稳定性试验方案

StabilityLab稳定性实验室StabilityStudyProtocolforExhibitBatchofChloroquinePhosphateTabletsUSP,250mg规格为250mg的USP磷酸氯喹片长期、中期及加速稳定性研究方案ProjectNo.项目号DP-ST-001-2008PreparedBy:Date:起草者：日期：ReviewedByQA:Date:审核者：日期：ApprovedBy:Date:StabilityLabPage2/9稳定性实验室批准者：日期：StartingDate:CompletedDate:开始日期：结束日期：StabilityLab稳定性实验室Contents目录StabilityLabPage1/9稳定性实验室StabilityLabPage2/9稳定性实验室1.Purpose目的ThepurposeofstabilitytestingistoprovideevidenceofhowtheQuality,Strength,DegradationProductsandPurityoftheChloroquinePhosphateTabletsUSP,250mgwillchangewithtimeundertheinfluenceofenvironmentalroomtemperatureandrelativehumidityconditions.Datacollectedfromthestabilitystudywillenablerecommendedstorageconditionsandprovidejustificationforestablishingandsubmittingthedatatoregulatoryauthoritiesforapprovingtheshelflifeformarketingpurposes.Inaddition,3monthsofthestabilitydatawillbesubmittedtoUSFDAasrequiredforsubmissionpurposesoftheANDAapplication.此稳定性研究的目的是为了考察磷酸氯喹片在环境因素的影响下(例如：温度和湿度)其性质、规格、降解产物和含量等随时间而变化的规律，依据稳定性研究的数据确定该产品的储藏条件和有效期。2.Scope范围StabilityLabPage3/9稳定性实验室ThisprocedureisapplicabletoFinishedProductStabilityLabatHisunPharmaceutical(Hangzhou)Co.Ltd.Fuyang,Hangzhou.适用于浙江台州海正药业成品药稳定性实验室。3.References参考资料3.1ICHHarmonizedTripartiesGuidelineforStabilityTestingofNewDrugSubstancesandDrugProduct06,2003.[ICHQ1A(R2)]新原料药和新制剂的稳定性测试指南06,2003.[ICHQ1A(R2)]3.2ASSAYMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USP,APIANDCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025A)磷酸氯喹原料药、250mg和500mg片的含量测定方法验证报告。3.3RELATEDSUBSTANCESMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USP,APIANDCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025B)磷酸氯喹原料药、250mg和500mg片有关物质方法验证报告。StabilityLabPage4/9稳定性实验室3.4DISSOLUTIONMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025C)磷酸氯喹250mg和500mg片溶出度方法验证报告。4.GeneralInformation基本信息4.1StabilitySamples稳定性样品4.1.1OneExhibitBatchfor250mgstrengthwillbeincludedinthestabilitystudy.规格为250mg的磷酸氯喹片各一批。4.1.2Onebatchof250mgreferenceproductwillalsobeplacedonstabilitystudy.规格为250mg和的磷酸氯喹对照制剂各一批。StabilityLabPage5/9稳定性实验室4.2ProductOutline样品信息BatchNo.批号Strength规格(mg)PackageSize包装规格BatchSize批量(Tablets)Mfg.Date生产日期Pkg.Date包装日期Manufacturer生产商50Tablets/Bottle100Tablets/Bottle500Tablets/Bottle250360,,000Hisun海正61924A25050Tablets/BottleNANANAWest-ward4.3Formulation处方StabilityLabPage6/9稳定性实验室4.3.1TheformulationofChloroquinePhosphateUSPTablets,250mg,isasfollows:规格为250mg的USP磷酸氯喹片处方如下：Table1.FormulaandbatchsizeBatchsize:360,000tablets(172.8Kg)成分Ingredientsmg/片mg/tabletKg/批Kg/batchManufacturer原料药API*25090IPCA微晶纤维素(102)MCC(Type102)15455.44JRS二水磷酸氢钙DibasicCalciumPhosphateDihydrate4014.4JRS滑石粉Talc248.64MerckStabilityLabPage7/9稳定性实验室胶体二氧化硅ColloidalSiliconDioxide(Aerosil200)4.81.728Degussa硬脂酸镁MagnesiumStearate7.22.592PeterGreven总量Total480172.84.4不适用StabilityLabPage8/9稳定性实验室4Container-ClosureSystems包装PackingMaterial包材BatchNo.批号PackingMaterialDescription包材描述Manufacturer供应商60ccHDPEbottle60ccHDPE瓶WE070601Bottle:60ccopaquewhiteHDPEroundbottle瓶：60cc白色不透明HDPE圆瓶Cap:φ32mmopaquewhiteCRCcap,withinductionsealing盖：φ32mm白色不透明CRC圆盖，带内封TriveniPolymersPvt.Ltd(Bottle)VBCInc.