingArea:ManualhandlingconsiderationsAccesstoisolationvalvesLiftingmethodoffilterhousingsContamination:AllfeedlinesslopedwithnodeadlegsMinimisejointsminimisescontamination.InternalfinishespolishedforeaseofCIP/SIP9Exercise-AnswerMobileVessel:ManualhandlingconsiderationsWeightoffullvesselandmethodoftransportAccesstosightglass/isolationvalvesContamination:AllfeedlinesslopedwithnodeadlegsMinimisejointsminimisescontamination.InternalfinishpolishedforeaseofCIP/SIP.10ProcessStages4.ContainerPreparation–CleaningandSterilisationofEmptyproductContainersCleaningWashingandrinsingofcontainersusingsuitablegradeofwatertoremoveextraneousparticlesandchemicalsInitialrinsescanbecarriedoutusingPurifiedwaterFinalrinsemustuseWFI(Waterforinjection)ContainersblowndryusingsterileairEquipmentRotaryWasherLinearWasher11VialWashingMachine-RotaryWasherBoschRRN2020RotaryWasherBausch&StröbelFAW1120RotaryWasher12ProcessStages–VialWasherIMA/Libra-Hydra-LinearWasherWORKINGPROCESS13ProcessStagesContainerPreparationSterilisationDryheatDepyrogenationofcleancontainerstodeactiviatebioburden(viablecontamination)anddegradeendotoxins(non-viablepyrogeniccontamination)Heat-up,sterilisationandcoolingzonesCombinationofresidencetimeandsetpointtemperature(250oC–350oC)insterilisationzonetoachieverequireddegreeofdepyrogenationTypically6logreductionofbioburdenrequired14ProcessStagesEquipmentDryHeatOvenContinuousDepyrogenationtunnelTunnelPressureProfilesHOTZONECOOLINGZONESterilearea15DepyrogenationTunnel16DepyrogenationTunnelTunnelAirFlow17ProcessStages5.StopperPreparationStoppersmustbesterileastheyareindirectcontactwiththeproductatsometimeduringstorage,handlingoruseWashingandrinsingtoremoveextraneousparticulatesandchemicalsDetergentwashingsometimesusedforendotoxinloadreductionStoppermaybesiliconisedforeaseofinsertionofstoppersintovialsStoppersmustreceiveafinalrinseofWFIStoppersmustbesterilised(typicallyusingcleansteam)StoppersmustbedriedusingsterileairStoppersmustmaintainsterilityduringtransfertofillerEquipmentRotatingDrumStopperProcessorFluidisedBedStopperProcessor18StopperProcessorThestoppersaresimplyandquicklyloadedthroughhatchesinthedrumTheloadeddrumisslidintothechamberonitscarriage.Asthedoorishingedshutthemagneticallycoupleddrive