Design, Construction,

Commission, and
Qualification of Critical
Utility Systems
Part I: Overview
B Y D AV I D W. V I N C E N T A N D H E R B E RT M AT H E S O N

INTRODUCTION
Overview of Critical Utility Systems
The use of critical utility systems in the pharmaceutical
industry is very important to final product quality. That is
why the design, construction, commissioning, qualification,
and routine monitoring of these systems is important in enssuring that the end product will maintain a reproducible
quality. Critical utility systems can be considered the backbone of any production facility and should be the first systems to be validated. Without properly functioning utilities,
the quality of any product will be open to question.
Critical utilities found in pharmaceutical, medical device,
and biotechnology production facilities usually support various equipment and processes. These utilities must meet both
quantitative and qualitative specifications in order to be considered satisfactory. The actual criteria may vary from one
utility system to another and may even be influenced by the
particular equipment being supported. The design, construction, commissioning, qualification, and monitoring of each
utility will vary depending on the system. Therefore, it is important to follow a logical, comprehensive scheme when attempting to validate or monitor these systems.
This article will discuss the various phases of design,
construction, commissioning, qualification, and the routine
monitoring of various critical utility systems. While it takes
a great deal of time and effort to qualify most critical utili-

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ties, this article will only cover general procedures used to

bring these systems to a validated state and, once they are
validated, to establish a routine environmental program. The
Routine Environmental Monitoring (REM) program is designed to ensure that the validation lifecycle is maintained
for these systems. The REM program also ensures that the
systems are capable of maintaining the same quality output
throughout the life of the system.
This article will not describe the detailed procedures
needed to validate these systems. It is impractical to discuss
all the existing methods and procedures used to validate
utility systems within the scope of this article. However, this
article will discuss an approach to integrate the commissioning and qualification phases of the project in order to
streamline the qualification phase while verifying that the
critical utilities meet their pre-determined design features.
The critical utilities that will be addressed in the article
are as follows:
1. Water systems
2. Clean steam system
3. Heating Ventilation and Air Conditioning (HVAC)
systems
4. Process gases
This article is the first of three-parts. Part I is an
overview of critical utility systems and the planning needed
before specific utilities may be addressed.

David W. Vincent and Herbert Matheson

User Requirement Specifications

The development of User Requirement Specifications
(URS) is one of the most critical elements in the compliance
documentation process. A successful project is dependent
on clear definition, communication, the understanding of
project scope and objectives, as well as other stakeholder
requirements as defined by them and the end user. At the
outset of the project, after the front end conceptual study has
been completed, the user must specify the requirements for
individual aspects of the utility systems in terms of function,
throughput, operation, and applicable regulatory requirements to the engineering service provider. This enables the
development and assessment of specific engineering options. These requirements are normally formalized in a detailed URS document.
The URS describes critical installation and operating parameters. It includes performance standards that are required for the intended use of the equipment and provides
the basis for the qualification and maintenance of equipment. The URS should be prepared by the equipment owner
in collaboration with representatives from departments that
will participate in qualifying and maintaining the equipment, and from departments that will be affected by the operation of that equipment.

Design Specifications and the

Design Review Phase
Design specifications for each system are established
based on engineering and manufacturing provisions, as well
as input from various organizations and departments. Design
specifications are the foundation for the development of the
qualification document acceptance criteria. It is necessary to
track compliance with specifications throughout the validation project. In the end, validation activities will demonstrate
that the design intent has been achieved through the proper
tracking and control of design specifications.
A formal design review process at the beginning of the
project will decrease the number of deviations associated
with improper control of design specifications during the
execution of Installation and Operational Qualification
(I/OQ) protocols. A design review process compares the design of equipment and systems with the applicable user and
process requirements as defined in the current URS, processing requirements, product specifications, license commitments, manufacturing records, and applicable Standard
Operating Procedures (SOP). The design review is intended

to ensure and record that system design meets user requirements.

One of the first steps that should be considered is defining which areas are to be qualified and what their intended
uses will be. A facility room classification or design specification should be based on the product being manufactured
and the processes being used. It is important that the Architecture and Engineering (A/E) team who are creating the
design and layout are aware of those areas.
The reasons for this are as follows:1
To define exactly those areas for which qualification data must be developed.
To prevent any misunderstanding, either by the
owner or the Food and Drug Administration
(FDA), as to what areas will be subject to qualification. During a pre-construction review of the
drawings with the FDA, the list of areas that were
specified should be discussed. Then, if there are
any differences of opinion between the owner and
the FDA, they can be resolved before construction
starts. It should also be added that drawings are required of the entire facility noting production features and functions. If the A/E firm knows ahead of
time that as-built drawings are required, the field
people who are responsible for monitoring the construction activities will make the changes to the
drawings as the actual changes are being made in
the field. This is the way to be assured that as-built
drawings will truly be as builts, instead of I
think-builts.
Good Manufacturing Practices (GMPs) call for the following pertaining to layouts:
Smooth flow of personnel and product
Adequate space to perform each operation
Spatial separation, where appropriate, to prevent
product mix-ups, component mix-ups, etc.
Adequate lighting
Environmental controls
The design and construction of any facility requires a
team effort. The Design Qualification (DQ) phase of the
project requires the assistance of various departments and
professionals such as Quality Control (QC) and Quality Assurance (QA), Regulatory Affairs (RA), Facilities/Engineering, Validation, Manufacturing, as well as the general contractor and sub-contractors.

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System Level Impact Assessment

A simplified approach can be summarized as follows:
Determine facility design task force (QA, QC, Engineering, Manufacturing, Validation, etc.)
Determine process environment requirements
Determine operation requirements, including personnel flow and material and waste flows
Quantify production, process, and equipment space
requirements
Develop conceptual layout
Approve final facility layout
Develop detail system engineering
Prepare designs and specifications
Obtain acceptance of the design review team
Prepare bidding documents
Determine bidding and acceptance process
Determine construction start date
It is important to remember that the products and manufacturing processes usually determine the design and layout
of the facility. It is also important to arrange a pre-construction meeting with the FDA. This meeting can decrease the
effort expended in justifying the design after the fact. By developing a formalized and well-documented design review
process, the critical component, design specification, and parameters can be referenced in the validation protocols,
thereby decreasing and streamlining the amount of information that requires verification in the qualification protocols.

