Q2(R1)中英文对照.doc

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1、Four short words sum up what has lifted most successful individuals above the crowd: a little bit more.-author-dateQ2(R1)中英文对照REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USEREQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE人用药品的注册要求ICH HARMONISED TRIPARTITE GUIDELINE ICH协调

2、的三方指导原则VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY 分析方法验证：正文和方法学Q2(R1) Current Step 4 version 现行第4阶段版本Parent Guideline dated 27 October 1994 最初指导原则起于1994年10月27日(Complementary Guideline on Methodology dated 6 November 1996 incorporated in November 2005) （方法学补充指导原则完成于1996年11月6日，于2005年11月

3、合并）This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Ja

4、pan and USA.此指导原则由适当的ICH专家工作组起草，经调整团磋商，于ICH过程一致。在第四阶段，最终的草案推荐给欧盟，日本和美国的监管机构采用。Q2(R1) Document HistoryQ2(R1) 文件历史First Codification 初次法典化History 历史Date 时间New Codification November 2005Parent Guideline: Text on Validation of Analytical Procedures 最初的指导原则：分析方法的验证Q2 Approval by the Steering Committee un

5、der Step 2 and release for public consultation. 在第2阶段经策划委员会批准，作为公用的咨询26 October 2003 2003-10Q2 Q2A Approval by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies. 在第4阶段经侧环委员会同意并推荐给三方ICH监管机构采用27 October 1994 1994-10-27Q2 Guideline on Validation of A

6、nalytical Procedures: Methodology developed to complement the Parent Guideline 分析方法验证的指导原则：扩展的方法学作为最初指导原则的补充Q2B Approval by the Steering Committee under Step 2 and release for public consultation. 在第2阶段经策划委员会批准，作为公用的咨询29 November 1995 in Q2(R1) Q2B Approval by the Steering Committee under Step 4 and

7、 recommendation for adoption to the three ICH regulatory bodies 在第4阶段经侧环委员会同意并推荐给三方ICH监管机构采用Current Step 4 version 现行Q2A and Q2B The parent guideline is now renamed Q2(R1) as the guideline Q2B on methology has been incorporated to the parent guideline. The new title is “Validation of Analytical Proc

8、edures: Text and Methodology”. 最初的指导原则现在更名为Q2(R1)因为指导原则Q2B方法学已经合并到最初的指导原则中。新标题“分析方法验证：正文和方法学”November 2005 Q2(R1) PART I: TEXT ON VALIDATION OF ANALYTICAL PROCEDURES 分析方法验证文件ICH Harmonised Tripartite Guideline ICH协调三方指导原则Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting

9、on 27 October 1994, this guideline is recommended for adoption to the three regulatory parties to ICH1994年10月27日的ICH策划委员会会议已经进入了ICH进程的第4阶段，此指导原则推荐给ICH三个监管部门采纳1. Introduction This document presents a discussion of the characteristics for consideration during the validation of the analytical procedure

10、s included as part of registration applications submitted within the EC, Japan and USA. This document does not necessarily seek to cover the testing that may be required for registration in, or export to, other areas of the world. Furthermore, this text presentation serves as a collection of terms,

11、and their definitions, and is not intended to provide direction on how to accomplish validation. These terms and definitions are meant to bridge the differences that often exist between various compendia and regulators of the EC, Japan and USA. 1 介绍作为递交给欧共体，日本和美国新药注册申请资料的一部分，对分析方法验证需考虑事项的特征的讨论在此文件呈现

12、出来。没有必要在此文件寻找覆盖在世界其他地区的药品的注册或出口所要求的测试。此外，此文作为术语的收集，和他们的定义而服务的，并没有想提供怎样完成验证的指示。这些项目和定义是连接那些常存在于欧共体，日本和美国的各种药典和规定之间的差异的桥梁。The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose. A tabular summation of the characteristics applicable to iden

13、tification, control of impurities and assay procedures is included. Other analytical procedures may be considered in future additions to this document. 分析方法验证的目的是为了阐述分析方法是适用于它要分析的目的的。应用于鉴别，杂质控制和含量测定方法的特征项的综合，可能考虑会加入到今后的文件中。2. Types of Analytical Procedures to be Validated 2所要验证的分析方法的类型The discussion

14、 of the validation of analytical procedures is directed to the four most common types of analytical procedures: 分析方法验证的讨论通常集中在以下分析方法的四个最通用的方面：- Identification tests; -鉴别试验；- Quantitative tests for impurities content; -杂质含量的定量测试；- Limit tests for the control of impurities; -杂质控制的限度测试；- Quantitative t

15、ests of the active moiety in samples of drug substance or drug product or other selected component(s) in the drug product.-原料药或制剂或其他药品中选择性的组分的样品的活性部分的定量测试； Although there are many other analytical procedures, such as dissolution testing for drug products or particle size determination for drug subst

