稳定性试验方案

StabilityStudyProtocolforExhibitBatchof

ChloroquinePhosphateTabletsUSP,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:批准者：日期：StartingDate: CompletedDate:开始日期：结束日期：ContentsTOC\o"1-5"\h\zPurpose目的 1Scope范围 1References 参考资料 1GeneralInformation基本信\o"CurrentDocument"StabilitySamples稳定性研究样品 1ProductOutline样品概述 3\o"CurrentDocument"Formulation处方 3Container-ClosureSystems包装 4\o"CurrentDocument"Labeling标签 4\o"CurrentDocument"SamplesandPackage样品与包装 5StabilityTesting 稳定性测试 5\o"CurrentDocument"SampleReceiptandStorage样品接收与储存 5StorageConditionsandTestingTime Points 储存条件与检测时间点 5\o"CurrentDocument"Sampling取样 6TestingMatrix稳定性测试项目表 7ParametersandAcceptanceCriteria 检测项目及质量标准 7Degradationproducts降解产物 8Data Presentation数据汇总 8Reporting报告 8\o"CurrentDocument"IntermediateReports中期报告 8\o"CurrentDocument"SummaryReport总结报告 8\o"CurrentDocument"StabilityDocuments稳定性文件夹 8A p p e n d i x 附件 9Purpose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：温度和湿囿其性质、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。Scope范围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。References参考资料ICHHarmonizedTripartiesGuidelineforStabilityTestingofNewDrugSubstancesandDrugProduct06,2003.[ICHQ1A(R2)]新原料药和新制剂的稳定性测试指南06,2003.[ICHQ1A(R2)]ASSAYMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,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。RELATEDSUBSTANCESMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,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。DISSOLUTIONMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025C)磷酸氯喹250mg和500mg片溶出度方法验证报告。GeneralInformation基本信息StabilitySamples稳定性样品OneExhibitBatchfor250mgstrengthwillbeincludedinthestabilitystudy.规格为250mg的磷酸氯喹片各一批。Onebatchof250mgreferenceproductwillalsobeplacedonstabilitystudy.规格为250mg和的磷酸氯喹对照制剂各一批。ProductOutline样品信息BatchNo.批号Strength规格(mg)PackageSize包装规格BatchSize批：B(Tablets)Mfg.Date生产日期Pkg.Date包装日期Manufacturer生产商25050Tablets/Bottle360,,000Hisun海正100Tablets/Bottle500Tablets/Bottle61924A25050Tablets/BottleNANANAWest-wardFormulation处方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Talc248.64Merck胶体二氧化硅ColloidalSiliconDioxide(Aerosil200)4.81.728Degussa硬脂酸镁MagnesiumStearate7.22.592PeterGreven总量Total480172.8不适用

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:①32mmopaquewhiteCRCcap,withinductionsealing盖：①32mm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:①36mmopaquewhiteCRCcap,withinductionsealing盖：①36mm白色不透明CRC圆盖，带内封TriveniPolymersPvt.Ltd(Bottle)VBCInc.(CRCCap)Tekniplex(Liner)上海海昌450ccHDPEbottle450ccHDPE瓶WA080101Bottle:450ccopaquewhiteHDPEroundbottle瓶：450cc白色不透明HDPE圆瓶Cap:①58mmopaquewhiteCTcap,withinductionsealing盖：桢8mm白色不透明CT圆盖，带内封TriveniPolymersPvt.Ltd(BottleandCap)Tekniplex(Liner)上海海昌Labeling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。IHISUNFPStabilityLab、■萌正药业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:SamplesandPackage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。StabilityTesting稳定性试验SampleReceiptandStorage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。BatchNo.批号Strength规格PackageSize包装规格StorageCondition储存条件SampleSize样品数量250mg50Tablets/Bottle100Tablets/Bottle500Tablets/Bottle25℃±2℃/60%RH±5%RH23Bottles/Packagesize30℃±2℃/65%RH±5%RH15Bottles/Packagesize40℃±2℃/75%RH±5%RH12Bottles/Packagesize7011671250mg50Tablets/Bottle25℃±2℃/60%RH±5%RH2Bottles40℃±2℃/75%RH±5%RH1BottleNote注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%RH24Months0,3,6,9,12,18,24Intermediate1中期30℃±2℃/65%RH±5%RH12Months0,3,6,9,12Accelerated加速40℃±2℃/75%RH±5%RH3Months0,1,2,3Note注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。ReferencesampleswillbepulledoutandanalysedaccordingtoSOPARD-ST009.对照样品依据SOPARD-ST009取样检测。Sampling取样Strength^格PackageSize包装规格StorageCondition储存条件SamplingSize取样量250mg50Tablets/Bottle100Tablets/Bottle*500Tablets/Bottle25℃±2℃/60%RH±5%RH1Bottle30℃±2℃/65%RH±5%RH40℃±2℃/75%RH±5%RHTheadditionalsamplespackedinbottleswillbedestroyedaccordingtorelatedSOPsbysupervisorofstabilityLabortheappointedpersonaftercompletingeachtimepointtest.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。TestingMatrix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250mg50Tablets/BottleTTT100Tablets/Bottle500Tablets/BottleTTTParametersandAcceptanceCriteria(toberevisedasperspecifications)检测项目及质量标准addMicrotestingattime0andendoflifeItems检测项目Method方法Specification质量标准Appearance性状ESS-GM026250mgWhiteuncoatedtablets,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。Watercontent*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-011AChloroquinePhosphateTabletscontainnotlessthan93.0percentandnotmorethan107.0percentofthelabeledamountofC18H26clN『2H3PO4.应为标示量的93.0%-107.0%。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。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%DataPresentation海汇总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。Reporting报告IntermediateReports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。SummaryReport总结报告Oncompletionofthestudy,thestabilitylaboratorywillissueareportsummarywithsignatureanddateaccordingtoappendixB.在完成稳定性研究后，按照附件B进行总结报告。StabilityDocuments稳定性文件夹Thestabilitydocumentsshouldincludethefollowing,butnotlimitedto:稳定性文件夹应该包括但不局限于以下内容：Nameanddescriptionofdrugproduct品名及产品描述Manufacturer,batchNo.,batchsize(s),mfg.date,packagetypeandpackagedate产品生产厂商、批号、