1、起草/修訂人：Author日期：Date部門主管審查：Dept. Head Approval日期：DateQA批準：Approved by QA日期：Date分 發：Distribution:QA, QC, R&D目的：描述化驗室對照品的接收、確認、貯存、庫存、分發、使用的規程。PURPOSE:This procedure describes a process used by Lab operation for the receipt, qualification, storage, inventory, distribution and use of analytical refe

2、rence standard范圍：適用于化驗室內所用的對照品，包括基準對照品、第二對照品。SCOPE:This procedure is applicable to analytical reference standards used in QC lab, includes the Primary Reference Standards and the Secondary Reference Standards參考文件：REFERENCE AND ATTACHMENT:SOP/題目 SOP/TITLE記錄/附件/題目 FORMS/ATTACHMENTS/TITLE3-0002OOS調查附件1

3、：對照品標簽樣例Investigation of Out-of-Specification ResultAttachment 1: Reference Standard Label (Example)F-03-010對照品登記臺帳Reference Standard Inventory Log SheetF-03-011對照品接收記錄Reference Standard Receiving LogbookF-03-012對照品使用記錄Use Record of Reference Standard 定 義：DEFINITIONS:基準對照品以廣泛分析表明具有可信的、高純度的物質。這類標準品可以

4、：1）來源于法定機構；2）獨立合成；3）來自于高純度的現有生產物料；4）用進一步精制現有生產物料的方法來制備。Reference Standard, Primary A substance that has been shown by an extensive set of analytical tests to be authentic material that should be of high purity. This standard could be: (1) obtained from an officially recognized source, (2) prepared b

5、y independent synthesis, (3) obtained from existing production material of high purity, or (4) prepared by further purification of existing production material.第二對照品與基準對照品比較顯示有規定的質量和純度，并用作日常檢驗分析的參考標準品。Reference Standard, Secondary A substance of established quality and purity, as shown by comparison

6、 to a primary reference standard, used as a reference standard for routine laboratory analysis.規 程：PROCEDURE:責 任 人操 作RESPONSIBILITYACTION1.對照品接收RECEIPT OF REFERENCE STANDARDQC主管1.1QC主管指定專人負責對照品的管理；對照品管理員負責對照品的接收、貯存以及發放等的管理。QC SupervisorQC Supervisor designee is responsible for the management of all

7、reference standards, such as the receipt, storage and distribution of reference standard.對照品管理員1.2接收對照品時，應檢查對照品的包裝是否完好、是否提供檢驗報告書、檢驗報告書是否與實物相符，等等。Control ClerkUpon receipt, verify the package of the reference standards, confirm whether the certificate of analysis is available, and the reference stand

8、ards received are the same as the certificate of analysis, etc.1.3將對照品的相關信息在對照品登記臺帳上作好記錄，每批對照品建立一份管理臺帳。Enter reference standard information into the Reference Standard Receiving logbook, and establish a Reference Standard Inventory log sheet for each lot. 1.4接收后的對照品給定公司內批號。Assign the lot number for

9、received reference standards對照品的批號由：類別號年號流水號組成：The lot number is consist of: Sort number + digit number of the calendar Year + sequential number:.1類別號：Sort number.1.1基準對照品：RSP（Reference Standard, Primary）.1.2第二對照品：RSS（Reference Standard, Secondary）.2年號：用2位數的年份表示Year: 2 digit number of the year desig

10、nation.3流水號：用2位數字表示。Sequential number: 2 digit number.1.5對照品接收后，在每批對照品的每個包裝上貼簽（附件1），標明名稱、批號、數量、來源、瓶號/總瓶數（比如，共有10瓶，其中第2瓶為：2/10）、接收人簽名/日期等內容。At time of receipt, label each standard container (attachment 1), with the reference standard name, lot number, quantity, source, container number/total containe

