穩(wěn)定性試驗方案10頁

1、Stability Study Protocol穩(wěn)定性方案Chloroquine Phosphate Tablets Protocol No.: PRO-ST-001-2008(1.2)磷酸氯喹片 方案編號：PRO-ST-001-2008(1.2)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.項目號DP-ST-001-2008Prepared By: Date:起草者： 日期： R

2、eviewed By QA: Date:審核者： 日期： Approved By: Date:批準者： 日期： Starting Date: Completed Date:開始日期： 結(jié)束日期： Stability Lab Page 8/ 9穩(wěn)定性實驗室Contents目 錄1.Purpose目的12.Scope范圍.13.References參考資料.14.General Information基本信息.14.1Stability Samples穩(wěn)定性研究樣品14.2Product Outline樣品概述.14.3Formulation處方14.4Container-Closure Syst

3、ems包裝14.5Labeling標簽.14.6Samples and Package樣品與包裝.15.Stability Testing穩(wěn)定性測試15.1Sample Receipt and Storage樣品接收與儲存15.2Storage Conditions and Testing Time Points儲存條件與檢測時間點15.3Sampling取樣15.4Testing Matrix穩(wěn)定性測試項目表15.5Parameters and Acceptance Criteria檢測項目及質(zhì)量標準15.6Degradation products降解產(chǎn)物16.Data Presentati

4、on數(shù)據(jù)匯總17.Reporting報告17.1Intermediate Reports中期報告17.2Summary Report總結(jié)報告17.3Stability Documents穩(wěn)定性文件夾18.Appendix附件11. Purpose目的The purpose of stability testing is to provide evidence of how the Quality, Strength, Degradation Products and Purity of the Chloroquine Phosphate Tablets USP, 250mg will chan

5、ge 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 for establishing and submitting the data to regulatory authorities for approving the shelf

6、 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 Finishe

7、d 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)定性實驗室。3. References參考資料3.1 ICH Harmonized Triparties Guideline for Stability Testing of New Drug Substances and Drug Product 06, 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

8、 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證報告。3.3 RELATED SUBSTANCES METHOD VALIDATION REPORT FOR CHLOROQUINE PHOSPHATE, USP, API AND CHLOROQUINE PHOSPHATE, USP TABLETS, 250 mg AND 5

9、00 mg. (ARD-VDR-FPTM025B)磷酸氯喹原料藥、250mg和500mg片有關(guān)物質(zhì)方法驗證報告。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片溶出度方法驗證報告。4. 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

10、be included in the stability study.規(guī)格為250mg的磷酸氯喹片各一批。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。4.2 Product Outline樣品信息Batch No.批號Strength規(guī)格(mg)Package Size包裝規(guī)格Batch Size批量(Tablets)Mfg. Date生產(chǎn)日期Pkg. Date包裝日期Manufacturer生產(chǎn)商25050 Tablets/ Bo

11、ttle360,000Hisun海正100 Tablets/ Bottle500 Tablets/ Bottle61924A25050 Tablets/ BottleNANANAWest-ward4.3 Formulation處方4.3.1 The formulation of Chloroquine 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Ingredi

12、entsmg / 片 mg / tabletKg / 批 Kg / batchManufacturer 原料藥API*25090IPCA微晶纖維素(102)MCC (Type 102)15455.44JRS二水磷酸氫鈣Dibasic Calcium Phosphate Dihydrate 4014.4JRS滑石粉Talc248.64Merck膠體二氧化硅Colloidal Silicon Dioxide (Aerosil 200)4.81.728Degussa硬脂酸鎂Magnesium Stearate7.22.592Peter Greven總量Total480172.84.4 不適用4Con

13、tainer-Closure Systems包裝Packing Material包材Batch No.批號Packing Material Description包材描述Manufacturer供應(yīng)商60 cc HDPE bottle60 cc HDPE瓶WE070601Bottle: 60 cc opaque white HDPE round bottle瓶：60cc白色不透明HDPE圓瓶Cap: 32 mm opaque white CRC cap, with induction sealing 蓋：32mm白色不透明CRC圓蓋，帶內(nèi)封Triveni Polymers Pvt. Ltd (

14、Bottle) VBC Inc. (CRC Cap)Tekniplex (Liner) 上海海昌120 cc HDPE bottle120 cc HDPE瓶KQ080101Bottle: 120 cc opaque white HDPE round bottle瓶：120cc白色不透明HDPE圓瓶Cap: 36 mm opaque white CRC cap, with induction sealing 蓋：36mm白色不透明CRC圓蓋，帶內(nèi)封Triveni Polymers Pvt. Ltd (Bottle) VBC Inc. (CRC Cap)Tekniplex (Liner) 上海海昌

