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制定人Preparedby审核人Reviewedby批准人Approvedby签名/日期Sign/Date名字Name职务Designation文件编码Doc.No.:颁发日期：IssueDate:生效日期：EffectiveDate:复审日期：ReviewDate:标准操作程序StandardOperatingProcedure替代：Supersedes:页码：第1页共13页PageNo.:1of13标题：稳定性研究程序TITLE:PROCEDUREFORSTABILITYSTUDIES1.0目的Purpose制定一个稳定性研究程序，以确定在推荐包装和储存条件下原料药的复验期和制剂的有效期。TodefineaprocedureforperformingstabilitystudyofDrugSubstance(API)andDrugProduct(DP)forestablishingaRe-testdate/Expirydateintherecommendedpackandstoragecondition.2.0范围Scope2.1此程序适用于公司生产的原料药和制剂的稳定性研究。ThisprocedureappliestostabilitystudiesofDrugSubstancesandDrugProducts.2.2.此程序中涵盖了稳定性研究的环境条件、研究周期和检验频率。Thisprocedurecoversenvironmentalconditions,period/frequencyoftestsforthestabilitystudy.2.3此程序中也包括恒温恒湿箱出现任何故障时的处理方法。Thisprocedurealsomentionsstepstobetakenincaseofanyfailuresorbreakdownsofthestabilitychambers.3.0定义Definitions:3.1稳定性Stability:药物在整个适当的复验期或有效期内，保持它原有的成分，质量和纯度符合既定的质量标准的程度。Thecapacityofadrugsubstancetoremainwithinestablishedspecificationstoensureitsidentity,qualityandpuritythroughouttheretestperiodorexpirationdatingperiod,asappropriate.3.2复验日期RetestDate:文件编码Doc.No.:PageNo.:2of13标题：稳定性研究程序TITLE:PROCEDUREFORSTABILITYSTUDIES制定人Preparedby审核人Reviewedby批准人Approvedby签名/日期Sign/Date名字Name职务DesignationAPI放置一段时间后，再某个给定日期后，API样品需经复验以确保该物料仍然符合其质量标准，并且仍然适用于某个给定制剂产品的生产。Thedate,afterwhich,samplesofthedrugsubstanceshouldbeexaminedtoensurethatthematerialsarestillincompliancewiththespecifications,andthussuitableforuseinthemanufactureofagivendrugproduct.3.3复验期Re-testperiod:一段时期。在这段时期里，该原料药始终符合其质量标准。当该原料药储存在特定的条件下，在该时期内，该原料药仍能用于某个给定制剂产品的生产。这个时期后，一批原料药在供制剂产品生产使用前，应重新检验来确认其是否仍然符合质量标准。Theperiodoftime,duringwhich,thedrugsubstanceisexpectedtoremainwithinitsspecifications.Drugsubstancecanbeusedinthemanufactureofagivendrugproduct,providedthatithasbeenstoredunderdefinedconditions.Afterthisperiod,abatchofdrugsubstancedestinedforuseinthemanufactureofadrugproductshouldbere-testedforcompliancewithspecificationsbeforeuse.3.4Expirydate有效期:制剂容器的标签上注明的日期，在此规定时间内，当该制剂在规定条件下贮存时，该产品仍符合质量标准，超过这一期限则不应当使用。Thedateplacedonthecontainerlabelofadrugproductdesignatingthetimepriortowhichabatchofthedrugproductisexpectedtoremainwithintheapprovedshelflifespecificationifstoredunderdefinedconditions,andafterwhichitmustnotbeused.3.5Productionbatch(Commercialbatch)生产批次（销售批次）:使用工艺技术文件规定的生产设施及设备按生产规模或销售规模生产出来的一批原料药/制剂产品。Abatchofdrugsubstance/drugproductmanufacturedatproduction/commercialscalebyusingproductionequipmentinaproductionfacilityasspecifiedinanapplication.4.0责任Responsibility:4.1QC负责进行稳定性研究样品的分析。