ASTM E2475-23

Standard Guide for Process Understanding Related to Pharmaceutical Manufacture and Control

SCOPE
1.1 The purpose of this guide is to establish a framework and context for process understanding for pharmaceutical manufacturing using the principles of quality by design (QbD) (Juran, 1992;2 ICH Q8). The framework is applicable to both drug substance (DS) and drug product (DP) manufacturing. High (detailed) level process understanding can be used to facilitate production of product which consistently meets required specifications. It can also play a key role in continual process improvement efforts.  
1.2 Process Analytical Technology (PAT) is one element that can be used for achieving control over those inputs determined to be critical to a process. It is important for the reader to recognize that PAT is defined as:    
“…a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in process materials and processes, with the goal of ensuring final product quality. It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner. The goal of PAT is to enhance understanding and control the manufacturing process…” (USFDA PAT)  
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 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.

General Information

• Status: Published
• Publication Date: 14-Nov-2023
• ICS: 11.120.01 - Pharmaceutics in general
• Technical Committee: E55 - Manufacture of Pharmaceutical and Biopharmaceutical Products
• Drafting Committee: E55.11 - Process Design

Relations

• Replaces: ASTM E2475-10(2016) - Standard Guide for Process Understanding Related to Pharmaceutical Manufacture and Control
• Effective Date: 15-Nov-2023
• Referred By: ASTM E3326-22 - Standard Guide for Application of Continuous Manufacturing (BioCM) in the Biopharmaceutical Industry
• Effective Date: 15-Nov-2023
• Referred By: ASTM E2968-23 - Standard Guide for Application of Continuous Manufacturing (CM) in the Pharmaceutical Industry
• Effective Date: 15-Nov-2023

Standards Content (Sample)

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: E2475 − 23
Standard Guide for
Process Understanding Related to Pharmaceutical
1
Manufacture and Control
This standard is issued under the fixed designation E2475; 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.
1. Scope 2. Referenced Documents
3
2.1 ASTM Standards:
1.1 The purpose of this guide is to establish a framework
E456 Terminology Relating to Quality and Statistics
and context for process understanding for pharmaceutical
E2281 Practice for Process Capability and Performance
manufacturing using the principles of quality by design (QbD)
2 Measurement
(Juran, 1992; ICH Q8). The framework is applicable to both
E2617 Practice for Validation of Empirically Derived Mul-
drug substance (DS) and drug product (DP) manufacturing.
tivariate Calibrations
High (detailed) level process understanding can be used to
4
2.2 U.S. Government Publications:
facilitate production of product which consistently meets
ICH Quality Implementation Working Group Points To
required specifications. It can also play a key role in continual
Consider (R2) ICH-Endorsed Guide for ICH Q8/Q9/Q10
process improvement efforts.
Implementation
ICH Q8 Pharmaceutical Development
1.2 Process Analytical Technology (PAT) is one element
ICH Q9 Quality Risk Management
that can be used for achieving control over those inputs
ICH Q10 Pharmaceutical Quality Systems
determined to be critical to a process. It is important for the
ICH Q11 Development and Manufacture of Drug Substances
reader to recognize that PAT is defined as:
ISO 14971 Medical devices—Application of risk manage-
“{a system for designing, analyzing, and controlling manufacturing through
ment to medical devices
timely measurements (i.e., during processing) of critical quality and performance
attributes of raw and in process materials and processes, with the goal of
USFDA PAT Guidance Document, Guidance for Industry
ensuring final product quality. It is important to note that the term analytical in
PAT—A Framework for Innovative Pharmaceutical
PAT is viewed broadly to include chemical, physical, microbiological,
Manufacturing and Quality Assurance
mathematical, and risk analysis conducted in an integrated manner. The goal of
PAT is to enhance understanding and control the manufacturing process{”
(USFDA PAT)
3. Terminology
1.3 This standard does not purport to address all of the
3.1 Definitions of Terms Specific to This Standard:
safety concerns, if any, associated with its use. It is the
3.1.1 critical inputs, n—critical process parameters and
responsibility of the user of this standard to establish appro-
critical raw material attributes for a given process.
priate safety, health, and environmental practices and deter-
3.1.2 empirical, adj—any conclusion based on experimental
mine the applicability of regulatory limitations prior to use.
data and past experience, rather than on theory.
1.4 This international standard was developed in accor-
3.1.3 expert system, n—an expert system is a computer
dance with internationally recognized principles on standard-
program that simulates the judgment and behavior of a human
ization established in the Decision on Principles for the
or an organization that has expert knowledge and experience in
Development of International Standards, Guides and Recom-
a particular field.
mendations issued by the World Trade Organization Technical
3.1.3.1 Discussion—Typically, such a system contains a
Barriers to Trade (TBT) Committee.
knowledge base containing accumulated experience and a set
of rules for applying the knowledge base to each particular
1
This guide is under the jurisdiction of ASTM Committee E55 on Manufacture
3
of Pharmaceutical and Biopharmaceutical Products and is the direct responsibility of For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Subcommittee E55.11 on Process Design. contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
Current edition approved Nov. 15, 2023. Published December 2023. Originally Standards volume information, refer to the standard’s Document Summary page on
approved in 2010. Last previous edition approved in 2016 as E2475 – 10 (2016). the ASTM website.
4
DOI:10.1520/E2475-23. Available from U.S. Government Printing Office Superintendent of Documents,
2
Juran, J., Juran on Quality by Design: The New Steps for Planning Quality Into 732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http://
Goods and Se
...

