M4 Quality Step4 sept02.docx

M4 Quality Step4 sept02.docx

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M4QualityStep4sept02

INTERNATIONALCONFERENCEONHARMONISATIONOFTECHNICALREQUIREMENTSFORREGISTRATIONOFPHARMACEUTICALSFORHUMANUSE

ICHHarmonisedTripartiteGuideline

TheCommonTechnicalDocumentforthe

RegistrationofPharmaceuticalsforHumanUse:

Quality–M4Q

QualityOverallSummaryofModule2

Module3:

Quality

HavingreachedStep4oftheICHProcessattheICHSteeringCommitteemeeting

on9November2000,thisguidelineisrecommendedfor

adoptiontothethreeregulatorypartiestoICH

（NumberingandSectionHeadershavebeeneditedforconsistencyanduseine-CTDasagreedattheWashingtonDCMeeting,September11-12,2002）

ThisGuidelinehasbeendevelopedbytheappropriateICHExpertWorkingGroupandhasbeensubjecttoconsultationbytheregulatoryparties,inaccordancewiththeICHProcess.AtStep4oftheProcessthefinaldraftisrecommendedforadoptiontotheregulatorybodiesoftheEuropeanUnion,JapanandUSA.

TheCommonTechnicalDocumentforthe

RegistrationofPharmaceuticalsforHumanUse:

Quality

QualityOverallSummaryofModule2

Module3:

Quality

ICHHarmonisedTripartiteGuideline

HavingreachedStep4oftheICHProcessattheICHSteeringCommitteemeeting

on9November2000,thisguidelineisrecommendedfor

adoptiontothethreeregulatorypartiestoICH

（NumberingandSectionHeadershavebeeneditedforconsistencyanduseine-CTDasagreedattheWashingtonDCMeeting,September11-12,2002）

TABLEOFCONTENTS

MODULE2:

COMMONTECHNICALDOCUMENTSUMMARIES1

2.3:

QUALITYOVERALLSUMMARY（QOS）1

INTRODUCTION1

2.3.SDRUGSUBSTANCE（NAME,MANUFACTURER）1

2.3.S.1GeneralInformation（name,manufacturer）1

2.3.S.2Manufacture（name,manufacturer）1

2.3.S.3Characterisation（name,manufacturer）2

2.3.S.4ControlofDrugSubstance（name,manufacturer）2

2.3.S.5ReferenceStandardsorMaterials（name,manufacturer）2

2.3.S.6ContainerClosureSystem（name,manufacturer）2

2.3.S.7Stability（name,manufacturer）2

2.3.PDRUGPRODUCT（NAME,DOSAGEFORM）3

2.3.P.1DescriptionandCompositionoftheDrugProduct（name,dosageform）3

2.3.P.2PharmaceuticalDevelopment（name,dosageform）3

2.3.P.3Manufacture（name,dosageform）3

2.3.P.4ControlofExcipients（name,dosageform）3

2.3.P.5ControlofDrugProduct（name,dosageform）3

2.3.P.6ReferenceStandardsorMaterials（name,dosageform）3

2.3.P.7ContainerClosureSystem（name,dosageform）3

2.3.P.8Stability（name,dosageform）3

2.3.AAPPENDICES4

2.3.A.1FacilitiesandEquipment（name,manufacturer）4

2.3.A.2AdventitiousAgentsSafetyEvaluation

（name,dosageform,manufacturer）4

2.3.A.3Excipients4

2.3.RREGIONALINFORMATION4

Module3:

