ICH-Q8(中英文)

ICHQ8（中英文）blueski推荐[2009-12-20]出处：Julia的blog作者：不详INTERNATIONALCONFERENCEONHARMONISATIONOFTECHNICALREQUIREMENTSFORREGISTRATIONOFPHARMACEUTICALSFORHUMANUSE人用药物注册技术要求国际协调会议ICHHarmonisedTripartiteGuidelineICH三方协调指南PharmaceuticalDevelopment药物开发Q8RecommendedforAdoptionatStep4oftheICHProcesson10November2005bytheICHSteeringCommitteeICH指导委员会2005年11月10日ICH第四阶段推荐采用ThisGuidelinehasbeendevelopedbytheappropriateICHExpertWorkingGroupandhasbeensubjecttoconsultationbytheregulatoryparties,inaccordancewiththeICHProcess.AtStep4oftheProcessthefinaldraftisrecommendedforadoptiontotheregulatorybodiesoftheEuropeanUnion,JapanandUSA.本指南根据ICH规程由合适的ICH专家工作组起草并经向法规部门咨询。在规程的第4步，建议欧洲共同体、日本和美国的药政部门采用其最终的草案。TABLEOFCONTENTS目录1.INTRODUCTION简介...11.1ObjectiveoftheGuideline指南目的...11.2Scope范围...12.PHARMACEUTICALDEVELOPMENT药物开发...12.1ComponentsoftheDrugProduct制剂产品的组分...42.1.1DrugSubstance活性成分...42.1.2Excipients辅料...42.2DrugProduct制剂...52.2.1FormulationDevelopment配方开发...52.2.2Overages超量...62.2.3PhysicochemicalandBiologicalProperties物化和生化性质...72.3ManufacturingProcessDevelopment制造工艺开发...72.4ContainerClosureSystem容器系统...92.5MicrobiologicalAttributes微生物属性...92.6Compatibility兼容性...103.GLOSSARY术语...111.INTRODUCTION简介1.1ObjectiveofGuideline指南目的Thisguidelinedescribesthesuggestedcontentsforthe3.2.P.2(PharmaceuticalDevelopment)sectionofaregulatorysubmissionintheICHM4CommonTechnicalDocument(CTD)format.本指南就CTD格式申请文件中第3.2.P.2章：药物开发需要叙述的内容给出了建议。ThePharmaceuticalDevelopmentsectionprovidesanopportunitytopresenttheknowledgegainedthroughtheapplicationofscientificapproachesandqualityriskmanagement(fordefinition,seeICHQ9)tothedevelopmentofaproductanditsmanufacturingprocess.Itisfirstproducedfortheoriginalmarketingapplicationandcanbeupdatedtosupportnewknowledgegainedoverthelifecycleofaproduct.ThePharmaceuticalDevelopmentsectionisintendedtoprovideacomprehensiveunderstandingoftheproductandmanufacturingprocessforreviewersandinspectors.Theguidelinealsoindicatesareaswherethedemonstrationofgreaterunderstandingofpharmaceuticalandmanufacturingsciencescancreateabasisforflexibleregulatoryapproaches.Thedegreeofregulatoryflexibilityispredicatedonthelevelofrelevantscientificknowledgeprovided.药物开发一章给申请企业提供了一个机会，来阐述其应用科学的方法和风险管理手段，在产品及其生产工艺的开发过程中所获得的知识。它既可以被用于原始的制剂上市申请，又可以经过更新后被用于支持产品生命周期内所获得的新知识。本指导文件也说明了在什么情况下，药物和生产方面的最大程度的理解可以形成灵活的药政管理办法的基础。药物开发一章旨在为审核官和检查官就产品和生产工艺提供更详尽的理解。1.2Scope范围ThisguidelineisintendedtoprovideguidanceonthecontentsofSection3.2.P.2(PharmaceuticalDevelopment)fordrugproductsasdefinedinthescopeofModule3oftheCommonTechnicalDocument(ICHguidelineM4).Theguidelinedoesnotapplytocontentsofsubmissionsfordrugproductsduringtheclinicalresearchstagesofdrugdevelopment.However,theprinciplesinthisguidelineareimportanttoconsiderduringthosestagesaswell.Thisguidelinemightalsobeappropriateforothertypesofproducts.Todeterminetheapplicabilityofthisguidelinetoaparticulartypeofproduct,applicantscanconsultwiththeappropriateregulatoryauthorities.本指导文件就CTD模块3（ICH标题M4）中所定义的制剂的第3.2.P.2（药物开发）一章中的内容提供了指南。本指导文件不适用于临床研究阶段制剂递交文件的内容。然而，在这些阶段对本指导文件中的原则进行考虑也是重要的。本指南可能也适用于其他一些类型的产品。申请者向合适的药政管理当局进行咨询来确定本指导文件是否适用于某一特定类型的产品。2.PHARMACEUTICALDEVELOPMENT药物开发Theaimofpharmaceuticaldevelopmentistodesignaqualityproductanditsmanufacturingprocesstoconsistentlydelivertheintendedperformanceoftheproduct.Theinformationandknowledgegainedfrompharmaceuticaldevelopmentstudiesandmanufacturingexperienceprovidescientificunderstandingtosupporttheestablishmentofthedesignspace,specifications,andmanufacturingcontrols.药物开发的目的在于设计符合质量要求的产品及符合重复生产模式的制造工艺。在药物开发和研究过程中所获得的信息和知识将为建立质量标准和生产控制提供科学的依据。Informationfrompharmaceuticaldevelopmentstudiescanbeabasisforqualityriskmanagement.Itisimportanttorecognizethatqualitycannotbetestedintoproducts;i.e.,qualityshouldbebuiltinbydesign.Changesinformulationandmanufacturingprocessesduringdevelopmentandlifecyclemanagementshouldbelookeduponasopportunitiestogainadditionalknowledgeandfurthersupportestablishmentofthedesignspace.Similarly,inclusionofrelevantknowledgegainedfromexperimentsgivingunexpectedresultscanalsobeuseful.Designspaceisproposedbytheapplicantandissubjecttoregulatoryassessmentandapproval.Workingwithinthedesignspaceisnotconsideredasachange.Movementoutofthedesignspaceisconsideredtobeachangeandwouldnormallyinitiatearegulatorypostapprovalchangeprocess.药物开发研究过程中所获得的信息是风险评估的基础。质量是通过设计建立起来的，而不是通过对产品的检测得来的，认识这一点是很重要的。开发过程中的配方和生产工艺的变更应当被看成是获得更多额外知识的机会，以进一步支持设计空间的建立。包括从失败实验中获得的知识也是有用的，也可以用于支持所选择的产品及其生产工艺。ThePharmaceuticalDevelopmentsectionshoulddescribetheknowledgethatestablishesthatthetypeofdosageformselectedandtheformulationproposedaresuitablefortheintendeduse.Thissectionshouldincludesufficientinformationineachparttoprovideanunderstandingofthedevelopmentofthedrugproductanditsmanufacturingprocess.Summarytablesandgraphsareencouragedwheretheyaddclarityandfacilitatereview.药物开发一章应当阐述为满足申请中所规定的目的，建立所选择的剂型和拟定的配方的知识基础。在本章节中的每一个部分都应当要包括足够的资料用以理解制剂及其生产工艺的开发。鼓励使用表格和图表进行概述。Ataminimum,thoseaspectsofdrugsubstances,excipients,containerclosuresystems,andmanufacturingprocessesthatarecriticaltoproductqualitysho