稳定性试验方案

Stability Study Protocol for Exhibit Batch ofChloroquine Phosphate Tablets USP, 250mg规格为250 mg的USP磷酸氯喹片长期、中期及加速稳定性研究方案Project No.工程号DP-ST-001-2021Prepared By:Date:起草者：日期：Reviewed By QA:Date:审核者：日期：Approved By:Date:Stability Lab批准者：Starting Date:开始日期：日期：Completed Date:结束日期：StabilityStability LabContents目录Stability1. Purpose目的The purpose of stability testing is to provide evidence of how theQuality, Strength, Degradation Products and Purity of the ChloroquinePhosphate Tablets USP, 250mg will change with time under the influence ofenvironmental room temperature and relative humidity conditions. Data collected from the stability study will enable recommended storage conditions and provide justification for establishing and submitting the data to regulatory authorities for approving the shelf life for marketing purposes.In addition, 3 months of the stability data will be submitted to US FDAas required for submission purposes of the ANDA application.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This procedure is applicable to Finished Product Stability Lab at HisunPharmaceutical (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3.1 ICH Harmonized Triparties Guideline for Stability Testing of NewDrug Substances and Drug Product06, 2003. ICH Q1A (R2) 新原料药和新制剂的稳定性测试指南 06, 2003. ICH Q1A(R2)3.2 ASSAY METHOD VALIDATION REPORT FOR CHLOROQUINEPHOSPHATE, USP, API AND CHLOROQUINE PHOSPHATE, USPTABLETS, 250 mg AND 500 mg. (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。3.3 RELATED SUBSTANCES METHOD VALIDATION REPORTFOR CHLOROQUINEPHOSPHATE, USP, API AND CHLOROQUINEPHOSPHATE, USP TABLETS, 250 mg AND 500 mg.(ARD-VDR-FPTM025B)磷酸氯喹原料药、 250mg 和 500mg 片有关物 质方法验证报告。3.4 DISSOLUTION METHOD VALIDATION REPORT FOR CHLOROQUINE PHOSPHATE, USP TABLETS, 250 mg AND 500 mg. (ARD-VDR-FPTM025C)磷酸氯喹 250mg 和 500mg 片溶出度方法 验证报告。4. General Information根本信息4.1 Stability Samples稳定性样品4.1.1 One Exhibit Batch for 250mg strength will be included in the stability study.规格为 250mg 的磷酸氯喹片各一批。4.1.2 One batch of 250mg reference product willalso be placed onstability study.规格为 250mg 和的磷酸 氯喹对照制剂各一批。Stability4.2 Product Outline样品信息BatchStrePackageBatchMfPkgManuNo.ngthSizeSizeg. Date Datefacturer批号规格包装规格批量生包生产(mg)(Tablets)产日期装日期商50 Tablets/BottleHisu100360,00250Tablets/ Bottle0n海正500Tablets/ Bottle619250 Tablets/West250NANANA4ABottle-ward4.3 Formulation处方Stability431 The formulation of Chloroquine Phosphate USP Tablets,250 mg, is as follows:规格为250mg的USP磷酸 氯喹片处方如下：Table 1. Formula andbatch sizeBatch size: 360,000 tablets ( 172.8 Kg )成分Ingredientsmg /片mg /tabletKg /批Kg /batchManufacturer原料药API*25090IPCA微晶纤维素(102)JRSMCC(Type154102)一水磷酸氢钙JRSDibasic Calcium40Phosphate Dihydrate滑石粉Talc24MerckStability胶体二氧化硅Colloidal SiliconDioxide (Aerosil 200)Degussa硬脂酸镁PeterMagnesiumGrevenStearate总量Total480不适用Stability4Container-Closure Systems包装PackingMaterial包材Batc h No.