ASTM E2537-16
(Guide)Standard Guide for Application of Continuous Process Verification to Pharmaceutical and Biopharmaceutical Manufacturing
Standard Guide for Application of Continuous Process Verification to Pharmaceutical and Biopharmaceutical Manufacturing
SIGNIFICANCE AND USE
4.1 Application of the approach described within this standard guide applies science-based concepts and principles introduced in the FDA’s initiative on pharmaceutical CGMPs for the 21st century.4
4.2 This guide supports, and is consistent with, elements from ICH Q8 – Q11 and guidelines from USFDA, European Commission, Pharmaceutical Inspection Co-operation Scheme, and the China Food and Drug Administration.8
4.3 According to FDA Guidance for Industry, PAT, “With real time quality assurance, the desired quality attributes are ensured through continuous assessment during manufacture. Data from production batches can serve to validate the process and reflect the total system design concept, essentially supporting validation with each manufacturing batch.” In other words, the accumulated product and process understanding used to identify the Critical Quality Attributes (CQAs), together with the control strategy, will enable control of the CQAs, providing the confidence needed to show validation with each batch. This is as opposed to a traditional discrete process validation approach.
SCOPE
1.1 This guide describes Continuous Process Verification as an alternate approach to process validation where manufacturing process (or supporting utility system) performance is continuously monitored, evaluated, and adjusted (as necessary). It is a science-based approach to verify that a process is capable and will consistently produce product meeting its predetermined critical quality attributes. Continuous Process Verification (ICH Q8) is similarly described as Continuous Quality Verification.
1.2 Pharmaceutical and biopharmaceutical product manufacturing companies are required to provide assurance that the processes used to manufacture regulated products result in products with the specified critical quality attributes of strength identity and purity associated with the product safety and efficacy. Process validation is a way in which companies provide that assurance.
1.3 With the knowledge obtained during the product lifecycle, a framework for continuous quality improvements will be established where the following may be possible: (1) risk identified, (2) risk mitigated, (3) process variability reduced, (4) process capability enhanced, (5) process design space defined or enhanced, and ultimately (6) product quality improved. This can enable a number of benefits that address both compliance and operational goals (for example, real time release, continuous process improvement).
1.4 The principles in this guide may be applied to drug product or active pharmaceutical ingredient/drug substance pharmaceutical and biopharmaceutical batch or continuous manufacturing processes or supporting utility systems (for example, TOC for purified water and water for injection systems, and so forth).
1.5 The principles in this guide may be applied during the development and manufacturing of a new process or product or for the improvement or redesign, or both, of an existing process.
1.6 Continuous process verification may be applied to manufacturing processes that use monitoring systems that provide frequent and objective measurement of process data in real time. These processes may or may not employ in-, on-, or at-line analyzers/controllers that monitor, measure, analyze, and control the process performance. The associated processes may or may not have a design space.
1.7 This guide may be used independently or in conjunction with other proposed E55 standards to be published by ASTM International.
General Information
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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: E2537 − 16
Standard Guide for
Application of Continuous Process Verification to
1
Pharmaceutical and Biopharmaceutical Manufacturing
This standard is issued under the fixed designation E2537; 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 1.5 The principles in this guide may be applied during the
development and manufacturing of a new process or product or
1.1 This guide describes Continuous Process Verification as
for the improvement or redesign, or both, of an existing
an alternate approach to process validation where manufactur-
process.
ing process (or supporting utility system) performance is
1.6 Continuous process verification may be applied to
continuously monitored, evaluated, and adjusted (as neces-
manufacturing processes that use monitoring systems that
sary). It is a science-based approach to verify that a process is
provide frequent and objective measurement of process data in
capable and will consistently produce product meeting its
real time. These processes may or may not employ in-, on-, or
predetermined critical quality attributes. Continuous Process
at-line analyzers/controllers that monitor, measure, analyze,
Verification (ICH Q8) is similarly described as Continuous
and control the process performance. The associated processes
Quality Verification.
may or may not have a design space.
1.2 Pharmaceutical and biopharmaceutical product manu-
1.7 This guide may be used independently or in conjunction
facturing companies are required to provide assurance that the
with other proposed E55 standards to be published by ASTM
processes used to manufacture regulated products result in International.
products with the specified critical quality attributes of strength
1.8 This international standard was developed in accor-
identity and purity associated with the product safety and
dance with internationally recognized principles on standard-
efficacy. Process validation is a way in which companies
ization established in the Decision on Principles for the
provide that assurance.
