穩(wěn)定性試驗(yàn)方案教學(xué)提綱

1、穩(wěn)定性試驗(yàn)方案精品文檔Stability Study Protocol for Exhibit Batch of Chloroquine Phosphate Tablets USP, 250mg規(guī)格為 250 mg 的 USP 磷酸氯喹片長期、中期及加速穩(wěn)定性研究方案Project No.項(xiàng)目號DP-ST-001-2008Prepared By:Date:起草者：日期：Reviewed By QA:Date:審核者：日期：Approved By:Date:批準(zhǔn)者：日期：Starting Date:Completed Date:開始日期：結(jié)束日期：收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔Co

2、ntents目 錄1.Purpose12.Scope.13.References. . 14.General Information.14.1StabilitySamples14.2Product Outline. 34.3Formulation34.4Container-Closure Systems44.5Labeling.44.6Samples and Package .55.Stability Testing55.1Sample Receipt andStorage55.2Storage Conditions and Testing Time Points55.3Sampling65.

3、4Testing Matrix75.5Parametersand Acceptance Criteria75.6Degradationproducts86.Data Presentation87.Reporting87.1IntermediateReports87.2SummaryReport87.3StabilityDocuments88.Appendix9收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔1.Purpose目的The purpose of stability testing is to provide evidence of how the Quality, Strength,

4、Degradation Products and Purity of the Chloroquine Phosphate Tablets USP, 250mg will change with time under the influence of environmental room temperature and relative humidity conditions. Data collected from the stability study will enable recommended storage conditions and provide justification f

5、or 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 FDA as required for submission purposes of the ANDA application.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(zhì)、規(guī)格、降解產(chǎn)物

6、和含量等隨時間而變化的規(guī)律，依據(jù)穩(wěn)定性研究的數(shù)據(jù)確定該產(chǎn)品的儲藏條件和有效期。2. Scope范圍This procedure is applicable to Finished Product Stability Lab at Hisun Pharmaceutical (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(shí)驗(yàn)室。3.References參考資料3.1 ICH Harmonized Triparties Guideline for Stability Testing of New Drug Substances and D

7、rug Product06, 2003. ICH Q1A (R2)新原料藥和新制劑的穩(wěn)定性測試指南06, 2003. ICH Q1A(R2)3.2 ASSAY METHOD VALIDATION REPORT FOR CHLOROQUINE PHOSPHATE, USP, API AND CHLOROQUINE PHOSPHATE, USP TABLETS, 250 mg AND 500 mg. (ARD-VDR-FPTM025A)磷酸氯喹原料藥、 250mg 和 500mg 片的含量測定方法驗(yàn)證報告。3.3 RELATED SUBSTANCES METHOD VALIDATION REPOR

8、T FOR CHLOROQUINE PHOSPHATE, USP, API AND CHLOROQUINE PHOSPHATE, USP TABLETS, 250 mg AND 500 mg. (ARD-VDR-FPTM025B)磷酸氯喹原料藥、 250mg 和 500mg 片有關(guān)物質(zhì)方法驗(yàn)證報告。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 片溶出度方法驗(yàn)證報告。4.

9、General Information基本信息4.1 Stability Samples穩(wěn)定性樣品4.1.1 One Exhibit Batch for 250mg strength will be included in the stability study.規(guī)格為 250mg 的磷酸氯喹片各一批。收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔4.1.2 One batch of 250mg reference product will also be placed on stability study.規(guī)格為 250mg 和的磷酸氯喹對照制劑各一批。收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品

10、文檔4.2 Product Outline樣品信息Batch No.StrengthPackage SizeBatch Size Mfg. Date Pkg. Date Manufacture批號規(guī)格 (mg)包裝規(guī)格批量 (Tablets) 生產(chǎn)日期 包裝日期 r生產(chǎn)商50 Tablets/ Bottle250100 Tablets/ Bottle360,000Hisun500 Tablets/ Bottle海正61924A25050 Tablets/ BottleNANANAWest-ward4.3 Formulation處方4.3.1 The formulation of Chloroq

11、uine Phosphate USP Tablets, 250 mg, is as follows: 規(guī)格為 250mg 的 USP磷酸氯喹片處方如下： Table 1. Formula and batch size Batch size: 360,000 tablets ( 172.8 Kg )成分mg / 片Kg / 批ManufacturerIngredientsmg / tabletKg / batchIPCA原料藥 API *25090微晶纖維素 (102)15455.44JRSMCC (Type 102)JRS二水磷酸氫鈣14.4Dibasic Calcium40Phosphate

