对照品管理SOP双语

1、起草/修订人：Author日期：Date部门主管审查：Dept. Head Approval日期：DateQA批准：Approved by QA日期：Date分 发：Distribution:QA, QC, R&D目的：描述化验室对照品的接收、确认、贮存、库存、分发、使用的规程。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范围：适用于化验室内所用的对照品，包括基准对照品、第二对照品。SCOPE:This procedure is applicable to analytical reference standards used in QC lab, includes the Primary Reference Standards and the Secondary Reference Standards参考文件：REFERENCE AND ATTACHMENT:SOP/题目 SOP/TITLE记录/附件/题目 FORMS/ATTACHMENTS/TITLE3-0002OOS调查附件1

3、：对照品标签样例Investigation of Out-of-Specification ResultAttachment 1: Reference Standard Label (Example)F-03-010对照品登记台帐Reference Standard Inventory Log SheetF-03-011对照品接收记录Reference Standard Receiving LogbookF-03-012对照品使用记录Use Record of Reference Standard 定 义：DEFINITIONS:基准对照品以广泛分析表明具有可信的、高纯度的物质。这类标准品可以

4、：1）来源于法定机构；2）独立合成；3）来自于高纯度的现有生产物料；4）用进一步精制现有生产物料的方法来制备。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.第二对照品与基准对照品比较显示有规定的质量和纯度，并用作日常检验分析的参考标准品。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.规 程：PROCEDURE:责 任 人操 作RESPONSIBILITYACTION1.对照品接收RECEIPT OF REFERENCE STANDARDQC主管1.1QC主管指定专人负责对照品的管理；对照品管理员负责对照品的接收、贮存以及发放等的管理。QC SupervisorQC Supervisor designee is responsible for the management of all

7、reference standards, such as the receipt, storage and distribution of reference standard.对照品管理员1.2接收对照品时，应检查对照品的包装是否完好、是否提供检验报告书、检验报告书是否与实物相符，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将对照品的相关信息在对照品登记台帐上作好记录，每批对照品建立一份管理台帐。Enter reference standard information into the Reference Standard Receiving logbook, and establish a Reference Standard Inventory log sheet for each lot. 1.4接收后的对照品给定公司内批号。Assign the lot number for

9、received reference standards对照品的批号由：类别号年号流水号组成：The lot number is consist of: Sort number + digit number of the calendar Year + sequential number:.1类别号：Sort number.1.1基准对照品：RSP（Reference Standard, Primary）.1.2第二对照品：RSS（Reference Standard, Secondary）.2年号：用2位数的年份表示Year: 2 digit number of the year desig

10、nation.3流水号：用2位数字表示。Sequential number: 2 digit number.1.5对照品接收后，在每批对照品的每个包装上贴签（附件1），标明名称、批号、数量、来源、瓶号/总瓶数（比如，共有10瓶，其中第2瓶为：2/10）、接收人签名/日期等内容。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.责 任 人操 作RESPONSIBILITYACTION对照品管理员1.6将对照品放入标有“待确认对照品”的干燥器中，存放于28冰箱中，或者存放于对照品所规定的贮存条件。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对照品应存放于棕色玻璃瓶中，对于不符合此要求的，在接收后，将对照品装入或分装于棕色玻璃瓶中。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.对照品确认QUALIFICAITON OF REFERENCE STANDARDSQC2.1对照品应从法定机构购买（如，USP、EP、CP等）；并且，只要是适用的，内部使用的对照品应根据这些从法定机构购买来的对照品进行确认。如果法定对照品不能得到，则内部使用的对照品必须根据一个确认的标准品进行确认，或必须根据本SOP中下面的要求的进行全部的确认。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对照品的确认包括：The qualification of reference standard includes:2.2.1基准对照品的确认Qualification of Primary Reference Standard2.2.2第二对照品的确认Qualification of Secondary Reference Standards2.2.2.1根据法定对照品（如，USP、EP、CP等）或其他已确认的标准，对内部