Impact Assessments
Impact assessments are a formal process used to identify
systems and the components of those systems that have a direct impact on product quality. Direct impact systems are
expected to have an impact on the product quality, whereas
an indirect impact system is not expected to have an impact on the product quality. Both systems require commissioning; however, the direct impact system will be subject to
qualification practices to meet the additional regulatory requirements of the FDA and other regulatory authorities. The
impact assessment process decreases the scope of IQ/OQ
protocols by allowing the validation activities to focus on
those systems and components that have been identified as
having a direct impact on product quality, rather than all systems and components within those processes.
Impact assessments should be performed on two levels:
the system level and the component level.

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System impact assessments are performed to differentiate those systems that have a direct impact on product quality from those having indirect or no impact on product quality. The system impact assessments are preliminary until the
completion of subsequent component impact assessments
for each of the systems. The results of the component impact assessments could change the results of the system impact assessments, which is why the initial system impact assessment should be considered preliminary.
The advantage of performing system impact assessments is that only direct impact systems require qualification. Indirect impact and no impact systems are subject to
less stringent test and inspection procedures based on business risk and typical Good Engineering Practices (GEPs). A
number of utility systems that were commonly qualified in
the past, such as plant steam, chill water, industrial cold
water, and heating hot water, are typically no longer qualified based on the results of system impact assessments.
The following summarizes the system impact assessment process:
Identification of the system and system number:
This information is typically obtained from the
project Process and Instrumentation Diagrams
(P&IDs). Complete the system description with a
general narrative of the system and its major components, design, operation, functional capabilities,
and critical functions.
System Boundary Definition: Identifying the
boundaries and scope of the system is typically
done using the system P&IDs as well as other
drawings and specifications, as appropriate. The
easiest and clearest way to accomplish this is to
mark the system P&IDs to identify the system
boundaries and all components of the system included within those bounds. Specify system
boundaries by inserting a horizontal or vertical line
at the boundary. These lines should be placed to
clearly identify whether or not the adjacent component is part of the system.

David W. Vincent and Herbert Matheson

Figure
1
______________________________________________________________________________
Impact Assessment Questions
Challenge
1.

2.
3.
4.
5.

6.

7.

Yes

No

Does the system have direct contact with the product (e.g. air quality) or
direct contact with a product contact surface [e.g.: Clean in Place (CIP)
solution]?
Does the system provide an excipient, or produce an ingredient or solvent
[e.g.: Water For Injection (WFI)]?
Is the system used in cleaning, sanitizing, or sterilizing (e.g.: clean steam)?
Does the system preserve product status (e.g.: nitrogen purge for oxygen
sensitive products)?
Does the system produce data that is used to accept or reject product (e.g.:
electronic batch record system, critical process parameter chart recorder, or
release laboratory instrument)?
Is the system a process control system (e.g., PLC, DCS) or does it contain a
process control system that may affect the product quality and there is no
system for independent verification of control system performance in place?
Is the system expected to not have a direct impact on product quality, but
supports a direct impact system?

To help in establishing a system boundary, utilize the

following general guidelines (there may be exceptions to
these guidelines):
If the component number of a valve, etc., is labeled as part of the main system being assessed,
then it generally will be part of that system.
The control system I/O for a given system will
become part of that system.
Disposable, flexible piping connectors, portable
tanks, etc., should not be highlighted as part of
the system and should be noted either on the
drawing or in the comments section of the form
so it is clear that not highlighting them was intentional.
System Impact Assessment: Once the system has
been identified and the system boundaries defined,
the impact of the system may be determined. The
impact of the system is determined by answering a
series of seven questions about the system. In Figure
1, the Impact Assessment Questions show how the
assessment could be completed for the example of a
hypothetical nitrogen gas system.

System Classification
The system is classified as direct impact, indirect impact, or no impact as follows:
If the response to any of challenges one through six
in Figure 1 is Yes, then the system shall be classified as a direct impact system.
If the response to challenges one through six is
No, but the response to challenge seven is Yes,
the system shall be classified as an indirect impact system.
If the response to challenges one through seven is
No, the system shall be classified as a no impact system.
Based on the above criteria, the hypothetical nitrogen
system would be classified as direct impact because it has
direct product contact. Document the reasons for this classification with a brief explanation to ensure the understanding of future reviewers and approvers.

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Component Criticality Assessments

After system impact assessments have been completed,
component criticality assessments are performed to identify
those components within a system that have direct, indirect
or no impact on product quality. The results of the component criticality assessments have a direct bearing on the validation of the system, in that IQ and OQ testing of the system can be focused on those components identified as having a direct impact on product quality.
Volume 5, Commissioning and Qualification, of the
International Society for Pharmaceutical Engineering
(ISPE) Pharmaceutical Engineering Guides for New and
Renovated Facilities recommends that components within
direct impact, indirect impact, and in some cases, no impact
systems, should be assessed for criticality. This is suggested
to ensure that systems previously judged to have indirect or
no impact in the early, high level assessment, have not subsequently acquired a critical function as the detailed design
has progressed to conclusion.
The component criticality assessment process requires
the detailed review of the system P&IDs and system instrument lists. Like the system impact assessment, the component criticality assessment is performed by answering a series of questions about each of the system components. The
questions proposed by the ISPE Commissioning and Qualification Guideline are as follows below in Figure 2.

System Classification
A positive answer to any questions in Figure 2
identifies the component as a critical component
that should be verified during IQ and OQ testing.
When answers to all the questions in Figure 2 are
in the negative, the component is thereby identified
as a non-critical component of the system that does
not require verification during IQ and OQ testing.

Component Approval
The construction contractors translate the project specifications and design documents created by the A/E team
into a completed facility. The project specifications created
by the A/E team are typically detailed and often specify a
component to a specific manufacturer and model, allowing
the use of an approved equal. The construction contractors are required to submit to the A/E team technical data on
the components that they intend to use during the construction of the facility so that the A/E team can approve the proposed components.
Due to a number of legitimate reasons, including cost
and availability, the components that contractors submit for
use often do not match all the detailed specifications created
by the A/E team. The A/E team reviews the technical data
provided by the contractor to determine whether the proposed components are acceptable for use. Oftentimes, the

Figure
2
______________________________________________________________________________
Component Criticality Assessment Questions
Challenge
1.
2.
3.
4.
5.
6.
7.