11、rs number (e.g., the total container is 10 bottles, then second bottle is 2/10), and initial and date of the receiver.責 任 人操 作RESPONSIBILITYACTION對照品管理員1.6將對照品放入標有“待確認對照品”的干燥器中，存放于28冰箱中，或者存放于對照品所規定的貯存條件。Control ClerkPlace reference standard into desiccator (marked with “Reference Standard, to be qua

12、lified”) in refrigerator (temperature controlled within 2 to 8 Degree C), or place in required storage condition in accordance with reference standard.1.7對照品應存放于棕色玻璃瓶中，對于不符合此要求的，在接收后，將對照品裝入或分裝于棕色玻璃瓶中。The reference standard should be stored in brown glass bottles. If it is found not meeting the requi

13、rement, it should be placed into or subdivided into brown glass bottles after receipt.2.對照品確認QUALIFICAITON OF REFERENCE STANDARDSQC2.1對照品應從法定機構購買（如，USP、EP、CP等）；并且，只要是適用的，內部使用的對照品應根據這些從法定機構購買來的對照品進行確認。如果法定對照品不能得到，則內部使用的對照品必須根據一個確認的標準品進行確認，或必須根據本SOP中下面的要求的進行全部的確認。Reference standards should be purchase

14、d from an officially recognized source (e.g., USP, EP, and CP) and in-house reference standards should be qualified against them, whenever applicable. If officially reference standard is not available or applicable, in-house reference standards must be qualified against a qualified standard or full

15、qualification must be performed according to the following requirement of this SOP.2.2對照品的確認包括：The qualification of reference standard includes:2.2.1基準對照品的確認Qualification of Primary Reference Standard2.2.2第二對照品的確認Qualification of Secondary Reference Standards2.2.2.1根據法定對照品（如，USP、EP、CP等）或其他已確認的標準，對內部

16、使用的對照品的確認。Qualification of in-house reference standards against an official reference standard (e.g., USP, EP, CP, etc.) or other qualified standard.2.2.2.2當沒有法定對照品（如，USP、EP、CP等），或其他已確認的對照品時，內部使用的對照品的確認。Qualification of an in-house reference standard when official reference standard (e.g., USP, EP,

17、CP, etc.), or other qualified standard is not available.責 任 人操 作RESPONSIBILITYACTIONQC, QA2.3基準對照品的確認Qualification of Primary Reference Standard2.3.1從法定機構購買的基準對照品，在根據“1. 接收”的規程接收后，將與該批對照品有關的資料轉至QA審核。經QA審核后，發放檢驗報告書。The primary reference standard purchased from officially recognized source. After refe

18、rence standard has been received according to the requirement of “1. Receipt of Reference Standard”, submit the documents related to that batch reference standard to QA for review. After review, QA shall issue the certificate of analysis.2.4根據法定對照品（如，USP、EP、CP等）或其他已確認的標準，對內部使用的對照品的確認Qualification of

19、 in-house reference standard against an official reference standard (e.g., USP, EP, CP, etc.) or other qualified standard:2.4.1起草一份對照品的確認方案，方案包括下面的信息：Prepare a qualification protocol of reference standard, including the following information:2.4.1.1物料的鑒別，包括來源（如，生產廠家）以及批號。Identification of the materi

20、al, including source (e.g., manufacturer) and lot number.2.4.1.2檢驗報告書：檢驗報告書應包括所有法定對照品的檢驗結果，若適用。如果沒有，或如果生產廠家的檢驗報告書事先沒有驗證，則完整的法定對照品的檢驗是必需的，檢驗可以在公司內完成，也可以由批準的公司外的適當的實驗室完成。物料必須符合所有的檢驗要求。如果沒有法定對照品，則該建議的內部使用的對照品必須符合所有適用的質量標準。Certificate of Analysis: the COA should include results from all official RS test

