ECA新闻20181203：新ICH主题Q14以及Q2修订

翻江鼠

03.12.2018

New ICH Topic Q14 and Revision of Q2

新ICH主题Q14以及Q2修订

The ICH recently announced that the Q2(R2)/Q14 Expert Working Group (EWG) will develop a new ICH Quality Guideline, ICH Q14, on Analytical Procedure Development, and revise the ICH Q2(R1) Guideline on Validation of Analytical Procedures. These proposed guidelines (Q2(R2) and Q14) are intended to complement the existing ICH Q8 to Q12 guidelines, as well as the on-going ICH Q13 guideline for Continuous Manufacturing.

ICH最近宣布Q2(R2)/Q14专家工作组（EWG）将起草新的ICH质量指南ICH Q14，内容为分析方法开发，并对ICHQ2(R1)指南分析方法验证进行修订。此提议意在对现有ICH Q8-Q12指南和正在制订中的ICHQ13持续生产指南进行补充。

Background to the Proposal 提议背景

According to ICH, an EWG composed of experts with expertise in the area of analytical chemistry and pharmaceutical control will work on the new Analytical Procedure Development guideline (Q14), which will be relevant for the sections S4, P4 and P5 of the CTD and which will complement with Q8(R2) and Q11. Using the enhanced approach for analytical procedures can contribute to resource-efficient drug development and post-approval CMC changes. The revised Q2(R1) guideline will also be relevant for the sections S4, P4 and P5 of the CTD with emphasis on systematic Analytical Development. As analytical development activities are followed by analytical validation activities, the two tasks will be conducted by one EWG.

据ICH消息，由分析化学和药物控制领域专家组成的EWG将起草新的分析方法开发指南（Q14），该指南与CTD的S4、P4和P5内容相关，将补充Q8(R2)和Q11。对分析方法使用加强的方法将有助于药物资源有效开发和批准后的CMC变更。修订后的Q2(R1)指南亦将与CTD的S4、P4和P5有关，重点关注系统性分析方法开发。由于分析开发活动之后是分析方法验证活动，因此2个任务将由同一个EWG执行。

Q2(R1) Revision 对Q2(R1)的修订

According to ICH, the current Q2(R1) “Guideline on Validation of Analytical Procedures: Text and Methodology” does not cover modern analytical procedures, (e.g., Near Infrared (NIR) Spectroscopy orRaman Spectroscopy). The lack of guidance for these analytical methods can lead to submissions with inadequate validation data for such analytical procedures, resulting in recursive information requests and responses, which can delay application approval. This is particularly the case for procedures reliant onmultivariate models, a category for which currently no ICH validation guideline exists. NIR or Raman Spectroscopy are commonly used in process control and real time release testing (RTRT) using multivariate analysis methods. According to ICH, the scope of the revision of ICH Q2(R1) will therefore specifically address validation of modern analytical procedures including a discussion of statistical aspects in validation together with common validation characteristics for procedures, like NIR, nuclear magnetic resonance spectroscopy (NMR), and hyphenated techniques, for example CE-MS, CE-ICP-MS, LC-NMR, GC-MS, LC-MS.

据ICH消息，当前Q2(R1)“分析方法验证指南：正文与方法学”并未覆盖现代化分析方法（例如，近红外（NIR）光谱或拉曼光谱）。缺乏对这些分析方法的指南可能会导致此类分析方法的验证数据提交不充分，结果是反复要求补充资料和回复，这就可能延迟申报批准。对于依赖于多变量模型的情形尤其如此，目前尚无针对此类方法的ICH验证指南。NIR或拉曼光谱通常用于使用了多种分析方法的工艺控制和实时放行检测（RTRT）。根据ICH说法，ICH Q2(R1)修订后其范围将具体说明现代化分析方法的验证，包括在验证中讨论统计学问题，以及方法如NIR、核磁共振（NMR）和联用技术如CE-MS\CE-ICP-MS、LC-NMR、GC-MS和LC-MS.的常见验证特征.

