上海CMC培训 Overview of Regulatory Framework and CMC Requirements in the US.ppt

PoskaCMCOverview062810 1 OverviewofRegulatoryFrameworkandCMCRequirementsintheUS richard poska GlobalPharmaceuticalRegulatoryAffairs CMCRequirementsandStrategiesWorkshop28June2010 PoskaCMCOverview062810 2 PresentationGoals ExploretheroleofscienceinFDAandICHpolicyReviewFDAregulatoryCMCsubmissionrequirementsandexpectationsOutlineFDAsubmissionreviewprocessandoutcomesSummarizescience riskbasedapproachedtoCMCsubmissionsImpactofcollaborativepartnerships Industry academia andFDA PoskaCMCOverview062810 3 Theonewhomovesamountainbeginsbycarryingsmallstones PoskaCMCOverview062810 4 USDrugRegulationMilestones 1820UnitedStatesPharmacopeiaestablished1906Food DrugsActInterstateCommerce Adulterated MisbrandedDrugs1937Sulfanilamide DiethyleneGlycol1938FD CAct FD CA passedSafetydata FactoryInspections1962ThalidomideKefauver Harrisamendments efficacy PoskaCMCOverview062810 5 FrameworkforUSPharmaceuticalRegulation Laws Regulations Review PublicStandards Compliance PoskaCMCOverview062810 6 USManufacturingChanges 25Yearsago PriorapprovalperFD CAct MagnitudeofManufacturingChange IntrinsicRiskofMolecule PoskaCMCOverview062810 8 TheValueofGuidances PoskaCMCOverview062810 9 CMCRequirements PostApproval Categoriesforreportingchangeisgaugedonpotentialforadverseeffects Major PriorApproval SubstantialpotentialModerate CBE ModeratepotentialMinor AR Minimalpotential USManufacturingChanges Today PriorapprovalperFDAMA Allotherchanges ARperPACRegulations Guidances MagnitudeofManufacturingChange IntrinsicRiskofMolecule DesiredState PriorapprovalperFDAMA ARperPAC MagnitudeofManufacturingChange IntrinsicRiskofMolecule HIGHRISKMolecular ProductClinicalExperienceGMPIssues ProcessUnderstanding QbD LOWRISK ControlStrategies PAT PoskaCMCOverview062810 12 GeneralCharacteristicsof Traditional Guidances Prescriptive expectationsandrequirementsdefined AllowsdefinedflexibilityHelpsbothregulatorsandindustryfocusondetailsContributestouniforminterpretationandlevel playingfield forall PoskaCMCOverview062810 13 Guidancesthatare prescriptive Scale UpandPostApprovalChanges SUPAC ImmediateReleaseTabletsEquipmentAddenda PoskaCMCOverview062810 14 Non prescriptiveGuidance ChangestoanApprovedNDA ANDAContainerClosureSystemsBiopharmaceuticsClassificationSystem StratifiedSamplingandBUDraft ComparabilityProtocols PoskaCMCOverview062810 15 Whatroledoes shouldscienceplay PoskaCMCOverview062810 16 ImpactofKnowledge risk Sciencebasedinformation TIME PoskaCMCOverview062810 17 ProcessUnderstanding Thedriverfornewstandardsofpharmaceuticalmanufacturequalityandregulation GordonMunro Ph D 9thArdenHouseEuropeanConference PoskaCMCOverview062810 18 AssessingtheProduct Doesdatasupport fitnessforuse PoskaCMCOverview062810 19 A ProcessUnderstanding GeneratenecessarydatatoidentifycriticalparametersExistingdataModifiedDOEDemonstratethatprocesscontrolsallvariabilityStatisticalTools SPC CpK PoskaCMCOverview062810 20 Non TraditionalGuidance WhitePapers ModelsandInitiatives PhilosophicalAbundantVisionandScope lessfocusondetailsFlexibilityallowsforcreative butvaried approachesRelyonunderstandingofformulation processandproduct PoskaCMCOverview062810 21 PharmaceuticalQualityforthe21stCentury http www fda gov bbs topics NEWS 2002 NEW00829 html August21 2002 AjazHussain