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1. Principle 原则 2. General 常规 3. Pharmacopoeial methods 药典方法 4. Non-pharmacopoeial methods 非药典方法 5. Method validation 方法验证 6. Method verification 方法确认 7. Method transfer 方法转移 8. Revalidation 再验证 9. Characteristics of analytical procedures 分析方法的特征 1. PRINCIPLE 原则 1.1 This appendix presents some information on the characteristics that should be considered during validation of analytical methods. Approaches other than those specified in this appendix may be followed and may be acceptable. Manufacturers should choose the validation protocol and procedures most suitable for testing of their product. 本附录给出了一些分析方法验证过程中中需要考虑的特性信息。除了在附录里指定的方法以外，其它方法也可以采用。 厂家应选择适合自身样品检验的验证方案和程序。 1.2 The manufacturer should demonstrate (through validation) that the analytical procedure is suitable for its intended purpose. 厂家应当证明(通过验证)分析的程序是符合预期目的的 1.3 Analytical methods, whether or not they indicate stability, should be validated. 分析方法是否稳定,都应该被验证 1.4 The analytical method should be validated by research and development before being transferred to the quality control unit when appropriate. 适当时，分析方法在转移给质量控制部门之前, 需要在研发进行验证 1.5 The recommendations as provided for in good laboratory practices and guidelines for transfer of technology should be considered, where applicable, when analytical method validation is organized and planned. 如适用，在组织和计划方法验证时, GLP和技术转移指南所推荐的条目应该被考虑 2. GENERAL 一般原则 2.1 There should be specifications for both materials and products. The tests to be performed should be described in the documentation on standard test methods 原料和成品的分析方法应该有规范, 需要执行的分析应该在文件中描述标准的测试方法 2.2 Specifications and standard test methods in pharmacopoeias (“pharmacopoeial methods”), or suitably developed specifications or test methods (“non-pharmacopoeial methods”) as approved by the national regulatory authority (NRA) may be used. 可以使用药典中规定的规范和标准测试方法(药典方法)或者经过适当开发的经国家药品监督管理部门认可的规范或方法(非药典方法) 2.3 Well-characterized reference materials, with documented purity, should be used in analysis. 应该在分析中使用具有文件证明其纯度的特定对照物 2.4 The most common analytical procedures include identification tests, assay of drug substances and pharmaceutical products, quantitative tests for content of impurities and limit tests for impurities. Other analytical procedures include dissolution testing and determination of particle size. 常见的分析程序包括鉴别、含量、杂质定量测试和杂质限度，其他分析程序还包括溶出度和粒径测定 2.5 The results of analytical procedures should be accurate, legible, contemporaneous, original, reliable and reproducible. All results should be archived for an appropriate period of time as defined by the laboratory and be in compliance with NRA requirements. 检验的结果应精确，清晰，同步，原始，可靠，并可再现。所有结果应该按照实验室定义的时间周期妥善保存并符合国家监管要求。 2.6 The procedure should become part of a continuous verification procedure to demonstrate that it meets the predefined criteria over the life of the procedure. 该程序应成为持续确认程序的一部分，以证实它在其生命周期内符合既定的标准。 2.7 Trend analysis and risk assessment should be considered at intervals to ensure that the method is appropriate for its intended application. 应该考虑定期进行趋势分析和风险评估以确保该分析方法符合其预期用途 2.8 Changes to methods should be managed in accordance with the authorized change control procedure. The variability of reference materials and other factors such as changes in the process for synthesis of the drug substance, changes in the composition of the finished product, changes in the analytical procedure, when analytical methods are transferred from one laboratory to another (when method transfer is not possible) or when major pieces of equipment instruments change should be considered. These should be understood, controlled and, where possible, reduced. Verification or revalidation should be considered where appropriate. 分析方法的变更应该按照批准的变更管理规程进行管理。当分析方法从一个实验室转移到另一个或当主要设备仪器变化时应考虑对照物的可变性以及其他因素如药品合成工艺的变化，药品组分的变化，分析程序的变化。这些应该被理解，控制和适当的减少。适当时，应该考虑进行确认或再验证。 2.9 The scope of verification or degree of revalidation depend on the nature of the change(s) and the outcome of risk assessment. 验证的范围或再验证的程度取决于变更的性质和风险评估的结果 2.10 There should be evidence that the analysts, who are responsible for certain tests, are appropriately qualified to perform those analyses (“analyst proficiency”). 应有证据表明负责某一测试的分析师应该被确认可以执行该测试（分析熟练程度） 2.11 The data obtained during method validation and verification should be considered covered by good anything practices (GxP) requirements and are expected to follow the principles of good data and record management practices (2). Their associated metadata are also expected to be retained and subjected to good data and record management practices. 在分析方法验证和方法分析方法验证和确认过程中获得的数据应符合GXP的要求和遵循良好数据和记录管理规范的要求。它们的元数据也应该被保存并符合良好数据和记录管理规范要求。 2.12 When computerized systems are used to obtain and process data relating to method validation and verification, they should comply to the principles enunciated in Appendix 5 – Validation of computerized systems. 当使用计算机化系统获取和处理方法验证和确认相关的数据时，应该遵循附录5—计算机化系统验证的原则。 2.13 Adequate attention should be paid to the method of sample preparation. The description of this step should be as detailed as possible, especially if it can have a significant impact on tests results (e.g. particular attention should be paid to details such as sonication time, sonication bath temperature and mixing and to samples where demixing is known to occur). 