最ICH指導建議建議原則專家講座

ICHGuidelines第1頁說明ICH論題主要分為四類，所以ICH依據論題類別不一樣而進行對應編碼分類：“Q”類論題：Q代表QUALITY，指那些與化工和醫藥，質量確保方面相關論題?！癝”類論題：S代表SAFETY，指那些與試驗室和動物試驗，臨床前研究方面相關論題。3.“E”類論題：E代表EFFICACY，指那些與人類臨床研究相關課題。4.“M”類論題：M代表MULTIDISCIPLINARY,指那些不可單獨劃入以上三個分類交叉包括論題。同時M又細分為5個小類

M1:慣用醫學名詞（MedDRA）

M2:藥政信息傳遞之電子標準

M3:與臨床試驗相關臨床前研究時間安排

M4:常規技術文件(CTD)

M5:藥品詞典數據要素和標準第2頁一、QualityGuidelines

質量研究指導標準

HarmonisationachievementsintheQualityareaincludepivotalmilestonessuchastheconductofstabilitystudies,definingrelevantthresholdsforimpuritiestestingandamoreflexibleapproachtopharmaceuticalqualitybasedonGoodManufacturingPractice(GMP)riskmanagement.

第3頁Q1A-Q1FStability穩定性

Q1A(R2)StabilityTestingofNewDrugSubstancesandProducts

新原料藥和制劑穩定性試驗Q1BStabilityTesting:PhotostabilityTestingofNewDrugSubstancesandProducts

新原料藥和制劑光穩定性試驗Q1CStabilityTestingforNewDosageForms新劑型穩定性試驗Q1DBracketingandMatrixingDesignsforStabilityTestingofNewDrugSubstancesandProducts

原料藥和制劑穩定性試驗交叉和矩陣設計Q1EEvaluationofStabilityData穩定性數據評定Q1FStabilityDataPackageforRegistrationApplicationsinClimaticZonesIIIandIV

在氣候帶III和IV，藥品注冊申請所提供穩定性數據

第4頁Q2AnalyticalValidation分析驗證Q2(R1)ValidationofAnalyticalProcedures:TextandMethodology分析程序驗證：正文及方法論

第5頁Q3A-Q3DImpurities雜質Q3A(R2)ImpuritiesinNewDrugSubstances新原料藥中雜質Q3B(R2)ImpuritiesinNewDrugProducts新制劑中雜質Q3C(R5)Impurities:GuidelineforResidualSolvents雜質：殘留溶劑指南Q3DGuidelineforElementalImpurities-NEWQ3DImplementationofGuidelineforElementalImpurities第6頁Q4-Q4BPharmacopoeias藥典

Q4Pharmacopoeias藥典

Q4APharmacopoeialHarmonisation藥典協調Q4BEvaluationandRecommendationofPharmacopoeialTextsforUseintheICHRegions藥典內容評定及推薦為用于ICH地域Q4BAnnex1R1ResidueonIgnition/SulphatedAshGeneralChapter附錄1關于灼燒殘渣/灰分常規篇Q4BAnnex2R1TestforExtractableVolumeofParenteralPreparationsGeneralChapter關于注射劑可提取容量測試常規篇Q4BAnnex3R1TestforParticulateContamination:Sub-VisibleParticlesGeneralChapter附錄3關于顆粒污染物測試:不溶性微粒常規篇Q4BAnnex4AR1MicrobiologicalExaminationofNon-SterileProducts:MicrobialEnumerationTestsGeneralChapter

第7頁Q4-Q4BPharmacopoeias藥典

Q4BAnnex4BR1MicrobiologicalExaminationofNon-SterileProducts:TestsforSpecifiedMicro-OrganismsGeneralChapterQ4BAnnex4CR1MicrobiologicalExaminationofNon-SterileProducts:AcceptanceCriteriaforPharmaceuticalPreparationsandSubstancesforPharmaceuticalUseGeneralChapterQ4BAnnex5R1DisintegrationTestGeneralChapterQ4BAnnex6UniformityofDosageUnitsGeneralChapterQ4BAnnex7R2DissolutionTestGeneralChapterQ4BAnnex8R1SterilityTestGeneralChapter