批号Packing Material Description 包材描述Manufacturer供给商TriveniPolymers Pvt.Bottle: 60 cc opaque white60 ccHDPE round bottleLtd (Bottle)HDPE bottleWE瓶：60cc白色不透明HDPE圆瓶VBC Inc.Cap: 32 mm opaque white60 cc070601CRC cap, with induction sealing(CRC Cap)HDPE 瓶盖：32mm白色不透明CRCTekniplex圆盖，带内封(Liner)上海海昌rr Triveni120 ccBottle: 120 cc opaque whitePolymers Pvt.HDPE bottleKQ0HDPE round bottle瓶：120cc白色不透明HDPE圆Ltd (Bottle)120 cc80101瓶VBC Inc.HDPE 瓶Cap: 36 mm opaque whiteCRC cap, with induction sealing(CRC Cap)盖：36mm白色不透明CRC圆盖，带内封Tekniplex(Liner)上海海昌TtiveniBottle: 450 cc opaque whiteHDPE round bottlePolymers Pvt.450 cc瓶：450cc白色不透明HDPE圆Ltd (Bottle andHDPE bottleWA瓶Cap)450 cc080101Cap: 58mm opaque white CTcap, with induction sealingTekniplexHDPE 瓶盖：58mm白色不透明CT圆(Liner)盖，带内封上海海昌4.5 Labeling标签The Product Name, Batch Number, Strength, Storage Condition,Package Type, No. and Stored by/ Store Date will be included on the labe L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。FP Stability LabStability成品药稳定性实验室Product Name品名：Batch No./Strength批号/规格：StorageCondition储存条件：Package type包装类型：No.编号：Stored By/ Date 储存人/日期:Stability4.6 Samples and Package样品与包装The drug product for stability testing will be packaged in the sameconfiguration as that for the marketing purposes 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. Stability Testing稳定性试验5.i Sample Receipt and Storage样品接收与储存As soon as received from QA or Formulation DevelopmentDepartment, each batch of samples will be labeled and placed in storagechambers under the required conditions 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。BatcStrPackageStorage ConditionSampleh No.批号ength储存条件规格Size包装规格Size样品数250mg50 Tablets/Bottle100Tablets/ Bottle500Tablets/ Bottle7011250671mg50 Tablets/BottleNoteStability25 C 2C/60%Bottles/5% RH30 C 2 C/65%Bottles/5% RH40 C 2 C/75%Bottles/5% RH23RH 土Package size15RH 土Package size12RH 土Package size25 C 2C/60% RH 土 2 Bottles5% RH40 C 2 C/75% RH 1 Bottle5% RHLab1 RLD recommended storage condition as Store at 20-25 C(68-77F) (Controlled Room Temperature) and Protect from light and moisture 室温参照仓库温度要求，室温通常不超过30 C。The reference product (RLD) will also be labeled and placed in storagechambers under the required conditions at the same time.同时也将对照制剂RLD按规定条件贴好标签并储存。Storage Conditions and Testing Time Points储存条件和检测点StudyType稳定性类型StorageCondition 储存条件Perio d周期Time Points2months时间点月LongTerm长期25 C 2 C/60% RH土 5%RH24Months0, 3, 6, 9, 12, 18,24Interme30 C 2 C/65% RH120, 3, 6, 9, 12StabilityPage 13/ 9diate 1中期土 5%RHMonthsAccelerated加速40 C 2 C/75% RH土 5%RH3Months0,1,2,3Note11ntermediate stability samples will be pulled and analyzed only if the ambient (long term) stability results falls outside of the set specifications.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 Reference samples will be pulled out and analysed accordingto SOP ARD-ST009.对照样品依据SOP ARD-ST009取样检测。5.3 Sampling取样StrenPackageStorage ConditionSamplingPage 14/ 9gth规格Size包装规格储存条件Size取样量250mg50 Tablets/Bottle100 Tablets/Bottle *500 Tablets/Bottle25 C 2C/60% RH5% RH土土1 Bottle土30 C 2 C/65% RH5% RH40 C 2 C/75% RH5% RHThe additional samples packed in bottles will be destroyed according to related SOPs by supervisor of stability Lab or the appointed person after completing each time point test. And the samples packed in pail willbesealed again and stored in warehouse 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* Usually these samples are not used for testing, unless results on other conditions are not satisfactory or fail the specifications.正常情况下不取 样检测，除非客户有特殊要求。