(CRCCap)Tekniplex(Liner)上海海昌120ccHDPEbottle120ccHDPE瓶KQ080101Bottle:120ccopaquewhiteHDPEroundbottle瓶：120cc白色不透明HDPE圆瓶Cap:φ36mmopaquewhiteCRCcap,withinductionsealingTriveniPolymersPvt.Ltd(Bottle)VBCInc.(CRCCap)StabilityLabPage9/9稳定性实验室盖：φ36mm白色不透明CRC圆盖，带内封Tekniplex(Liner)上海海昌450ccHDPEbottle450ccHDPE瓶WA080101Bottle:450ccopaquewhiteHDPEroundbottle瓶：450cc白色不透明HDPE圆瓶Cap:φ58mmopaquewhiteCTcap,withinductionsealing盖：φ58mm白色不透明CT圆盖，带内封TriveniPolymersPvt.Ltd(BottleandCap)Tekniplex(Liner)上海海昌4.5Labeling标签TheProductName,BatchNumber,Strength,StorageCondition,PackageType,No.andStoredby/StoreDatewillbeincludedonthelabel.标签应包括品名、批号、规格、储存条件、包装类型、编号及储存人/日期。FPStabilityLabStabilityLabPage10/9稳定性实验室成品药稳定性实验室ProductName品名：BatchNo./Strength批号/规格：StorageCondition储存条件：Packagetype包装类型：No.编号：StoredBy/Date储存人/日期：StabilityLabPage11/9稳定性实验室4.6SamplesandPackage样品与包装Thedrugproductforstabilitytestingwillbepackagedinthesameconfigurationasthatforthemarketingpurposes.稳定性研究样品与上市的包装要一致，同时药品的大包装也进行稳定性实验。5.StabilityTesting稳定性试验5.1SampleReceiptandStorage样品接收与储存AssoonasreceivedfromQAorFormulationDevelopmentDepartment,eachbatchofsampleswillbelabeledandplacedinstoragechambersundertherequiredconditions.从QA部门或者制剂研发部门接收到样品，按规定条件贴好标签并储存。BatcStrPackageStorageConditionSampleStabilityLabPage12/9稳定性实验室hNo.批号ength规格Size包装规格储存条件Size样品数量25℃±2℃/60%RH±5%RH23Bottles/Packagesize30℃±2℃/65%RH±5%RH15Bottles/Packagesize50Tablets/Bottle100Tablets/Bottle500Tablets/Bottle40℃±2℃/75%RH±5%RH12Bottles/Packagesize250mg25℃±2℃/60%RH±5%RH2Bottles7011671250mg50Tablets/Bottle40℃±2℃/75%RH±5%RH1BottleNote注StabilityLabPage13/9稳定性实验室1.RLDrecommendedstorageconditionasStoreat20-25℃(68-77F)(ControlledRoomTemperature)andProtectfromlightandmoisture.室温参照仓库温度要求，室温通常不超过30℃。Thereferenceproduct(RLD)willalsobelabeledandplacedinstoragechambersundertherequiredconditionsatthesametime.同时也将对照制剂（RLD）按规定条件贴好标签并储存。5.2StorageConditionsandTestingTimePoints储存条件和检测点StudyType稳定性类型StorageCondition储存条件Period周期TimePoints（months）2时间点（月）LongTerm长期25℃±2℃/60%RH±5%RH24Months0,3,6,9,12,18,24Interme30℃±2℃/65%RH120,3,6,9,12StabilityLabPage14/9稳定性实验室diate1中期±5%RHMonthsAccelerated加速40℃±2℃/75%RH±5%RH3Months0,1,2,3Note注1.Intermediatestabilitysampleswillbepulledandanalyzedonlyiftheambient(longterm)stabilityresultsfallsoutsideofthesetspecifications.当完成加速稳定性研究且无重大变化时，停止中期稳定性研究。2.ReferencesampleswillbepulledoutandanalysedaccordingtoSOPARD-ST009.对照样品依据SOPARD-ST009取样检测。5.3Sampling取样StrenPackageStorageConditionSamplingStabilityLabPage15/9稳定性实验室gth规格Size包装规格储存条件Size取样量25℃±2℃/60%RH±5%RH30℃±2℃/65%RH±5%RH250mg50Tablets/Bottle100Tablets/Bottle*500Tablets/Bottle40℃±2℃/75%RH±5%RH1BottleTheadditionalsamplespackedinbottleswillbedestroyedaccordingtorelatedSOPsbysupervisorofstabilityLabortheappointedpersonaftercompletingeachtimepointtest.Andthesamplespackedinpailwillbesealedagainandstoredinwarehouse.瓶装样品在每个检测点检验完毕后，样品如果有剩余，应交回给稳定性实验室主管或指定人员做销毁处理。桶装样品封好继续在仓库中储存。Note注*Usuallythesesamplesarenotusedfortesting,unlessresultsonotherconditionsarenotsatisfactoryorfailthespecifications.正常情况下不取样检测，除非客户有特殊要求。