穩(wěn)定性試驗方案計劃

PAGE8StabilityStudyProtocolforExhibitBatchofChloroquinePhosphateTabletsUSP,250mg規(guī)格為250mg的USP磷酸氯喹片長期、中期及加速穩(wěn)定性研究方案ProjectNo.項目號DP-ST-001-2008PreparedBy:Date:起草者：日期：ReviewedByQA:Date:審核者：日期：ApprovedBy:Date:批準者：日期：StartingDate:CompletedDate:開始日期：結束日期：Contents目錄TOC\o"1-3"\p""\h\z\u1. Purpose目的…………………………12. Scope范圍…………………………..13. References參考資料…………………..14. GeneralInformation基本信息………………………..1 StabilitySamples穩(wěn)定性研究樣品…………1 ProductOutline樣品概述………………..……1 Formulation處方………………1 Container-ClosureSystems包裝……………1 Labeling標簽…………………..1 SamplesandPackage樣品與包裝………….15. StabilityTesting穩(wěn)定性測試…………1 SampleReceiptandStorage樣品接收與儲存……………1 StorageConditionsandTestingTimePoints儲存條件與檢測時間點……1 Sampling取樣…………………1 TestingMatrix穩(wěn)定性測試項目表……………1 ParametersandAcceptanceCriteria檢測項目及質量標準………………1 Degradationproducts降解產物……………16. DataPresentation數據匯總…………17. Reporting報告………………………1 IntermediateReports中期報告………………1 SummaryReport總結報告…………………1 StabilityDocuments穩(wěn)定性文件夾…………18. Appendix附件…………………………1

Purpose目的ThepurposeofstabilitytestingistoprovideevidenceofhowtheQuality,Strength,DegradationProductsandPurityoftheChloroquinePhosphateTabletsUSP,250mgwillchangewithtimeundertheinfluenceofenvironmentalroomtemperatureandrelativehumidityconditions.Datacollectedfromthestabilitystudywillenablerecommendedstorageconditionsandprovidejustificationforestablishingandsubmittingthedatatoregulatoryauthoritiesforapprovingtheshelflifeformarketingpurposes.Inaddition,3monthsofthestabilitydatawillbesubmittedtoUSFDAasrequiredforsubmissionpurposesoftheANDAapplication.此穩(wěn)定性研究的目的是為了考察磷酸氯喹片在環(huán)境因素的影響下(例如：溫度和濕度)其性質、規(guī)格、降解產物和含量等隨時間而變化的規(guī)律，依據穩(wěn)定性研究的數據確定該產品的儲藏條件和有效期。Scope范圍ThisprocedureisapplicabletoFinishedProductStabilityLabatHisunPharmaceutical(Hangzhou)Co.Ltd.Fuyang,Hangzhou.適用于浙江臺州海正藥業(yè)成品藥穩(wěn)定性實驗室。References參考資料ICHHarmonizedTripartiesGuidelineforStabilityTestingofNewDrugSubstancesandDrugProduct06,2003.[ICHQ1A(R2)]新原料藥和新制劑的穩(wěn)定性測試指南06,2003.[ICHQ1A(R2)]ASSAYMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USP,APIANDCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025A)磷酸氯喹原料藥、250mg和500mg片的含量測定方法驗證報告。RELATEDSUBSTANCESMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USP,APIANDCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025B)磷酸氯喹原料藥、250mg和500mg片有關物質方法驗證報告。DISSOLUTIONMETHODVALIDATIONREPORTFORCHLOROQUINEPHOSPHATE,USPTABLETS,250mgAND500mg.(ARD-VDR-FPTM025C)磷酸氯喹250mg和500mg片溶出度方法驗證報告。GeneralInformation基本信息StabilitySamples穩(wěn)定性樣品4.1.1OneExhibitBatchfor250mgstrengthwillbeincludedinthestabilitystudy.規(guī)格為250mg的磷酸氯喹片各一批。4.1.2Onebatchof250mgreferenceproductwillalsobeplacedonstabilitystudy.規(guī)格為250mg和的磷酸氯喹對照制劑各一批。

