ICH发布统一的Q8 Q9 Q10培训材料

HowICHQ8,Q9,Q10guidelinesareworkingtogetherthroughouttheproductlifecycle

Disclaimer TheinformationwithinthispresentationisbasedontheICHQ-IWGmembersexpertiseandexperience,andrepresentstheviewsoftheICHQ-IWGmembersforthepurposesofatrainingworkshop.©ICH,November2010精选pptOutlineWorkshopGoalsandObjectivesICHQ8,Q9&Q10HowtheguidelinesareworkingtogetherthroughouttheproductlifecycleUtilityofICHQ8,Q9&Q10KeymessagesConclusion©ICH,November2010精选pptWorkshopGoalsandObjectivesThispresentationisintendedtooutlinethelinkagebetweenQ8,9&10andhowtheguidelinesareworkingtogetherThispresentationisNOTintendedtooutlineregulatoryexpectations(assessmentand/orinspection)Thisworkshopwill:ProvidetrainingontheintegratedimplementationofQ8,Q9andQ10AllowparticipantstoshareimplementationstrategiesandexperiencesSeekparticipants’inputandidentifyimplementationissueandconcerns©ICH,November2010精选pptNov2005&Nov2008November2005June2008ICHQ8,Q9andQ10Highlevelguidances

(notprescriptive)Scienceandrisk-basedEncouragessystematicapproachesApplicableoverentireproductlifecycleIntendedtoworktogethertoenhancepharmaceuticalproductquality©ICH,November2010精选pptPharmaceuticalDevelopment-Q8(R2)Describesscienceandrisk-basedapproachesforpharmaceuticalproductandmanufacturingprocessdevelopmentIntroducedconceptsofdesignspaceandflexibleregulatoryapproachesIntroducedconceptsofQualitybyDesign(QbD)andprovidedexamplesofQbDdevelopmentapproachesanddesignspace©ICH,November2010精选pptQ8(R2)-ExampleQbDApproachQualityTargetProductProfile(QTPP)

Determine“potential”criticalqualityattributes(CQAs)

LinkrawmaterialattributesandprocessparameterstoCQAsandperformriskassessmentDevelopadesignspace(optionalandnotrequired)

Designandimplementacontrolstrategy

Manageproductlifecycle,includingcontinualimprovement©ICH,November2010精选pptQualityRiskManagement–Q9Describessystematicprocessesfortheassessment,control,communicationandreviewofqualityrisksAppliesoverproductlifecycle:development,manufacturinganddistributionIncludesprinciples,methodologiesandexamplesoftoolsforqualityriskmanagementAssessmentofrisktoqualityshould:BebasedonscientificknowledgeLinktotheprotectionofthepatientExtendoverthelifecycleoftheproduct©ICH,November2010精选pptQualityRiskManagementProcess-Q9ProcessDevelopmentControlStrategyDevelopmentContinualImprovement

oftheproduct©ICH,November2010精选pptPharmaceuticalQualitySystem-Q10DescribeskeysystemsthatfacilitateestablishmentandmaintenanceofastateofcontrolforprocessperformanceandproductqualityFacilitatescontinualimprovementAppliestodrugsubstanceanddrugproductthroughoutproductlifecycleSoundpharmaceuticaldevelopment(Q8R(2))incombinationwitharobustPQS(Q10)provideopportunitiesforflexibleregulatoryapproaches.RelevantPQSelementsincludesystemsfor:TrackandtrendproductqualityMaintainandupdatemodelsasneededInternallyverifythatprocesschangesaresuccessful©ICH,November2010精选pptPharmaceuticalQualitySystem-Q10©ICH,November2010精选pptICHQ8,Q9andQ10WorkingTogetherFormulationActivities:QTPPDefinitionPre-FormulationStudiesFormulationScreeningOptimization&SelectionProcessDevelopmentActivities:ProcessScreeningLabScaleDevelopmentScale-UpStudiesManufacturingActivities:CommercialScale

