ASTM E3177-18

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.

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.