ASTM E2500-07
(Guide)Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment
Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment
SIGNIFICANCE AND USE
Application of the approach described within this guide is intended to satisfy international regulatory expectations in ensuring that manufacturing systems and equipment are fit for intended use, and to satisfy requirements for design, installation, operation, and performance.
The approach described in this guide applies concepts and principles introduced in the FDA initiative, Pharmaceutical cGMPs for the 21st Century—A Risk-Based Approach.
This guide supports, and is consistent with, the framework described in ICH Q8 and ICH Q9.
This guide may be used independently or in conjunction with other proposed E55 standards to be published by ASTM International.
SCOPE
1.1 This guide is applicable to all elements of pharmaceutical and biopharmaceutical manufacturing systems including: facility equipment, process equipment, supporting utilities, associated process monitoring and control systems, and automation systems that have the potential to affect product quality and patient safety.
1.2 For brevity, these are referred to throughout the rest of this guide as manufacturing systems.
1.3 This guide may also be applied to laboratory, information, and medical device manufacturing systems.
1.4 This guide is applicable to both new and existing manufacturing systems. The approach may be used for the implementation of changes to existing systems, and their continuous improvement during operation.
1.5 This guide is applicable throughout the life-cycle of the manufacturing system from concept to retirement.
This standard does not address employee health and safety, environmental, or other non-GxP regulations. 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 health practices and determine the applicability of regulatory limitations prior to use.
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Designation:E2500 −07
StandardGuide for
Specification, Design, and Verification of Pharmaceutical
and Biopharmaceutical Manufacturing Systems and
Equipment
This standard is issued under the fixed designation E2500; 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 2.2 Other Publications:
ICH Q8 Pharmaceutical Development Handbook
1.1 This guide is applicable to all elements of pharmaceu-
ICH Q9 Quality Risk Handbook
tical and biopharmaceutical manufacturing systems including:
Pharmaceutical cGMPs for the 21st Century —A Risk-
facility equipment, process equipment, supporting utilities,
Based Approach
associated process monitoring and control systems, and auto-
mation systems that have the potential to affect product quality
3. Terminology
and patient safety.
3.1 Definitions:
1.2 For brevity, these are referred to throughout the rest of
3.1.1 For definitions of terms used in this guide, refer to
this guide as manufacturing systems.
Terminology E2363.
3.1.2 acceptance criteria—the criteria that a system or
1.3 This guide may also be applied to laboratory,
component must satisfy in order to be accepted by a user or
information, and medical device manufacturing systems.
other authorized entity.
1.4 This guide is applicable to both new and existing
3.1.3 design reviews—planned and systematic reviews of
manufacturing systems. The approach may be used for the
specifications, design, and design development and continuous
implementation of changes to existing systems, and their
improvement changes performed as appropriate throughout the
continuous improvement during operation.
life-cycle of the manufacturing system. Design reviews evalu-
1.5 This guide is applicable throughout the life-cycle of the
ate deliverables against standards and requirements, identify
manufacturing system from concept to retirement.
problems, and propose required corrective actions.
1.6 This standard does not address employee health and
3.1.4 manufacturing systems—elements of pharmaceutical
safety, environmental, or other non-GxP regulations. This
and biopharmaceutical manufacturing capability, including
standard does not purport to address all of the safety concerns,
manufacturing systems, facility equipment, process equipment,
if any, associated with its use. It is the responsibility of the user
supporting utilities, associated process monitoring and control
of this standard to establish appropriate safety and health
systems, and automation systems, that have the potential to
practices and determine the applicability of regulatory limita-
affect product quality and patient safety.
tions prior to use.
3.1.5 subject matter experts (SMEs)—individuals with spe-
cific expertise and responsibility in a particular area or field
2. Referenced Documents
(for example, quality unit, engineering, automation,
2.1 ASTM Standards: development, operations, and so forth).
E2363 Terminology Relating to ProcessAnalytical Technol-
3.1.6 verification—a systematic approach to verify that
ogy in the Pharmaceutical Industry
manufacturing systems, acting singly or in combination, are fit
for intended use, have been properly installed, and are operat-
ing correctly. This is an umbrella term that encompasses all
types of approaches to assuring systems are fit for use such as
This guide is under the jurisdiction of ASTM Committee E55 on Manufacture
of Pharmaceutical Products and is the direct responsibility of Subcommittee E55.03
on General Pharmaceutical Standards.