ManufacturingBatchReleaseContinualVerification&

ImprovementQ8PharmaceuticalDevelopmentQ9QualityRiskManagementQ10PharmaceuticalQualitySystems©ICH,November2010精选pptHowcanthethreeguidelinesworktogetherThefollowingfourslides(slides14-17)areintendedtoshowhowQ8,Q9,Q10canworktogetheratdifferentstagesoftheproductlifecycle

ItisimportanttonotethattheyareNOTintendedtoshowcompleteactivitiesateachstageNORtoshowtheexacttiming(stage)forthoseactivities©ICH,November2010精选pptFormulationDevelopmentActivitiesICHQ8(R2)–Pharmaceutical

Development

RelatedActivitiesICHQ9–QRMRelated

ActivitiesICHQ10–PQSRelatedIntegratedActivitiesQualityTargetProductProfile(QTPP)Clinicalandnon-clinicalstudiesondrug

substance:bioavailability,PK/PD,and

safetyInformaland/orformalrisk

assessmenttoevaluatepatient

needsandpotentialmedication

risks

KnowledgeManagement/

PriorKnowledge(relevant

informationtosupportthe

understanding,risk

assessmentandscopeof

DOE)-Laboratorynotebook

documentation-Developmentreport-Etc…Pre-FormulationStudies

Characterizationofdrugsubstance

(physicalproperties)Chemicalstabilityofdrugsubstance,

degradationandpotentialformulation

interactionsDevelopmentofanalyticaltestsDeterminefailuremodesandrisk

factorsfordrugsubstance

physicalandchemicalstabilityFormulationScreeningExcipientcompatibilityDissolutionmethoddevelopmentScreeningDOEsDeterminefailuremodesandrisk

factorsforexcipientinteractionsFormulationOptimizationandSelection

Excipientanddrugsubstancematerial

property&characterizationDOEsforexcipientamountsStabilityofdrugproductandstorage

conditionsDevelopIVIVCrelationshipsOpportunitiesforformalrisk

assessment©ICH,November2010精选pptProcessDevelopmentActivitiesICHQ8(R2)–PharmaceuticalDevelopmentRelatedActivitiesICHQ9–QRM

Related

ActivitiesICHQ10–PQS

RelatedIntegratedActivitiesProcessScreeningExplorationofunitoperationsCharacterizationofprocess

intermediatesDeterminefailuremodes,riskfactors

forunitoperationsandrankrisk

Batchrecordsand

operationalguidelines

formanufacturingTechTransferreportIdentificationand

selectionofsuppliers

thatmeetrawmaterial

needsProcessDevelopmentandOptimization

(LabScale)DOEsforprocessparametersand

interactionswithmaterialattributesDevelopmentofDesignSpaceOperationalrangesforscale-

independentparametersunderstandingofcriticalprocess

operationsScreeningriskassessmentto

determinepotentialparameters

impactingproductquality(e.g.,

Ishikawa)Determinecriticalprocesssteps,

processparametersandmaterial

attributes(e.g.,FMEA)PotentialissuesofscaleProcessDevelopmentandOptimization

(PilotScale)PilottoverifylabscaleknowledgeDOEandmodelingeffectsofscaleDevelopmentofdesignspaceDevelopmentofon-line

measurementtechnologiesDevelopmentofcontrolstrategyto

controlrisksincl.forscaleup©ICH,November2010精选pptTechnologyTransferICHQ8(R2)–PharmaceuticalDevelopmentRelatedActivitiesICHQ9–QRM

Related

ActivitiesICHQ10–PQS

RelatedIntegrated

ActivitiesGainproductandprocessknowledgeKnowledgesupportstransferbetween

developmentandmanufacturingto

achieveproductrealizationFormsthebasisforthemanufacturing

processImproveseffectivenessofcontrol

strategyContributestoprocessesvalidationand

ongoingcontinualimprovementAdvanceunderstandingthroughscale-

upactivitiesProvidepreliminaryindicationof

processperformanceandsuccessful

integrationintomanufacturingGainknowledgefromtransferand

scaleupactivitiestoenhancethe

basisforthecontrolstrategy©ICH,November2010精选pptCommercialManufacturingActivitiesICHQ8(R2)–PharmaceuticalDevelopmentRelatedActivitiesICHQ9–QRM