21、s, when applicable. If it dose not or if the manufacturers COA has not been previously validated, then complete official RS testing is necessary and may be performed in-house or by an approved and appropriate outside laboratory. The material must pass all test requirements. When official RS is not a

22、pplicable, the proposed in-house reference standard must meet all applicable specifications.2.4.1.3用于對比的法定對照品或其他已確認的對照品的鑒別。Identity of official reference standards or other qualified reference standard used for comparison.責 任 人操 作RESPONSIBILITYACTION2.4.1.4檢驗方法和結果：內部使用的對照品的檢驗通常應包括其所使用時的方法。在確認之前，建議的內

23、部使用的對照品應采用法定對照品或其他已確認的對照品一致的方法進行干燥，若適用。Methods of Analysis and Results: testing in-house reference standard should always include the method for which it is to be used. The proposed in-house reference standard, when applicable, should be dried in the same manner as the official RS or other qualified

24、 RS prior to qualification.2.4.1.4.1根據內部使用的對照品所要用于檢驗的，所適用的產品的方法中標準溶液的配制方法，對內部使用的對照品，以及法定或其他已確認的對照品進行檢驗。Test proposed in-house reference standard according to the method for which it shall be used by following only the standard preparation procedure in the applicable product for both the proposed in-

25、house reference standard and the official or other qualified reference standard.2.4.1.4.2線性：根據建議的對照品所要用于的方法，配制三個溶液。根據方法中所規定的范圍限度，配制高、中、低三個濃度的溶液。如果范圍沒有規定，則在目前水平的±15%配制。用同樣的方法配制法定對照品或其他已確認的對照品。檢測儀器對所有溶液的三個讀數的響應，按面積歸一化法計算。相關系數（r2）應³ 0.995。Linearity: Prepare three concentrations of the propose

26、d standard material according to the method for which it is to be used. Prepare these solutions at the upper, mid and lower limit of the range specified in the method. If a range is not specified, prepare solutions at ±15% of the target level. Prepare the official RS or other qualified RS in th

27、e same manner. Measure instrument response for three readings of all solutions and perform least squares fit analysis. The correlation coefficient (r2) should be ³ 0.995.責 任 人操 作RESPONSIBILITYACTION2.4.1.4.3含量：根據所要用于的方法，配制五份待確認對照品的溶液（雙人）。用同樣的方法配制法定對照品或其他已確認的對照品溶液。結果必須符合法定對照品的質量標準，或其他適用的質量標準，且標準

28、偏差必須£ 2.0%。Assay: Prepare five solutions of the standard material under qualification according to the method for which it is to be used (two different analysts). Prepare the official RS or other qualified RS in the same manner. The results must comply with the official RS specification or othe

29、r applicable specifications and the standard deviation must be £ 2.0%.2.4.1.4.4有關物質：按藥典方法或內部方法進行檢驗。Related substance: Perform this test when available as a compendial monograph test or an in-house method.2.4.1.4.5水分：在標準品確認時檢驗。Water: Perform this test at the time of standard qualification.2.4.1.

30、4.6殘留溶劑：按藥典方法或內部方法進行檢驗。Residual solvents: Perform this test when available as a compendial monograph test or an in-house method.2.5當沒有法定對照品（如，USP、EP、CP等），或其他已確認的對照品時，內部使用的對照品的確認。Qualification of an in-house reference standard when official reference standard (e.g., USP, EP, CP, etc.), or other quali

31、fied standard is not available.2.5.1起草一份對照品的確認方案，方案包括下面的信息：Prepare a qualification protocol of reference standard, including the following information:2.5.1.1物料的鑒別，包括來源（如，生產廠家）以及批號。Identification of the material, including source (e.g., manufacturer) and lot number.責 任 人操 作RESPONSIBILITYACTION2.5.1.

