质量授权人审核。

Traditional process validation 传统工艺验证

5.18. In the traditional approach, a number of batches of the finished product are manufactured under routine conditions to confirm reproducibility. 5.18.

在传统方式中，需要在正常条件下生产出很多批成品才能确认其重现性。

5.19. The number of batches manufactured and the number of samples taken should be based on quality risk management principles, allow the normal range of variation and trends to be established and provide sufficient data for evaluation. Each manufacturer must determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product.

5.19. 生产批次数和取样样品数量都应基于质量风险管理的原则，如果能够提

供足够的数据进行评估，允许规定变动和趋势的范围。生产商需要确定和交代必须生产多少批次才可以表明工艺能够持续生产出优质产品的高水平保证度。 5.20. Without prejudice to 5.19, it is generally considered acceptable that a minimum of three consecutive batches manufactured under routine conditions could constitute a validation of the process. An alternative number of batches may be justified taking into account whether standard methods of manufacture are used and whether similar products or processes are already used at the site. An initial validation exercise with three batches may need to be supplemented with further data obtained from subsequent batches as part of an on-going process verification exercise.

5.20. 一般来说，在不违背5.19的情况下，正常生产条件下至少连续生产三个批次可被认为满足工艺验证要求。若使用其他批次数，需从该场地是否使用标准操作方法、是否有类似产品或工艺进行评估。初次的三批验证可能需要后续足够批次生产数据来补充，并作为连续工艺确认的一部分。

5.21. A process validation protocol should be prepared which defines the critical process parameters (CPP), critical quality attributes (CQA) and the associated acceptance criteria which should be based on development data or documented process knowledge. 5.21.

应准备工艺验证方案，根据研发数据或工艺知识明确关键工艺参数、关

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键质量属性和相关的可接受标准。

5.22. Process validation protocols should include, but are not limited to the following: 5.22.

工艺验证方案应包括但不局限以下内容：

i. A short description of the process and a reference to the respective Master Batch Record; i.

工艺的简要描述和对应的主批记录的列表；

ii. Functions and responsibilities; ii.

功能与职责划分；

iii. Summary of the CQAs to be investigated; iii.

将被研究的关键质量属性列表；

iv. Summary of CPPs and their associated limits; iv.

关键质量属性及其限度的汇总表；

v. Summary of other (non-critical) attributes and parameters which will be investigated or monitored during the validation activity, and the reasons for their inclusion;

v. 在验证活动中被研究或监控的其他质量属性（非关键的）和参数一览表，并说明选择它们的理由；

vi. List of the equipment/facilities to be used (including

measuring/monitoring/recording equipment) together with the calibration status; vi.

将被使用的设备/设施（含测量、监控、记录设备）一览表及其校准状态；

vii. List of analytical methods and method validation, as appropriate. vii.

如适用，应有分析方法及其方法验证列表；

viii. Proposed in-process controls with acceptance criteria and the reason(s) why each in-process control is selected; viii.

拟定有可接受标准的中控措施及为何选择它们作为中控的理由；

ix. Additional testing to be carried out with acceptance criteria;

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ix. 含有可接受标准的其它将要进行的附加测试；

x. Sampling plan and the rationale behind it; x.

取样计划及其合理性；

xi. Methods for recording and evaluating results; xi.

结果的记录和评价方法；

xii. Process for release and certification of batches (if applicable). xii.

放行流程及批合格证的发放（适用时）。

Continuous process verification 持续工艺确认

5.23. For products developed by a quality by design approach, where it has been scientifically established during development that the established control strategy provides a high degree of assurance of product quality, then continuous process verification can be used as an alternative to traditional process validation.

5.23. 对于采用质量源于设计的理念开发出来的药品，由于其工艺在研发期间已被科学地建立，所建立的控制策略提供了高水平的产品质量保证，那么持续性工艺确认可以作为传统工艺验证的替代性选择。

5.24. The method by which the process will be verified should be defined. There should be a science based control strategy for the required attributes for incoming materials, critical quality attributes and critical process parameters to confirm product realisation. This should also include regular evaluation of the control strategy. Process Analytical Technology and multivariate statistical process control may be used as tools. Each manufacturer must determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product.

5.24. 应当明确过程采用哪种方法进行验证，应该有针对原辅料、关键质量属性和关键工艺参数的基于科学基础的控制策略以确保产品实现要求的质量标准，这也包括对控制策略的定期评估。过程分析技术和多变量的统计学手段可以作为工具使用。生产商需要确定和交代必须生产多少批次才可以表明工艺能够持续生产出优质产品的高水平保证度。

5.25. The general principles laid down in 5.1 – 5.14 above still apply.

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5.25. 上述5.1~5.14的基本原则仍然适用。

Hybrid approach 混合型方法

5.26. A hybrid of the traditional approach and continuous process verification could be used where there is a substantial amount of product and process knowledge and understanding which has been gained from manufacturing experience and historical batch data.

5.26. 在有大量的产品与工艺知识和基于生产经验及历史批生产数据支持，对工艺有良好认识的基础上，可以使用传统方法和持续性工艺确认组成的混合型方法。

5.27. This approach may also be used for any validation activities after changes or during ongoing process verification even though the product was initially validated using a traditional approach.

5.27. 这种方法也适用于变更后或首次使用了传统的验证方法并正在进行持续性工艺确认期间的任何验证活动。

Ongoing Process Verification during Lifecycle 生命周期中的连续工艺确认

5.28. Paragraphs 5.28-5.32 are applicable to all three approaches to process validation mentioned above, i.e. traditional, continuous and hybrid. 5.28.

本文5.28~5.32款适用于传统、持续性、混合型的工艺验证方法。

5.29. Manufacturers should monitor product quality to ensure that a state of control is maintained throughout the product lifecycle with the relevant process trends evaluated.

5.29. 生产商应通过评估相关的工艺趋势来监控产品质量以确保其在整个生命周期中始终处于受控状态。

5.30. The extent and frequency of ongoing process verification should be reviewed periodically. At any point throughout the product lifecycle, it may be appropriate to modify the requirements taking into account the current level of process understanding and process performance.

5.30. 应定期审核连续性工艺确认的程度和频率，考虑到对现有工艺的理解程度和工艺性能，允许在产品生命周期的任何一点上对工艺要求进行修改。

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