Related

ActivitiesICHQ10–PQS

RelatedIntegrated

ActivitiesCommercialScaleManufacturingforDrugProductDefinitionofcommercial

processdesignCommercialscalerunstoverify

processdesign,withadditional

samplingtoverify

understandingImplementationofon-line

measurementtechnologiesDevelopmentofacontrol

strategyforcommercial

manufacturing,includingin-

processcontrols,end-product

testing,rawmaterialcontrols

andchangecontrolCheckproceduresinthePQS

regardingriskfromProcess

specificprocedure(e.g.,

samplingplans,designspace

andmodelverification,change

controlformovementwithin

designspace)Process-specificoperating

procedures(e.g.samplingplans,

designspaceetc.)Documentationtosupporton-line

testingmethodsValidationtodemonstrateprocess

andanalyticalmethod

reproducibilityStorageofdevelopmentreports,

riskassessmentsContinualProcessVerificationandContinualImprovementOn-goinganalysisandtrending

ofprocessdata,(multivariate

SPC,etc.)Evaluationofprocesschanges

andassociatedeffecton

intermediatesandproductsManagerisksofprocessor

materialattributechange

(includingchangeswithinor

outsideofdesignspace)Reviewrisksin

audits/inspectionsand

implementrisk-basedCAPAsProceduresonprocess

monitoringandactionlimitsChangecontrolprocedures

includinghowandwhentodorisk

assessmentforprocesschanges

andevaluationofthechangeMaintenanceandupdateof

knowledgemanagement

©ICH,November2010精选pptTheUtilityofICHQ8,9&10

TheimplementationofQ8,9&10isvaluableforalldrugproducts,pharmaceuticaldevelopmentapproachesandregulatorysystemsNew/innovator,marketed/legacyandgenericsSimpleandcomplexdosageformsSmallmoleculeandbiotechTraditionaldevelopmentandQbDWithinandoutsideICHregionsGoodscientificdevelopment(Q8)incombinationwithQRM(Q9)andPQS(Q10)willimprovedrugqualityandefficiencyofpharmaceuticalmanufacturingQualityisimportantforalldrugproductsthroughoutproductlifecycle(new,legacyandgenerics)©ICH,November2010精选pptKeyMessagesICHQ8,Q9andQ10arelinkedtogethertoprovideasystematic,modernrisk-andscience-basedapproachtopharmaceuticalmanufacturinganddevelopmentComprehensiveimplementationofthethreeguidelinestogetherisessentialtoachieveICHQualityVisionGuidelinesareapplicableoverentireproductlifecycleGuidelinescanbeutilizedbyallstakeholdersIndustryandregulatorsAssessorsandinspectorsareexpectedtoincorporateQRMduringregulatoryprocesses©ICH,November2010精选pptKeyMessagesTraditionaldevelopmentapproaches,asoutlinedinICHQ8(R2)partI,areacceptableEnhancedapproaches(QbD)providehigherassuranceofproductqualityandadditionalopportunitiesformanufacturingefficiencyandflexibilityTheuseofqualityriskmanagementprocess,methodologiesandtools(Q9)isbeneficialregardlessofdevelopmentormanufacturingapproachesusedPharmaceuticalQualitySystems(Q10)appliestodrugsubstanceanddrugproductthroughoutproductlifecycleandprovidetoolstofacilitatescontinualimprovement©ICH,November2010精选pptConclusionsWorkshopmaterials,plenarypresentations,andbreakoutdiscussionswillprovideusefulinformationtofacilitatepharmaceuticaldevelopmentandmanufacturing,andrelatedregulatoryaspectsTrainingmaterialsprovideonlyillustrativee