ProductOutline樣品信息BatchNo.批號Strength規(guī)格(mg)PackageSize包裝規(guī)格BatchSize批量(Tablets)Mfg.Date生產日期Pkg.Date包裝日期Manufacturer生產商25050Tablets/Bottle360,,000Hisun海正100Tablets/Bottle500Tablets/Bottle61924A25050Tablets/BottleNANANAWest-wardFormulation處方TheformulationofChloroquinePhosphateUSPTablets,250mg,isasfollows:規(guī)格為250mg的USP磷酸氯喹片處方如下：Table1.FormulaandbatchsizeBatchsize:360,000tablets(172.8Kg)成分Ingredientsmg/片mg/tabletKg/批Kg/batchManufacturer原料藥API*25090IPCA微晶纖維素(102)MCC(Type102)154JRS二水磷酸氫鈣DibasicCalciumPhosphateDihydrate40JRS滑石粉Talc24Merck膠體二氧化硅ColloidalSiliconDioxide(Aerosil200)Degussa硬脂酸鎂MagnesiumStearatePeterGreven總量Total480不適用

4Container-ClosureSystems包裝PackingMaterial包材BatchNo.批號PackingMaterialDescription包材描述Manufacturer供應商60ccHDPEbottle60ccHDPE瓶WE070601Bottle:60ccopaquewhiteHDPEroundbottle瓶：60cc白色不透明HDPE圓瓶Cap:φ32mmopaquewhite蓋：φ32mm白色不透明TriveniPolymersPvt.Ltd(Bottle)VBCInc.(CRCCap)Tekniplex(Liner)上海海昌120ccHDPEbottle120ccHDPE瓶KQ080101Bottle:120ccopaquewhiteHDPEroundbottle瓶：120cc白色不透明HDPE圓瓶Cap:φ36mmopaquewhite蓋：φ36mm白色不透明TriveniPolymersPvt.Ltd(Bottle)VBCInc.(CRCCap)Tekniplex(Liner)上海海昌450ccHDPEbottle450ccHDPE瓶WA080101Bottle:450ccopaquewhiteHDPEroundbottle瓶：450cc白色不透明HDPE圓瓶Cap:φ58mmopaquewhiteCT蓋：φ58mm白色不透明CT圓蓋，帶內封TriveniPolymersPvt.Ltd(BottleandCap)Tekniplex(Liner)上海海昌Labeling標簽TheProductName,BatchNumber,Strength,StorageCondition,PackageType,No.andStoredby/StoreDatewillbeincludedonthelabel.標簽應包括品名、批號、規(guī)格、儲存條件、包裝類型、編號及儲存人/日期。FPStabilityLab成品藥穩(wěn)定性實驗室ProductName品名：BatchNo./Strength批號/規(guī)格：StorageCondition儲存條件：Packagetype包裝類型：No.編號：StoredBy/Date儲存人/日期：

SamplesandPackage樣品與包裝Thedrugproductforstabilitytestingwillbepackagedinthesameconfigurationasthatforthemarketingpurposes.穩(wěn)定性研究樣品與上市的包裝要一致，同時藥品的大包裝也進行穩(wěn)定性實驗。StabilityTesting穩(wěn)定性試驗SampleReceiptandStorage樣品接收與儲存AssoonasreceivedfromQAorFormulationDevelopmentDepartment,eachbatchofsampleswillbelabeledandplacedinstoragechambersundertherequiredconditions.從QA部門或者制劑研發(fā)部門接收到樣品，按規(guī)定條件貼好標簽并儲存。BatchNo.批號Strength規(guī)格PackageSize包裝規(guī)格StorageCondition儲存條件SampleSize樣品數量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RLDrecommendedstorageconditionasStoreat20-25℃(68-77F)(ControlledRoomTemperature)andProtectfromlightandmoisture.室溫參照倉庫溫度要求，室溫通常不超過30℃。Thereferenceproduct(RLD)willalsobelabeledandplacedinstoragechambersundertherequiredconditionsatthesametime.同時也將對照制劑（RLD）按規(guī)定條件貼好標簽并儲存。StorageConditionsandTestingTimePoints儲存條件和檢測點StudyType穩(wěn)定性類型StorageCondition儲存條件Period周期TimePoints（months）2時間點（月）LongTerm長期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.當完成加速穩(wěn)定性研究且無重大變化時，停止中期穩(wěn)定性研究。ReferencesampleswillbepulledoutandanalysedaccordingtoSOPARD-ST009.對照樣品依據SOPARD-ST009取樣檢測。Sampling取樣Strength規(guī)格PackageSize包裝規(guī)格StorageCondition儲存條件SamplingSize取樣量250mg50Tablets/Bottle100Tablets/Bottle*500Tablets/Bottle25℃±2℃/60%RH±5%RH1Bottle30℃±2℃/65%RH±5%RH40℃±2℃/75%RH±5%RHTheadditionalsamplespackedinbottleswillbedestroyedaccordingtorelatedSOPsbysupervisorofstabilityLabortheappointedpersonaftercompletingeachtimepointtest.Andthesamplespackedinpailwillbesealedagainandstoredinwarehouse.瓶裝樣品在每個檢測點檢驗完畢后，樣品如果有剩余，應交回給穩(wěn)定性實驗室主管或指定人員做銷毀處理。桶裝樣品封好繼續(xù)在倉庫中儲存。Note注*Usuallythesesamplesarenotusedfortesting,unlessresultsonotherconditionsarenotsatisfactoryorfailthespecifications.正常情況下不取樣檢測，除非客戶有特殊要求。