第8頁Q4-Q4BPharmacopoeias藥典

Q4BAnnex9R1TabletFriabilityGeneralChapterQ4BAnnex10R1PolyacrylamideGelElectrophoresisGeneralChapterQ4BAnnex11CapillaryElectrophoresisGeneralChapterQ4BAnnex12AnalyticalSievingGeneralChapterQ4BAnnex13BulkDensityandTappedDensityofPowdersGeneralChapterQ4BAnnex14BacterialEndotoxinsTestGeneralChapterQ4BFAQsFrequentlyAskedQuestions第9頁Q5A-Q5EQualityofBiotechnologicalProducts

生物技術產品質量Q5A(R1)ViralSafetyEvaluationofBiotechnologyProductsDerivedfromCellLinesofHumanorAnimalOrigin

源于人或者動物細胞系生物技術產品病毒安全性評定Q5BAnalysisoftheExpressionConstructinCellsUsedforProductionofr-DNADerivedProteinProducts

生物技術產品質量：源于重組DNA蛋白質產品生產中所用細胞中表示構建分析Q5CStabilityTestingofBiotechnological/BiologicalProducts

生物技術產品質量：生物技術/生物產品穩定性試驗Q5DDerivationandCharacterisationofCellSubstratesUsedforProductionofBiotechnological/BiologicalProducts

用于生產生物技術/生物產品細胞底物起源和特征描述Q5EComparabilityofBiotechnological/BiologicalProductsSubjecttoChangesintheirManufacturingProcess

基于不一樣生產工藝生物技術產品/生物產品可比較性

第10頁Q6A-Q6BSpecifications規格Q6ASpecifications:TestProceduresandAcceptanceCriteriaforNewDrugSubstancesandNewDrugProducts:ChemicalSubstances質量規格：新原料藥和新制劑檢驗程序和可接收標準：化學物質(包含決定過程)Q6BSpecifications:TestProceduresandAcceptanceCriteriaforBiotechnological/BiologicalProducts

質量規格：生物技術/生物產品檢驗程序和可接收標準

第11頁Q7GoodManufacturingPractice

(原料藥GMP規范)Q7GoodManufacturingPracticeGuideforActivePharmaceuticalIngredients活性藥品成份GMP指南

Q7Q&AsQuestionsandAnswers:GoodManufacturingPracticeGuideforActivePharmaceuticalIngredients第12頁Q8PharmaceuticalDevelopment藥品開發Q8(R2)PharmaceuticalDevelopment

藥品開發Q8/9/10Q&AsR4Q8/Q9/Q10-Implementation第13頁Q9QualityRiskManagement

質量風險管理Q9QualityRiskManagement

Q8/9/10Q&AsR4Q8/Q9/Q10-Implementation第14頁Q10PharmaceuticalQualitySystem藥品質量體系Q10PharmaceuticalQualitySystem

藥品質量體系

Q8/9/10Q&AsR4Q8/Q9/Q10-Implementation實施第15頁Q11DevelopmentandManufactureofDrugSubstances原料藥研發與生產Q11DevelopmentandManufactureofDrugSubstances(ChemicalEntitiesandBiotechnological/BiologicalEntities)Q11Q&AsQuestions&Answers:SelectionandJustificationofStartingMaterialsfortheManufactureofDrugSubstances

第16頁Q12LifecycleManagement

生命周期管理

Q12TechnicalandRegulatoryConsiderationsforPharmaceuticalProductLifecycleManagement第17頁Cross-cuttingTopicsCross-cuttingGuidelines第18頁二、SafetyGuidelines

安全性評價指導標準

ICHhasproducedacomprehensivesetofsafetyGuidelinestouncoverpotentialriskslikecarcinogenicity,genotoxicityandreprotoxicity.Arecentbreakthroughhasbeenanon-clinicaltestingstrategyforassessingtheQTintervalprolongationliability:thesinglemostimportantcauseofdrugwithdrawalsinrecentyears.第19頁S1A-S1CCarcinogenicityStudies致癌性研究S1RodentCarcinogenicityStudiesforHumanPharmaceuticalsS1ANeedforCarcinogenicityStudiesofPharmaceuticalsS1BTestingforCarcinogenicityofPharmaceuticalsS1C(R2)DoseSelectionforCarcinogenicityStudiesofPharmaceuticals

