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16th–17thApril2012,BeijingPQLI:BringingQbDtoLiferogernosalVicePresidentPfizerGlobalChemistry,Manufacturing&ControlsContents•ICH–QbDConcepts•PQLI–QbDApplication&Implementation–TranslatingICHQ8R/Q9/Q10/Q11conceptstoreality–ProductRealizationGuidelines–ApplicationofQbDPrinciples•CanweachieveGlobalHarmonizationthroughtheapplicationofQbD?2ICHPharmaceuticalQualityVision“Developaharmonisedpharmaceuticalqualitysystemapplicableacrossthelifecycleoftheproductemphasizinganintegratedapproachtoqualityriskmanagementandscience.”BruxellesJuly2003Industry’sVersionofVision•Globallyharmonizedregulatoryacceptanceofpharmaceuticaldevelopment&manufacturingthatprovides–Improvedqualityassurancethroughincreasedproductknowledge&processunderstanding–Regulatoryflexibilitytocontinuouslyimprovethroughoutproductlifecycle3ICHGuidelines•ICHQualityGuidelines(seeICHwebsiteforlatestversions)–Q8(R):PharmaceuticalDevelopment–Q9:QualityRiskManagement(QRM)–Q10:PharmaceuticalQualitySystem(PQS)–Q11:Development&ManufactureofDrugSubstances•QualityImplementationWorkingGroup(QIWG)onQ8,Q9andQ10–Questions&Answers–PointstoConsider4UnionofICHQ8,Q9,Q10&Q11/Q1156KeyElements&‘Flow’ofQbDTargetProductProfileControlStrategyPriorKnowledgeProduct/ProcessDev.Product/ProcessDesignSpaceDefinitionofProductIntendedUse&pre-definitionofQualitytargets(wrtclinicalrelevance,efficacy&safety)SummaryofScientificUnderstandingofProduct&ProcessJustificationanddescriptionofMulti-dimensionalSpacethatAssuresQuality(interrelation-shipsandboundariesofClinicalRelevance).DefinitionofControlStrategybasedonDesignSpaceleadingtoControlofQuality&QualityRiskMgmt.(ProcessRobustness)OverviewofQualitybyDesignkeyactions&decisionstakentodevelopNewScientificKnowledge,e.g.DoE,PAT,RiskAssessment&RiskControlSummaryofPriorScientificKnowledge(drugsubstance,excipients;similarformulations&processes).InitialRiskAssessmentRegulatoryFlexibilityProposalofRegulatoryFlexibilitybasedonProduct&ProcessScientificKnowledge&QualityRiskMgmt.(Materials,Site,Scaleetc)EFPIAWorkingGroup8PeopleEquipmentMeasurementProcessMaterialsEnvironmentINPUTS(X)ProcessUnderstandingy=ƒ(x)OUTPUTyInputstotheprocesscontrolvariabilityoftheOutputPQLI®VisionandPurposeDefinitions•PharmaceuticalQualityLifecycleImplementationisISPE’sinitiativetodevelopguidanceonhowtopragmaticallyimplementtheconceptsdescribedinICHguidelinesQ8®,Q9,Q10&Q11Vision•ISPEisanintegratorofpharmaceuticaldisciplinestoadvancemanufacturingsciencestoachieveexcellenceindrugdevelopmentandpharmaceuticalproduction.ManufacturingSciencesaretheintegratedapplicationofscientificknowledge,technicalinnovationandqualityriskmanagementtodeliverproductandprocessunderstanding.Purpose•Topromoteexcellenceinpharmaceuticalproductionembracingproductquality,efficiency,andsustainability(environmentallyfriendly)aswellasregulatorycooperationandcompliance.9PQLI®ImportancetoIndustryApr094ISPEPapersJul05OriginalFederalRegisterNoticeCMCPilotMar11FDA/EMApilotforParallelAssessmentJun07ISPELaunchedPQLI®-WashingtonDCMar06DeadlineforCMCPilotParticipantRequestMay06ISPELaunchedPQLI®ConceptSep07ISPELaunchedPQLI®-BerlinMar10ISPEPQLI®OverviewofProductDesignSep09BiotechCMCPilotMar10INDSubmissionAug02FDA21stCenturyMay08ISPELaunchedPQLI®Feb09ISPEPQLI®CurrentStatus/FuturePlansJul08BiotechCMCPilotNov07ISPELaunchedPQLI®-LasVegasApr08ISPELaunchedPQLI®CopenhagenSep11ICH8,9&10TrainingProgram-CanadaNov08ICH8(R1)Oct09ICH8,9&10Q&ANov05ICHQ8PharmaceuticalDevelopmentApr09ICH8,9&10Q&AOct09ICH8(R2)Sep03ICHQ8ConceptPaperNov05ICH9QualityRiskManagementConceptPaperNov10ICH8,9&10Q&AJun11ICH8,9&10PTCJan08ICHQ11DevelopmentandManufactureofDrugSubstances(ChemicalEntitiesandBiotechnological/BiologicalEntities)Jun08ICH10PharmaceuticalQualitySystemConceptPaperNov03ICH9QualityRiskManagementConceptPaperMay11ICHQ11Step2Sep05ICH10PharmaceuticalQualitySystemConceptPaperOct10ICH8,9&10TrainingProgramJun09ICH8,9&10Q&AApr11ICH8,9&10TrainingProgram-JapanJun10ICH8,9&10TrainingProgramRegulations&GuidelinesISPEPQLI®10PQLI®ProductRealizationUsingQbDQualityTargetProductProfileProcessOutlineProcessDev.DesignSpaceDefineProductIntendedUseandpre-defineQualityTargets(wrtclinicalrelevance,efficacyandsafety)SummariseScientificUnderstandingofMaterial&ProcessAttributes.JustificationanddescriptionofMulti-dimensionalDesignSpacethatAssuresQuality(interrelationshipsandboundariesofClinicalRelevance).ControlStrategyDefineControlStrategyoptionallybasedonDesignSpaceleadingtoCommercialManufacturingPerformworktodevelopNewScientificKnowledge,e.g.UsingDoE,PAT,RiskAssessmentandRiskControlSummarisePriorScientificKnowledge(drugsubstance,processes,Unitopsetc).InitialRiskAssessmenttoidentifyCriticalQualityAttributesExtendRAtoprioritisepotentialCPPstostudyContinualImprovementProposalforLifecycleManagementbasedonProductandProcessScientificKnowledgeandusingQualityRiskMgmt.(Materials,Site,Scaleetc)PriorKnowledgeListUnitOperationsthatleadtointendeddrugsubstanceordrugproduct11PQLI®=ProductRealizationUsingQbD•DemystifiesCriticality,DesignSpace&ControlStrategy–PracticalapplicationofICHQ8(R),Q