StabilityLabPage16/9稳定性实验室5.4TestingMatrix稳定性测试项目表TestingMatrix测试项目表Long-termConditions长期稳定性IntermediateConditions中期稳定性AcceleratedCondition加速稳定性50Tablets/BottleTTT100Tablets/Bottle250mg500Tablets/BottleTTT5.5ParametersandAcceptanceCriteria(toberevisedasperspecifications)检测项目及质量标准addMicrotestingattime0andendoflifeItems检测项目Method方法Specification质量标准StabilityLabPage17/9稳定性实验室250mgWhiteuncoatedtablets,roundbiconvexdebossedASCover109ononeside,bisectedononeside.白色非包衣片，圆形两面凸的，片一面刻字“ASC109”，另一面中间带有刻痕。Appearance性状ESS-GM026Watercontent*水分ESS-GM036.待定。Dissolution溶出度ESS-STM-011CNotlessthan75%(Q)ofthelabeledamountin45minutes.45分钟内溶出度不少于75%（Q）。Assay含量ESS-STM-011AChloroquinePhosphateTabletscontainnotlessthan93.0percentandnotmorethan107.0percentofthelabeledamountofC18H26ClN3·2H3PO4.应为标示量的93.0%-107.0%。StabilityLabPage18/9稳定性实验室Relatedsubstances/degradationproducts有关物质/降解产物ESS-STM-011BIndividualunspecifiedimpurityisNMT0.10%.单个未知杂质不得过0.10%。TotalimpurityisNMT1.0%.总杂质不得过1.0%。*ItisonlyapplicabletoChloroquinePhosphateTablets,500mg.仅适用于500mg磷酸氯喹片。StabilityLabPage19/9稳定性实验室5.6Relatedsubstances/Degradationproducts有关物质/降解产物Maximumdailydose最大日剂量Reportingthreshold报告限Identificationthreshold鉴定限Qualificationthreshold界定限1,000mgLOQ0.2%0.2%6.DataPresentation数据汇总ThestabilitydatawillbepresentedintheStabilitySummaryReport(seeexamplesinAppendixB).StabilitySummaryReportwillbecompletedforeachstorageconditionofdrugproductplacedonstability.稳定性研究数据填写在稳定性研究汇总报告中（见附件B），按产品的储存条件分别填写附件B。7.Reporting报告StabilityLabPage20/9稳定性实验室7.1IntermediateReports中期报告ThestabilitylaboratorywillissueintermediatereportsaccordingtoAppendixBwithin30daysateachtestingtimepoints.Thewrittenexplanationshouldbeprovidediftestresultisnotreportedwithinrequiredtime.在检测点30天内对该检测点数据按附件B进行中期报告，如果没有按规定时间进行报告，必须有书面说明。7.2SummaryReport 总结 初级经济法重点总结下载党员个人总结TXt高中句型全总结.doc高中句型全总结.doc理论力学知识点总结pdf 报告Oncompletionofthestudy,thestabilitylaboratorywillissueareportsummarywithsignatureanddateaccordingtoappendixB.在完成稳定性研究后，按照附件B进行总结报告。7.3StabilityDocuments稳定性文件夹Thestabilitydocumentsshouldincludethefollowing,butnotlimitedto:StabilityLabPage21/9稳定性实验室稳定性文件夹应该包括但不局限于以下 内容 财务内部控制制度的内容财务内部控制制度的内容人员招聘与配置的内容项目成本控制的内容消防安全演练内容 ：●Nameanddescriptionofdrugproduct品名及产品描述●Manufacturer,batchNo.,batchsize(s),mfg.date,packagetypeandpackagedate产品生产厂商、批号、批量、生产日期、包装类型和包装日期●Drugproductstrength产品规格●APImanufacturer/supplierAPI厂商●Methodvalidationreports方法验证报告●Allanalyticalandphysicaldata,includingidentitytest,chemistryassay,physicaltest所有检验数据，包括鉴别、含量及测试。●AcceptancecriteriaStabilityLabPage22/9稳定性实验室质量标准●Whereapplicable,adescriptionofstatisticalmethodologyapplied,includingparametersestimated,assumptionsmade,andmodel(s)used;transformations,calculationsoroperationsperformedonthedata;anexplanationandstatementoftheconclusionsdrawnfromthestatisticalanalysisrelativetotheobjective(s)ofthestudy;thename(s)ofsoftwareemployedinthestatisticalevaluations.实验数据和结果所采用的分析方法、统计方法、转换计算、假设、采用模式及相应软件信息等，所得结论及相关说明。●Thenumbersandtitlesofstandardoperatingproceduresapplied采用的Sop编号和标题●Asignedanddatedstatementofintermediatereports中期报告●Therecordsofallsamples,originaldataandtestingreports样品的原始数据和测试报告●RequiringformforstabilitystudyStabilityLabPage23/9稳定性实验室稳定性研究申请表8.Appendix附件AppendixB1:STABILITYSTUDYSUMMARYREPORT(Hisunproducts/250mg)附件B1：稳定性研究报告(海正产品/250mg)AppendixB2:STABILITYSTUDYSUMMARYREPORT(Brand)附件B3：稳定性研究报告(Brand)