16、ance, these have not been addressed in the initial text on validation of analytical procedures. Validation of these additional analytical procedures is equally important to those listed herein and may be addressed in subsequent documents. 虽然有许多其他的分析方法，诸如药品的溶解性试验或药品微粒大小测试，在分析方法验证最初的正文中并未给出。那些额外的分析方法的

17、验证和在这里列出来的分析方法同样重要，且有可能在后来的文件中提出。A brief description of the types of tests considered in this document is provided below. 对于此文件中考虑到的测试的类型的简短描述如下：- Identification tests are intended to ensure the identity of an analyte in a sample. This is normally achieved by comparison of a property of the sample (

18、e.g., spectrum, chromatographic behavior, chemical reactivity, etc) to that of a reference standard; - 鉴别试验是为了鉴定样品中某个分析物存在。通常将适当的样品与参考标准品进行比较（例如，光谱，色谱行为，化学反应等）。- Testing for impurities can be either a quantitative test or a limit test for the impurity in a sample. Either test is intended to accurate

19、ly reflect the purity characteristics of the sample. Different validation characteristics are required for a quantitative test than for a limit test;- 杂质测试是对样品中的杂质进行定性或定量试验。这两种试验都是为了准确的反应样品中杂质的特性。与限度试验相比，定量试验要求不同的验证试验项。- Assay procedures are intended to measure the analyte present in a given sample.

20、 In the context of this document, the assay represents a quantitative measurement of the major component(s) in the drug substance. For the drug product, similar validation characteristics also apply when assaying for the active or other selected component(s). The same validation characteristics may

21、also apply to assays associated with other analytical procedures (e.g., dissolution).- 含量测试方法是为了测定给定样品中的被测物的量。此文件的内容中，含量测试代表原料药中的主成分的定量的测试。对于药物制剂中的活性组分或其他选择性组分进行含量测定时，相似的验证特征也同样应用。同样的验证特征也可以应用到与其他分析方法相关联的含量测试中（如，溶解）。The objective of the analytical procedure should be clearly understood since this wi

22、ll govern the validation characteristics which need to be evaluated. Typical validation characteristics which should be considered are listed below: 分析方法的目的应该清晰易懂，因为它将制约需要被评价的验证特征。应考虑的典型的验证特征如下：Accuracy 准确度Precision 精密度Repeatability 重复性Intermediate Precision 中间精密度Specificity 特异性Detection Limit 检测限Qu

23、antitation Limit 定量限Linearity 线形Range 范围Each of these validation characteristics is defined in the attached Glossary. The table lists those validation characteristics regarded as the most important for the validation of different types of analytical procedures. This list should be considered typical

24、 for the analytical procedures cited but occasional exceptions should be dealt with on a case-by-case basis. It should be noted that robustness is not listed in the table but should be considered at an appropriate stage in the development of the analytical procedure. 每一个验证特征在附属的术语中有定义。此表列出了那些验证特征，它们

25、被认为是分析方法不同类型验证的最重要的部分。Furthermore revalidation may be necessary in the following circumstances: 此外，以下情况可能有必要重新验证。- changes in the synthesis of the drug substance; -原料药合成路线变更；- changes in the composition of the finished product; -成品组分变更- changes in the analytical procedure. -分析方法变更The degree of reval

26、idation required depends on the nature of the changes. Certain other changes may require validation as well. 要求重新验证的程度取决于变更的性质。某些其他变更可能也要重新验证。TABLE Type of analytical procedure分析方法的类型IDENTIFICATION鉴别试验TESTING FOR IMPURITIES杂质测试ASSAY- dissolution(measurement only)- content/potency含量测试-溶解度（只是测量）-含量/效力

27、characteristics特征quantitat.定量limit限度Accuracy准确度-+-+Precision精密度Repeatability重复性Interm.Precision中间精密度-+ (1)-+ (1)Specificity (2) 特异性（2）+Detection Limit检测限- (3)+-Quantitation Limit定量限-+-Linearity 线性-+-+Range 范围-+-+- signifies that this characteristic is not normally evaluated - 表示此项特征通常不用评价+ signifies

28、 that this characteristic is normally evaluated +表示此项特征通常要评价(1) in cases where reproducibility (see glossary) has been performed, intermediate precision is not needed (1)如果重复性（见术语表）已经履行，中间精密度不做要求(2) lack of specificity of one analytical procedure could be compensated by other supporting analytical p

29、rocedure(s) (2) 一个分析方法特异性缺乏，可以通过其他支持性的分析方法补充(3) may be needed in some cases(3)某些情况下可能需要GLOSSARY 术语1. ANALYTICAL PROCEDURE The analytical procedure refers to the way of performing the analysis. It should describe in detail the steps necessary to perform each analytical test. This may include but is n

