1216 ICH Q3D 元素杂质指南 1解析Word文件下载.docx
《1216 ICH Q3D 元素杂质指南 1解析Word文件下载.docx》由会员分享，可在线阅读，更多相关《1216 ICH Q3D 元素杂质指南 1解析Word文件下载.docx（18页珍藏版）》请在冰豆网上搜索。
Date
ApprovalbytheSteeringCommitteeunderStep2a.
6June2013
ApprovalbytheSteeringCommitteeunderStep2bandreleaseforpublicconsultation.
Postsign-offcorrigendumin:
●
Table4.1WandA1wereremovedfromthelistofincludedelementalimpuritiesinClass2Band3respectively.
TableA2.1theClassforNiwaschangedtoread3insteadof2
14June2013
Postsign-offminoreditorialcorrectionsincluding:
removalofreferencestoAppendix5（pgsi&
13）;
deletionofredundanttext（pg4）;
changeofOption2toOption2a（pg10）;
insertionoftextunderSafetyLimitingToxicity（pg35）;
referenceto“metals”intextand“metal”inTableA4.7titlewith“elementals”and“elements”（pg73）;
anddeletionofheaderTableA4.10（pg75）.
26July2013
Additionoflinenumberstofacilitatetheprovisionofcommentsbystakeholders.
30September2013
ApprovalbytheSteeringCommitteeunderStep4andrecommendationforadoptiontotheICHregulatorybodies.
12November2014
CurrentStep4Version
Corrigendumtocorrect:
themodifyingfactorinthetextofthesafetyassessmentforSelenium（changedto2insteadof10consistentwithSection3.1）;
andtworeferencesforconsistencyinthesafetyassessmentsforBarium（deletedreference）andVanadium（reviewedreference）.
16December2014
Legalnotice:
Thisdocumentisprotectedbycopyrightandmaybeused,reproduced,incorporatedintootherworks,adapted,modified,translatedordistributedunderapubliclicenseprovidedthatICH'
scopyrightinthedocumentisacknowledgedatalltimes.Incaseofanyadaption,modificationortranslationofthedocument,reasonablestepsmustbetakentoclearlylabel,demarcateorotherwiseidentifythatchangesweremadetoorbasedontheoriginaldocument.Anyimpressionthattheadaption,modificationortranslationoftheoriginaldocumentisendorsedorsponsoredbytheICHmustbeavoided.
Thedocumentisprovided"
asis"
withoutwarrantyofanykind.InnoeventshalltheICHortheauthorsoftheoriginaldocumentbeliableforanyclaim,damagesorotherliabilityarisingfromtheuseofthedocument.
Theabove-mentionedpermissionsdonotapplytocontentsuppliedbythirdparties.Therefore,fordocumentswherethecopyrightvestsinathirdparty,permissionforreproductionmustbeobtainedfromthiscopyrightholder.
ICHHarmonisedGuideline
Havingreached
oftheICHProcessattheICHSteeringCommitteemeetingon12November2014,thisguidelineisrecommendedforadoptiontotheregulatorypartiestoICH.
TABLEOFCONTENTS
目录
1.INTRODUCTION
前言
2.SCOPE
范围
3.SAFETYASSESSMENTOFPOTENTIALELEMENTALIMPURITIES
潜在元素杂质的安全评估
3.1PrinciplesoftheSafetyAssessmentofElementalImpuritiesforOral,ParenteralandInhalationRoutesofAdministration
口服、注射和吸入给药中元素杂质安全评估的原则
3.2OtherRoutesofAdministration
其它给药途径
3.3JustificationforElementalImpurityLevelsHigherthananEstablishedPDE
元素杂质水平高于已建立的PDE时的论证
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
通用原则
5.2PotentialSourcesofElementalImpurities
元素杂质的潜在来源
5.3IdentificationofPotentialElementalImpurities
潜在元素杂质的识别
5.4RecommendationsforElementstobeConsideredintheRiskAssessment
建议中风险评估中考虑的元素
5.5Evaluation
评估
5.6SummaryofRiskAssessmentProcess
风险评估过程总结
5.7SpecialConsiderationsforBiotechnologically-DerivedProducts
生物技术衍生产品特殊考虑
6.CONTROLOFELEMENTALIMPURITIES
元素杂质的控制
7.CONVERTINGBETWEENPDESANDCONCENTRATIONLIMITS
PDE和关注限度之间的转换
8.SPECIATIONANDOTHERCONSIDERATIONS
物种形成和其它考虑
9.ANALYTICALPROCEDURES
分析方法
10.LIFECYCLEMANAGEMENT
生命周期管理
GLOSSARY
术语
REFERENCES
参考文献
Appendix1:
MethodforEstablishingExposureLimits
附录1：
建立暴露限度的方法
Appendix2:
EstablishedPDEsforElementalImpurities
附录2：
已建立的元素杂质PDE
Appendix3:
IndividualSafetyAssessments
附录3：
单独安全评估
Appendix4:
IllustrativeExamples
附录4：
举例说明
1.INTRODUCTION
介绍
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会有几个来源，它们可能是有意加入合成反应的催化剂的残留，也可能是作为杂质出现（例如，通过与工艺设备或容器/密闭系统相互反应，或出现在药品的组分中）。
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、为每个毒性关注元素建立PDE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示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。
该方法提供了一个基于风险控制策略的平台来限制药品中的元素杂质。
2.SCOPE
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定义）和含有已有原料药的新药品。
含有纯化后的蛋白质和多肽（包括采用复合或非复合来源生产的蛋白质和多肽）的药品、其衍生物，以及其复方药品（例如，偶合物）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,cellularbloodcomponentsorbloodderivativesincludingplasmaandplasmaderivatives,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。
在有些地区，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
3.1PrinciplesoftheSafetyAssessmentofElementalImpuritiesforOral,ParenteralandInhalationRoutesofAdministration
口服、注射和吸入给药途径的元素杂质安全评估原则
ThemethodusedforestablishingthePDEforeachelementalimpurityisdiscussedindetailinAppendix1.Elementsevaluatedinthisguidelinewereassessedbyreviewingthepubliclyavailabledatacontainedinscientificjournals,governmentresearchreportsandstudies,internationalregulatorystandards（applicabletodrugproducts）andguidance,andregulatoryauthorityresearchandassessmentreports.ThisprocessfollowstheprinciplesdescribedinICHQ3C:
ResidualSolvents.Theavailableinformationwasreviewedtoestablishtheoral,parenteralandinhalationPDEs.Forpracticalpurposes,thePDEstobeappliedtothedrugproductthatarepresentedinAppendix2TableA.2.1havebeenroundedto1or2
升级会员 