1.1 本文件将用作过程分析技术（PAT）仪器采样的指南，涵盖收集PAT数据的样本和用于参考分析的样本。ASTM对指南的定义是不建议具体行动方案的信息或一系列选项的概要。指南的目的是提高对给定主题领域信息和方法的认识，因此，本指南应作为确定PAT文书样本实践时考虑的要点的整理。这不是一种需要遵循的做法。作为第一步，应确定PAT测量的总体目标。定义后，本指南描述了与实现总体PAT目标必须满足的具体要求相关的各种考虑因素，包括待测量的属性、过程规模的影响以及测量系统与制造设备的接口（包括采样系统可靠性）。 此外，还讨论了有效样本量的估计和验证以及对测量的总体贡献。还涵盖了数据收集和数据处理的相关方面，以及使用风险评估优化采样和了解潜在采样错误的影响。此外，还考虑了过程控制以及与样品提取和保留有关的方面。最后，与批量制造相比，连续制造过程需要特殊考虑，因为与连续操作相关的时间依赖性，因此需要对此类过程的采样进行特殊考虑。 1.2 本指南仅限于对适用于任何类型药物制造（例如，活性药物成分（API）、固体口服剂型等）的PAT的采样注意事项进行高水平概述。其目的不是提供技术- 或应用特定采样指南，或两者兼有。相反，目的是在开发PAT应用程序时引发围绕采样的思考过程。虽然主要关注固体、液体和气体在线/在线应用（即原位PAT测量）的采样注意事项，但许多注意事项也适用于在线和离线应用，其中样品从过程中提取，随后提交分析。 1.3 本国际标准是根据世界贸易组织技术性贸易壁垒（TBT）委员会发布的《关于制定国际标准、指南和建议的原则的决定》中确立的国际公认标准化原则制定的。 ====意义和用途====== 4.1 本指南的应用应使PAT方法开发人员能够设计和实施可靠的PAT应用程序，避免采样周围的许多常见错误源。 取样是方法和工艺验证计划的关键要素。 4.1.1 许多ASTM标准讨论取样；然而，几乎所有这些都非常特定于某个领域或应用。例如，“石油和石油产品自动取样标准实施规程”( D4177 )具体包括自动设备的设计、安装、测试和操作信息，用于从流动流中提取石油和石油产品的代表性样本，并将其存储在样本接收器中。 4.1.2 其他有用的ASTM标准包括: E105 （材料概率抽样实施规程）， E122 （计算样本量以指定精度估计批次或过程特征平均值的标准实施规程）， E1402 （抽样设计标准指南），以及 E456 （与质量和统计有关的术语）。这些标准审查了与本指南中所述内容类似的考虑因素，可以参考这些标准以了解如何处理特定样本类型或情况。 然而，应仔细审查此类标准与药物应用的相关性。

1.1 This document is to be used as a guide to Process Analytical Technology (PAT) instrument sampling, and covers both the sample from which PAT data is collected and the sample that is taken for reference assay. The ASTM definition of a guide is a compendium of information or series of options that does not recommend a specific course of action. The intention of a guide is to increases the awareness of information and approaches in a given subject area, as such this guide should serve as a collation of points to consider when determining a sample practice for PAT instruments. It is not intended to serve as a practice to be followed. As a first step, one should define the overall goal of the PAT measurement. Once defined, this guide describes various considerations as they relate to the specific requirements that must be met to achieve the overall PAT goal, including the attributes to be measured, impact of the scale of the process, and interfacing of the measurement system to manufacturing equipment (including sampling system reliability). Additionally, it discusses the estimation and validation of the effective sample size and the overall contribution to the measurement. Related aspects of data collection and data processing as well as the use of risk assessments to optimize sampling and to understand the impact of potential sampling errors are also covered. Furthermore, considerations for process control and aspects pertaining to sample withdrawal and retention are also included. Lastly, continuous manufacturing processes require special considerations due to the time dependency associated with continuous operations as compared to batch manufacturing and special considerations are needed for sampling of such processes. 1.2 This guide is limited to a high level overview of sampling considerations for PAT applied to any type of pharmaceutical manufacturing (for example, active pharmaceutical ingredient (API), solid oral dosage form, etc.). It is not intended to provide technology- or application-specific sampling guidance, or both. Instead, the intent is to evoke a thought process around sampling when developing a PAT application. While the focus is mainly on sampling considerations for on/in-line applications in solids, liquids, and gases (that is, in situ PAT measurements), many of the considerations also apply to at-line and off-line applications in which a sample is withdrawn from the process and subsequently presented for analysis. 1.3 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee. ====== Significance And Use ====== 4.1 Application of this guidance should enable PAT method developers to design and implement reliable PAT applications that avoid many common sources of error around sampling. Sampling is a key element of method and process validation plans. 4.1.1 Many ASTM standards discuss sampling; however, almost all are very specific to a certain field or application. For example, the “Standard Practice for Automatic Sampling of Petroleum and Petroleum Products” ( D4177 ) specifically covers information for the design, installation, testing, and operation of automated equipment for the extraction of representative samples of petroleum and petroleum products from a flowing stream and storing them in a sample receiver. 4.1.2 Other useful ASTM standards include: E105 (Practice for Probability Sampling of Materials), E122 (Standard Practice for Calculating Sample Size to Estimate, With a Specified Precision, the Average for a Characteristic of a Lot or Process), E1402 (Standard Guide for Sampling Design), and E456 (Terminology Relating to Quality and Statistics). These standards review similar considerations as those addressed in this guidance and can be consulted for additional insight on how to deal with specific sample types or situations. However, such standards should be carefully reviewed for relevance to pharmaceutical applications.