StabilityPage 15/ 95.4 Testing Matrix稳定性测试工程表Testing Matrix测试工程表Long-ter m Conditions长期稳定 性Intermediate Conditions中期稳定 性Accelerat ed Condition加速稳定 性50Tablets/TBottleTT250mg100BottleTablets/500Tablets/TBottleTT5.5 Parameters and AcceptanceCriteria (to be revised as perspecifications)检测项 目及质量标准 add Micro testing at time 0 and end of lifeItems检测项目Method方法Specification质量标准StabilityPage 16/ 9AppearaESS-White uncoated tablets, round biconvexneeGM026debossed ASC over 109 on one side, bisected2性状on one side.50 mg白色非包衣片，圆形两面凸的，片一面刻字ASC 109 ，另一面中间带有刻痕。WaterESS-content *GM036待定。水分DissolutESS-Not less than 75%(Q) of the labeled amount inionSTM-01145 minutes 溶出度C45分钟内溶出度不少于75%Q。AssayESS-Chloroquine Phosphate Tablets contain not less含量STM-011than 93.0 percent and not more than 107.0 percent ofAthe labeled amount of C 18H26ClN 3 2H3PO4.1826334应为标示量的93.0%-107.0%。StabilityPage 17/ 9RelatedESS-substances/STM-011Individual unspecified impurity is NMT 0.10%.degradationB单个未知杂质不得过。0.10%productsTotal impurity is NMT 1.0%.有关物总杂质不得过1.0%。质/降解产物* It is only applicable to Chloroquine Phosphate Tablets, 500 mg.仅适用于500mg磷酸氯喹片。StabilityPage 18/ 9Related substances/ Degradation products有关物质/降解产物MaximumReportingIdentificationQualificationdaily dosethresholdthresholdthreshold最大日剂量报告限鉴定限界定限1,000 mgLOQ0.2%0.2%6. Data Presentation数据汇总The stability data will be presented in the Stability Summary Report(see examples in Appendix B). Stability Summary Report will be completed for each storage condition of drug product placed on stabilit y.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StabilityPage 19/ 97.1 Intermediate Reports中期报告The stability laboratory will issue intermediate reports according to Appendix B within 30 days at each testing time points. The written explanation should be provided if test result is not reported within required time.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。7.2 Summary Report总结报 告On completion of the study, the stability laboratory will issue a report summary with signature and date according to appendix B.在完成稳定性研究后，按照附件 B 进行总结报告。7.3 Stability Documents稳定性文件 夹The stability documents should include the following, but not limited to:稳定性文件 夹应该包括但不局限于以下内容： Name and description of drug product品名及产品描述 Manufacturer, batch No., batch size(s), mfg. date, package type and package date产品生产厂商、批号、批量、生产日期、包装类型和包装日期 Drug product strength产品规格 API manufacturer/supplierAPI 厂商 Method validation reports方法验证报告 All analytical and physical data, including identity test, chemistry assay, physical test所有检验数据，包括鉴别、含量及测试。 Acceptance criteria质量标准 Where applicable, a description of statistical methodology applied, including parameters estimated, assumptions made, and model(s) used; transformations, calculations or operations performed on the data; an explanation and statement of the conclusions drawn from the statistical analysis relative to the objective(s) of the study; the name(s)of softwareemployed in the statistical evaluations.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。 The numbers and titles of standard operating procedures applied采用的 Sop 编号和标题 A signed and dated statement of intermediate reports中期报告 The records of all samples, original data and testing reports样品的原始数据和 测试报告 Requiring form for stability study稳定性研究申 请表8. Appendix(Hisun附件Appendix B1: STABILITY STUDY SUMMARY REPORT products/ 250 mg)附件Bl :稳定性研究 报告(海正产品/250mg)Appendix B2: STABILITY STUDY SUMMARY REPORT (Brand)附件 B3 :稳定性研究 报告 (Brand)Stability