32、2檢驗報告書：結構確證數據，如元素分析、NMR、MS、LC-MS、和IR；純度不低于98.0%；水分；殘留溶劑；有關物質。如果這些沒有，則有關的檢驗是必需的，檢驗可以在公司內完成，也可以在批準的適當的公司外實驗室完成。如果物料的含量低于98.0%，通過適當的檢驗，以及QC和QA的批準，仍可以批準為內部使用的對照品（如，雜質對照品的含量可低于98.0%）。如果物料為現有的原料，則必須符合所有適用的原料的質量標準。Certificate of Analysis: Characterization data, e.g. Elemental Analysis, NMR, MS, LC-MS and I

33、R; a purity of at least 98.0%; water content; residual solvents; and related substance. If this is not available then the related testing is necessary and may be performed in-house or at an approved and appropriate laboratory. If the material is less than 98.0%, it may still be approved as an in-hou

34、se RS with appropriate testing and the approval of QC and QA (e.g., impurity RS may be < 98.0%). If the material is an existing raw material, it must meet all applicable raw material specifications.2.5.1.3檢驗方法和結果：內部使用的對照品的檢驗通常必須包括其所使用時的方法。Methods of Analysis and Results: Testing of in-house refer

35、ence standard must always include the method for which it is to be used.2.5.1.3.1根據內部使用的對照品所要用于檢驗的，所適用的產品的方法中標準溶液的配制方法，對內部使用的對照品進行檢驗。Test the proposed in-house reference standard according to the method for which it should be used by following only the standard preparation procedure in the applicabl

36、e product for the proposed in-house reference standard.責 任 人操 作RESPONSIBILITYACTION2.5.1.3.2線性：根據建議的對照品所要用于的方法，配制三個溶液。根據方法中所規定的范圍限度，配制高、中、低三個濃度的溶液。如果范圍沒有規定，則在目前水平的±15%配制。檢測儀器對所有溶液的三個讀數的響應，按面積歸一化法計算。相關系數（r2）應³ 0.995。Linearity: Prepare, in triplicate, three concentrations of the proposed sta

37、ndard material according to the method for which it is to be used. Prepare the solutions at the upper, mid and lower limit of the range specified in the method. If a range is not specified, prepare the solutions at ±15% of the target level. Measure instrument response for three readings of all

38、solutions and perform least squares fit analysis. The correlation coefficient (r2) should be ³ 0.995.2.5.1.3.3含量：根據所要用于的方法，配制五份待確認對照品的溶液（雙人）。檢測儀器對溶液的響應。結果必須符合質量標準，且標準偏差£ 2.0%。Assay: Prepare five solutions of the standard material under qualification according to the method for which it is

39、to be used (two different analysts). Measure instrument response for the solutions. The results must comply with specifications with a standard deviation of £ 2.0%.2.5.1.4.4有關物質：按生產廠家或內部方法進行檢驗。Related substances: Perform this test when available as a manufacturers test or an in-house method.2.5

40、.1.4.5水分：在標準品確認時檢驗。Water: Perform this test at the time of standard qualification.2.5.1.4.6殘留溶劑：按生產廠家或內部方法進行檢驗。Residual solvents: Perform this test when available as a manufacturers test or an in-house method.2.6對于由研發轉來的對照品For reference standards transferred from the R&D department.2.6.1研發部門應提供相

41、應的檢驗報告書、圖譜，以及任何有關的文件，并提供該對照品的制備方法（若為自己合成）。R&D Department should provide the appropriate certificate of analysis, chromatogram, and any other related documents; and provide the synthesis process, if it is prepared in-house.責 任 人操 作RESPONSIBILITYACTIONQC2.6.2化驗室接收后，根據上面的確認要求，起草相應的確認方案進行對照品的確認。Afte

42、r receipt, QA should prepare the appropriate qualification protocol of the proposed reference standard according to the above qualification requirements.2.6對于雜質對照品，根據雜質對照品的性質（如，定性的或定量的），根據上面的要求，制訂適當的確認方案。For impurity standards, appropriate qualification protocol should be prepared according to the n