240

Is the component used to demonstrate compliance with the registered

process?
Does the normal operation or control of the component have a direct effect
on product quality?
Will the failure or alarm of the component have a direct effect on product
quality or efficacy?
Is information from this component recorded as part of the batch record, lot
release data, or other GMP-related documentation?
Does the component have direct contact with the product or product components?
Are the component controls critical process elements that may affect product
quality without independent verification of the control system performance?
Is the component used to create or preserve a critical status of a system?

Journal of Validation Technology

Yes

No

David W. Vincent and Herbert Matheson

A/E team determines that a component is acceptable even

though it does not exactly match all of the project specifications; they indicate approval with a stamp on the submittal.
In the real world, gaps in the submittal process are common, such as in the following situations:
Contractors often submit generic product data
sheets that do not adequately specify the component that will be installed. In example, a generic
valve data sheet may identify the options available
for materials and finishes, but may not identify
which of these options the contractor will select.
The submittal process is often slow and may not be
completed for all components before the components are installed in the facility.
Submittals are often stamped as approved by the
A/E but not by a designated representative of the
client for whom the facility is being constructed.

Submittal Review
A review and approval of the submittals by the building
owner is a useful process to resolve these discrepancies and
to improve the efficiency of the IQ process. A submittal review should be completed for each of the critical components identified by the component criticality assessment.
The submittal review process proceeds as follows:
Identify the critical component by description and
tag number as appropriate.
Identify the system that contains the component.
Identify the specification number that applies to the
critical component.
Identify the submittal number that applies to the
critical component.
In a Specified Attribute column, list the critical
attributes of the component as indicated in the applicable specification, such as manufacturer, model
number, materials of construction, capacity, etc.
In an Actual Attribute column, enter the existent
component information for each of the critical attributes as determined by the component vendor.
Note: It is especially important to identify
where the component varies from the specified attribute in order for reviewers to make
an informed decision as to the acceptability
of the component.

Attach supporting vendor technical literature to the

submittal review form.
Appropriate representatives of the building owner
should check the submittal review package. These
representatives typically should include the system
owner along with Facilities, Engineering, and Quality Assurance personnel. The acceptability of a component is determined based on its intended use and
its compliance with project specifications. The disposition of a component is identified typically as
ACCEPTED, ACCEPTED WITH COMMENTS, or
REJECTED. The reviewers then approve the form.
This process ensures that there is an approved submittal
package for each of the critical components identified during the component criticality review.
Note: The IQ protocols can be simplified, because the IQ need only verify that the installed critical components match the approved submittals by manufacturer and
model numbers. This is allowed because the
critical attributes of the components have already been approved through the submittal
review process.

Systematic Risk Assessment for System

Qualifications
The Risk Assessment section discusses the potential impact on current Good Manufacturing Practice (cGMP) operations associated with the use of the equipment, and the
steps that will be taken to reduce those risks. Identify conditions that could lead to failure of the equipment and the effects of failure on cGMP operations. Evaluate the degree of
risk to product quality, company operations, and the safety
of personnel and equipment.
During the risk assessment, it is important to perform an
impact assessment on the system. An impact assessment is
the process by which the effects of the system - and the critical components within those systems - on product quality
are evaluated. System risk assessment is measured in a minimum of three categories: direct product impact, indirect
product impact, and no direct product impact. By performing design impact assessments, companies can reduce the
scope of the systems and the components subject to qualification, and allow appropriate focus to be placed on the components that may present a potential risk to the product.

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Risk Assessment Example

The elements in Figures 3 and 4 indicate one example of how applying risk assessment to a validatable
system can be beneficial in developing a scientific rationale and justification for the selection of the different types of qualification needed to support a system.

Figure
3
______________________________________________________________________________
Impact Analysis
Summarize risks and associated controls in an impact and complexity analysis. Rate the impact of the
equipment on product quality, safety, and purity, and on the safety of personnel and equipment. Evaluate
the systems in place to control those risks.
A. Quality Impact

Score

No impact: Equipment will not be directly or indirectly associated with cGMP activity.
Minimal impact: Equipment indirectly affects cGMP processes or procedures. (Non-direct
product impact)
Potential Impact: Equipment performs or directly supports a cGMP process or procedure;
failure could potentially affect product quality. Equipment failure could negatively impact
operational efficiency or costs. (Indirect product impact)
Direct Impact: Equipment is an essential component of a cGMP process or procedure, or
is in direct contact with the drug substance or product. Equipment failure could result in
loss of product; safety hazard; damage to materials, equipment, or facility; or negative inspection findings. (Direct product impact)
B. Quality Risk Management

Journal of Validation Technology

1
2
3

Score

No risk control necessary.

Failure of the equipment would be detected immediately and be corrected before affecting
a cGMP process or procedure.
Failure could not go undetected. Systems and procedures are in place to detect negative
impact on product quality safety or purity before significant loss of productivity.
Failure could potentially go undetected and cause failure of other processes or procedures.

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0
1
2
3

David W. Vincent and Herbert Matheson

Figure
4
______________________________________________________________________________
Complexity Analysis
Describe the technological risks and controls associated with the equipment. The complexity analysis
evaluates the risk of failure due to technical sophistication of the equipment, and the relative difficulty of
maintaining the equipment in a state of control.
C. Technology Risk

Score

Very simple system; minimal chance of failure.

Commonly understood technology, rugged equipment; low probability of failure.
Somewhat complex equipment, generally reliable technology, components, and controls.
Highly complex or sensitive equipment, sophisticated technology, unique components,
or processes.
D. Technology Risk Management

0
1
2
3
Score

Control and repair possible without impacting cGMP activities.

Equipment requires that minimal training, simple maintenance procedures; backup, repair,
or like-for-like replacement is readily available.
Requires trained operators and maintenance technicians. Backup systems, repair,
maintenance, and replacement are readily available.
Operators and maintenance technicians must be highly trained. Maintenance, repair, or
replacement requires specialized or time-consuming effort; backup systems, repair,
maintenance, or replacement are not readily available.

0
1
2
3

Risk Score
The calculation used to evaluate the overall risk (as seen in Figure 4) of the equipment combines the individual impact and complexity scores in the following formula:
(A + B) x (C + D)

Where:

A = Quality Impact
B = Quality Risk Management
C = Technology Risk
D = Technology Risk Management

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Validation Requirements
Identify the qualification requirement for the equipment based on the impact and complexity analysis as
shown in Figure 5. For smaller, less complex system qualification, protocols can be combined into I/OQ or
IQ/OQ and Procedure Qualification (PQ) protocols. Any additional information to support and justify the validation requirements should be included.

