ICH-Q3D_中英_step-4-最新版

1学习之名（译注）GUIDELINEFORELEMENTALIMPURITIES元素杂质指南TABLEOFCONTENTS目录1.INTRODUCTION简介2.SCOPE范围3.SAFETYASSESSMENTOFPOTENTIALELEMENTALIMPURITIES潜在元素杂质的安全性评估3.1PrinciplesoftheSafetyAssessmentofElementalImpuritiesforOral,ParenteralandInhalationRoutesofAdministration口服、注射和吸入给药途径的元素杂质安全性评估规则3.2OtherRoutesofAdministration其他给药途径3.3JustificationforElementalImpurityLevelsHigherthananEstablishedPDE元素杂质水平高于已建立的PDE阈值的合理性说明3.4ParenteralProducts注射用药4.ELEMENTCLASSIFICATION元素分类5.RISKASSESSMENTANDCONTROLOFELEMENTALIMPURITIES元素杂质的风险评估和控制5.1GeneralPrinciples通用准则5.2PotentialSourcesofElementalImpurities元素杂质潜在的来源5.3IdentificationofPotentialElementalImpurities潜在元素杂质的识别5.4RecommendationsforElementstobeConsideredintheRiskAssessment建议在风险评估中考虑的元素5.5Evaluation评估5.6SummaryofRiskAssessmentProcess风险评估总结5.7SpecialConsiderationsforBiotechnologically-DerivedProducts生物技术衍生产品的特殊考虑6.CONTROLOFELEMENTALIMPURITIES元素杂质控制7.CONVERTINGBETWEENPDESANDCONCENTRATIONLIMITSPDE值和浓度限的相互转换8.SPECIATIONANDOTHERCONSIDERATIONS元素形态和其他考虑9.ANALYTICALPROCEDURES分析方法10.LIFECYCLEMANAGEMENT生命周期管理2学习之名（译注）GUIDELINEFORELEMENTALIMPURITIES元素杂质指南Q3DQ3D1.INTRODUCTION简介Elementalimpuritiesindrugproductsmayarisefromseveralsources;theymayberesidualcatalyststhatwereaddedintentionallyinsynthesisormaybepresentasimpurities(e.g.,throughinteractionswithprocessingequipmentorcontainer/closuresystemsorbybeingpresentincomponentsofthedrugproduct).Becauseelementalimpuritiesdonotprovideanytherapeuticbenefittothepatient,theirlevelsinthedrugproductshouldbecontrolledwithinacceptablelimits.Therearethreepartsofthisguideline:theevaluationofthetoxicitydataforpotentialelementalimpurities;theestablishmentofaPermittedDailyExposure(PDE)foreachelementoftoxicologicalconcern;andapplicationofarisk-basedapproachtocontrolelementalimpuritiesindrugproducts.Anapplicantisnotexpectedtotightenthelimitsbasedonprocesscapability,providedthattheelementalimpuritiesindrugproductsdonotexceedthePDEs.ThePDEsestablishedinthisguidelineareconsideredtobeprotectiveofpublichealthforallpatientpopulations.Insomecases,lowerlevelsofelementalimpuritiesmaybewarrantedwhenlevelsbelowtoxicitythresholdshavebeenshowntohaveanimpactonotherqualityattributesofthedrugproduct(e.g.,elementcatalyzeddegradationofdrugsubstances).Inaddition,forelementswithhighPDEs,otherlimitsmayhavetobeconsideredfromapharmaceuticalqualityperspectiveandotherguidelinesshouldbeconsulted(e.g.,ICHQ3A).药品中的元素杂质可能有多种来源，可能是合成过程中有意加入的金属催化剂残留或以杂质形式出现（例如，通过与工艺设备或容器/密闭系统的相互反应，或出现在药品成分中）。由于元素杂质并不给患者提供任何治疗益处，其在药品中的水平应被控制在可接受限度以内。