12、 DihydrateMerck滑石粉 Talc248.64膠體二氧化硅DegussaColloidal Silicon Dioxide4.81.728(Aerosil 200)Peter Greven硬脂酸鎂7.22.592Magnesium Stearate總量 Total480172.84.4不適用收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔4Container-Closure Systems包裝Packing MaterialBatch No.Packing Material Description包材批號包材描述Bottle: 60 cc opaque white HDPE round

13、 bottle60 cc HDPE bottle瓶： 60cc 白色不透明 HDPE 圓瓶WE070601Cap: 32mm opaque white CRC cap, with induction60 cc HDPE 瓶sealing蓋： 32mm 白色不透明 CRC 圓蓋，帶內(nèi)封Bottle: 120 cc opaque white HDPE round bottle120 cc HDPE bottle瓶： 120cc 白色不透明 HDPE 圓瓶KQ080101Cap: 36mm opaque white CRC cap, with induction120 cc HDPE 瓶sealin

14、g蓋： 36mm 白色不透明 CRC 圓蓋，帶內(nèi)封Bottle: 450 cc opaque white HDPE round bottle450 cc HDPE bottle瓶： 450cc 白色不透明 HDPE 圓瓶WA080101Cap: 58 mm opaque white CT cap, with induction450 cc HDPE 瓶sealing蓋： 58mm 白色不透明CT 圓蓋，帶內(nèi)封4.5 LabelingManufacturer 供應(yīng)商Triveni Polymers Pvt. Ltd (Bottle) VBC Inc. (CRC Cap) Tekniplex (L

15、iner)上海海昌Triveni Polymers Pvt. Ltd (Bottle) VBC Inc. (CRC Cap) Tekniplex (Liner)上海海昌Triveni PolymersPvt. Ltd (Bottle andCap)Tekniplex (Liner)上海海昌標(biāo)簽The Product Name, Batch Number, Strength, Storage Condition, Package Type, No.and Stored by/ Store Date will be included on the label.標(biāo)簽應(yīng)包括品名、批號、規(guī)格、儲存條件、

16、包裝類型、編號及儲存人/日期。FP Stability Lab成品藥穩(wěn)定性實(shí)驗(yàn)室Product Name品名：Batch No./ Strength 批號 /規(guī)格：Storage Condition 儲存條件：Package type包裝類型：No.編號：Stored By/ Date 儲存人 /日期：收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔4.6 Samples and Package樣品與包裝The drug product for stability testing will be packaged in the same configuration as that for the

17、marketing purposes.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(jìn)行穩(wěn)定性實(shí)驗(yàn)。5. Stability Testing穩(wěn)定性試驗(yàn)5.1 Sample Receipt and Storage樣品接收與儲存As soon as received from QA or Formulation Development Department, each batch of samples will be labeled and placed in storage chambers under the required conditions.從 QA 部門或者制劑研發(fā)部門接收到樣

18、品，按規(guī)定條件貼好標(biāo)簽并儲存。Batch No.StrengthPackage SizeStorage ConditionSample Size批號規(guī)格包裝規(guī)格儲存條件樣品數(shù)量25 ±2 / 60% RH±5% RH23 Bottles/ Packagesize50 Tablets/ Bottle15 Bottles/ Package100 Tablets/ Bottle30 ±2 / 65% RH±5% RH250 mgsize500 Tablets/ Bottle12 Bottles/ Package40 ±2 / 75% RH±

19、5% RHsize7011671250 mg25 ±2 / 60% RH±5% RH2 Bottles50 Tablets/ Bottle±5% RH1 Bottle40 ±2 / 75% RHNote注1. RLD recommended storage condition as Store at 20-25 ( 68-77F) (Controlled Room Temperature) and Protect from light and moisture.室溫參照倉庫溫度要求，室溫通常不超過30 。The reference product (RL

20、D) will also be labeled and placed in storage chambers under the required conditions at the same time.同時也將對照制劑（ RLD ）按規(guī)定條件貼好標(biāo)簽并儲存。5.2 Storage Conditions and Testing Time Points儲存條件和檢測點(diǎn)Study TypeStorage ConditionPeriodTime Points （ months ）2穩(wěn)定性類型儲存條件周期時間點(diǎn)（月）Long Term25 ±2/ 60% RH±5% RH24 Mo

21、nths0, 3, 6, 9, 12, 18, 24長期Intermediate130 ±2/ 65% RH±5% RH12 Months0, 3, 6, 9, 12中期Accelerated40 ±2/ 75% RH±5% RH3 Months0,1,2,3加速收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔Note注1. Intermediate stability samples will be pulled and analyzed only if the ambient (long term) stability results falls out