43、ature of impurity standards (such as qualitative or quantitative).3.評價、放行EVALUATION AND RELEASEQC, QA3.1確認結束后，化驗員將相關資料送QC主管審核，轉至QA進行最終的評價、放行。Upon completion of the qualification, analyst forwards the related documents to QC Supervisor for review, then submit to QA for final review and release.3.1.1基

44、準對照品Primary Reference Standard3.1.1.1一般純度應大于99.0%。In general, Purity should ³ 99.0%.3.1.1.2純度大于99.0%的，視其含量為100.0%，直接參與計算。If the purity > 99.0%, the assay could be regarded as 100.0%, and could directly used in calculation.QA3.1.1.3已知雜質、溶劑、水合物和無機鹽可能會使基準對照品的純度小于99.0%，此時，基準對照品的純度值應按實際標示，在樣品測定中應

45、加以折算。Known impurities, residual solvents, hydrate, and abio-salt could make the purity < 99.0%, in such case, the purity of the primary reference standard should be marked with the actual value, and it should be converted in sample testing.3.1.2第二對照品Secondary Reference Standard3.1.2.1經測得含量大于99.0%

46、的，純度為100.0%。If the assay > 99.0%, the purity could be regarded as 100.0%.3.1.2.2經測定含量小于99.0%的，按實際純度值進行折算。If assay < 99.0%, it should be converted based on the actual value.責 任 人操 作RESPONSIBILITYACTION3.2再確認期和有效期Re-qualification data and Expiry date3.2.1再確認期：在批準后，給定一年的再確認期。根據可利用的數據，給定在最初的再確認期以后

47、的再確認期。Re-qualification date: Upon approval, the reference standard should be assigned a one-year re-qualification date. Re-qualification date assigned after the initial re-qualification period should be established based on available data.3.2.1.1對于連續使用的，對照品必須在再確認日期之前完成再確認。For continued use, the stan

48、dard must be re-qualified prior to the re-qualification date.3.2.1.2采用與對照品最初批準時相同的方法、標準，對含量、有效物質和水分進行檢驗。Perform assay, related substances and water tests in the same manner and using the same criteria used for the initial standard approval.3.2.1.3對照品再確認的日期按對照品接收之日，或生產日期（若為自己合成）計算，除非生產商或供應商有規定的。The r

49、e-qualification date should be calculated on the date the RS received or manufactured (if it is prepared in-house), except it is specified by the manufacturer or supplier.注：如果對照品在再確認時，不符合規定，則根據SOP3-0002進行調查。Note: When a standard fails re-qualification, conduct an investigation according to SOP 3-000

50、2.3.2.2有效期：根據歷史數據，不穩定的對照品應給定有效期，超過有效期即不能再使用。Expiry date: Unstable standards should be assigned an expiry date, based on historical data, beyond which they may not be used.QA3.3檢驗報告書Certificate of Analysis (COA)3.3.1對照品批準后，QA出具檢驗報告書，經QA經理簽字批準后，予以放行使用。Upon approval, QA should issue COA, and

51、after approved by QA Manager, it could be released for use.3.3.2對照品的檢驗報告書應包括如下內容，包括但不僅限于：The COA of the reference standard should include the followings, but is not limited to:3.3.2.1對照品的名稱、公司內批號、類別。Reference standard name, in-house lot number, classification3.3.2.2供應商的名稱、批號。Suppliers name, batch number責 任 人操 作RESPONSIBILITYACTION3.3.2.3檢驗項目、標準規定、檢驗結果。Test items, specification, test results3.3.2.4貯藏條件、使用說明。Storage condition, instruction for use3.3.2.5其他需說明的事項。Any other items to be specified3.3.3對照品檢驗報告書號由：RS2位數年的年、月、日2位數的流水號組成。如“RS050908-01”表示為2005年9月8日簽發的第一份對照品檢驗