Q3A(R2)-新原料药中的杂质(中英文)

ImpuritiesInNewDrugSubstances新原料药中的杂质Page1of22INTERNATIONALCONFERENCEONHARMONISATIONOFTECHNICALREQUIREMENTSFORREGISTRATIONOFPHARMACEUTICALSFORHUMANUSEICHHARMONISEDTRIPARTITEGUIDELINEIMPURITIESINNEWDRUGSUBSTANCESQ3A(R2)CurrentStep4versiondated25October2006ThisGuidelinehasbeendevelopedbytheappropriateICHExpertWorkingGroupandhasbeensubjecttoconsultationbytheregulatoryparties,inaccordancewiththeICHProcess.AtStep4oftheProcessthefinaldraftisrecommendedforadoptiontotheregulatorybodiesoftheEuropeanUnion,JapanandUSA.ImpuritiesInNewDrugSubstances新原料药中的杂质Page2of22Q3A(R2)DocumentHistoryFirstCodificationHistoryDateNewCodificationNovember2005Q3ApprovalbytheSteeringCommitteeunderStep2andreleaseforpublicconsultation.15March1994Q3AQ3AApprovalbytheSteeringCommitteeunderStep4andrecommendationforadoptiontothethreeICHregulatorybodies.Q3wasrenamedQ3A.30March1995Q3AQ3A(R)ApprovalbytheSteeringCommitteeofthefirstRevisionunderStep2andreleaseforpublicconsultation.7October1999Q3A(R1)Q3A(R)ApprovalbytheSteeringCommitteeofthefirstRevisionunderStep4andrecommendationforadoptiontothethreeICHregulatorybodies.6February2002Q3A(R1)CurrentStep4versionQ3A(R2)ApprovalbytheSteeringCommitteeoftherevisionoftheAttachment2directlyunderStep4withoutfurtherpublicconsultation.25October2006Q3A(R2)ImpuritiesInNewDrugSubstances新原料药中的杂质Page3of22IMPURITIESINNEWDRUGSUBSTANCESICHHarmonisedTripartiteGuidelineHavingreachedStep4oftheICHProcessattheICHSteeringCommitteemeetingon7February2002,thisguidelineisrecommendedforadoptiontothethreeregulatorypartiestoICH.Attachment2hasbeenrevisedon25October2006.TABLEOFCONTENTS1.PREAMBLE............................................................................................................42.CLASSIFICATIONOFIMPURITIES....................................................................43.RATIONALEFORTHEREPORTINGANDCONTROLOFIMPURITIES....................................................................................................63.1OrganicImpurities..........................................................................................63.2InorganicImpurities........................................................................................73.3Solvents............................................................................................................74.ANALYTICALPROCEDURES..............................................................................85.REPORTINGIMPURITYCONTENTOFBATCHES...........................................96.LISTINGOFIMPURITIESINSPECIFICATIONS............................................107.QUALIFICATIONOFIMPURITIES...................................................................128.GLOSSARY...........................................................................................................14ATTACHMENT1........................................................................................................17ATTACHMENT2........................................................................................................18ATTACHMENT3........................................................................................................20ImpuritiesInNewDrugSubstances新原料药中的杂质Page4of22IMPURITIESINNEWDRUGSUBSTANCES新原料药中的杂质1.PREAMBLE序言Thisdocumentisintendedtoprovideguidanceforregistrationapplicationsonthecontentandqualificationofimpuritiesinnewdrugsubstancesproducedbychemicalsynthesesandnotpreviouslyregisteredinaregionormemberstate.Itisnotintendedtoapplytonewdrugsubstancesusedduringtheclinicalresearchstageofdevelopment.Thefollowingtypesofdrugsubstancesarenotcoveredinthisguideline:biological/biotechnological,peptide,oligonucleotide,radiopharmaceutical,fermentationproductandsemi-syntheticproductsderivedtherefrom,herbalproducts,andcrudeproductsofanimalorplantorigin.本文件旨在为化学合成的新原料药（这些新原料药尚未在任何地区或成员国注册）在注册申请时，对其杂质的含量和界定的申报提供指导。本报导原则不适用于临床研究期间所用的新原料药。本文件不涵盖生物／生物制品、肽、寡聚核苷酸。放射性药物、发酵和半合成产品、草药以及来源于动、植物的粗制品。Impuritiesinnewdrugsubstancesareaddressedfromtwoperspectives:新原料药中的杂质分两个方面阐述：ChemistryAspectsincludeclassificationandidentificationofimpurities,reportgeneration,listingofimpuritiesinspecifications,andabriefdiscussionofanalyticalprocedures;and化学方面：包括对杂质的分类和鉴定、杂质生成、规范中杂质的检查项目以及对分析方法的简要讨论。SafetyAspectsincludespecificguidanceforqualifyingthoseimpuritiesthatwerenotpresent,orwerepresentatsubstantiallylowerlevels,inbatchesofanewdrugsubstanceusedinsafetyandclinicalstudies.安全性方面：对用于安全性研究和临床研究的新原料药批次中不存在或含量很低的那些杂质的界定的指南。2.CLASSIFICATIONOFIMPURITIES杂质的分类Impuritiescanbeclassifiedintothefollowingcategories:杂质可分为下列类型:Organicimpurities(process-anddrug-related)有机杂质（与工艺和药物有关的）Inorganicimpurities无机杂质Residualsolvents残留溶剂ImpuritiesInNewDrugSubstances新原料药中的杂质Page5of22Organicimpuritiescanariseduringthemanufacturingprocessand/orstorageofthenewdrugsubstance.Theycanbeidentifiedorunidentified,volatileornon-volatile,andinclude:有机杂质可能会在新原料药的生产过程和（或）储存期间有所增加。这些杂质可能是已确定的或者是未确定的、挥发性的或者非挥发性的。它包括：Startingmaterials起始物By-products副产物Intermediates中间体Degradationproducts降解产物Reagents,ligandsandcatalysts试剂、配位体、催化剂Inorganicimpur