Figure
5
______________________________________________________________________________
Qualification and Validation Justification
Risk Score

Qualification Requirements

Document installation
and commissioning

1 to 3

IQ

Validation Maintenance Requirements

4 to 6

IQ/OQ

IQ/OQ/PQ

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Documentation maintained by
users or Facilities Department.
Installation, commissioning,
maintenance, and change control
documentation maintained by
QA.
Operate, maintain, and calibrate
according to written SOPs.
Document preventive and
corrective maintenance and
calibration according to SOPs.
Apply change control procedures
according to SOPs and change
control programs.
Perform operation, maintenance,
calibration, and performance
verification tasks according to
written procedures.
Document preventive and
corrective maintenance and
calibration according to SOPs.
Apply change control procedures
according to SOPs and change
control programs.

David W. Vincent and Herbert Matheson

Construction Qualification (CQ) Activities

The construction of a pharmaceutical manufacturing facility requires strict adherence to the requirements outlined
in the Code of Federal Regulations (CFR), title 21, section
211.42 of the cGMPs2 for processing human drugs and
newly proposed regulatory requirements. A great deal of
emphasis is placed on design compliance with cGMP requirements, but the effects of construction issues on cGMP
compliance are profound and must be understood by owners, facility operators, and contractors.
Integration of construction and qualification activities is
critical to a successful validation project. Document procurement and the verification and documentation of construction activities are critical to supporting Installation
Qualification (IQ).
The proper integration of qualification and construction,
commissioning, and startup activities will:
Accelerate the start-up effort.
Produce superior documentation.
Reduce time to completion of subsequent IQ
and OQ activities.
Ensure that product is produced in a GMPcompliant facility.
Critical Systems
The following are common critical systems that should
be inspected during the CQ phase:
Cleanroom HVAC
Purified Water (WP) system
Water For Injection (WFI) system
Computerized systems
Product contact compressed gases
Clean-in-Place (CIP) systems
Product Piping systems
Architectural finishes
Documentation
In order to utilize tests and inspections performed during
the construction phase of the project, it is necessary that the
tests be performed and documented in compliance with
cGMP requirements, including:
The tests and inspections must be performed per
written and approved procedures.
The personnel performing and documenting the
tests and inspections have been trained in the test
procedures, and that training has been documented.
The test results have been documented using Good
Documentation Practices (GDP).

The SOPs necessary to support these requirements must

be reviewed and approved by the appropriate contractor and
the QA Department owner. The following is a partial list of
typical SOPs necessary to support the integration of construction activities into the qualification process:
Contractor training
Good Documentation Practices
Equipment and component receipt verification
Red line drawing control
Air duct cleaning and inspection
Air duct leakage testing
HEPA filter installation
HEPA filter leak testing
Boroscope inspection procedures
Slope verification procedures
Weld inspection procedures
Weld log procedure
Welder qualification procedures
Piping system walk down procedures
Hydrostatic pressure testing
Pneumatic pressure testing
Cleaning and passivation
Clean build protocol
Coordinator and Team Members
Depending upon the project size, a CQ coordinator and
CQ team with engineering and construction background,
should be assigned to monitor and document the construction activities necessary to support the qualification process.
A CQ coordinator is most successful in the role when he or
she reports directly to the client or is a representative of the
client. This direct reporting relationship will eliminate the
conflict of interest that would derive from the coordinator
being part of the construction company.
The Construction Qualification Team is tasked to perform the following duties:
Work closely with the general contractor and mechanical contractors, to procure, verify, and organize documentation for the Turn Over Packages
(TOPs) for direct and indirect impact systems as
part of Good Engineering Practices:

Project specifications
Vendor or manufacturer submittals
Manufacturer mechanical specifications
Purchase orders
Vendor test reports

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Material certifications
Calibration data
State and local code compliance
ASME, ANSI, and other certifications
Pipe specifications
Cleaning and passivation reports
Stainless steel weld documentation
Instrumentation specifications
Drawings
Material and finish verification
MSDS
Any other useful documentation

Monitor the construction schedule as it relates to

validation activities to ensure that the required tests
and inspections are documented.
Verify during component receipt inspection that the
actual components delivered to the jobsite match
the components approved for use during the submittal review process. This requirement applies to
the components identified as being critical during
the component criticality assessments.
Witness tests and inspections performed during the
construction process necessary to support the qualification of the critical utility systems. The tests and
inspections should be witnessed to assure that the
procedures are performed according to specifications and should be fully documented.

Audit the construction site for cleanliness and compliance with specified construction sequences, practices, and craftsmanship standards. Enter observations into a Construction Site Audit Log.
Document and report any problems that may affect
the construction schedule or have a negative impact
on the qualification phase of the project.

Specific Documentation Packages Format

Items listed in the previous sections are included in the
CQ packages according to the following guidelines:
CQ Summary Sheet
The CQ Summary Sheet, placed before the CQ
packages defined here, will briefly describe CQ
findings. Specific items for discussion should include identification of construction and installation
contractor(s), start and completion dates, historical
overview of CQ effort, and a description of CQ
documentation. Both the CQ coordinator and project manager, serving as approval for the entire CQ
package, will approve the CQ Summary Sheet.
CQ Section Index
The CQ Section Index shall list all major CQ sections.

Figure
6
______________________________________________________________________________
Tests Required for Two Common Critical Utility Systems
System

Test or Inspection

HVAC

WFI

246

Critical component receipt inspection

Air duct cleaning and inspection
Air duct leakage testing
HEPA filter installation
HEPA filter leak testing
Drawing verification
Critical component receipt inspection
Weld documentation and inspection
Hydrostatic pressure testing
Slope verification procedures
Drawing verification
Cleaning and passivation

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David W. Vincent and Herbert Matheson

Project Specifications
Project specifications are provided by the architect(s) of the project and serve as guidelines for construction. Only those project specification sections
applicable to the CQ system should be included.
Purchase Orders
All available purchase orders for equipment and
materials within the system will be included. Each
individual purchase order will be included in a separate subsection. Dollar amounts may be removed.
Purchase Specification
The Purchase Specifications section will immediately follow "Purchase Orders." Purchase specifications should include documentation provided from
the vendors, contractors, and manufacturers.
Purchase specifications should serve as succeeding
documentation for the Installation Qualification (IQ)
protocol of the CQ system. In addition, those areas
of the purchase specification giving direct evidence
to IQ requirements should be highlighted, using a
single color.
Test Reports
The Test Reports section will immediately follow
Purchase Specifications. Test reports include documents such as pressure test reports, factory test reports, and certifications. Test reports included in CQ
packages should depict the static attributes of the
system, not operational testing. Wherever practical,
the CQ coordinator or validation team member
should witness tests.
Drawings
The Drawings section will be the final section of the
CQ package. Drawings will be classified as either
reference or as built. Reference drawings should be
reviewed and signed by at least one person, while
as-built drawings should be reviewed and signed
(and red lined, if necessary) by at least one person.
(It is desirable to have two reviewers for as-built
drawings.)