22、side of the set specifications.當(dāng)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。2. Reference samples will be pulled out and analysed according to SOP ARD-ST009. 對照樣品依據(jù) SOP ARD-ST009 取樣檢測。5.3 Sampling取樣StrengthPackage SizeStorage ConditionSampling Size規(guī)格包裝規(guī)格儲存條件取樣量50Tablets/ Bottle25 ±2/ 60% RH±5% RH250 mg100Ta

23、blets/ Bottle*30 ±2/ 65% RH±5% RH1 Bottle500 Tablets/ Bottle40 ±2/ 75% RH±5% 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

24、 in pail will be sealed again and stored in warehouse.瓶裝樣品在每個檢測點(diǎn)檢驗(yàn)完畢后，樣品如果有剩余，應(yīng)交回給穩(wěn)定性實(shí)驗(yàn)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* Usually these samples are not used for testing, unless results on other conditions are not satisfactory or fail the specifications.正常情況下不取樣檢測，除非客戶有特殊要求。收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔5.4

25、 Testing Matrix穩(wěn)定性測試項(xiàng)目表Testing MatrixLong-termIntermediateConditionsConditions測試項(xiàng)目表長期穩(wěn)定性中期穩(wěn)定性50 Tablets/ BottleTT250 mg100 Tablets/ Bottle500 Tablets/ BottleTT5.5 Parameters and Acceptance Criteria (to be revised as per specifications)AcceleratedCondition加速穩(wěn)定性TT檢測項(xiàng)目及質(zhì)量標(biāo)準(zhǔn) add Micro testing at time 0

26、and end of lifeItemsMethodSpecification檢測項(xiàng)目方法質(zhì)量標(biāo)準(zhǔn)AppearanceESS-GM026White uncoated tablets, round biconvex debossed ASC over 109 on one性狀side, bisected on one side.250 mg 白色非包衣片，圓形兩面凸的，片一面刻字“ ASC 109，”另一面中間帶有刻痕。Water content*ESS-GM036.水分待定。DissolutionESS-STM-011CNot less than 75%(Q) of the labeled a

27、mount in 45 minutes.溶出度45 分鐘內(nèi)溶出度不少于 75%（ Q）。AssayESS-STM-011AChloroquine Phosphate Tablets contain not less than 93.0 percent and not more含量than 107.0 percent of the labeled amount of C 18H 26ClN 3·2H 3PO4.應(yīng)為標(biāo)示量的 93.0%-107.0% 。Related substances/ESS-STM-011B Individual unspecified impurity is N

28、MT 0.10%.degradation products單個未知雜質(zhì)不得過 0.10%。有關(guān)物質(zhì) /降解產(chǎn)物Total impurity is NMT 1.0%.總雜質(zhì)不得過 1.0%。* It is only applicable to Chloroquine Phosphate Tablets, 500 mg.僅適用于 500mg 磷酸氯喹片。收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪除精品文檔5.6 Related substances/ Degradation products有關(guān)物質(zhì) /降解產(chǎn)物Maximum daily doseReportingIdentificationQualifi

29、cationthresholdthresholdthreshold最大日劑量報告限鑒定限界定限1,000 mgLOQ0.2%0.2%6. Data Presentation數(shù)據(jù)匯總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 stability.穩(wěn)定性研究

30、數(shù)據(jù)填寫在穩(wěn)定性研究匯總報告中（見附件 B），按產(chǎn)品的儲存條件分別填寫附件 B。7. Reporting報告7.1 Intermediate Reports中期報告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 tim

31、e.在檢測點(diǎn) 30 天內(nèi)對該檢測點(diǎn)數(shù)據(jù)按附件 B 進(jìn)行中期報告，如果沒有按規(guī)定時間進(jìn)行報告，必須有書面說明。7.2 Summary Report總結(jié)報告On completion of the study, the stability laboratory will issue a report summary with signature and date according to appendix B.在完成穩(wěn)定性研究后，按照附件B 進(jìn)行總結(jié)報告。7.3 Stability Documents穩(wěn)定性文件夾The stability documents should include the following, but not limited to:穩(wěn)定性文件夾應(yīng)該包括但不局限于以下內(nèi)容： Name and description of drug product品名及產(chǎn)品描述 Manufacturer, batch No., batch size(s), mfg. date, package type and package date產(chǎn)品生產(chǎn)廠商、批號、批量、生產(chǎn)日期、包裝類型和包裝日期 Drug productstrength產(chǎn)品規(guī)格 APImanufacturer/supplier API 廠商收集于網(wǎng)絡(luò)，如有侵權(quán)請聯(lián)系管理員刪