生物反應(yīng)器課件PATIntrodu課件

PATIntroductionPATProcessAnalyticalTechnologyWhatisPAT?WhatisPAT(andwhatisn’t)?PATEnabledSCADASomeKeyElementsofaPATincombinationwithSCADASpectrometryMetadata&ExperimentalcontextGettingmorefromyourdataIsPAT?Installingsomeshinynewequipment?Connectinganewprobe/cellcounter

toabioreactor?AlreadystandardpracticeinBioprocess

development?Littlebusinessbenefittoearlybioprocess

development?AnimportanttoolforQualitybyDesign?WhatisPATProcessanalyticaltechnology(PAT)hasbeendefinedbytheFDAasamechanismtodesign,analyze,andcontrolpharmaceuticalmanufacturingprocessesthroughthemeasurementofCriticalProcessParameters(CPP)whichaffectCriticalQualityAttributes(CQA).PATshouldaddressuncontrolledprocessvariationtomitigateriskofuncontrolledproductvariabilityPATSolutionsshouldbeanintegralpartofaQualitybyDesign(QbD)strategyLongtermgoalsreduceproductioncyclingtimepreventrejectionofbatchesenablerealtimereleaseincreaseautomationimproveenergyandmaterialusefacilitatecontinuousprocessingHowdowegetthere?DefineprocessandproductqualityWhatcausesvariance?Whatiscritical?UnderstandtheprocessHowcanwecontroltheprocesstothedesiredendproductquality?Onlinemonitoring(nearinfrared)Howdowegetthere?EliminateprimarysourcesofvarianceMediumcomposition:fromundefinedmedium(containingproteinextracts),tochemicallydefinedmediumwithbalancedC/NratioInoculum:reproducibleseedlotpreparation,freezeatfixedOD,duringmid-loggrowthphase.DefineQualityWhereshouldwefinish?ExperimentaldesignDesignspaceControlspaceFrom:D.Low,AmgenBioProduction2006,DublinTools:SCADAIsthetechnologyfitforpurpose?Howmuchdata?Howwillyoustoreit?Howwillyouannotatedata?IsthePATapplicationgoingtobeon-line?IssoftwareOPCcompliant?Ifnot,haveyouassessedinterfacingcosts?Tools:NIRFullSpectrumNearInfraredVibrationalspectroscopy(800–2500nm)Non-invasiveopticalsensingNIRhaswidespreadacceptanceinpharmaceuticalmanufacturingOperational&TechnicalFlexibilityCostEffective,Robust&ScalableTools:NIRHowever,Chemometricmodelsarerequiredtoextractbiomass,metabolite&catabolitedata(othermethodsarealsopossible)Inaddition,largedatasetsmakemodelbuildingdifficultResults:CalibrationsensorOneCHOrun(10days)@NewCastleUniverity(UK)1Spectraevery2min5500Spectra2000Absreadingperspectra10-15runsforeachcalibrationsEachBioreactorrunRawExportfile55MbOpusfiles75MbCalibrationtofullscaleNIRprobecalibrationdatacollectedinmultiplesmallscalevesselruninparallelBetterintegrationofNIRcalibrationintoDevelopmentlifecycleAugmentcalibrationsoverthedevelopmentlifecycleRun1Run2Run3Run4Run5SmallscaleBenchtopBioreactorsCalibrationsetValidationsetCalibrationModelTransferredtoFullscaleProductionbioreactorTemppHDOTFT-NIRFullScaleProductionBioreactorTimePharmaManufacturingBenchmarkingStudyData(2005)Broadsurveyof104Pharmacompanies.LimitedITsupportfortransitionfrombenchthroughprocessdevtocommercialisationUnstructuredinformationcollection,storage&retrievalresultsinmoretimesearchingfordataLimitedcoordinationacrossgroupsandsitesaffectstheabilitytomeetdevelopmentcycletimes(timetohuman,timetoclinic,etc)andproductcosttargetsLackofinformationvisibility&contextlimittheeffectivenessofportfolioandprojectmanagementprocesses5hrperweekonaveragelookingfordataCan’tfinddata25%oftimeleadingtorepeating8%ofexperimentsandincreasedR&DcostsLimitedandinefficienttraceability(paperbased)FewITsystemsfacilitatedatareuse&abilityto“drillacross”GenerallackofsatisfactionwithallPharmaITsystemsPharmaManufacturingBenchmarkingStudyData(2005)FuturerequirementsDevelopmentofconsistentannotationstandardstomakebioprocessdatameaningfulMetadatashouldenabledrillingdownandacrossdatasets,filterandsift&batchgenealogycreationFreetextwillnotbeappropriateforallfieldsReportingsoftwareformatsdatatoeasetransferintoanalysissoftwareWhatshouldSCADAdo?RecipedrivenbatchexecutionRecipetransferbetweenunitsSecureacquisition&storageofBioreactordataOfflinedatastorageEasyintegrationofnewsensorsthroughOPCRealtimeProcessviewWhatshouldBioreactorControllerdo?Metadata&AnnotationsentryBlankTagsforanalyservaluesviaOPCGenericPIDcontrollerwithOPCInputandconfigurableoutputsSCADALevelreporting60-70%ofanalysistimeisreformattingdataforimportingintoanalysistoolMostusershavesimplereportingrequirementsProcessmapofthedataflowSearch,Sift,Filter&