ASTM E2476-22
(Guide)Standard Guide for Risk Assessment and Risk Control as it Impacts the Design, Development, and Operation of PAT Processes for Pharmaceutical Manufacture
Standard Guide for Risk Assessment and Risk Control as it Impacts the Design, Development, and Operation of PAT Processes for Pharmaceutical Manufacture
SIGNIFICANCE AND USE
4.1 This guide is intended to provide guidance regarding the use of risk management in the development, day-to-day running, and continuous improvement of pharmaceutical processes incorporating Process Analytical Technology (PAT). A consistent approach to the use of risk methodologies should be adopted to ensure rapid transfer of process understanding within the development and manufacturing teams, and to the regulators where that is appropriate.
4.2 This guidance only covers those aspects of risk assessment related to “risk to product quality.” Other aspects (such as “risk to patient”) should be covered in the conventional manner.
SCOPE
1.1 This document provides guidance on the assessment of risks to product quality within and related to PAT processes in the pharmaceutical industry. It addresses those risks to product quality arising from, associated with, identified by, or modified by the implementation of PAT in pharmaceutical development and manufacturing for primary, secondary, and biotech sectors of the industry. It does not replace those assessments of risk currently undertaken by pharmaceutical companies, but is, rather, an additional component focused specifically upon the evaluation and design of PAT processes. See Guide E2500 and ICH Q8.
1.2 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. Note that safety in this context refers to operational and operator safety, not to patient safety.
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.
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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.
Designation: E2476 − 22
Standard Guide for
Risk Assessment and Risk Control as it Impacts the Design,
Development, and Operation of PAT Processes for
1
Pharmaceutical Manufacture
This standard is issued under the fixed designation E2476; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
INTRODUCTION
This document provides guidance on the implementation of risk assessment and risk control for
Process Analytical Technology (PAT) processes within the pharmaceutical industry. Wherever
possible, other appropriate standards on risk assessment/management have been referenced and
acknowledged. Where practical, further details of methods and additional references have been
provided for information within the appendixes.
The application of risk assessment and risk control is pivotal to the creation of PAT systems, which
are described as “science-based” and “risk-based.” Such application starts at an early stage in the
development of the process and continues throughout development and production. In the production
phase, it is a crucial component of applying continuous improvement to the process.
RELATIONSHIP TO ICH Q9
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use (ICH) Q9 Guideline for Quality Risk Management is intended for general application
within the pharmaceutical industry. ICH Q9 describes the requirements for pharmaceutical quality risk
management and considers the risk as “risk to the patient.”
This document provides specific guidance on the risk assessment and risk control phases identified
in ICH Q9 in a limited set of conditions. It is applicable where the manufacturing method is compliant
with Process Analytical Technology (PAT) principles, and where the primary considerations are
product quality and reduction of process and product variability. The only component of risk to patient
considered here is risk to product quality. Other components fall outside the scope of the document.
In addition, other areas identified in ICH Q9, such as general risk management and risk
communication, are not considered here.
This document provides guidance which applies to the design, development, and operation of PAT
systems. It should be considered as a specific extension, supporting the ICH Q9 guidance for these
processes.
1. Scope currently undertaken by pharmaceutical companies, but is,
rather, an additional component focused specifically upon the
1.1 This document provides guidance on the assessment of
evaluation and design of PAT processes. See Guide E2500 and
risks to product quality within and related to PAT processes in
ICH Q8.
the pharmaceutical industry. It addresses those risks to product
quality arising from, associated with, identified by, or modified
1.2 This standard does not purport to address all of the
by the implementation of PAT in pharmaceutical development
safety concerns, if any, associated with its use. It is the
and manufacturing for primary, secondary, and biotech sectors
responsibility of the user of this standard to establish appro-
of the industry. It does not replace those assessments of risk
priate safety, health, and environmental practices and deter-
mine the applicability of regulatory limitations prior to use.