Current edition approved June 1, 2007. Published August 2007. DOI: 10.1520/ Available from International Conference on Harmonisation of Technical
E2500-07. Requirements for Registration of Pharmaceuticals for Human Use (ICH), ICH
For referenced ASTM standards, visit the ASTM website, www.astm.org, or Secretariat, c/o IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20,
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM Switzerland, http://www.ich.org.
Standards volume information, refer to the standard’s Document Summary page on Available from Food and Drug Administration (FDA), 5600 Fishers Ln.,
the ASTM website. Rockville, MD 20857, http://www.fda.gov.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2500−07
qualification, commissioning and qualification, verification, 6.2.2 Two primary principles of quality risk management
system validation, or other. are identified in ICH Q9:
6.2.2.1 The evaluation of the risk to quality should be based
4. Summary of Guide
on scientific knowledge and ultimately link to the protection of
the patient.
4.1 This guide describes a risk-based and science-based
approach to the specification, design, and verification of 6.2.2.2 The level of effort, formality and documentation of
manufacturing systems and equipment that have the potential the quality risk management process should be commensurate
to affect product quality and patient safety. with the level of risk.
6.2.3 These principles should be applied to specification,
4.2 This guide describes a systematic, efficient, and effec-
design, and verification of manufacturing systems.
tive way of ensuring that manufacturing systems and equip-
6.2.4 The scope and extent of quality risk management for
ment are fit for intended use, and that risk to product quality,
specification, design, and verification activities and documen-
and consequently to patient safety, are effectively managed to
tationshouldbebasedontherisktoproductqualityandpatient
the extent that these are affected by such systems and equip-
safety.
ment.
4.3 The overall objective is to provide manufacturing capa-
6.3 Science-based Approach:
bility to support defined and controlled processes that can
6.3.1 Product and process information, as it relates to
consistently produce product meeting defined quality require-
product quality and patient safety, should be used as the basis
ments.
for making science- and risk-based decisions that ensure that
the manufacturing systems are designed and verified to be fit
4.4 The approach described within this guide also supports
for their intended use.
continuous process capability improvements and enables inno-
vation such as the implementation of Process Analytical 6.3.2 Examples of product and process information to
Technology (PAT). consider include: critical quality attributes (CQAs), critical
process parameters (CPPs), process control strategy informa-
4.5 The main elements of this guide are:
tion, and prior production experience.
4.5.1 The underlying key concepts that should be applied,
4.5.2 A description of the specification, design, and verifi-
6.4 Critical Aspects of Manufacturing Systems:
cation process, and
6.4.1 Critical aspects of manufacturing systems are typi-
4.5.3 A description of the required supporting processes.
cally functions, features, abilities, and performance or charac-
teristics necessary for the manufacturing process and systems
5. Significance and Use
to ensure consistent product quality and patient safety. They
5.1 Application of the approach described within this guide should be identified and documented based on scientific
product and process understanding.
is intended to satisfy international regulatory expectations in
ensuring that manufacturing systems and equipment are fit for
6.4.2 For brevity, these are referred to throughout the rest of
intended use, and to satisfy requirements for design, installa-
this guide as critical aspects.
tion, operation, and performance.
6.4.3 Verification activities should focus on these aspects of
manufacturing systems and should be documented. The veri-
5.2 The approach described in this guide applies concepts
fication process is defined in 7.4.
and principles introduced in the FDA initiative, Pharmaceuti-
cal cGMPs for the 21st Century—A Risk-Based Approach.
6.5 Quality by Design:
5.3 This guide supports, and is consistent with, the frame-
6.5.1 Quality by design concepts should be applied to
work described in ICH Q8 and ICH Q9.
ensurethatcriticalaspectsaredesignedintosystemsduringthe
specification and design process. The critical aspects of the
5.4 This guide may be used independently or in conjunction
design and associated acceptance criteria should be docu-
with other proposed E55 standards to be published by ASTM
mented.
International.
6.5.2 Assurance that manufacturing systems are fit for
6. Key Concepts
intended use should not rely solely upon verification after
installation, but be achieved by a planned and structured
6.1 This guide applies the following key concepts:
verification approach applied throughout the system life cycle.
Risk-based Approach
Science-based Approach
6.6 Good Engineering Practice:
Critical Aspects of Manufacturing Systems
6.6.1 Good Engineering Practice (GEP) should underpin
Quality by Design
Good Engineering Practice
and support the specification, design, and verification activi-
Subject Matter Expert
ties.