应该充分重视样品处理的方法，对这一步骤的描述应尽可能的详细，特别是当它对检测结果有重要影响时（例如应该特别重视如超声时间，超声池温度和搅拌和当已知会分层时进行取样等细节） 2.14 Failures occurring during method validation, and how these were overcome, should be included in the method validation report – it is not acceptable to present only the passing results as it will give a biased imaged on the reliability of the method and on how it should be applied. 方法验证过程中发生的失败，以及如何处理这些失败的，应该包括在方法验证报告中。仅仅包括合格的结果是不接受的，因为他会对方法的可靠性和如何应该该方法产生偏颇。 3. PHARMACOPOEIAL METHODS 药典方法 3.1 When pharmacopoeial methods are used, evidence should be available to prove that such methods are suitable for routine use in the laboratory (verification). 当使用药典的方法时,要有证据证明这种方法在该实验室日常使用是适用的。 3.2 Pharmacopoeial methods used for determination of content or impurities in pharmaceutical products should also have been demonstrated to be specific with respect to the substance under consideration (no placebo interference). 用于测定制剂产品中含量或杂质的药典方法均应被证明在有主含量成分存在时具有专属性（无空白干扰）。 4. NON-PHARMACOPOEIAL METHODS 非药典方法 4.1 Non-pharmacopoeial methods should be appropriately validated. 非药典方法应进行适当的验证 5. METHOD VALIDATION 方法验证 5.1 Validation should be performed in accordance with the validation protocol. The protocol should include procedures and acceptance criteria for all characteristics. The results should be documented in the validation report. 验证应当按照预定的验证方案进行,方案应该包括所有特性的验证程序和接受标准,结果应当记录在验证报告中。 5.2 Justification should be provided when non-pharmacopoeial methods are used if pharmacopoeial methods are available. Justification should include data such as comparisons with the pharmacopoeial or other methods. 如果存在药典方法可用，而使用了非药典方法，则需要提供论证。论证应包括数据，例如与药典或其它方法的比较。 5.3 Standard test methods should be described in detail and should provide sufficient information to allow properly trained analysts to perform the analysis in a reliable manner. As a minimum, the description should include the chromatographic conditions (in the case of chromatographic tests), reagents needed, reference standards, the formulae for the calculation of results and system suitability tests. 标准检测方法应详细描述，并提供充分的信息使得经过适当培训的化验员可以用可靠的方式进行分析。至少，描述应包括色谱条件（如果采用色谱测试），所需溶剂、标准对照品、结果计算公式和系统适用性检测。 6. METHOD VERIFICATION 方法确认 6.1 Method verification consists of partial validation. It should be performed for already validated analytical methods under the following circumstances: (a) when an already validated method is used on a product for the first time (e.g. in case of a change in active pharmaceutical ingredient (API) supplier, change in the method of synthesis or after reformulation of a drug product); (b) when an already validated method is used for the first time in a laboratory (in some cases, method transfer may be preferable). 方法确认包含方法验证的一部分,方法确认是针对已经验证过的方法的以下几种情形：(a)当使用一个验证过的方法进行首次对一个产品进行检测时，（例如：在API的供应商变更时，或者API合成方法变更或成品重新配方后）（b）方法第一次在一个实验室使用时（在某些情况下，方法转移更合意） 6.2 Method verification may include only the validation characteristics of relevance to the particular change. For instance, in the case of a change in API supplier, the only expected difference would be in the impurity profile or solubility of the API, and therefore, for a related substances method, there should be an appropriate verification that the method is able to detect and quantitate all potential impurities, even the late eluting ones. Specificity should be among the tests considered (see sections 9 and 10 below for more detail). 方法确认可能只是验证方法验证中最容易受影响的那一部分，例如通过API供应商的改变，来改变杂质的分布或者API的溶解度，因此对于一个检测方法，必须要进行适当的确认以确保该方法可以检测出该样品所有潜在的杂质甚至洗脱出的杂质，方法的特异性也是需要考虑的（第9和第10部分关于特异性会有更多的讲解） 6.3 Method verification is suitable in lieu of method validation for pharmacopoeial methods. 方法确认适用于对药典方法的验证 7. METHOD REVALIDATION 方法再验证 7.1 Methods should be maintained in a validated state over the life of the method (see point 2.6 above). Revalidation of an analytical procedure should be considered whenever there are changes made to the method, including: 方法应在其生命周期内保持验证状态（见上述2.6），当方法发生变更时，应考虑进行再验证，包括但不仅限于以下几个方面： ‒ changes to the mobile phase (please refer to The International Pharmacopoeia and other pharmacopoeias for the acceptance limits beyond which revalidation must be performed); 流动相变更（请参考国际药典和其它药典关于一定要再验证的可接受限度） ‒ changes to the column; 色谱柱变更 ‒ changes to the temperature of the column; 柱温变更 ‒ changes to the concentration/composition of the sample and standards; 样品和标准品浓度/成分变更 ‒ changes to the detector (change in detector type, e.g. if going from ultraviolet (UV)- visible detection to fluorimetry, or wavelength of detection). 检测器的变更（检测器类型的变更，如，从紫外可见检测变更为荧光检测或波长检测） 7.2 In case of repeated system suitability failures or when obtaining of doubtful results. In such cases an investigation of the root cause should be performed, the appropriate changes made and the method revalidated. 当重复的系统适应性失败或得到可疑结果时，应进行根本原因调查，适当的变更以及方法再验证。 7.3 Periodic revalidation of analytical methods should be considered according to a period that is scientifically justifiable. 应考虑分析方法的周期性再验证，验证的周期应进行科学的论证。 7.4 It is acceptable for revalidation to include only the validation characteristics of relevance to the particular change and method. 再验证时只包括某一变更和方法相关的验证特性是可接受的。
来源：GMP办公室/娜娜 |
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