usp36-467溶剂残留-中英文版

467溶剂残留简介：INTRODUCTIONThisgeneralchapterappliestoexistingdrugsubstances,excipients,andproducts.Allsubstancesandproductsaresubjecttorelevantcontrolofsolventslikelytobepresentinasubstanceorproduct.本章节适用于现有的原料药，辅料和制剂。应对原料药或制剂产品中可能存在溶剂的所有原料及制剂产品进行控制。Wherethelimitstobeappliedcomplywiththosegivenbelow,testsforresidualsolventsarenotgenerallymentionedinspecificmonographs,becausethesolventsemployedmayvaryfromonemanufacturertoanother.当限值与下面提供的数值相符合，残留溶剂的测试方法一般不会在专论中特别，因为不同制造商所使用的溶剂不同。Theobjectiveofthisgeneralchapteristoprovideacceptableamountsofresidualsolventsinpharmaceuticalsforthesafetyofthepatient.Thechapterrecommendstheuseoflesstoxicsolventsanddescribeslevelsconsideredtobetoxicologicallyacceptableforsomeresidualsolvents.本指导原则旨在介绍药物中残留溶剂在保证人体安全条件下的可接受量，指导原则建议使用低毒的溶剂，提出了一些残留溶剂毒理学上的可接受水平。Forpharmacopeialpurposes,residualsolventsinpharmaceuticalsaredefinedasorganicvolatilechemicalsthatareusedorproducedinthemanufactureofdrugsubstancesorexcipients,orinthepreparationofdrugproducts.Theresidualsolventsarenotcompletelyremovedbypracticalmanufacturingtechniques.Appropriateselectionofthesolventforthesynthesisofadrugsubstanceoranexcipientmayenhancetheyield,ordeterminecharacteristicssuchascrystalform,purity,andsolubility.Therefore,thesolventmaysometimesbeacriticalelementinthesyntheticprocess.Thisgeneralchapterdoesnotaddresssolventsdeliberatelyusedasexcipients,nordoesitaddresssolvates.However,thecontentofsolventsinsuchproductsshouldbeevaluatedandjustified.药物中的残留溶剂在此定义为在原料药或辅料的生产中，以及在制剂制备过程中产生或使用的有机挥发性化合物，它们在工艺中不能完全除尽。在合成原料药中选择适当的溶剂可提高产量或决定药物的性质，如结晶型、纯度和溶解度。因此有时溶剂是合成中非常关键的因素。通用章节中并没有将溶剂作为辅料或溶剂化物。然而在这些制剂中的溶剂含量也应进行评估和判定。Becauseresidualsolventsdonotprovidetherapeuticbenefit,theyshouldberemoved,totheextentpossible,tomeetingredientandproductspecifications,goodmanufacturingpractices,orotherquality-basedrequirements.Drugproductsshouldcontainnohigherlevelsofresidualsolventsthancanbesupportedbysafetydata.Solventsthatareknowntocauseunacceptabletoxicities(Class1,Table1)shouldbeavoidedintheproductionofdrugsubstances,excipients,ordrugproductsunlesstheirusecanbestronglyjustifiedinarisk-benefitassessment.Solventsassociatedwithlessseveretoxicity(Class2,Table2)shouldbelimitedinordertoprotectpatientsfrompotentialadverseeffects.Ideally,lesstoxicsolvents(Class3,Table3)shouldbeusedwherepractical.ThecompletelistofsolventsincludedinthisgeneralchapterisgiveninAppendix1.Thesetablesandthelistarenotexhaustive.ForthepurposesofthisPharmacopeia,whenamanufacturerhasreceivedapprovalfromacompetentregulatoryauthorityfortheuseofanewsolventnotcurrentlylistedinthisgeneralchapter,itistheresponsibilityofthatmanufacturertonotifytheUSPregardingtheidentityofthissolvent,theapprovedresidualsolventlimitinthearticle,andtheappropriatetestprocedureforthisresidualsolventinthearticle.TheUSPwillthenaddressthistopicintheindividualmonograph.WhenanewsolventhasbeenapprovedthroughtheICHprocess,thisnewsolventwillbeaddedtotheappropriatelistinthisgeneralchapter.Atthattime,considerationwillbegivenforremovalofthespecificsolventtestrequirementintheindividualmonograph.出于残留溶剂没有疗效，故所有残留溶剂均应尽可能去以符合产品规范、GMP或其他基本的质量要求。制剂所含残留溶剂的水平不能高于安全值。已知能引起不可接受毒性的溶剂（第一类，表1）应避免在原料、辅料、制剂生产中使用，除非其使用在风险效益评估下得到强力的证明。一些毒性不太大的溶剂（第二类，表2）应限制使用，以防止病人潜在的不良反应。使用低毒溶剂（第三类，表3）较为理想。附录1中列出了指导原则中的全部溶剂。表中所列溶剂并非详尽无遗，其他可能使用的溶剂有待日后补充列入。第一、二类溶剂的建议限度或溶剂的分类会随着新的安全性资料的获得而调整。出于药典目的，当一供应商从主管当局获得未收集在本章列表中的新溶剂批准时，厂家有责任通报美国药典关于此残留溶剂的特性和可接受限度及检查方法。美国药典将在个别专论解决此主题。当一个新的溶剂通过了ICH指南，该溶剂会被添加到本章节适当目录上。到那时将考虑在个别专论中去除专门的溶剂测试要求。Testingofdrugsubstances,excipients,anddrugproductsforresidualsolventsshouldbeperformedwhenproductionorpurificationprocessesareknowntoresultinthepresenceofsuchresidualsolvents.Itisonlynecessarytotestforresidualsolventsthatareusedorproducedinthemanufactureorpurificationofdrugsubstances,excipients,orproducts.指导原则范围包括原料药、辅料或制剂中所含残留溶剂，因此，当生产或纯化过程中会出现这些溶剂时，应进行残留溶剂的检验。也只有在上述情况下，才有必要作溶剂的检查。Althoughmanufacturersmaychoosetotestthedrugproduct,acumulativeproceduremaybeusedtocalculatetheresidualsolventlevelsinthedrugproductfromthelevelsintheingredientsusedtoproducethedrugproduct.Ifthecalculationresultsinalevelequaltoorbelowthatprovidedinthisgeneralchapter,notestingofthedrugproductforresidualsolventsneedbeconsidered.If,however,thecalculatedlevelisabovetherecommendedlevel,thedrugproductshouldbetestedtoascertainwhethertheformulationprocesshasreducedtherelevantsolventleveltowithintheacceptableamount.Adrugproductshouldalsobetestedifaresidualsolventisusedduringitsmanufacture.虽然生产商可以选择性地测定制剂，但也可以从制剂中各成分的残留溶剂水平来累积计算制剂中的残留溶剂。如果计算结果等于或低于本原则的建议水平，该制剂可考虑不检查残留溶剂，但如果计算结果高于建议水平则应进行检测，以确定制剂制备过程中是否降低了有关溶剂的量以达到可接受水平。如果制剂生产中用到某种溶剂，也应进行测定。ForthepurposesofthisPharmacopeia,whenamanufacturerhasreceivedapprovalfromacompetentregulatoryauthorityforahigherlevelofresidualsolvent,itistheresponsibilityofthatmanufacturertonotifytheUSPregardingtheidentityofthissolventandtheapprovedresidualsolventlimitinthearticle.TheUSPwillthenaddressthistopicintheindividualmonograph.该药典指出，当一个制造商从一个权威机构通过一个残留溶剂更高水平的批准，该制造商有责任告知美国药典关于该溶剂的鉴别及残留溶剂限度，美国药典将会在个别专论中解决此主题。SeeAppendix2foradditi