第20頁S2GenotoxicityStudies

遺傳毒性研究S2(R1)GuidanceonGenotoxicityTestingandDataInterpretationforPharmaceuticalsIntendedforHumanUseS2A:GuidanceonSpecificAspectsofRegulatoryGenotoxicityTestsforPharmaceuticals;S2B:Genotoxicity:AStandardBatteryforGenotoxicityTestingforPharmaceuticals;

第21頁S3A-S3BToxicokineticsandPharmacokinetics毒代動力學和藥代動力學

S3ANoteforGuidanceonToxicokinetics:TheAssessmentofSystemicExposureinToxicityStudiesS3AQ&AsQuestionsandAnswers:NoteforGuidanceonToxicokinetics:TheAssessmentofSystemicExposure-FocusonMicrosamplingS3BPharmacokinetics:GuidanceforRepeatedDoseTissueDistributionStudies第22頁S4ToxicityTesting毒性試驗S4DurationofChronicToxicityTestinginAnimals(RodentandNonRodentToxicityTesting)

第23頁S5ReproductiveToxicology

生殖毒理學S5(R2)DetectionofToxicitytoReproductionforMedicinalProducts&ToxicitytoMaleFertility第24頁S6BiotechnologicalProducts

生物技術制品S6(R1)PreclinicalSafetyEvaluationofBiotechnology-DerivedPharmaceuticals

第25頁S7A-S7B

PharmacologyStudies藥理學研究S7ASafetyPharmacologyStudiesforHumanPharmaceuticalsS7BTheNon-ClinicalEvaluationofthePotentialforDelayedVentricularRepolarization(QTIntervalProlongation)byHumanPharmaceuticals第26頁S8ImmunotoxicologyStudies

免疫毒理學研究S8ImmunotoxicityStudiesforHumanPharmaceuticals人類藥品免疫毒性研究第27頁S9NonclinicalEvaluationforAnticancerPharmaceuticals抗癌藥品非臨床評價

S9NonclinicalEvaluationforAnticancerPharmaceuticalsS9Q&AsQuestionsandAnswers:NonclinicalEvaluationforAnticancerPharmaceuticals第28頁S10PhotosafetyEvaluation

光安全評價S10PhotosafetyEvaluationofPharmaceuticals藥品光安全評價第29頁S11NonclinicalSafetyTesting

非臨床安全性試驗S11NonclinicalSafetyTestinginSupportofDevelopmentofPaediatricMedicines第30頁Cross-cuttingTopicsCross-cuttingGuidelinesSomeICHProductsdonotfituniquelyintooneoftheQuality,SafetyorEfficacycategories.ThoseProductscanbefoundunderthe

Mulidisciplinary

Section.第31頁三、EfficacyGuidelines

有效性評價指導標準

TheworkcarriedoutbyICHundertheEfficacyheadingisconcernedwiththedesign,conduct,safetyandreportingofclinicaltrials.Italsocoversnoveltypesofmedicinesderivedfrombiotechnologicalprocessesandtheuseofpharmacogenetics/genomicstechniquestoproducebettertargetedmedicines第32頁E1ClinicalSafetyforDrugsusedinLong-TermTreatment用于長久治療藥品臨床安全性

E1TheExtentofPopulationExposuretoAssessClinicalSafetyforDrugsIntendedforLong-TermTreatmentofNon-LifeThreateningConditions要評定用于非危及生命疾病長久治療藥品臨床安全性人群暴露程度第33頁E2A-E2FPharmacovigilance

藥品警戒E2AClinicalSafetyDataManagement:DefinitionsandStandardsforExpeditedReportingE2B(R3)ClinicalSafetyDataManagement:DataElementsforTransmissionofIndividualCaseSafetyReportsE2B(R3)IWGImplementation:ElectronicTransmissionofIndividualCaseSafetyReportsE2C(R2)PeriodicBenefit-RiskEvaluationReport第34頁E2C(R2)-E2FE2C(R2)