15、450 cc HDPE bottle450 cc HDPE瓶WA080101Bottle: 450 cc opaque white HDPE round bottle瓶：450cc白色不透明HDPE圓瓶Cap: 58 mm opaque white CT cap, with induction sealing 蓋：58mm白色不透明CT圓蓋，帶內(nèi)封Triveni Polymers Pvt. Ltd (Bottle and Cap) Tekniplex (Liner) 上海海昌4.5 Labeling標簽The Product Name, Batch Number, Strength, Stor

16、age Condition, Package Type, No. and Stored by/ Store Date will be included on the label.標簽應(yīng)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。FP Stability Lab成品藥穩(wěn)定性實驗室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：4.6 Samples and Package樣品與包裝The drug product

17、 for stability testing will be packaged in the same configuration as that for the 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行穩(wěn)定性實驗。5. Stability Testing穩(wěn)定性試驗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 labele

18、d and placed in storage chambers under the required conditions.從QA部門或者制劑研發(fā)部門接收到樣品，按規(guī)定條件貼好標簽并儲存。Batch No.批號Strength規(guī)格Package Size包裝規(guī)格Storage Condition儲存條件Sample Size樣品數(shù)量250 mg50 Tablets/ Bottle100 Tablets/ Bottle500 Tablets/ Bottle25 2/ 60% RH 5% RH23 Bottles/ Package size30 2/ 65% RH 5% RH15 Bottles

19、/ Package size40 2/ 75% RH 5% RH12 Bottles/ Package size7011671250 mg50 Tablets/ Bottle25 2/ 60% RH 5% RH2 Bottles40 2/ 75% RH 5% RH1 BottleNote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

20、 reference product (RLD) 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)定條件貼好標簽并儲存。5.2 Storage Conditions and Testing Time Points儲存條件和檢測點Study Type穩(wěn)定性類型Storage Condition儲存條件Period周期Time Points（months）2時間點（月）Long Term長期25 2/ 60% RH 5%

21、 RH24 Months0, 3, 6, 9, 12, 18, 24Intermediate1中期30 2/ 65% RH 5% RH12 Months0, 3, 6, 9, 12Accelerated加速40 2/ 75% RH 5% RH3 Months0, 1, 2, 3Note注1. Intermediate stability samples will be pulled and analyzed only if the ambient (long term) stability results falls outside of the set specifications.當完成加

22、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Strength規(guī)格Package Size包裝規(guī)格Storage Condition儲存條件Sampling Size取樣量250 mg50 Tablets/ Bottle100 Tablets/ Bottle*500 Tablets/ Bottle25 2/ 60% RH 5% RH1 Bottle30 2/

23、65% RH 5% RH40 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 in pail will be sealed again and stored in warehouse.瓶裝樣品在每個檢測點檢驗完畢后

24、，樣品如果有剩余，應(yīng)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* 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。5.4 Testing Matrix穩(wěn)定性測試項目表Testing Matrix測試項目表Long-term Conditions長期穩(wěn)定性Intermediate Conditions

25、中期穩(wěn)定性Accelerated Condition加速穩(wěn)定性250 mg50 Tablets/ BottleTTT100 Tablets/ Bottle500 Tablets/ BottleTTT5.5 Parameters and Acceptance Criteria (to be revised as per specifications) 檢測項目及質(zhì)量標準 add Micro testing at time 0 and end of lifeItems檢測項目Method 方法Specification 質(zhì)量標準Appearance性狀ESS-GM026250 mgWhite un

26、coated tablets, round biconvex debossed ASC over 109 on one side, bisected on one side.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*水分ESS-GM036.待定。Dissolution溶出度ESS-STM-011CNot less than 75%(Q) of the labeled amount in 45 minutes.45分鐘內(nèi)溶出度不少于75%（Q）。Assay含量ESS-STM-011AChloroquine Phosphate Tab

27、lets contain not less than 93.0 percent and not more than 107.0 percent of the labeled amount of C18H26ClN32H3PO4.應(yīng)為標示量的93.0%-107.0%。Related substances/ degradation products有關(guān)物質(zhì)/降解產(chǎn)物ESS-STM-011BIndividual unspecified impurity is NMT 0.10%.單個未知雜質(zhì)不得過0.10%。Total impurity is NMT 1.0%.總雜質(zhì)不得過1.0%。* It is

28、only applicable to Chloroquine Phosphate Tablets, 500 mg. 僅適用于500mg磷酸氯喹片。5.6 Related substances/ Degradation products有關(guān)物質(zhì)/降解產(chǎn)物Maximum daily dose最大日劑量Reporting threshold報告限Identification threshold鑒定限Qualification threshold界定限1,000 mgLOQ0.2%0.2%6. Data Presentation數(shù)據(jù)匯總The stability data will be presen

29、ted 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 interme

30、diate 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.在檢測點30天內(nèi)對該檢測點數(shù)據(jù)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。7.2 Summary Report總結(jié)報告On completion of the study, the stability laboratory

31、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 product strength 產(chǎn)品規(guī)格 API manufacturer/suppl