Development of International Standards, Guides and Recom-
mendations issued by the World Trade Organization Technical
1.3 With the knowledge obtained during the product
Barriers to Trade (TBT) Committee.
lifecycle, a framework for continuous quality improvements
will be established where the following may be possible: (1)
2. Referenced Documents
risk identified, (2) risk mitigated, (3) process variability
2
2.1 ASTM Standards:
reduced, (4) process capability enhanced, (5) process design
E2363 Terminology Relating to Manufacturing of Pharma-
space defined or enhanced, and ultimately (6) product quality
ceutical and Biopharmaceutical Products in the Pharma-
improved. This can enable a number of benefits that address
ceutical and Biopharmaceutical Industry
both compliance and operational goals (for example, real time
2.2 Other Publications:
release, continuous process improvement).
ICH Q8 (R2) Pharmaceutical Development (Step 4 version),
3
1.4 The principles in this guide may be applied to drug November 2009
ICH Q9 Quality Risk Management (Step 4 version), Novem-
product or active pharmaceutical ingredient/drug substance
3
pharmaceutical and biopharmaceutical batch or continuous ber 2005
ICH Q10 Pharmaceutical Quality System (Step 4 version),
manufacturing processes or supporting utility systems (for
3
June 2008
example, TOC for purified water and water for injection
systems, and so forth).
2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
1
This guide is under the jurisdiction of ASTM Committee E55 on Manufacture Standards volume information, refer to the standard’s Document Summary page on
of Pharmaceutical and Biopharmaceutical Products and is the direct responsibility of the ASTM website.
3
Subcommittee E55.11 on Process Design. Available from International Conference on Harmonisation of Technical
Current edition approved Dec. 1, 2016. Published January 2017. Originally Requirements for Registration of Pharmaceuticals for Human Use (ICH), ICH
approved in 2008. Last previous edition approved in 2008 as E2537 – 08. DOI: Secretariat, c/o IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20,
10.1520/E2537-16. Switzerland, http://www.ich.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United State
...
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: E2537 − 08 E2537 − 16
Standard Guide for
Application of Continuous QualityProcess Verification to
1
Pharmaceutical and Biopharmaceutical Manufacturing
This standard is issued under the fixed designation E2537; 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 This guide describes Continuous QualityProcess Verification (CQV) as an alternate approach to process validation where
manufacturing process (or supporting utility system) performance is continuously monitored, evaluated, and adjusted (as
necessary). It is a science-based approach to verify that a process is capable and will consistently produce product meeting its
predetermined critical quality attributes. CQV Continuous Process Verification (ICH Q8) is similarly described as Continuous
Quality Assurance (U.S. FDA) and Continuous Process Verification (ICH Q8). Verification.
1.2 Pharmaceutical and biopharmaceutical product manufacturing companies are required to provide assurance that the
processes used to manufacture regulated products result in products with the specified critical quality attributes of strength identity
and purity associated with the product safety,safety and efficacy. Process validation is a way in which companies provide that
assurance.
1.3 With the knowledge obtained during the product lifecycle, a framework for continuous quality improvementimprovements
will be established where the following may be possible: (1) risk mitigated,identified, (2) risk mitigated, (3) process variability
reduced, (3)(4) process capability enhanced, (4)(5) process design space defined or enhanced, and ultimately (5)(6) product quality
improved. This can enable a number of benefits that address both compliance and operational goals (for example, real time release,
continuous process improvement).
1.4 The principles in this guide may be applied to drug product or active pharmaceutical ingredient/drug substance
pharmaceutical and biopharmaceutical batch or continuous manufacturing processes or supporting utility systems (for example,
TOC for Purified Waterpurified water and Waterwater for Injectioninjection systems, and so forth).
1.5 The principles in this guide may be applied during the development and manufacturing of a new process or product or for
the improvement and/or redesign or redesign, or both, of an existing process.
1.6 Continuous qualityprocess verification may be applied to manufacturing processes that use monitoring systems that provide
frequent and objective measurement of process data. data in real time. These processes may or may not employ in-, on-, or at-line
analyzers/controllers that monitor, measure, analyze, and control the process performance. The associated processes may or may
not have a design space.
1.7 This guide may be used independently or in conjunction with other proposed E55 standards to be published by ASTM
International.
2. Referenced Documents
2
2.1 ASTM Standards:
E2363 Terminology Relating to Process Analytical Technology in the Pharmaceutical Industry
2.2 Other Publications:
3
ICH Q8 (R2) Pharmaceutical Development (Step 4 version), 10 November 20052009
3
ICH Q9 Quality Risk Management (Step 4 version), 9 November 2005
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 E55.03 on General Pharmaceutical Standards.
Current edition approved Jan. 1, 2008Dec. 1, 2016. Published February 2008January 2017. Originally approved in 2008. Last previous edition approved in 2008 as
E2537 – 08. DOI: 10.1520/E2537-08.10.1520/E2537-16.
2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
3
Available from International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), ICH Secretariat, c/o
IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20, Switzerland, http://www.ich.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
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E2537 − 16
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ICH
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