Use of Vendor Documentation
Continuous Process Improvement
6.6.2 Good Engineering Practice is defined as those estab-
lished engineering methods and standards that are applied
6.2 Risk-based Approach:
throughout the life cycle to deliver appropriate and effective
6.2.1 Risk management should underpin the specification,
solutions.
design, and verification process, and be applied appropriately
at each stage. 6.6.3 Examples of Good Engineering Practices include:
E2500−07
6.6.3.1 Specification, design, and installation activities 7. Process
should take full account of all applicable requirements, includ-
7.1 Overview—The process of specification, design, and
ing GxP, safety, health, environmental, ergonomic, operational,
verification of manufacturing systems should include the
maintenance, recognized industry standards, and other statu-
following activities:
tory requirements.
Requirements definition
6.6.3.2 Adequate provisions related to quality should be
Specification and design
included in specification, design, procurement, and other con- Verification
Acceptance and release
tractual documents.
7.1.1 Good Engineering Practice should be applied through-
6.6.3.3 Life-cycle documentation covering planning, speci-
out the process.
fication, design, verification, installation, acceptance, and
7.1.2 Risk management should be performed as appropriate
maintenance should be produced.
to evaluate the risks to product quality and patient safety
6.6.3.4 An appropriate degree of oversight and control
related to the manufacturing system and corresponding design
should be achieved by suitable verification of execution,
solution. Risk management is a supporting process and is
construction and installation activities.
defined in 8.2.
6.7 Subject Matter Experts:
7.1.3 Design reviews should be performed as appropriate
6.7.1 Subject matter experts are defined as those individuals
throughout the life-cycle of the manufacturing system. The
with specific expertise and responsibility in a particular area or
design review process is a supporting process and is defined in
field (for example, quality unit, engineering, automation,
8.3.
development, operations, and so forth).
7.1.4 Change management should be applied throughout the
6.7.2 Subject matter experts should take the lead role in the
process. The change management process is a supporting
verification of manufacturing systems as appropriate within
process and is defined in 8.4.
their area of expertise and responsibility.
7.2 Requirements Definition:
6.7.3 Subject matter expert responsibilities include planning
7.2.1 Specific requirements should be identified and should
and defining verification strategies, defining acceptance crite-
provide the basis of further specification, design, and verifica-
ria, selection of appropriate test methods, execution of verifi-
tion of the manufacturing system.
cation tests, and reviewing results.
7.2.2 These specific requirements relative to product quality
6.8 Use of Vendor Documentation:
and patient safety should be based upon:
6.8.1 Vendor documentation, including test documents may
7.2.2.1 Product knowledge and understanding,
be used as part of the verification documentation, providing the
7.2.2.2 Process knowledge and understanding,
regulated company has assessed the vendor, and has evidence
7.2.2.3 Regulatory requirements, and
of:
7.2.2.4 Company quality requirements.
6.8.1.1 An acceptable vendor quality system,
7.2.3 Product and process knowledge and understanding,
6.8.1.2 Vendor technical capability, and
including knowledge of sources of variability in the product
6.8.1.3 Vendor application of GEP such that information and process, the identification of critical quality attributes, and
obtained from the vendor will be accurate and suitable to meet process control strategy information, should be based on
the purpose of verification. scientific data gathered during experimental and development
work and manufacturing experience. Product and process
6.8.2 Ifinadequaciesarefoundinthevendorqualitysystem,
knowledge forms the basis of scientific understanding as
technical capability, or application of GEP, then the regulated
described in ICH Q8 and process control strategy.
company may choose to mitigate potential risks by applying
specific, targeted, additional verification checks or other con-
7.3 Specification and Design:
trols rather than repeating vendor activities and replicating
7.3.1 Firms should develop appropriate mechanisms to
vendor documentation.
communicate requirement inputs, including product quality
6.8.3 The decision and justification to use vendor documen-
considerations, to those responsible for design, so that the
tation, to support the verification of critical aspects of the
manufacturing system may be properly designed based upon
manufacturing element, should be based on the intended use of
relevant knowledge of product, process, and other require-
the manufacturing system, and should be documented and
ments.
approved by subject matter experts including the quality unit.
7.3.2 Specification and design activities should include a
focus on those aspects that have been identified as being
6.9 Continuous Improvement:
critical to product quality and patient safety. These critical
6.9.1 As experience is gained in commercial production,
aspects of the manufacturing system should be identified and
opportunities for improvements should be sought based on
documented by subject matter experts.
periodic review and evaluation, operational and performance
data, and root-cause analysis of failure
...
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