本指南分为三个部分：潜在元素杂质毒性数据的评估、为每个有毒性风险的元素建立PDE（日最大暴露量）值、以及应用基于风险的方法来控制药品中的元素杂质。如果药品中的元素杂质没有超过PDE阈值的话，申报人不需要根据其工艺能力加严元素杂质的限度。本指南中建立的PDE阈值足以保护所有患者人群的公共健康。在有些情况下，如果毒性阈值以下的元素杂质水平表现出对药品的其它质量属性有影响（例如，对药品降解有催化作用的元素），则可能需要保证一个更低的元素杂质水平。另外，对于具有较高PDE值的元素，可能需要从药品质量的角度，以及要参照的其它指南（例如ICHQ3A），来考虑其它的控制限度。ThisguidelinepresentsaprocesstoassessandcontrolelementalimpuritiesinthedrugproductusingtheprinciplesofriskmanagementasdescribedinICHQ9.Thisprocessprovidesaplatformfordevelopingarisk-basedcontrolstrategytolimitelementalimpuritiesinthedrugproduct.本指南给出一个采用ICHQ9中所述风险管理原则来评估和控制药品中元素杂质的方法。该方法为发展基于风险的控制策略来限制药品中的元素杂质的过程提供了一个平台。2.SCOPE范围Theguidelineappliestonewfinisheddrugproducts(asdefinedinICHQ6AandQ6B)andnewdrugproductscontainingexistingdrugsubstances.Thedrugproductscontainingpurifiedproteinsandpolypeptides(includingproteinsandpolypeptidesproducedfromrecombinantornon-recombinantorigins),theirderivatives,andproductsofwhichtheyarecomponents(e.g.,conjugates)arewithinthescopeofthisguideline,asaredrugproductscontainingsyntheticallyproducedpolypeptides,polynucleotides,andoligosaccharides.本指南适用于新的制剂产品（如ICHQ6A和Q6B中定义的产品）和含有已有原料药的新药品。含有纯化后的蛋白质和多肽（包括重组或非重组来源的蛋白质和多肽）的药品及其衍生物，以及其复方药品（例如，偶合物）都在本指南适用范围内。含有合成多肽、多核苷酸和低聚糖的药品也适用本指南。Thisguidelinedoesnotapplytoherbalproducts,radiopharmaceuticals,vaccines,cellmetabolites,DNAproducts,allergenicextracts,cells,wholeblood,cellularbloodcomponentsorbloodderivatives3学习之名（译注）includingplasmaandplasmaderivatives,dialysatesolutionsnotintendedforsystemiccirculation,andelementsthatareintentionallyincludedinthedrugproductfortherapeuticbenefit.Thisguidelinedoesnotapplytoproductsbasedongenes(genetherapy),cells(celltherapy)andtissue(tissueengineering).Insomeregions,theseproductsareknownasadvancedtherapymedicinalproducts.本指南不适用于草药产品、放射性药品、疫苗、细胞代谢物、DNA产品、过敏提取物、细胞、全血、细胞血成分或血液制品，包括血浆和血浆制品、非系统循环用透析液，和用于治疗用途加入的元素。本指南不适用于基于基因（基因治疗）、细胞（细胞治疗）和组织（组织工程）的药品。在一些领域，这些产品是作为先进治疗药品的。Thisguidelinedoesnotapplytodrugproductsusedduringclinicalresearchstagesofdevelopment.Asthecommercialprocessisdeveloped,theprinciplescontainedinthisguidelinecanbeusefulinevaluatingelementalimpuritiesthatmaybepresentinanewdrugproduct.本指南不适用于研发的临床研究阶段药品。由于商业过程是在不断发展的，评估新药中可能出现的元素杂质时也可应用本指南中的原则。ApplicationofQ3Dtoexistingproductsisnotexpectedpriorto36monthsafterpublicationoftheguidelinebyICH.在本指南由ICH发布后36个月内，不需要对已有产品应用Q3D。3.SAFETYASSESSMENTOFPOTENTIALELEMENTALIMPURITIES潜在元素杂质的安全性评估3.1PrinciplesoftheSafetyAssessmentofElementalImpuritiesforOral,ParenteralandInhalationRoutesofAdministration口服、注射和吸入给药途径的元素杂质安全性评估准则Themethodus