16、使用的对照品的确认。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当没有法定对照品（如，USP、EP、CP等），或其他已确认的对照品时，内部使用的对照品的确认。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.责 任 人操 作RESPONSIBILITYACTIONQC, QA2.3基准对照品的确认Qualification of Primary Reference Standard2.3.1从法定机构购买的基准对照品，在根据“1. 接收”的规程接收后，将与该批对照品有关的资料转至QA审核。经QA审核后，发放检验报告书。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根据法定对照品（如，USP、EP、CP等）或其他已确认的标准，对内部使用的对照品的确认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起草一份对照品的确认方案，方案包括下面的信息：Prepare a qualification protocol of reference standard, including the following information:2.4.1.1物料的鉴别，包括来源（如，生产厂家）以及批号。Identification of the materi

20、al, including source (e.g., manufacturer) and lot number.2.4.1.2检验报告书：检验报告书应包括所有法定对照品的检验结果，若适用。如果没有，或如果生产厂家的检验报告书事先没有验证，则完整的法定对照品的检验是必需的，检验可以在公司内完成，也可以由批准的公司外的适当的实验室完成。物料必须符合所有的检验要求。如果没有法定对照品，则该建议的内部使用的对照品必须符合所有适用的质量标准。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用于对比的法定对照品或其他已确认的对照品的鉴别。Identity of official reference standards or other qualified reference standard used for comparison.责 任 人操 作RESPONSIBILITYACTION2.4.1.4检验方法和结果：内部使用的对照品的检验通常应包括其所使用时的方法。在确认之前，建议的内

23、部使用的对照品应采用法定对照品或其他已确认的对照品一致的方法进行干燥，若适用。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根据内部使用的对照品所要用于检验的，所适用的产品的方法中标准溶液的配制方法，对内部使用的对照品，以及法定或其他已确认的对照品进行检验。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线性：根据建议的对照品所要用于的方法，配制三个溶液。根据方法中所规定的范围限度，配制高、中、低三个浓度的溶液。如果范围没有规定，则在目前水平的±15%配制。用同样的方法配制法定对照品或其他已确认的对照品。检测仪器对所有溶液的三个读数的响应，按面积归一化法计算。相关系数（r2）应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.责 任 人操 作RESPONSIBILITYACTION2.4.1.4.3含量：根据所要用于的方法，配制五份待确认对照品的溶液（双人）。用同样的方法配制法定对照品或其他已确认的对照品溶液。结果必须符合法定对照品的质量标准，或其他适用的质量标准，且标准

28、偏差必须£ 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有关物质：按药典方法或内部方法进行检验。Related substance: Perform this test when available as a compendial monograph test or an in-house method.2.4.1.4.5水分：在标准品确认时检验。Water: Perform this test at the time of standard qualification.2.4.1.

30、4.6残留溶剂：按药典方法或内部方法进行检验。Residual solvents: Perform this test when available as a compendial monograph test or an in-house method.2.5当没有法定对照品（如，USP、EP、CP等），或其他已确认的对照品时，内部使用的对照品的确认。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起草一份对照品的确认方案，方案包括下面的信息：Prepare a qualification protocol of reference standard, including the following information:2.5.1.1物料的鉴别，包括来源（如，生产厂家）以及批号。Identification of the material, including source (e.g., manufacturer) and lot number.责 任 人操 作RESPONSIBILITYACTION2.5.1.

32、2检验报告书：结构确证数据，如元素分析、NMR、MS、LC-MS、和IR；纯度不低于98.0%；水分；残留溶剂；有关物质。如果这些没有，则有关的检验是必需的，检验可以在公司内完成，也可以在批准的适当的公司外实验室完成。如果物料的含量低于98.0%，通过适当的检验，以及QC和QA的批准，仍可以批准为内部使用的对照品（如，杂质对照品的含量可低于98.0%）。如果物料为现有的原料，则必须符合所有适用的原料的质量标准。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检验方法和结果：内部使用的对照品的检验通常必须包括其所使用时的方法。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根据内部使用的对照品所要用于检验的，所适用的产品的方法中标准溶液的配制方法，对内部使用的对照品进行检验。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.责 任 人操 作RESPONSIBILITYACTION2.5.1.3.2线性：根据建议的对照品所要用于的方法，配制三个溶液。根据方法中所规定的范围限度，配制高、中、低三个浓度的溶液。如果范围没有规定，则在目前水平的±15%配制。检测仪器对所有溶液的三个读数的响应，按面积归一化法计算。相关系数（r2）应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：根据所要用于的方法，配制五份待确认对照品的溶液（双人）。检测仪器对溶液的响应。结果必须符合质量标准，且标准偏差£ 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有关物质：按生产厂家或内部方法进行检验。Related substances: Perform this test when available as a manufacturers test or an in-house method.2.5