PATtoCriticalPath PoskaCMCOverview062810 22 cGMPsforthe21stCentury ARisk BasedApproach EvaluateCMCreviewsandcGMPinspectionstoensurethat LatestadvancesintechnologyareusedCoordinateandsynergizesubmissionreviewsandinspectionsApplyregulationsandstandardsconsistentlyEncourage notimpede innovationResourcesareusedefficiently PoskaCMCOverview062810 23 Transition guidance fromFDA21stCenturyInitiatives GuidancePATQualitySystemsApproachtoGMPsModelsRiskModelforInspectionalOversightWhitePapersInnovationandContinuousImprovementinPharmaceuticalManufacturing PoskaCMCOverview062810 24 B ToolsMultivariateDataAcquisitionProcessAnalyzersProcessControlContinuousImprovement PAT ProcessAnalyticalTechnology RealTimeRelease A ProcessUnderstandingContinuouslearning RiskBasedApproach IntegratedSystems C RegulatoryStrategyRemoveHurdlesforimprovements PoskaCMCOverview062810 25 PQRI ProcessRobustnessSterileProductsPostApprovalChangesQbDSpecifications PoskaCMCOverview062810 26 Conformia CommercializationQbD PAT DesignSpaceICHQ8 9 10CollaborationCommunication DecisionMakingInformationBottlenecksFDAPerception PoskaCMCOverview062810 27 PQLI ToworkwithindustryandregulatoryagenciesworldwidetointroducepragmaticandpracticalimplementationofICHguidances basedonsoundscientific engineeringandbusinessprinciples TopicAreas CriticalvsNon CriticalDesignSpaceControlStrategy TraditionalvsNon TraditionalapproachbasedonQbDconcepts PoskaCMCOverview062810 28 IndustryandRegulatorsAgree StriveforcommonlanguageProcessunderstandingProvidesufficientdetailJustifyspecificationsasmeaningful PoskaCMCOverview062810 29 CommonTools GoodScienceDevelopmentandreviewCommunicationUnderstandsourcesof controlvariationUtilityofspecificationsUseofin processtestsLinktoproductquality attributes AssessriskAgreeondefinition methodsApplythroughoutlifecycle PoskaCMCOverview062810 30 TheRoadtoanApprovedProduct PoskaCMCOverview062810 31 FDAMission InsureSafety EfficacyofDrugProducts IdentityStrengthQualityPurityPotency PoskaCMCOverview062810 32 TheNDA AQuality Performancecontract license Specificationlimitsonqualityattributesareoftenchosenempiricallytoensureproductionofbatchesthatresemblethebatchestestedintheclinic Onlyensuresconsistentclinicalperformanceifrelationshipbetweenlimitsandclinicaloutcomeisunderstood Withoutthisunderstanding thelimitscouldbeoverlywide unnecessarilytight orcompletelyirrelevanttoclinicalperformance Evenworse other criticallyimportantattributesmaynotbeidentified measuredandcontrolled JanetWoodcock 2004 PoskaCMCOverview062810 33 USActivitiestoCommercialPharmaceutical PoskaCMCOverview062810 34 JourneytoDesiredState CURRENTSTATE TRANSITION DESIREDSTATE GuidancesQualityDetectionQualityByQualityTypeParadigm CFR210 211314 70SUPACs Reactive Proactive CorrectiveAction ContinuousImprovement Innovation MeasureableSpecs MeaningfulSpecs AttributeTesting Design 21stCenturyRiskBasedInitiatives Riskbasedregulatoryscrutinyisassociatedwiththelevelofscientificunderstanding PoskaCMCOverview062810 35 Wherearethe opportunities Knowyourprocess keepimprovingit shareinfoUnderstandyourmolecule BCSDefineandidentify critical ProcesscontrolsandparametersMakeinformationpartofpublicdomainThinkglobally Usenewtechnologieswhenjustifiedtolowermanufacturingrisks WillneedtoconsideroverallimpactCantheybecosteffective ConsiderPATcorrelationswhenmeanin