Figure
7
_____________________________________
Table of Contents Example for a Typical CQ
Package
Section 1 - General
1. DESIGN SPECIFICATIONS
2. PURCHASE ORDERS
Section 2 - Equipment
3. EQUIPMENT DATA SHEETS
4. EQUIPMENT CHECKLIST
5. SPARE PARTS LIST
6. VENDOR TEST REPORTS
7. VENDOR CERTIFICATION
ASME
ANSI
MATERIAL CERTIFICATIONS
8. OPERATION AND MAINTENANCE
MANUALS
9. DRAWINGS
Section 3 - Piping and Duct
10. SPECIFICATION LIST/INDEX
11. MATERIAL CERTIFICATIONS
12. WELD DOCUMENT
WELDER QUALIFICATIONS
WELD LOG
WELD INSPECTIONS
WELD AUDIT
13. HYDROSTATIC TEST REPORTS
14. CLEANING REPORTS
15. PASSIVATION REPORTS
16. LINE SLOPE VERIFICATION
17. VALVE LABEL VERIFICATION
18. LINE LABEL VERFICATION
19. TAG INSPECTION
20. LINE SUPPORT
Section 4 - Drawings
21. PIPING AND INSTRUMENTATION
DIAGRAMS
22. ISOMETRIC
23. RED-LINED DRAWINGS

Additional Sections
Any additional sections will be included in the CQ
between the Test Reports and the Drawings sections.

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Review
Once each document is received and verified, it
should be stamped "CONSTRUCTION QUALIFICATION Reviewed by" the CQ coordinator with
signature and date.

Note: There is no clear demarcation between

the construction qualification and commissioning phases of the project. CQ and commissioning activities will often take place
concurrently. As in the CQ phase, tests and
inspections performed during the commissioning phase of the project must be performed and documented in compliance with
written and approved SOPs.

CQ Section Index
The CQ Section Index listing all major CQ sections
should be included immediately following the CQ
Summary Sheet.

Aspects of Commissioning
Commissioning and Startup
The ISPE Baseline Guide, Volume 5, defines commissioning as:
"A well planned, documented, and managed
engineering approach to the start-up and
turnover of facilities, systems, and equipment
to the end-user that results in a safe and
functional environment that meets established design requirements and stakeholder
expectations."
The commissioning phase of the project, which typically occurs after mechanical completion of the system and
prior to turnover of the system to the owner, is another opportunity to integrate qualification activities into the facility
construction, commissioning, and start-up process. While
the qualification activities during the construction phase of
the project primarily support IQ, qualification activities during the commissioning and start-up phase will primarily
support Operational Qualification (OQ).
Pharmaceutical manufacturing facilities, laboratories,
and even office buildings demand a complete program of
start-up, functional challenge, training, documentation, and
turnover. It is incumbent upon the individuals responsible
for design and construction to finish the job by handing over
a completely operable and documented facility so that validation activities can follow with minimal problems. Too
often, an owner's project manager will move on to his or her
next big project before the whole job is finished, leaving
maintenance technicians, facility operators, and validation
personnel with the tasks of: struggling to locate as-built
documents, making equipment work, calling vendors for
training, working off the punch list, and attempting to enforce warranties.

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Commissioning activities should encompass all aspects

of the completion phase of any facility built. Some of the
key aspects include:

Organizing and planning

Factory testing
Static testing (pre-commissioning)
Operator training
Walk down and tagging
Startup reports
Full functional testing
Turnover and punch lists
As-built documentation
System and equipment manuals
Spare parts management
IQ documentation (as applicable)
OQ documentation (as applicable)

Commissioning Team
Every project team needs a leader who is empowered by
the company to manage the project from start to finish, from
inception to completion. "Completion" should be defined as
a time when the appropriate signatures on all punch lists,
commissioning documents, as-built drawings, validation
protocols, and SOPs are attained. The project leader or project manager should not leave the project until the "ink is dry"
on each of those documents. Organizing and planning for
commissioning are the keys to a successful project. Each of
the project members should report to one individual, who
can ensure that all project objectives (cost, quality, schedule,
safety, etc.) are continuously considered in decision making.
Commissioning suffers when the project team does not
plan or organize itself early enough. The commissioning
manager must be selected early and should report to the project manager. By early selection, the commissioning manager

David W. Vincent and Herbert Matheson

and team can plan for completion when project engineers

and construction staff are actively involved in the daily rigors of construction. Selection of the commissioning manager
is extremely important; the individual must have operations
experience as well as good planning and interpersonal skills.
The commissioning manager must then select an appropriate
complement of field technicians, calibration and metrology
staff, document specialists, and technical writers. Some of
these individuals may be sometimes "loaned" by maintenance and operation groups and then returned to those
groups after project completion. In fact, the loaning of team
members is often the best solution because it enables startup knowledge to transfer from project team to operations.

Pre-Delivery Activities
Provide detail and instructions for each pre-delivery activity.
Examples of pre-delivery activities include:
Control of specifications
Review of vendor submittals
Vendor audits
Third party inspections of off-site fabrication
Module and equipment vendor quality control and
inspections
Factory Acceptance Testing (FAT)
Factory inspection plan

Commission Plan
Equipment and Material Receipt Control
The commission plan is, properly, one of the most important criteria documents that will be used on the project.
The commissioning plan should indicate the various commission activities for both GMP and non-GMP systems.
The plan should identify the overall commissioning strategy
for the project and complement the Validation Master Plan
(VMP) to identify the integration of commissioning and
validation activities. It also should define the roles and responsibilities of each functional department and their vendors as they relate to the commissioning and integration of
the qualification activates.
The following items describe the key elements of successful commissioning plan:
A description of the equipment and systems to be commissioned including their means of automation
A description of the methods and tools to be used in
commissioning execution
A detailed description of the commissioning strategy including integration of commissioning and validation activities
Overall sequence of commissioning activities
A detailed description of project deliverables including
identification of the parties responsible for providing the
deliverables
Roles and responsibilities of personnel involved in the
commissioning effort throughout construction and commissioning
The commissioning plan should include a strategy for
integrating the qualification phase into the commissioning
activities.

