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I.INTRODUCTIONThisguidanceprovidesrecommendationstoapplicantsonsubmittinganalyticalprocedures,validationdata,andsamplestosupportthedocumentationoftheidentity,strength,quality,purity,andpotencyofdrugsubstancesanddrugproducts.1.绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。Thisguidanceisintendedtoassistapplicantsinassemblinginformation,submittingsamples,andpresentingdatatosupportanalyticalmethodologies.Therecommendationsapplytodrugsubstancesanddrugproductscoveredinnewdrugapplications(NDAs),abbreviatednewdrugapplications(ANDAs),biologicslicenseapplications(BLAs),productlicenseapplications(PLAs),andsupplementstotheseapplications.本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。这些建议适用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。TheprinciplesalsoapplytodrugsubstancesanddrugproductscoveredinTypeIIdrugmasterfiles(DMFs).Ifadifferentapproachischosen,theapplicantisencouragedtodiscussthematterinadvancewiththecenterwithproductjurisdictiontopreventtheexpenditureofresourcesonpreparingasubmissionthatmaylaterbedeterminedtobeunacceptable.这些原则同样适用于二类DMF所涉及的原料药和制剂。如果使用了其它方法，鼓励申请者事先和FDA药品评审中心的官员进行讨论，以免出现这种情况，那就是花了人力物力所准备起来的递交资料后来发现是不可用的。Theprinciplesofmethodsvalidationdescribedinthisguidanceapplytoalltypesofanalyticalprocedures.However,thespecificrecommendationsinthisguidancemaynotbeapplicabletocertainuniqueanalyticalproceduresforproductssuchasbiological,biotechnological,botanical,orradiopharmaceuticaldrugs.本指南中所述的分析方法验证的原则适用于各种类型的分析方法。但是，本指南中特定的建议可能不适用于有些产品所用的特殊分析方法，如生物药，生物技术药，植物药或放射性药物等。Forexample,manybioassaysarebasedonanimalchallengemodels,39immunogenicityassessments,orotherimmunoassaysthathaveuniquefeaturesthatshouldbeconsideredwhensubmittinganalyticalprocedureandmethodsvalidationinformation.比如说，许多生物分析是建立在动物挑战模式，免疫原性评估或其它有着独特特性的免疫分析基础上的，在递交分析方法和分析方法验证资料时需考虑这些独特的性质。Furthermore,specificrecommendationsforbiologicalandimmunochemicalteststhatmaybenecessaryforcharacterizationandqualitycontrolofmanydrugsubstancesanddrugproductsarebeyondthescopeofthisguidancedocument.而且，许多原料药和制剂的界定和质量控制所需的生物和免疫化学检测并不在本指南的范围之内。Althoughthisguidancedoesnotspecificallyaddressthesubmissionofanalyticalproceduresandvalidationdataforrawmaterials,intermediates,excipients,containerclosurecomponents,andothermaterialsusedintheproductionofdrugsubstancesanddrugproducts,validatedanalyticalproceduresshouldbeusedtoanalyzethesematerials.尽管本指南并不专门叙述原料，中间体，赋形剂，包装材料及原料药和制剂生产中所用的其它物料的分析方法及分析方法验证资料的递交，但是应该应用验证过的分析方法来分析检测这些物质。Forquestionsonappropriatevalidationapproachesforanalyticalproceduresorsubmissionofinformationnotaddressedinthisguidance,applicantsshouldconsultwiththeappropriatechemistryreviewstaffatFDA.对于本指南中未提及的关于分析方法验证和资料提交方面的问题，请向FDA相关的化学评审人员咨询。Thisguidance,whenfinalized,willreplacetheFDAguidanceforindustryonSubmittingSamplesandAnalyticalDataforMethodsValidation(February1987).本指南，一旦定稿，将取代FDA于1987年2月份发布的工业指南：分析方法验证所需提交的样品和分析资料。II.BACKGROUNDEachNDAandANDAmustincludetheanalyticalproceduresnecessarytoensuretheidentity,strength,quality,purity,andpotencyofthedrugsubstanceanddrugproduct,includingbioavailabilityofthedrugproduct(21CFR314.50(d)(1)and314.94(a)(9)(i)).II.背景每个NDA和ANDA都必需包括必要的分析方法以确保原料药和制剂的认定，剂量，质量，纯度和效力，还包括制剂的生物利用度(21CFR314.50(d)(1)和314.94(a)(9)(i))。FDA验证文件现场备查，可以不与DMF一起交。Datamustbeavailabletoestablishthattheanalyticalproceduresusedintestingmeetproperstandardsofaccuracyandreliability(21CFR211.165(e)and211.194(a)(2)).必须要有资料来论证所用的分析方法是符合一定的准确度和可靠性标准的。Methodsvalidationistheprocessofdemonstratingthatanalyticalproceduresaresuitablefortheirintendeduse.Themethodsvalidationprocessforanalyticalproceduresbeginswiththeplannedandsystematiccollectionbytheapplicantofthevalidationdatatosupporttheanalyticalprocedures.分析方法验证是论证某一分析方法适用于其用途的过程。分析方法的验证过程是从申请者有计划地系统性收集验证资料以支持分析方法开始的。ThereviewchemistevaluatestheanalyticalproceduresandvalidationdatasubmittedintheNDAorANDA.审评化学家会对NDA或ANDA中的分析方法和验证资料进行评审。OnrequestfromFDA,anNDAorANDAapplicantmustsubmitsamplesofdrugproduct,drugsubstance,noncompendialreferencestandards,andblankssothattheapplicant'sdrugsubstanceanddrugproductanalyticalprocedurescanbeevaluatedbyFDAlaboratories(21CFR314.50(e)and314.94(a)(10)).一旦FDA有要求，则NDA或ANDA的申请者必须提交制剂，原料药，非药典对照品和空白以使FDA实验室能对申请者所用分析方法进行评审(21CFR314.50(e)and314.94(a)(10))。TheFDAlaboratoryanalysisdemonstratesthattheanalyticalproceduresarereproduciblebylaboratorytesting.Thereviewchemistsandlaboratoryanalystsdeterminethesuitabilityoftheanalyticalproceduresforregulatorypurposes.FDA实验室的分析会论证该分析方法在实验室内是可以重现的。审评化学家和实验室分析家会从法规的角度确定该分析方法的适用性。FDAinvestigatorsinspecttheanalyticallaboratorytestingsitestoensurethattheanalyticalproceduresusedforreleaseandstabilitytestingcomplywithcurrentgoodmanufacturingpractices(CGMPs)(21CFRpart211)orgoodlaboratorypractices(GLPs)(21CFRpart58),asappropriate.FDA检查官会对分析实验室进行检查确保用于放行和稳定性实验的分析方法符合现行的GMP（21CFRpart211)和GLP(21CFRpart58)。EachBLAandPLAmustincludeafulldescriptionofthemanufacturingmethods,includinganalyticalprocedures,thatdemonstratethatthemanufacturedproductmeetsprescribedstandardsofsafety,purity,andpotency(21CFR601.2(a)and601.2(c)(1)(iv)).每个BLA和PLA都必须要有详细的生产工艺描述，包括分析方法，以说明所生产的产品是符合规