欧洲药典PAT草案

In Pharmeuropa 30.1 a draft monograph 5.25. Process Analytical Technology has been published for comment until March 31, 2018.

在欧洲药典在线30.1中发布了5.25过程分析技术，其征求意见截止日期为2018年3月31。

According to the draft chapter"process analytical technology (PAT) can be defined as asystem for designing, analysing and controlling manufacturing processes through timely measurements (i.e. during processing) of critical quality attributes (CQA),and critical performance characteristics of raw materials, in-process materialsand processes, in order to ensure the quality of the final product.

根据章节草案，“过程分析技术（PAT）可以定义为通过及时测量（即，在工艺过程中）关键质量属性（CQA）、原料的关键性能属性、中控物料和工艺来设计、分析和控制生产工艺，以确保最终产品的质量”。

Interfacing manufacturing processes with analytical techniques is essential in PAT, as it facilitates process development in accordance with quality by design (QbD) principles, enables real-time release testing (RTRT) and supports continuous manufacturing processes.

在PAT中，生产工艺与分析技术的接口是非常重要的，因为它有利于工艺开发符合质量源于设计（QbD）原则，使得实时放行测试（RTRT）成为可能，并支持连续生产工艺。

The draft emphasizes that"the term ‘analytical’ in PAT is used in a broad sense to includechemical, physical and microbiological measurements conducted in an integratedmanner and combined with data analysis". The interfacing mode (e.g.‘off-line’, ‘at-line’, ‘on-line’ and ‘in-line’) of analytical techniques withthe manufacturing process is central to the application of PAT. Thesemeasurements can generate very large volumes of data, representative of theprocess, which then have to be further processed.

草案强调“PAT中术语“分析”以所用含义为广义含义，其中包括以整合方式进行化学、物理和微生物测量，并与数据分析相合并”。接口模式（例如，离线、在线、近线和原位）分析技术与生产工艺是PAT申报的核心。这些测量可以生成非常大量的数据，可代表工艺，后续必须进行进一步处理。

Additionally the draft chapterprovides definitions for the various interfacing modes including examples of interfacing options for different unit operations and purposes together with the proposed measuring system and the typical result turnaround time. Furthermore, it contains sections on "Comparison of process analytical interfacing modes", "Statistical process control(SPC)", and "Ph. Eur. Texts supporting the application of PAT".The Ph. Eur. chapters which have been revised or elaborated to support the application of PAT include:

另外，草案还提供了不同接口模式的定义，包括不同单元操作的接口可用方式，以及所提议测量系统和典型结果获取时长。此外，它还包括了“工艺分析接口模式比较”、“统计学工艺控制（SPC）”和“药典支持PAT应用的内容”部分。欧洲药典一些章节已进行了修订或整理以支持PAT应用，其中包括：

• 1. General Notices, 通则

• 2.2.25 Absorption spectrophotometry, ultraviolet and visible, 吸收光谱，紫外和可见光

• 2.2.37 X-Ray fluorescence spectrometry, X射线荧光光谱

• 2.2.40 Near-infrared spectroscopy, 近红外光谱

• 2.2.48 Raman spectroscopy,拉曼光谱

• 2.9.47 Demonstration of uniformity of dosage units using large sample sizes, 使用大量样品证明剂型均一性

• 5.1.6 Alternative methods for control of microbiological quality, 微生物质量控制替代方法

• 5.21 Chemometric methods applied to analytical data, 化学计量方法在分析数据中的应用

• 5.24 Chemical imaging. 化学成像

In section 1.1 of General Notices under Demonstration of compliance with the pharmacopoeia, it is stated that "a substance can be demonstrated to be of pharmacopoeial quality on the basis of product design, together with itscontrol strategy and data derived, for example, from validation studies of the manufacturing process". Furthermore, it is also stated that "an enhanced approach to quality control could utilize PAT and/or real-time release testing strategies (including parametric release) as alternatives to end-product testing alone". This is also in line with the draft Annex 17 of the EU GMP Guide on Real Time Release Testing, which is expected to be released as final, without further modifications, in the first quarter 2018. 

在通则的1.1部分证明药典符合性部分下说“一种物质也在产品设计结合其控制策略和所衍生的数据基础上证明其具备药典质量，例如来自生产工艺验证研究的数据”。还说“可以使用PAT和/或实时放行测试策略（包括参数放行）替代仅测试成品来加强质量控制的方法”。这也与EU GMP指南附录17草案实时放行测试相一致。附录17草案预期将于2018年第1季度不做进一步修订即最终定稿。

After registration on the Pharmeuropa Website you will have access to the draft monograph 5.25. Process Analytical Technology.  

详细内容参见药典官网。