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)

• 1.5 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)

• 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.

  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。

• 2.7 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。

• 2.8 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。

• 2.9 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。

• 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. 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)。

• 2.12 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。

• 2.13 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。

• (...)

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)

• 6.1 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)。

• 6.2 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。

• (...)

7. Method revalidation (New): 方法再验证(新)

• 7.1 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)

• 7.2 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。

• 7.3 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

• (...)

8. Method transfer  (New) 方法转移(新)

• 8.1 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。

• (...)

• 8.3 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。

• 8.4 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。

• (...)

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

• 9.3.1 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,

• 9.3.2 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。

• 9.3.3 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 appendix 4 parallels certain considerations of the current USP lifecycle approach for analytical method validation. However, QbD concepts and the Analytical Target Profile (ATP) - which is equivalent to the Quality Target Product Profile (QTPP) - have not yet been introduced in the WHO draft.

修订后的附录4同时也考虑了USP分析方法验证生命周期方法。但是,QBD的概念和目标分析概况(ATP)---与目标产品质量概况(QTPP)----还没有引入到WHO草案中。

According to WHO the draft of Appendix 4 will also be placed on the WHO Medicines website under Current projects.

根据WHO的说法,附录4的草案也会被放在WHO药物的网站上“当前项目”下。

Members of the ECA Academy are able to access the new WHO Guidelines on Validation - Appendix 4 Analytical Method Validation in the ECA Members Area.

ECA会员可以通过会员区获得新的WHO验证指南附录4分析方法验证。