Describe the procedures, documentation, and methods of

control to be utilized for equipment and material receipt.
The system should include the following:
Approving and rejecting components and equipment
Defining storage locations and conditions for critical components (direct contact copper tubing verses
non-critical copper) to minimize mix-up
Separation of non-GMP materials from GMP materials
Construction Quality Assurance Activities
It is critical to define the role and responsibility of the
quality unit during the commissioning phase. While it is
clearly understood that commissioning is usually an engineering function, sometimes it is not clear what the Quality
Unit role is during the commissioning phase of the project.
During the engineering phase of the project, QA may audit
the approved equipment and utility system vendors to verify that they have the necessary quality systems in place to
ensure the quality of their product or service. Part of the integration concept also involves auditing design and construction activities for compliance with cGMPs, verifying
documentation, and keeping a close eye on the installation
progress throughout the projects construction phase.
The Quality Unit must be aware that GMP requires qualification activities. Whether some of the qualification is performed during the commission phase or not, the regulations
require these activities be reviewed and signed-off by the
Quality Unit. Therefore, if any aspects of the qualification

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activities are being captured during the commissioning

phase, the Quality Unit must at least agree and sign-off on
the commissioning plan or strategy. (Because some qualification activities are integrated into the commissioning phase
does not mean that they are no longer GMP activities.)
Describe the roles and responsibilities for all project quality control and quality assurance activities.
Define the scope of the quality control program,
authorized documentation, and responsibilities for
the implementation and maintenance of the program.
Detail the requirements for in-process inspections
and the methods to be used to document the inspections.
Describe the requirements for the creation, maintenance, and verification of red-line, as-built drawings
Specify the requirements, methods, and procedures
to be utilized for foreign material exclusion for direct impact components and materials.

Startup and Formal Commissioning

This section of the commission plan should describe, in detail, the components of startup and
commissioning execution.
Components may include:
Special pre-startup checks
Notification to stake holders that startup activities will commence that may affect certain
process equipment or systems, i.e.: backup generator, etc.
Startup procedures
Setting to work and initial shakedown
Software structural testing
Inspections
Functional testing
Cycle development
Special testing
Commissioning Documentation and Turnover Packages

Commissioning Execution
Pre-Commissioning
A pre-commissioning phase includes the completion of tasks necessary to verify that the system is
mechanically complete and ready for the initiation
of subsequent commissioning activities.
These activities include:
Mechanical completion
Safety reviews
Code inspections
Site Acceptance Testing
Tagging and labeling verification
Valve or damper lineups
Installation of temporary strainers and filters
Walk down of the system

This section of the commission plan should describe, in detail, the commissioning documents and
requirements for turnover packages.
Components may include:
Commissioning Documentation that specifies the
requirements for commissioning including: required documentation, references, documentation practices, and final reports.
Turnover Packages, which provide an outline of
the procedures and requirements for the assembly and turnover of system manuals and other
turnover packages.
Commissioning Completion and Turnover to Owner
This section of the commission plan should describe, in detail, the commissioning completion
and turnover to owner. Project closeout procedures,
deliverables, and responsibilities must be clearly
defined well before construction commences. The
method of project turnover, whether phased or in
single project completion turnover package, should
be clearly defined in this section.

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David W. Vincent and Herbert Matheson

Components of turnover strategy may include:

Deliverables including final release of liens, certificate of occupancy, final as-built drawings and
specifications, turnover packages, finalized
punch list, etc.
Project supplied training
Spare parts
Owner acceptance of operational responsibilities

Commissioning Documentation List

Commissioning starts with the preparation of many lists,
which ultimately form the foundation for planning and document management. An orderly set of equipment lists, instrument lists, vendor lists, etc., will allow the commissioning manager to organize his thoughts and begin paying attention to details early.
The key to preparing the needed lists is an exhaustive
review of all systems in the facility and selecting the right
number of turnover packages. This is best accomplished by
reviewing Process Flow Diagrams (PFDs) or P&IDs, key
documents for any manufacturing facility. These diagrams
are best used to distinguish the boundaries of each system.
The turnover packages will become a central theme for
commissioning and will be described later in more detail.
The various lists may well be the most tedious and timeconsuming part of the commissioning manager's job.
A few of the key lists and the related data are recommended below:
Drawings and Specifications List
Drawing or revision number(s)
Drawing title
Drawing status
Drawing developed by . . .
Final walk down completed on . . .
Applicable system number (cross reference)
Equipment List
Equipment tag number
(should match maintenance system tag)
Equipment name
Critical or non-critical?
P&ID reference
Vendor name
Installation date
Vendor submittal received (date and time)
SOP required? (yes or no)

Start-up date
Applicable system number (cross reference)
Instrument List
Instrument tag number
Instrument name
Critical or non-critical?
P&ID reference
Vendor name
Manufacturer submittal received (date and time)
Local or panel mounted

The Role of Qualification Phase

in Commissioning
Qualification is a process that focuses on systems affecting product quality - those defined as direct impact systems
during the system impact assessment process. However, this
represents only a fraction of what must be done to properly
commission and document an entire facility. The qualification phase, therefore, must be considered a part of the commissioning umbrella. IQ and OQ activities should be
planned to take advantage of key commissioning activities,
which take place in parallel.
As the schedule indicates, commissioning and qualification should start together and should be executed together.
Validation documents should be considered supplemental
and complimentary to commissioning documents, and duplication should be avoided. This approach, if adopted, will
yield the earliest possible project delivery. Figure 8 is a typical validation flow chart.
Use of an Integrated and Streamlined Validation Approach
One cost effective method for managing the validation
project is the using of an integrated and streamlined approach to optimize commissioning and validation activities
on a project.
Using an integrated approach, project success would include the following benefits:
Reduced project schedules and better overall
schedule management
Reduced start-up time needed in the field
Reduced project costs
Fewer defects or deviations during the qualification
phase
Reduced internal resource needs at the end of the
project

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David W. Vincent and Herbert Matheson

Figure
8
______________________________________________________________________________
Typical Validation Flowcart