30、ot limited to: the sample, the reference standard and the reagents preparations, use of the apparatus, generation of the calibration curve, use of the formulae for the calculation, etc. 1分析方法分析方法是指分析测试进行的方式。它应该详细地描述执行每个分析试验的必要的步骤。可能包括但不限于：样品，参考标准品和试剂制备，适用的仪器，标准曲线的产生，采用的计算公式，等等。2. SPECIFICITY Specifi

31、city is the ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical pr

32、ocedure(s). This definition has the following implications: Identification: to ensure the identity of an analyte. Purity Tests: to ensure that all the analytical procedures performed allow an accurate statement of the content of impurities of an analyte, i.e. related substances test, heavy metals, r

33、esidual solvents content, etc. Assay (content or potency): to provide an exact result which allows an accurate statement on the content or potency of the analyte in a sample. 2 特异性（专属性）特异性是指清晰地评价组分中认为可能存在的被测物的能力。典型的包括：杂质，降解产物，辅料等。一个单独的分析方法的专属性缺乏，可以通过其他可支持的分析方法来补充。此定义有以下含义：鉴别：确保某个分析物的身分。纯度测试：确保所执行的所有

34、分析方法对被测物的杂质的含量有一个准确的陈述，如，有关物质测试，重金属，残留溶剂，等。含量测试（含量或效力）提供准确的结果，对样品中被测物的含量或效力有准确的陈述。3. ACCURACY The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found. This

35、is sometimes termed trueness. 3。准确度 分析方法的准确度表达了可接受值，包括常规真值或可接受的参考值，与测得值之间的一致性的接近程度。4. PRECISION 4精密度The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under

36、the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility. 分析方法的精密度表达了，在给定条件下，获得的一系列的同一均匀样品的多次取样的测量值之间的一致性的接近程度（分散度）。精密度可以从三个水平考虑：重复性，中间精密度。重现性。Precision should be investigated using homogeneous, authentic samples. However, if i

37、t is not possible to obtain a homogeneous sample it may be investigated using artificially prepared samples or a sample solution. 精密度应该用同一均匀，权威样品进行考察。然而，如果不能获得同一均匀样品，可以用人工制备样品或样品溶液进行考察。The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of

38、 variation of a series of measurements. 分析方法的精密度常用一系列测量值的变异，标准偏差，或变异系数来表达。4.1. Repeatability Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision.4.1重复性重复性表示在短期时间间隔内，同样操作条件下的精密度。重复性也叫批内分析精密度。 4.2.

39、Intermediate precision Intermediate precision expresses within-laboratories variations: different days, different analysts, different equipment, etc. 4.2中间精密度中间精密度表示在同一试验室下的变异：不同天，不同试验者，不同仪器，等。4.3. Reproducibility Reproducibility expresses the precision between laboratories (collaborative studies, u

40、sually applied to standardization of methodology). 4.3重现性重现性表示试验室之间的精密度（合作性研究，通常用于分析方法学的标准化）。5. DETECTION LIMIT The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value. 5检测限一个分析方法的检测

41、限是样品中分析物能被检测到但是没必要作为精确值定量的最小量。6. QUANTITATION LIMIT The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for l

42、ow levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products. 6定量限一个分析方法的定量限是样品中分析物能够定量测定，具有合适的精密度和准确度的最低量。定量限是样品基质中最低含量的化合物的定量分析的一个参数，特别用于测定杂质和/或降解产物。7. LINEARITY The linearity of an analytical procedure is its ability (within a

43、 given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. 7线性分析方法的线性是获得的测试结果与样品中被测物的浓度成直接比例的能力。8. RANGE The range of an analytical procedure is the interval between the upper and lower concentration (amounts) of analyte in the sample

44、 (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity. 8范围分析方法的范围是样品中被测物的最高浓度和最低浓度之间的间隔（包括最高和最低浓度），在此区间内，已经证明分析方法有合适的精密度，准确度和线性。9. ROBUSTNESS The robustness of an analytical procedure is a measure

45、of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. 9耐用性分析方法的耐用性是，在故意对分析方法的参数进行微小变化后，方法仍然能保持不受影响的能力的一种测试，并且提供在正常范围内使用的可靠性说明。PART II: VALIDATION OF ANALYTICAL PROCEDURES: METHODOLOGY ICH Harmo

46、nised Tripartite Guideline 第II部分:分析方法的验证方法学ICH协调的三方指导原则Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 6 November 1996, and incorporated into the core guideline in November 2005, this guideline is recommended for adoption to the three regulatory parties to ICH INTRO

47、DUCTION 介绍This document is complementary to the parent document which presents a discussion of the characteristics that should be considered during the validation of analytical procedures. Its purpose is to provide some guidance and recommendations on how to consider the various validation characteristics for each analytical procedure. In some cases (for example, demonstration of specificity), the overall capabilities of a number of analytical procedures in combination may be investigated in or