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 analysis. 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 collection 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 included. Lastly, continuous manufacturing processes differ from batch manufacturing due to the time dependency associated with continuous operations 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. It is not intended to provide technology- or application-specific sampling guidance. 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situ PAT measurements), many of the considerations also apply to at-line and off-line applications in which a sample is withdrawn from the process and subsequently presented for analysis.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.

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 analysis. 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 collection 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 included. Lastly, continuous manufacturing processes differ from batch manufacturing due to the time dependency associated with continuous operations 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. It is not intended to provide technology- or application-specific sampling guidance. 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.

1.1 This guide covers an evaluation approach that is designed to provide information on the corrosion properties of wrought iron- and nickel-based alloys for the chemical process industries. This guide incorporates test conditions for general corrosion measurements in a variety of environments, crevice corrosion resistance in chloride environments, and stress corrosion cracking resistance in chloride environments.

1.2 The values stated in SI units are to be regarded as standard. The values given in parentheses are for information only.

1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and to determine the applicability of regulatory limitations prior to use.

1.4 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.

1.1 This guide covers an evaluation approach that is designed to provide information on the corrosion properties of wrought iron- and nickel-based alloys for the chemical process industries. This guide incorporates test conditions for general corrosion measurements in a variety of environments, crevice corrosion resistance in chloride environments, and stress corrosion cracking resistance in chloride environments.

1.2 The values stated in SI units are to be regarded as standard. The values given in parentheses are for information only.

1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and to determine the applicability of regulatory limitations prior to use.

1.4 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.

1.1 This guide describes the verification of process analytical technology (PAT) enabled control systems using a science- and risk-based approach. It establishes principles for determining the scope and extent of verification activities necessary to ensure that the PAT-enabled control system is fit for purpose, properly implemented, and functions as expected.

1.2 In this guide, a PAT-enabled control system is considered to be the system that adjusts the manufacturing process using timely measurements (that is, during processing) of attributes of raw and in-process materials to determine responses that assure the process remains within specified boundaries and minimizes variability in the output material. The overall aim of the PAT-enabled control system is to ensure product quality. The PAT-enabled control system of a manufacturing process provides the capability to determine the current status of the process and drive the process to ensure the output material has the desired quality characteristics. The control system should be able to respond to process variations in a timely manner, providing corrections that ensure that the process follows the desired process trajectory to reach the desired outcome. PAT-enabled control systems may use process models based on first principles understanding or empirical models derived from experimental investigations or both. In addition to automated controls, a PAT-enabled control system may include components where there is manual intervention.

1.3 Principles described in this guide may be applied regardless of the complexity or scale of the PAT-enabled control system or whether applied to batch or continuous processing, or both. The intention of this standard is to describe and support the implementation of a PAT enabled Control Strategy, as described in ICH Q8(R2).

1.4 The principles described in this guide are applicable to a PAT-enabled control system and also to its component subsystems. This guide does not cover the requirements for continuous quality verification of the overall process, which are covered in Guide E2537, or for validation of PAT methods, which is covered in Guide E2898.

1.5 For information on science- and risk-based approaches in the pharmaceutical industry, reference should be made to ICH Q8(R2), ICH Q9, and ICH Q10. For guidance on PAT systems in the pharmaceutical industry, reference should be made to FDA Guidance for Industry—PAT and FDA Guidance for Industry—Process Validation, as well as EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use and EU Guideline on Process Validation for Finished Products.

1.6 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.7 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.

1.1 This guide describes the verification of process analytical technology (PAT) enabled control systems using a science- and risk-based approach. It establishes principles for determining the scope and extent of verification activities necessary to ensure that the PAT-enabled control system is fit for purpose, properly implemented, and functions as expected.

1.2 In this guide, a PAT-enabled control system is considered to be the system that adjusts the manufacturing process using timely measurements (that is, during processing) of attributes of raw and in-process materials to determine responses that assure the process remains within specified boundaries and minimizes variability in the output material. The overall aim of the PAT-enabled control system is to ensure product quality. The PAT-enabled control system of a manufacturing process provides the capability to determine the current status of the process and drive the process to ensure the output material has the desired quality characteristics. The control system should be able to respond to process variations in a timely manner, providing corrections that ensure that the process follows the desired process trajectory to reach the desired outcome. PAT-enabled control systems may use process models based on first principles understanding or empirical models derived from experimental investigations or both. In addition to automated controls, a PAT-enabled control system may include components where there is manual intervention.

1.3 Principles described in this guide may be applied regardless of the complexity or scale of the PAT-enabled control system or whether applied to batch or continuous processing, or both. The intention of this standard is to describe and support the implementation of a PAT enabled Control Strategy, as described in ICH Q8(R2).

1.4 The principles described in this guide are applicable to a PAT-enabled control system and also to its component subsystems. This guide does not cover the requirements for continuous quality verification of the overall process, which are covered in Guide E2537, or for validation of PAT methods, which is covered in Guide E2898.

1.5 For information on science- and risk-based approaches in the pharmaceutical industry, reference should be made to ICH Q8(R2), ICH Q9, and ICH Q10. For guidance on PAT systems in the pharmaceutical industry, reference should be made to FDA Guidance for Industry—PAT and FDA Guidance for Industry—Process Validation, as well as EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use and EU Guideline on Process Validation for Finished Products.

1.6 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.7 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.