Engineering

Validation

Front End Concept Study

Validation Master Plan (VMP)
Engineering Specifications/User
Requirement Specification (URS)

Functional and Detail Design

Generate
and Address
Snag List

GMP Audit, Design Qualification

(DQ) and Impact Assessment

Factory Acceptance Test (FAT)

Tender

Procedure and Construct

Generate
and Address
Snag List

Pre-delivery Inspection (PDI)

Protocol Development

Install

Commission

Generate
and Address
Snag List

Formal Project Turnover

Generate
and Address
Snag List

Formal Installation Qualification (IQ)/

Operational Qualification (OQ)

Formal Equipment Performance

Qualification (EPQ)

Release and Use

Decommissioning

Periodic Review, Change Control

and Revalidation

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David W. Vincent and Herbert Matheson

Adherence to compliance requirements

Overall project quality improvement
During streamlining, the commissioning and validation
activities should adhere to the following basic principles:
Start the project by evaluating the impact of a system
on product quality
Focus resources on the qualification of systems with
"direct impact" on product quality according to
GMP
Focus on critical components that will have a direct
impact on the project quality
Establish system boundaries in the early phase of the
project
Evaluate system design from both a quality perspective and a risk-based approach
Provide contractors, vendors, and engineers with the
project validation requirements up-front to enable
them to plan installations to meet these requirements
Design and commission those systems that have no
"direct impact" on product quality according to GEP
Enhance the commissioning, qualification, and validation documentation generation, review, and approval processes
Integrate the commissioning and qualification activities to avoid duplication of work
Conduct training of employees, contractors, consultants, and other personnel early in the project
lifecycle

Strategies
The following section includes some detailed strategies
that could be followed to reduce project resource requirements and improve the efficiencies of the commissioning
and validation programs.
Integrate Validation Schedules into the Overall Project
Schedule
The project manager, with support of team members,
should ensure the development of a commissioning and validation plan as an integral part of the project plan and schedule. Integrating validation into the overall project schedule
can save both time and money. Integrated schedules should
be developed with input from the construction and validation project teams and be maintained and updated at regular
intervals.
IQ/OQ may be conducted as part of the physical com-

pletion of the facility, thus tying IQ/OQ closely to the construction contractors scope of work that includes commissioning. To avoid the effort and inconvenience of discovering and rectifying basic problems, it is recommended that
all systems go through an informal shakedown phase before
IQ/OQ commences. This will help ensure a smooth transition between IQ and OQ, and will minimize the number of
deviations that may occur during the IQ and OQ phases.
Scheduling of PQ is particularly critical because PQ
testing is often the most time consuming part of the qualification. Scheduling should take into account any prerequisites that should be achieved prior to PQ execution (such as
commissioning of all support systems, availability of SOPs,
system interdependencies). The PQ protocol often receives
the greatest amount of scrutiny from the approval team.
Again, it is important that IQs and OQs are completed and
that there are no major deviations that may have negative
impact on the PQ phase.
Integrate Commissioning with Validation Activities
There are considerable advantages of time, cost, and
quality in integrating the many functions carried out by
skilled resources, such as engineering, contractor, and validation teams. The responsibility for timely and appropriate
execution should be a combination of both the validation and
engineering teams, this will reduce the time spent on validating the facility and scaling up to production. The use of a
competent, expert, multi-disciplinary team will ensure that
best practice is deployed and that duplication of activities is
avoided.
Integrating activities such as Design Qualification, Construction Qualification, Factory Acceptance Testing, Site Acceptance Testing and commissioning into qualification and
validation activities can control validation costs and minimize project delays. Instruments, components, and equipment can be verified at the vendor site during the FAT and
CQ phases of the project. This reduces delays caused by
identifying potential problems before equipment is delivered
to the job site. If these items are not altered or dismantled in
any way for transport, these checks, if properly documented,
could be used in support of SAT or qualification activities.
For OQ, the duration of the testing can be shortened by
identifying the critical operational criteria that require testing prior to the facility, utility, or equipment being used in
production and planning the schedule accordingly. This
can be performed by determining which functional controls are critical and non critical in the early stages of the
DQ phase of the project. Testing the non-critical functions

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David W. Vincent and Herbert Matheson

during the FAT or SAT will reduce the amount of testing

required during OQ phase.
If FAT is executed for equipment, i.e., alarms and interlocks testing, some or all of these tests can be performed at
the vendor site, or these tests can be performed as part of
commissioning, and can be used in support of the OQ. Performance testing carried out as part of commissioning can
contribute to PQ when performed consistently with qualification practices. Thus, if the integrated approach is used and
proper inspections, field verification, documentation, and
certain required field execution work is accomplished by the
construction vendors and contractors, then the qualification
scope can be reduced to that of review, verification, cross
linkage to FAT and SAT documents, monitoring, and compiling. The integration of commissioning and qualification
merges activities, minimizes resource requirements, and
streamlines the validation effort by reducing the number of
protocols and reports.
Approaches to streamline the amount of paperwork required to give sufficient documented evidence of validation
may include:
Using standardized protocol and report templates
wherever possible, so that reviewers become accustomed to protocol formats and contents.
Using procedures and forms that can minimize redundancy normally found in qualification protocols.
Structuring executed protocols as reports to obviate
the need for writing a separate report.
Combining IQ and OQ documents (to I/OQ) will
result in fewer documents to develop, track, review,
and approve. However, the IQ section must be
completed before OQ commences.
Including only critical tests in the protocol, and not
repeating non-critical ones already conducted in
FAT or SAT phases, simply verifying that these test
have been performed in the qualification protocols.
Understanding upfront the critical and test items to
be included in the qualification can reduce both
cost and unnecessary deviations.
Establishing realistic protocol acceptance criteria
based upon the process demands for reproducibility and product quality.
Recording deviations in the qualification protocol
attachments and then having them immediately reviewed and approved by the Quality Unit rather
then waiting until the entire protocol is executed.
Ensuring that commissioning documentation for
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Journal of Validation Technology

direct impact systems are appropriately planned,

created, organized, and authorized so that they may
become an integral part of the qualification support
documentation.
Combining engineering and validation information
to minimize duplication.
Once qualification protocols are written, they should be
approved, and this may be a time consuming process. Several ways to streamline this process include:
Minimizing the number of approvals required by
developing approval matrixes.
Clarifying the review process with all parties early
in the project.
Instituting a formalized protocol tracking process.
Minimizing the number of review cycles allowed
by the team.
Implementing a simple review and approval procedure with time limit for the review cycle.
Instituting protocol review meetings for all parties
involved.
Ensuring the protocol review and approval process
is included in the overall project schedule.
Define which activities the vendors are responsible for
executing when utilizing an integrated approach to commissioning and validation activities. Figure 9 is an example
of the integration of commissioning, qualification testing,
and verification activities related to WFI skid and distribution system (See Figure 9):
Note: Vendors performs 100% loop check
during commissioning phase. Validation
engineer performs 10% during Qualification Phase. If failure is detected during
the 10% verification, then 100% inspection is performed by validation engineer
or validation engineer witnesses 100%
performed by vendor.