Q&AsQuestions&Answers:PeriodicBenefit-RiskEvaluationReportE2D

Post-ApprovalSafetyData

Management:DefinitionsandStandardsforExpeditedReportingE2E

Pharmacovigilance

PlanningE2F

DevelopmentSafetyUpdateReport

第35頁E3ClinicalStudyReports

臨床研究匯報E3StructureandContentofClinicalStudyReportsE3Q&AsR1Questions&Answers:StructureandContentofClinicalStudyReports

第36頁E4Dose-ResponseStudies

劑量反應研究E4Dose-ResponseInformationtoSupportDrugRegistration支持藥品注冊劑量反應信息第37頁E5EthnicFactors民族原因

E5(R1)EthnicFactorsintheAcceptabilityofForeignClinicalDataE5Q&As(R1)Questions&Answers:EthnicFactorsintheAcceptabilityofForeignClinicalData第38頁E6GoodClinicalPractice

臨床試驗規范E6(R1)GoodClinicalPracticeE6(R2)Addendum:GoodClinicalPractice

第39頁E7ClinicalTrialsinGeriatricPopulation

在老年人群中臨床試驗

E7StudiesinSupportofSpecialPopulations:GeriatricsE7Q&AsQuestions&Answers:StudiesinSupportofSpecialPopulations:Geriatrics第40頁

E8GeneralConsiderationsforClinicalTrials

臨床試驗普通考慮

E8GeneralConsiderationsforClinicalTrials第41頁E9StatisticalPrinciplesforClinicalTrials

臨床試驗統計學原理

E9StatisticalPrinciplesforClinicalTrials

E9(R1)Addendum:StatisticalPrinciplesforClinicalTrials第42頁E10ChoiceofControlGroupinClinicalTrials臨床試驗中對照組選擇

E10ChoiceofControlGroupandRelatedIssuesinClinicalTrials在臨床試驗中對照組和相關問題選擇第43頁E11ClinicalTrialsinPediatricPopulation在兒科臨床試驗

E11ClinicalInvestigationofMedicinalProductsinthePediatricPopulation

E11(R1)Addendum:ClinicalInvestigationofMedicinalProductsinthePediatricPopulation第44頁E12ClinicalEvaluationbyTherapeuticCategory治療類別臨床評價

E12PrinciplesforClinicalEvaluationofNewAntihypertensiveDrugs第45頁E14ClinicalEvaluation臨床評價E14TheClinicalEvaluationofQT/QTcIntervalProlongationandProarrhythmicPotentialforNon-AntiarrhythmicDrugs

E14Q&AsR2Questions&Answers:TheClinicalEvaluationofQT/QTcIntervalProlongationandProarrhythmicPotentialforNon-AntiarrhythmicDrugs第46頁E15DefinitionsinPharmacogenetics/Pharmacogenomics藥理學/藥品基因組學定義

E15DefinitionsforGenomicBiomarkers,Pharmacogenomics,Pharmacogenetics,GenomicDataandSampleCodingCategories第47頁E16QualificationofGenomicBiomarkers

基因組生物標志物資格

E16BiomarkersRelatedtoDrugorBiotechnologyProductDevelopment:Context,StructureandFormatofQualificationSubmissions藥品或生物技術產品開發相關生物標志物：上下文，結構和資格文件格式第48頁E17Multi-RegionalClinicalTrials多區域臨床試驗

E17Generalprincipleonplanning/designingMulti-RegionalClinicalTrials在規劃/設計多區域臨床試驗普通標準第49頁E18GenomicSamplingMethodologies

基因組取樣方法

E18GenomicSamplingMethodologiesforFutureUse第50頁Cross-cuttingTopicsCross-cuttingGuidelines

第51頁四、MultidisciplinaryGuidelines

多學科指南

Thosearethecross-cuttingtopicswhichdonotfituniquelyintooneoftheQuality,SafetyandEfficacycategories.Itincludes