Quality5

3.1.TABLEOFCONTENTSOFMODULE35

3.2.BODYOFDATA5

3.2.SDRUGSUBSTANCE（NAME,MANUFACTURER）5

3.2.S.1GeneralInformation（name,manufacturer）5

3.2.S.1.1Nomenclature（name,manufacturer）5

3.2.S.1.2Structure（name,manufacturer）6

3.2.S.1.3GeneralProperties（name,manufacturer）6

3.2.S.2Manufacture（name,manufacturer）6

3.2.S.2.1Manufacturer（s）（name,manufacturer）6

3.2.S.2.2DescriptionofManufacturingProcessandProcessControls（name,manufacturer）6

3.2.S.2.3ControlofMaterials（name,manufacturer）8

3.2.S.2.4ControlsofCriticalStepsandIntermediates（name,manufacturer）8

3.2.S.2.5ProcessValidationand/orEvaluation（name,manufacturer）8

3.2.S.2.6ManufacturingProcessDevelopment（name,manufacturer）9

3.2.S.3Characterisation（name,manufacturer）9

3.2.S.3.1ElucidationofStructureandotherCharacteristics（name,manufacturer）9

3.2.S.3.2Impurities（name,manufacturer）10

3.2.S.4ControlofDrugSubstance（name,manufacturer）10

3.2.S.4.1Specification（name,manufacturer）10

3.2.S.4.2AnalyticalProcedures（name,manufacturer）10

3.2.S.4.3ValidationofAnalyticalProcedures（name,manufacturer）10

3.2.S.4.4BatchAnalyses（name,manufacturer）10

3.2.S.4.5JustificationofSpecification（name,manufacturer）10

3.2.S.5ReferenceStandardsorMaterials（name,manufacturer）10

3.2.S.6ContainerClosureSystem（name,manufacturer）10

3.2.S.7Stability（name,manufacturer）11

3.2.S.7.1StabilitySummaryandConclusions（name,manufacturer）11

3.2.S.7.2Post-approvalStabilityProtocolandStabilityCommitment（name,manufacturer）11