TestingMatrix穩(wěn)定性測試項目表TestingMatrix測試項目表Long-termConditions長期穩(wěn)定性IntermediateConditions中期穩(wěn)定性AcceleratedCondition加速穩(wěn)定性250mg50Tablets/BottleTTT100Tablets/Bottle500Tablets/BottleTTTParametersandAcceptanceCriteria(toberevisedasperspecifications)檢測項目及質量標準addMicrotestingattime0andendoflifeItems檢測項目Method方法Specification質量標準Appearance性狀ESS-GM026250mgWhiteuncoatedtablets,roundbiconvexdebossedASCover109ononeside,bisectedononeside.白色非包衣片，圓形兩面凸的，片一面刻字“ASC109”，另一面中間帶有刻痕。Watercontent*水分ESS-GM036.待定。Dissolution溶出度ESS-STM-011CNotlessthan75%(Q)ofthelabeledamountin45minutes.45分鐘內溶出度不少于75%（Q）。Assay含量ESS-STM-011AChloroquinePhosphateTabletscontainnotlessthanpercentandnotmorethanpercentofthelabeledamountofC18H26ClN3·2H3PO4.應為標示量的%%。Relatedsubstances/degradationproducts有關物質/降解產物ESS-STM-011BIndividualunspecifiedimpurityisNMT%.單個未知雜質不得過%。TotalimpurityisNMT%.總雜質不得過%。*ItisonlyapplicabletoChloroquinePhosphateTablets,500mg.僅適用于500mg磷酸氯喹片。

Relatedsubstances/Degradationproducts有關物質/降解產物Maximumdailydose最大日劑量Reportingthreshold報告限Identificationthreshold鑒定限Qualificationthreshold界定限1,000mgLOQ%%DataPresentation數據匯總ThestabilitydatawillbepresentedintheStabilitySummaryReport(seeexamplesinAppendixB).StabilitySummaryReportwillbecompletedforeachstorageconditionofdrugproductplacedonstability.穩(wěn)定性研究數據填寫在穩(wěn)定性研究匯總報告中（見附件B），按產品的儲存條件分別填寫附件B。Reporting報告IntermediateReports中期報告ThestabilitylaboratorywillissueintermediatereportsaccordingtoAppendixBwithin30daysateachtestingtimepoints.Thewrittenexplanationshouldbeprovidediftestresultisnotreportedwithinrequiredtime.在檢測點30天內對該檢測點數據按附件B進行中期報告，如果沒有按規(guī)定時間進行報告，必須有書面說明。SummaryReport總結報告Oncompletionofthestudy,thestabilitylaboratorywillissueareportsummarywithsignatureanddateaccordingtoappendixB.在完成穩(wěn)定性研究后，按照附件B進行總結報告。StabilityDocuments穩(wěn)定性文件夾Thestabilitydocumentsshouldincludethefollowing,butnotlimitedto:穩(wěn)定性文件夾應該包括但不局限于以下內容：●Nameanddescriptionofdrugproduct品名及產品描述●Manufacturer,batchNo.,batchsize(s),m