Jingwang Zheng_EN 2011.10上海ISPE

ISPE-CCPIECHINACONFERENCE2011October25-282011Shanghai1SystematicpractisewithinsterilecoreareaandcomplianceJinwangZhengShanghaiTofflonScienceandTechnologyCo.,Ltd.ISPE-CCPIECHINACONFERENCE20111.Riskidentificationoftraditionalfreeze-dryingproductionline2.Classificationoffreeze-dryingautoloadingandunloadingsystem3.SummaryContentISPE-CCPIECHINACONFERENCE20113AsepticallyProcessedProducts（ISPEBaseline）ISPE-CCPIECHINACONFERENCE20114NestedManufacturingZones（ISPEBaseline)ISPE-CCPIECHINACONFERENCE2011TraditionalStopperTransportISPE-CCPIECHINACONFERENCE2011ManualUnscramblingISPE-CCPIECHINACONFERENCE2011ManualLoading/UnloaingISPE-CCPIECHINACONFERENCE2011•Operatorputsthetrayswithvialsintothefreezedryerorthetrolleymanually,thenputthetraysontheshelvesofthefreezedryer,theopenangleofthefreezedryer’sdooriswide,thewholechamberisexposedintheexternalenvironment.•Duringthetransportofthevials,theoperatorisveryclosetovials.Peopleisthemaincontaminationsourcetothesterileproduct.Itisverydifficulttoverificationthesterileprotectionoftheprocess.•Thecontaminationriskisveryhighwhentransferthevialsintothefreezedryerafterfillingaswellastakethevailstothecappingmachineafterfreezedried。LyophilizationRiskISPE-CCPIECHINACONFERENCE2011Amajorpharmaceuticalcompanyhasdeterminedtheaveragepercentageofriskdistributionofeachasepticprocessstage,baseonmediafillresults,asfollows:AsepticCompoundingRisk10%AsepticSet-upRisk10%AsepticFillingRisk50%LyophilizationRisk30%•RiskSource:PersonnelAgownedoperatormayreleaseasmanyas10.000CFU/hour。•RiskRoute:Airborne。Freeze-driedProductManualLoadingandUnloadingISPE2007TampaConferenceISPE-CCPIECHINACONFERENCE20111.Small-bore,highspeedfillingwithlowrisk,exceptthevialsiseasytofall。2.Big-bore,lowspeedfillingwithhighrisk。3.Isolatedtransporttoreducetherisk。4.Itishighriskwhentheproductisexposedintheexternalenvironment,eventheproductunderthegradeA。5.Isolationandautomationcanreducetherisk。6.Operatetheasepticequipmentmanuallyneedhighskillsanditishighrisk。RiskAnalysisofTraditionalFreezeDryingProductionLineISPE-CCPIECHINACONFERENCE20111.RiskIdentificationoftraditionalfreeze-dryingproductionline2.Classificationoffreeze-dryingautoloadingandunloadingsystem3.SummaryContentISPE-CCPIECHINACONFERENCE2011WasherDepyroTunnelFillingAutomaticLoadingandUnloadingFreezeDryingCappingOutsideWasherInspectPackingStopperRawmaterialDispensingCompoundingWaterwaterequipmentSteamVialsHVACSystematicallyDesignedProductionLineISPE-CCPIECHINACONFERENCE2011DefinitionofSystematicallyDesignedProductionLine•SystematicProductionLine:Thewholefreezedryingproductionlineisautomatic,isolatedandprocesscontinued。•Automation：inthecorearea,alltheoperationisautomatictoreducethehumanintervention。•Isolation：theproductandtheoperatorwillbeseparatedbyusingthebarriersorisolatortechnologytoprotectboththeproductandoperator。•Processcontinue:alltheequipments,processoftheproductionlinearecontinued。ISPE-CCPIECHINACONFERENCE2011•ReducethehumaninterventionsinthegradeAareaReductioninbio-burdenandtheprobabilityofcontaminationGreaterassuranceofproductsterilityReduceoperatingcost•ProtectionofoperatorsPotentproducts•Verified,GoodRepeatability•Reducetheairconditioningcost•Achievedunmannedoperation,improvedthepracticalapplicabilityTheAdvantageoftheSystematicallyDesignedProductionLineISPE-CCPIECHINACONFERENCE2011•Higherreliabilityofequipmentsrequired。•Highercostofinitialfacility。•Thevalidationiscomplicated(Softwarevalidationandprocessvalidation)。•Themoreadvancedproductiontechnologyshouldbeadopted,morereliablequalitymonitoringandqualitymonitoringdeviceshouldbeadoptedduringthewholeproductionprocess。DisadvantageofSystematicallyDesignedProductionLineISPE-CCPIECHINACONFERENCE2011•Flexiblesystems•Fixedsystems•MixedsystemsTheClassificationofTheAutoloadingandUnloadingSystemISPE-CCPIECHINACONFERENCE2011FlexibleSystems•ConsistsofIS,AGVandOS。•oneshelfonetimeforfinishingtheloadingandunloading•Suitablefor2setsormorefreezedryers。•Unilateralloadingandunloadingoronesideloadingwhiletheothersideisunloading。•SuitableforLAF,RABS。•Thespacebetweenthelyophilizercanbemorecompact。•Thedoorofthelyophilizerisinthecleanroom。ISPE-CCPIECHINACONFERENCE2011FlexibleSystemsSketchMapISPE-CCPIECHINACONFERENCE2011AutomaticGuidedVehicleISPE-CCPIECHINACONFERENCE2011InfeedSystems(IS)ISPE-CCPIECHINACONFERENCE2011OutfeedSystem（OS)ISPE-CCPIECHINACONFERENCE2011FixedSystems•Aswecalled“RowbyRow”•loadingandunloadingrowbyrow。•Suitableforoneortwolyophilizers。•Suitablefortoxicproduct。•Suitableforlowtemperatureloadingprocess。•SuitableforLAF、RABS、cRABS、ISOLATOR。•Thechamberdoorisinthemechanicalroom,whilethepizzadoorisinthecleanroom。ISPE-CCPIECHINACONFERENCE2011FixedSystemsSketchMapISPE-CCPIECHINACONFERENCE2011FixedSystemsISPE-CCPIECHINACONFERENCE2011FixedSystemsWorkshopLayoutISPE-CCPIECHINACONFERENCE2011PictureofFixedSystemswithcRABSISPE-CCPIECHINACONFERENCE2011PictureofFixedSystemswithcRABSISPE-CCPIECHINACONFERENCE2011PictureofFixedSystemswithRABSISPE-CCPIECHINACONFERENCE2011InsidePictureofRABSISPE-CCPIECHINACONFERENCE2011PictureofFixedSystemswit