Note that safety in this context refers to operational and
1
This guide is under the jurisdiction of ASTM Committee E55 on Manufacture
of Pharmaceutical and Biopharmaceutical Products and is the direct responsibility of operator safety, not to patient safety.
Subcommittee E55.11 on Process Design.
1.3 This international standard was developed in accor-
Current edition approved Nov. 1, 2022. Published December 2022. Originally
dance with internationally recognized principles on standard-
approved in 2009. Last previous edition approved in 2016 as E2476 – 16. DOI:
10.1520/E2476-22. ization established in the Decision on Principles for the
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
1
---------------------- Page: 1 ----------------------
E2476 − 22
Development of International Standards, Guides and Recom- 4.2 This guidance only covers those aspects of risk assess-
mendations issued by the World Trade Organization Technical ment related to “risk to product quality.” Other aspects (such as
Barriers to Trade (TBT) Committee. “risk to patient”) should be covered in the conventional
manner.
2. Referen
...
This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: E2476 − 16 E2476 − 22
Standard Guide for
Risk Assessment and Risk Control as it Impacts the Design,
Development, and Operation of PAT Processes for
1
Pharmaceutical Manufacture
This standard is issued under the fixed designation E2476; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
INTRODUCTION
This document provides guidance on the implementation of risk assessment and risk control for
Process Analytical Technology (PAT) processes within the pharmaceutical industry. Wherever
possible, other appropriate standards on risk assessment/management have been referenced and
acknowledged. Where practical, further details of methods and additional references have been
provided for information within the appendixes.
The application of risk assessment and risk control is pivotal to the creation of PAT systems, which
are described as “science-based” and “risk-based.” Such application starts at an early stage in the
development of the process and continues throughout development and production. In the production
phase, it is a crucial component of applying continuous improvement to the process.
RELATIONSHIP TO ICH Q9
The ICH International Council for Harmonisation of Technical Requirements for Pharmaceuticals
for Human Use (ICH) Q9 Guideline for Quality Risk Management is intended for general application
within the pharmaceutical industry. ICH Q9 describes the requirements for pharmaceutical quality risk
management and considers the risk as “risk to the patient.”
This document provides specific guidance on the risk assessment and risk control phases identified
in ICH Q9 in a limited set of conditions. It is applicable where the manufacturing method is compliant
with Process Analytical Technology (PAT) principles, and where the primary considerations are
product quality and reduction of process and product variability. The only component of risk to patient
considered here is risk to product quality. Other components fall outside the scope of the document.
In addition, other areas identified in ICH Q9, such as general risk management and risk
communication, are not considered here.
This document provides guidance which applies to the design, development, and operation of PAT
systems. It should be considered as a specific extension, supporting the ICH Q9 guidance for these
processes.
1. Scope
1.1 This document provides guidance on the assessment of risks to product quality within and related to PAT processes in the
pharmaceutical industry. It addresses those risks to product quality arising from, associated with, identified by, or modified by the
implementation of PAT in pharmaceutical development and manufacturing for primary, secondary, and biotech sectors of the
1
This guide is under the jurisdiction of ASTM Committee E55 on Manufacture of Pharmaceutical and Biopharmaceutical Products and is the direct responsibility of
Subcommittee E55.01 on Process Understanding and PAT System Management, Implementation and Practice.
Current edition approved Nov. 1, 2016Nov. 1, 2022. Published November 2016December 2022. Originally approved in 2009. Last previous edition approved in 20092016
as E2476 – 09.E2476 – 16. DOI: 10.1520/E2476-16.10.1520/E2476-22.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
1
---------------------- Page: 1 ----------------------
E2476 − 22
industry. It does not replace those assessments of risk currently undertaken by pharmaceutical companies, but is, rather, an
additional component focused specifically upon the evaluation and design of PAT processes. See Practice E2474, Guide E2500,
and ICH Q8.
1.2 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 safety, health, and healthenvironmental practices and determine the
applicability of regulatory limitations prior to use. Note that safety in this context refers to operational and operator safety, not
to patient safety.
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
...
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