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: E2475 − 10 (Reapproved 2016) E2475 − 23
Standard Guide for
Process Understanding Related to Pharmaceutical
1
Manufacture and Control
This standard is issued under the fixed designation E2475; 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.
1. Scope
1.1 The purpose of this guide is to establish a framework and context for process understanding for pharmaceutical manufacturing
2
using the principles of quality by design (QbD) (Juran, 1992; FDA/ICH Q8).ICH Q8). The framework is applicable to both active
pharmaceutical ingredient (API) and to drug substance (DS) and drug product (DP) manufacturing. High (detailed) level process
understanding can be used to facilitate production of product which consistently meets required specifications. It can also play a
key role in continuouscontinual process improvement efforts.
1.2 Process Analytical Technology (PAT) is one element that can be used for achieving control over those inputs determined to
be critical to a process. It is important for the reader to recognize that PAT is defined as:
“{a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing)
of critical quality and performance attributes of raw and in process materials and processes, with the goal of ensuring final
product quality. It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical,
microbiological, mathematical, and risk analysis conducted in an integrated manner. The goal of PAT is to enhance
understanding and control the manufacturing process{” (U.S. FDA PAT)
“{a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing)
of critical quality and performance attributes of raw and in process materials and processes, with the goal of ensuring final
product quality. It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical,
microbiological, mathematical, and risk analysis conducted in an integrated manner. The goal of PAT is to enhance
understanding and control the manufacturing process{” (USFDA PAT)
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 and healthsafety, health, and environmental practices and 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.
2. Referenced Documents
3
2.1 ASTM Standards:
E456 Terminology Relating to Quality and Statistics
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 E55.11 on Process Design.
Current edition approved Sept. 1, 2016Nov. 15, 2023. Published September 2016December 2023. Originally approved in 2010. Last previous edition approved in 20102016
as E2475 – 10. DOI:10.1520/E2475-10R16.10 (2016). DOI:10.1520/E2475-23.
2
Juran, J., Juran on Quality by Design: The New Steps for Planning Quality Into Goods and Services, Free Press, New York, N.Y., 1992.
3
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
1

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E2475 − 23
E2281 Practice for Process Capability and Performance Measurement
4
E2474 Practice for Pharmaceutical Process Design Utilizing Process Analytical Technology (Withdrawn 2020)
E2617 Practice for Validation of Empirically Derived Multivariate Calibrations
4
2.2 U.S. Government Publications:
ICH Quality Implementation Working Group Points To Consider (R2) ICH-Endorsed Guide for ICH Q8/Q9/Q10 Implementa-
tio
...