40、.1.4.5水分：在标准品确认时检验。Water: Perform this test at the time of standard qualification.2.5.1.4.6残留溶剂：按生产厂家或内部方法进行检验。Residual solvents: Perform this test when available as a manufacturers test or an in-house method.2.6对于由研发转来的对照品For reference standards transferred from the R&D department.2.6.1研发部门应提供相

41、应的检验报告书、图谱，以及任何有关的文件，并提供该对照品的制备方法（若为自己合成）。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.责 任 人操 作RESPONSIBILITYACTIONQC2.6.2化验室接收后，根据上面的确认要求，起草相应的确认方案进行对照品的确认。Afte

42、r receipt, QA should prepare the appropriate qualification protocol of the proposed reference standard according to the above qualification requirements.2.6对于杂质对照品，根据杂质对照品的性质（如，定性的或定量的），根据上面的要求，制订适当的确认方案。For impurity standards, appropriate qualification protocol should be prepared according to the n

43、ature of impurity standards (such as qualitative or quantitative).3.评价、放行EVALUATION AND RELEASEQC, QA3.1确认结束后，化验员将相关资料送QC主管审核，转至QA进行最终的评价、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、准对照品Primary Reference Standard3.1.1.1一般纯度应大于99.0%。In general, Purity should ³ 99.0%.3.1.1.2纯度大于99.0%的，视其含量为100.0%，直接参与计算。If the purity > 99.0%, the assay could be regarded as 100.0%, and could directly used in calculation.QA3.1.1.3已知杂质、溶剂、水合物和无机盐可能会使基准对照品的纯度小于99.0%，此时，基准对照品的纯度值应按实际标示，在样品测定中应

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第二对照品Secondary Reference Standard3.1.2.1经测得含量大于99.0%

46、的，纯度为100.0%。If the assay > 99.0%, the purity could be regarded as 100.0%.3.1.2.2经测定含量小于99.0%的，按实际纯度值进行折算。If assay < 99.0%, it should be converted based on the actual value.责 任 人操 作RESPONSIBILITYACTION3.2再确认期和有效期Re-qualification data and Expiry date3.2.1再确认期：在批准后，给定一年的再确认期。根据可利用的数据，给定在最初的再确认期以后

47、的再确认期。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对于连续使用的，对照品必须在再确认日期之前完成再确认。For continued use, the stan

48、dard must be re-qualified prior to the re-qualification date.3.2.1.2采用与对照品最初批准时相同的方法、标准，对含量、有效物质和水分进行检验。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对照品再确认的日期按对照品接收之日，或生产日期（若为自己合成）计算，除非生产商或供应商有规定的。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：如果对照品在再确认时，不符合规定，则根据SOP3-0002进行调查。Note: When a standard fails re-qualification, conduct an investigation according to SOP 3-000

50、2.3.2.2有效期：根据历史数据，不稳定的对照品应给定有效期，超过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检验报告书Certificate of Analysis (COA)3.3.1对照品批准后，QA出具检验报告书，经QA经理签字批准后，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对照品的检验报告书应包括如下内容，包括但不仅限于：The COA of the reference standard should include the followings, but is not limited to:3.3.2.1对照品的名称、公司内批号、类别。Reference standard name, in-house lot number, classification3.3.2.2供应商的名称、批号。Suppliers name, batch number责 任 人操 作RESPONSIBILITYACTION3.3.2.3检验项目、标准规定、检验结果。Test items, specification, test results3.3.2.4贮藏条件、使用说明。Storage condition, instruction for use3.3.2.5其他需说明的事项。Any other items to be specified3.3.3对照品检验报告书号由：RS2位数年的年、月、日2位数的流水号组成。如“RS050908-01”表示为2005年9月8日签发的第一份对照品检验