WHO分析方法验证文件草案

技术帖 WHO 公布 验证指南附录 4 分析方法验证文件 草案 2016 08 01 JuliaBlog 洛施德 GMP 咨询 洛施德 GMP 咨询 WHO Draft on Analytical Method Validation WHO 分析方法验证草案 In June 2016 the World Health Organization WHO published a draft document Guidelines on Validation Appendix 4 Analytical Method Validation Comments on the text should be sent to WHO until July 30 2016 在 2016 年 6 月 WHO 公布了 验证指南 附录 4 分析方法验证 文件草案 征求意 见截止日期为 2016 年 7 月 30 日 The appendix 4 of the published Supplementary guidelines on good manufacturing practices validation WHO Technical Report Series No 937 2006 Annex 4 has been revised in view of current trends in validation The appendix presents some information on the characteristics that should be considered during validation of analytical methods Approaches other than those specified in the Appendix may be followed and may be acceptable 已发布的 GMP 增补指南 验证 的附录 4 WHO 技术报告第 937 号 附录 4 已经 根据目前验证趋势进行了修订 附录里给出一些分析方法验证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 The new Appendix 4 is structured as follows New and revised 新的附录 4 结构如下 新的修订过后的 1 Principle revised 原则 修订过 o1 5 The recommendations as provided for in good laboratory practices and guidelines for transfer of technology WHO Technical Report Series No 961 2011 Annex 7 should be considered where applicable when analytical method validation is organized and planned 1 5 在组织和计划分析方法验证时 如适用 应考虑优良化验室规范和技术转 移指南 WHO 技术报告第 961 号 2011 年附录 7 中所提供的建议 2 General revised 概述 修订过 o2 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 2 6 程序应成为持续确认程序的一部分以证明其在程序的生命周期中符合既定 的标准 o2 7 Trend analysis and risk assessments should be considered at intervals to ensure that the method is appropriate for its intended application 2 7 趋势分析和风险评估应定期考虑 以确保分析方法适合其既定用途 o2 8 Changes to methods should be managed in accordance with the authorized change control procedure 2 8 对分析方法的变更应根据批准的变更控制程序进行管理 o2 9 The scope of verification or degree of revalidation depend on the nature of the change s and the outcome of risk assessment 2 9 确认的范围和再验证的程度取决于变更的性质和风险评估的结果 o2 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 Their associated metadata are also expected to be retained and subjected to good data and record management practices WHO Technical Report Series No 996 2016 Annex 5 2 11 在分析方法验证和确认中获得的数据应考虑符合 GXP 要求 应遵守优良 数据和记录管理规范原则 其相关的元数据也应保存 并符合优良数据和记录 管理规范 WHO 技术报告第 996 号 2016 年 附录 5 o2 12 When computerized systems are used to obtain and process da ta relating to method validation and verification they should comply to the principles enunciated in Appendix 5 Validation of computerized systems 2 12 当计算机化系统被用于获取和处理与分析方法验证和确认相关的数据时 他们应该符合附录 5 计算机化系统的验证 中所阐明的原则 o2 13 Adequate attention should be paid to the method of sample preparation 2 13 样品的制备方法要有足够的重视 o 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 New 方法确认 新 o6 1 Method verification should be performed for already validated analytical methods for example when it is used on a product for the first time e g in case of a change in API supplier change in method of synthesis or after reformulation of a drug product 6 1 已验证过的分析方法应进行方法确认 例如 当首次用于一个产品时 例 如 如果对原料药供应商进行变更 对合成方法进行变更 或者在药品重新配 方后 o6 2 Method verification may include on ly the validation characteristics of relevance to the particular change 6 2 分析方法确认可能包括只有与特殊变更相关的验证特性 o 7 Method revalidation New 方法再验证 新 o7 1 Methods should be maintained in a validated state over the life of the method Revalidation see also ICH Q2 should be considered whenever there are changes made to the analytical method e g changes to mobile phase column column temperature detector 7 1 分析方法应在其生命周期内维持在一个经过验证的状态 当对分析方法有 变更 例如 变更流动相 色谱柱 柱温 检测器 时要考虑进行再验证 参 见 ICH Q2 o7 2 In case of repeated SST 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 7 2 如果 SST 重复失败 或者是得到受质疑的结果 则要调查根本原因 要对 方法进行适当地变更 对方法进行再验证 o7 3 Periodic revalidation of analytical methods should be considered according to a period that is scientifically justifiable 7 3 分析方法定期再确认应根据科学论证 o 8 Method transfer New 方法转移 新 o8 1 During method transfer documented evidence should be established to prove that a method has equivalent performance when used in a laboratory different from that where it has been originally validated 8 1 在分析方法转移中 应建立文件证据来证明一个方法在用于与原始验证的 实验室不同的另一实验室时可以获得相等同的性能 o o8 3 The two sets of results should be statistically compared and the differences between the two sets of test results should be within an acceptable range 8 3 两套结果应进行统计学比较 两套结果之间的差异应在可接受范围内 o8 4 Method transfer should be performed before testing of samples for obtaining critical da ta for a dossier such as process validation or stability studies or applied for routine use 8 4 方法转移应在注册文件所用关键数据获取的样品测试之前实施 例如 工 艺验证 稳定性试验或者是常规使用 o 9 Characteristics of analytical procedures revised 9 3 System suitability testing 分析方法 特性 修订过 9 3 系统适用性测试 o9 3 1 The suitability of the entire system should be confirmed prior to and during method validation tests as well as during the test of samples 9 3 1 整个系统的适用性应在方法验证测试之前和期间 以及样品测试中进行确 认 o9 3 2 System suitability runs should include on ly established standards or reference materials of known concentration to provide an appropriate comparator for the potential variability of the instrument 9 3 2 系统适用性运行只能使用已知浓度的标准品或对照物质 为仪器可能的波 动提供适当的对比 o9 3 3 Where a sample is used for system suitability or a trial run written procedures should be established and followed and the results of all such trial runs be included in the results and da ta review process A sample can be used on ly if it is a well characterized material Characterization in such a case should be performed prior to the use of this sample as part of system suitability testing The sample material or product under test should not be used for trial run purposes or to evaluate suitability of the system see WHO guidelines on good data and record management practices 9 3 3 如果使用样品来运行系统适用性或试验运行的话 则应建立书面程序并遵 守之 所有这类试验运行的结果必须包括在结果和数据审核过程 只有当样品 是已被明确确证的物料时才可以使用 在这种情况下 确证可以在该样品使用 之前进行 作为系统适用性试验的一部分 用于测试的样品物料或产品不应该 被用于试验运行或者是用于评估系统适用性 参见 WHO 优良数据和记录管理 规范指南 The revised version of