David W. Vincent and Herbert Matheson

Figure
9
______________________________________________________________________________
Commissioning and Qualification Integration Approach

Tests and Verification

Activities
Functional Design, Verification,
and Design Specifications
Facility As-built and Piping and
Instrumentation Drawings
Electrical drawings
Critical Component Verification
Materials of Construction
Welding Documentation
Alarm and Interlock Test
Control System Component
Verification
Hydrostatics Testing
Material Incoming Receipt
Cleaning and Passivation
Steam in Place Startup
Surface Finish Documentation
Report
Vent Filter Integrity
Spare Part Inventory
Operation Control Function
Non-Critical
Operation Control Function
Critical
Software Installation Verification
Operation and Maintenance
Procedures Verification
Pump and Motor Checkouts (Rotation, Lube, Alignment, Belt, etc.)
Control System Function
*Loop Check Verification
Compliance (ASME Certifications)
Control System Security Access
and Password Protection
Sequence of Operations
Radio Frequency Interference Test
Voltage test
Shut Down and Startup
sequence
Data Trending Ability
Operation Parameter Control
Baseline Performance
CQ = Construction Qualification
IQ = Installation Qualification
SAT = Site Acceptance Testing

Commissioning Phase

Qualification Phase

CQ

FAT

SAT

IQ

PQ

OQ

DQ = Design Qualification
OQ = Operational Qualification

FAT = Factory Acceptance Testing

PQ = Performance Qualification

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This is the first part of a three-part article. Parts II and III

will be published in the Journal of Validation Technology in
the August and November 2005 issues, respectively.

About the Author

David W. Vincent has over 25 years experience in the
Biopharmaceutical industry with 19 years dedicated
to the fields of validation and engineering. He has a
BS degree in Microbiology and Mechanical Engineering Technology; Mr. Vincent has consulted for many
companies both nationally and internationally. He has
presented many training seminars and has written
numerous articles and technical guides regarding validation topics. Mr. Vincent teaches "Validation Program for the Pharmaceutical, Biotechnology, and
Medical Device Industries" at San Diego State University (SDSU) for their Regulatory Affairs Master Degree program.
Currently, Dave is the Chief Executive Office (CEO)
for Validation Technologies Incorporated (VTI), a
worldwide validation and technical services company.
VTI is also a certified commissioning company that
offers commissioning and startup functions for the
healthcare industry. Dave can be reached by phone
at 800-930-9222, by fax at 858-638-5532, or by email at david@validation.org. (Web Site is located at
www.validation.org)

The following references are those applicable to Part I.

The full list of references used in the three-part article
will appear with Part III in the November 2005, Journal
of Validation Technology.

References
1. Center for Drugs and Biologics, Center for Devices and
Radiographic Health, "Guidelines on General Principles
of Process Validation," FDA Rockville, Maryland, 1987.
2. "cGMP Compliance in Architecture and Construction of
Biopharmaceutical Manufacturing Facilities" BioPharm,
Prepared January-February, 1993.
3. "Code of Federal Regulations Section 21 Parts 200 to
299 and Parts 600 to 799," Food and Drugs Administration (FDA).
4. "Guidelines for Bulk Drug Manufacturers," Food and
Drugs Administration (FDA).
5. Center for Drug Evaluation and Research, Center for
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Journal of Validation Technology

Article Acronym Listing

A/E
ANSI
ASME
CFR
cGMP
CIP
CQ
DCS
DQ
FAT
FDA
GDP
GEP
GMP
HEPA
HVAC
I/O
IQ
ISPE
MSDS
OQ
P&ID
PFD
PLC
PQ
PW
QA
QC
RA
REM
SAT
SOP
TOP
URS
VMP
WFI

Architecture and Engineering

American National Standards Institute
American Society of Mechanical
Engineers
Code of Federal Regulations
Current Good Manufacturing Practice
Clean in Place
Construction Qualification
Design Qualification
Factory Acceptance Test
Food and Drug Administration
Good Documentation Practice
Good Engineering Practice
Good Manufacturing Practice
High Efficiency Particulate Air
Heating, Ventilation,
and Air Conditioning
Input/Output
Installation Qualification
International Society for
Pharmaceutical Engineering
Material Safety Data Sheet
Operational Qualification
Process and Instrumentation Diagram
Process Flow Diagram
Performance Qualification
Purified Water
Quality Assurance
Quality Control
Regulatory Affairs
Routine Environmental Monitoring
Site Acceptance Testing
Standard Operating Procedure
Turn Over Package
User Requirement Specification
Validation Master Plan
Water For Injection

Biologics Evaluation and Research, Office of Regulatory Affairs, "Guidelines on Sterile Drug Products Produced by Aseptic Processing," FDA Rockville, Maryland, June 1987.
6. Center for Drug Evaluation and Research, Center for
Biologics Evaluation and Research, Office of Regulatory Affairs, "Guidelines on Sterile Drug Products Pro-

David W. Vincent and Herbert Matheson

duced by Aseptic Processing," FDA Rockville, Maryland, June 1987.

7. PDA Environmental Task Force, "Fundamentals of a Microbiological Environmental Monitoring Program," Vol.
44, Supplement 1990.
8. "Microbiological Control and Validation," The Institute
for Applied Pharmaceutical Sciences, March 7-9, 1994.
9. Powell-Evans, K., "Streamlining Validation; Value
Added Qualifications." Institute of Validation Technology. December 2000. Newsletter.
10. Graham C. Wrigley, Pfizer Global Manufacturing, and
Jan L. du Preez, Ph.D., "Research Institute for Industrial Pharmacy Facility Validation: A Case Study for Integrating and Streamlining the Validation Approach to
Reduce Project Resources," Volume 8, Number 2, February 2002.

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