Q14 Analytical Procedure Development Guideline Q14分析方法开发指南

Since there is currently  no ICH guideline on Analytical Procedure Development, applicants often report analytical validation results aloneand rarely present performance evaluation with analytical development outcomes.This makes regulatory communication ineffective especially when non-conventional analytical procedures are employed (for example, RTRT and multivariate models for process control). Additionally, the lack of guidelines precludes the applicant from an opportunity to present scientific basis for flexible regulatory approaches (e.g., Quality by Design (QbD) concept) to post-approval analytical procedure changes.

由于目前ICH并没有分析方法开发指南，申报人通常会只报告分析方法验证结果，而很少呈交性能评估和方法开发结果。这使得注册沟通颇为低效，尤其是当使用了非传统分析方法（如RTRT和工艺控制多变量模型）时。另外，缺少指南也让申报人失去了在批准后分析方法变更中呈交科学基础获得灵活注册方法的机会（例如，质量源于设计（QBD）概念）。

According to ICH, the new guideline is proposed to harmonize the scientific approaches of analytical procedure development, and to provide the principles relating to the description of the analytical procedure development process. The new guideline is intended to improve regulatory communication between industry and regulators and facilitate more efficient, sound scientific and risk-based approval as well as post-approval change management of analytical procedures.

根据ICH信息，新指南提案是为了统一分析方法开发的科学方法，并提供与分析方法开发过程描述有关的原则。新指南意在提高企业与药监之间的注册沟通，并推进对分析方法执行更为有效、科学合理和基于风险的批准，以及批准后变更管理。

Issues to be addressed 要解决的问题

Q14 Analytical Procedure Development guideline Q14分析方法开发指南

Main technical and scientific elements, which require harmonization,include:

需要统一的主要技术和科学要素包括：

• Submission of analytical procedure development and related information in CTD format,   
  
• 分析方法开发和相关信息以CTD模式提交
• The concept and strategy of enhanced approaches for analytical procedures,
• 分析方法加强方法的概念与策略
• Performance criteria of analytical procedures,
• 分析方法的性能标准
• In line with ICH Q8 and ICH Q11, a greater understanding of analytical procedures can create the basis for more efficient, sound science and risked-based lifecycle management (e.g., using analytical QbD (AQbD) principles),
• 与ICH Q8和ICH Q11保持一致，更好理解分析方法可以创建更为有效、科学合理和基于风险的生命周期管理基础（例如使用分析质量源于设计（AQBD）原则）
• Key elements and terminology,
• 关键要素与术语
• Demonstration of suitability for RTRT.
• 证明RTRT适用性
  
  

Q2(R1) Revision Q2(R1)的修订

For procedures reliant on multivariate methods the following willbe addressed:

对于依赖于多变量方法的程序，将解决以下问题

• Definition of validation characteristics applicable to multivariate methods which may differ with the area of application (e.g., identification vs. quantitation, batch vs. continuous process, dosage form assay vs. blending monitoring),
• 应用于多变更方法的验证特征的定义，它可能不同于申报领域（例如鉴别VS定量、间歇生产VS连续生产、制剂含量检测VS混合监测）
• Important method parameters (e.g., the number of latent variables) established during method development,
• 在方法开发期间建立的重要方法参数（例如潜在变量的数量）
• Robustness which is well understood, however does not have a quantitative measure,
• 很好地理解了耐用性，但没有定量方法
• Inclusion of post-approval verification and maintenance considerations as a part of the validation (control strategy),
• 将批准后确认和维护考量作为验证的一部分包括在其中（控制策略）
• Requirements for validation data sets.
• 验证数据系列的要求
  
  

The possible Step 2a/2b endorsement for both guidelines is currently expected for spring 2020. More information can be found on the ICH Quality Guidelines webpage.

2份指南可能的2a/2b阶段采纳目前预期是2020年春天。更多信息参见ICH官网。

本文摘自 Julia法规翻译

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使用分析质量源于设计（AQBD）原则，

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