缓控释口服固体制剂放大和批准后的辅料变更指南

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1、III.COMPONENTSANDCOMPOSITION—NONRELEASECONTROLLINGEXCIPIENT组分和成分--非释放控制辅料Thissectionoftheguidancefocusesonchangesinnonreleasecontrollingexcipientsinthedrugproduct.Formodifiedreleasesolidoraldosageforms,considerationshouldbegivenastowhethertheexcipientiscriticalornotc

2、riticaltodrugrelease.Thesponsorshouldprovideappropriatejustificationsforclaiminganyexcipient(s)asanonreleasecontrollingexcipientintheformulationofthemodifiedreleasesolidoraldosageform.Thefunctionalityofeachexcipientshouldbeidentified.Changesintheamountofthedrugsubsta

3、ncearenotaddressedbythisguidance.Changesincomponentsorcompositionthathavetheeffectofaddinganewexcipientordeletinganexcipientaredefinedatlevel3(definedbelow),exceptasdescribedbelowinSectionIII.A.1.a.Waiverofbioequivalencetestingforachangeincompositionwhichinvolvesonly

4、adifferentcolor,flavororpreservativemaybepermissibleasdescribedin21CFR320.22(d)(4).本指南这部分主要针对药品非释放控制辅料的变更。对于缓控释固体口服制剂，应该对辅料是否为药物释放的关键辅料或非关键辅料进行考虑。发起人如果判定任何辅料为缓控释固体口服制剂中的非释放控制辅料，应该提供相应的理由。应该对每种辅料的功能进行识别。本指南未对药品中原料药量的变更进行规定。对组分或成分的变更中涉及到新增或删除辅料时，归类为3级变更，第III.A.1.a中的情况除

5、外。成分的变更如果只涉及到变更颜色、口味或防腐剂，按照21CFR320.22(d)(4)的规定可能允许豁免生物等效性测试。A.Level1Change一级变更1.DefinitionofLevel级别定义Level1changesarethosethatareunlikelytohaveanydetectableimpactonformulationqualityandperformance.一级变更指那些不太可能对剂型的质量和功效有可检测的影响的变更。Examples:例如a.Deletionorpartialdeletion

6、ofaningredientintendedtoaffectthecolororflavorofthedrugproduct;orchangeintheingredientoftheprintinginktoanotherapprovedingredient.删除或部分删除组分，这个组分会影响药品的颜色或口味；或者将印刷用油墨成分变更为另一种已批准成分。b.Changesinnonreleasecontrollingexcipients,expressedaspercentage(w/w)oftotalformulation,l

7、essthanorequaltothefollowingpercentranges:非释放控制辅料的变更，以总配方的百分比表示，小于等于以下百分比范围：NonreleaseControllingExcipient非释放控制辅料PercentExcipient(w/w)OutOfTotalTargetDosageFormWeight辅料占总剂型重量的百分比Filler填充剂±5Disintegrant崩解剂Starch淀粉Other其他±3±1Binder粘合剂±0.5Lubricant润滑剂CaorMgstearate钙或镁硬脂

8、酸盐Other其他±0.25±1Glidant助流剂Talc滑石粉Other其他FilmCoat包衣±1±0.1±1Thesepercentagesarebasedontheassumptionthatthedrugsubstanceintheproductis