3.2.S.7.3StabilityData（name,manufacturer）11

3.2.PDRUGPRODUCT（NAME,DOSAGEFORM）11

3.2.P.1DescriptionandCompositionoftheDrugProduct（name,dosageform）11

3.2.P.2PharmaceuticalDevelopment（name,dosageform）12

3.2.P.2.1ComponentsoftheDrugProduct（name,dosageform）12

3.2.P.2.1.1DrugSubstance（name,dosageform）12

3.2.P.2.1.2Excipients（name,dosageform）12

3.2.P.2.2DrugProduct（name,dosageform）12

3.2.P.2.2.1FormulationDevelopment（name,dosageform）12

3.2.P.2.2.2Overages（name,dosageform）12

3.2.P.2.2.3PhysicochemicalandBiologicalProperties（name,dosageform）12

3.2.P.2.3ManufacturingProcessDevelopment（name,dosageform）12

3.2.P.2.4ContainerClosureSystem（name,dosageform）13

3.2.P.2.5MicrobiologicalAttributes（name,dosageform）13

3.2.P.2.6Compatibility（name,dosageform）13

3.2.P.3Manufacture（name,dosageform）13

3.2.P.3.1Manufacturer（s）（name,dosageform）13

3.2.P.3.2BatchFormula（name,dosageform）13

3.2.P.3.3DescriptionofManufacturingProcessandProcessControls（name,dosageform）13

3.2.P.3.4ControlsofCriticalStepsandIntermediates（name,dosageform）14

3.2.P.3.5ProcessValidationand/orEvaluation（name,dosageform）14

3.2.P.4ControlofExcipients（name,dosageform）14

3.2.P.4.1Specifications（name,dosageform）14

3.2.P.4.2AnalyticalProcedures（name,dosageform）14

3.2.P.4.3ValidationofAnalyticalProcedures（name,dosageform）14

3.2.P.4.4JustificationofSpecifications（name,dosageform）14

3.2.P.4.5ExcipientsofHumanorAnimalOrigin（name,dosageform）14

3.2.P.4.6NovelExcipients（name,dosageform）15

3.2.P.5ControlofDrugProduct（name,dosageform）15

3.2.P.5.1Specification（s）（name,dosageform）15

3.2.P.5.2AnalyticalProcedures（name,dosageform）15

3.2.P.5.3ValidationofAnalyticalProcedures（name,dosageform）15

3.2.P.5.4BatchAnalyses（name,dosageform）15

3.2.P.5.5CharacterisationofImpurities（name,dosageform）15

3.2.P.5.6JustificationofSpecification（s）（name,dosageform）15

3.2.P.6ReferenceStandardsorMaterials（name,dosageform）15

3.2.P.7ContainerClosureSystem（name,dosageform）15

3.2.P.8Stability（name,dosageform）16

3.2.P.8.1StabilitySummaryandConclusion（name,dosageform）16

3.2.P.8.2Post-approvalStabilityProtocolandStabilityCommitment（name,dosageform）16

3.2.P.8.3StabilityData（name,dosageform）16

3.2.AAPPENDICES16

3.2.A.1FacilitiesandEquipment（name,manufacturer）16

3.2.A.2AdventitiousAgentsSafetyEvaluation（name,dosageform,

manufacturer）16

3.2.A.3Excipients17

3.2.RREGIONALINFORMATION17

3.3LITERATUREREFERENCES18

MODULE2:

COMMONTECHNICALDOCUMENTSUMMARIES

2.3:

QUALITYOVERALLSUMMARY（QOS）

TheQualityOverallSummary（QOS）isasummarythatfollowsthescopeandtheoutlineoftheBodyofDatainModule3.TheQOSshouldnotincludeinformation,dataorjustificationthatwasnotalreadyincludedinModule3orinotherpartsoftheCTD.

TheQOSshouldincludesufficientinformationfromeachsectiontoprovidetheQualityreviewerwithanoverviewofModule3.TheQOSshouldalsoemphasisecriticalkeyparametersoftheproductandprovide,forinstance,justificationincaseswhereguidelineswerenotfollowed.TheQOSshouldincludeadiscussionofkeyissuesthatintegratesinformationfromsectionsintheQualityModuleandsupportinginformationfromotherModules（e.g.qualificationofimpuritiesviatoxicologicalstudiesdiscussedundertheCTD-Smodule）,includingcross-referencingtovolumeandpagenumberinotherModules.

ThisQOSnormallyshouldnotexceed40pagesoftext,excludingtablesandfigures.Forbiotechproductsandproductsmanufacturedusingmorecomplexprocesses,thedocumentcouldbelongerbutnormallyshouldnotexceed80pagesoftext（excludingtablesandfigures）.

Theitalicisedtextbelowindicateswheretables,figures,orotheritemscanbeimporteddirectlyfromModule3.

INTRODUCTION

Theintroductionshouldincludeproprietaryname,non-proprietarynameorcommonnameofthedrugsubstance,companyname,dosageform（s）,strength（s）,routeofadministration,andproposedindication（s）.

2.3.SDRUGSUBSTANCE（NAME,MANUFACTURER）

2.3.S.1GeneralInformation（name,manufacturer）

Informationfrom3.2.S.1shouldbeincluded.

2.3.S.2Manufacture（name,manufacturer）

Informationfrom3.2.S.2shouldbeincluded:

∙Informationonthemanufacturer;

∙Abriefdescriptionofthemanufacturingprocess（including,forexample,referencetostartingmaterials,criticalsteps,andreprocessing）andthecontrolsthatareintendedtoresultintheroutineandconsistentproductionofmaterial（s）ofappropriatequality;

∙Aflowdiagram,asprovidedin3.2.S.2.2;

∙AdescriptionoftheSourceandStartingMaterialandrawmaterialsofbiologicaloriginusedinthemanufactureofthedrugsubstance,asdescribedin3.2.S.2.3;

∙Adiscussionoftheselectionandjustificationofcriticalmanufacturingsteps,processcontrols,andacceptancecriteria.Highlightcriticalprocessintermediates,asdescribedin3.2.S.2.4;

∙Adescriptionofprocessvalidationand/orevaluation,asdescribedin3.2.S.2.5.

∙Abriefsummaryofmajormanufacturingchangesmadethroughoutdevelopmentandconclusionsfromtheassessmentusedtoevaluateproductconsistency,asdescribedin3.2.S.2.6.TheQOSshouldalsocross-refertothenon-clinicalandclinicalstudiesthatusedbatchesaffectedbythesemanufacturingchanges,asprovidedintheCT