TheresponsibilityofperformingtheanalysisofstabilitysampleslieswithQualitycontrol.4.2QA负责监督稳定性计划的执行，负责稳定性数据的审核和评估。文件编码Doc.No.:PageNo.:3of13标题：稳定性研究程序TITLE:PROCEDUREFORSTABILITYSTUDIES制定人Preparedby审核人Reviewedby批准人Approvedby签名/日期Sign/Date名字Name职务DesignationTheresponsibilityformonitoringofstabilityprogramandperformingthereview/evaluationofstabilitydatalieswithQualityAssurance.5.0程序Procedure:稳定性试验/监控的目的是为原料药/制剂的质量在不同环境因素如温度，湿度和光的影响下，随着时间的变化而变化的情况提供证据。以此来确定/评估在推荐的包装和储存条件下原料药的复验期/制剂的有效期。Thepurposeofstabilitytesting/monitoringistoprovideevidenceonhowthequalityofadrugsubstance/drugproductvarieswithtimeundertheinfluenceofavarietyofenvironmentalfactorssuchastemperature,humidity,andlightandalsotodetermine/estimatethere-testperiodofthedrugsubstance/expiryperiodofthedrugproductintherecommendedpackandstorageconditions.5.1批次的选择SelectionofBatches:5.1.1生产批次的前三批（工艺验证批）应进行稳定性研究，此后至少每年一批原料药/制剂（除非当年没有生产）需添加到稳定性监控计划中。那些经过如挤压，微粉化等物理操作的批次也得同时在所要求的稳定性条件下进行稳定性研究。只有经QC批准的批次才能用于稳定性研究。Thestabilitystudyshouldbeperformedonfirstthreecommercialproductionbatches(processvalidationbatches).Thereafteratleastonebatchperyear(unlessnoneisproducedintheyear)shouldbeaddedtothestabilitymonitoringprogram.Batcheswhicharemodifiedbythephysicaloperationslikecompactionand/ormicronizationetc.shouldalsobesubjectedtostabilitystudyatrequiredconditions.OnlybatchesapprovedbyQualityControlshouldbeconsideredforstabilitystudy.5.1.2以下情形的批次要求进行额外的稳定性研究Theadditionalstabilitystudyisrequiredinfollowingconditions:5.1.2.1变更处方或者辅料配比Changeinformulationorpercentageofexcipients.5.1.2.2扩大或缩小验证批次的大小Scale-uporscale-downofthevalidatedbatchsize.5.1.2.3生产工艺变更Changeinmanufacturingprocess5.1.2.4关键工艺步骤的变更Changeincriticalprocesssteps.文件编码Doc.No.:PageNo.:4of13标题：稳定性研究程序TITLE:PROCEDUREFORSTABILITYSTUDIES制定人Preparedby审核人Reviewedby批准人Approvedby签名/日期Sign/Date名字Name职务Designation5.1.2.5返工/重新加工的批次Reprocessed/Reworkedbatches5.1.2.6生产地点/车间/生产线的变化Changeinmanufacturingsite/blockmodule.5.1.2.7使用回收溶剂/回收物质Useofrecoveredsolvent/recoveredmaterial.5.1.2.8原料药的起始物料和内包装材料供应商发生变更ChangeinsourceofAPIstartingmaterial/primarypackagingmaterial.5.1.3在各自的变更控制中应评估稳定性批次的数量，稳定性试验条件，期限和测试频率。Thenumberofbatchestobestudied,stabilityconditions,periodandfrequencyofthestudyshouldbeevaluatedintherespectivechangecontrol.5.2包装容器Containerclosuresystem:5.2.1稳定性样品应储存在与市售包装相类似的容器中。Thestabilitysampleshouldbestoredincontainersthatsimulatethemarketablepack.5.3检验规程Testingmethods:5.3.1稳定性试验的检验方法应经过验证。Thetestmethodsusedforthestabilitytestingshouldbestabilityindicatinganddulyvalidated.5.4检验项目Specif