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STIMULI TO THE REVISION PROCESS

Stimuli articles do not necessarily reflect the policies
of the USPC or the USP Council of Experts

Analytical Instrument and System (AIS)

Qualification: The Qualification
Life Cycle Process
Christopher Burgessa, Rosty Slabickyb, Oscar Quattrocchic, ML Jane Weitzeld, Jean-Marc Roussele, Joachim Ermerf, Gabriel Vivó-Truyolsg, Dwight
Stollh, and Lucy L. Botrosi
Correspondence should be addressed to: Edmond Biba, Principal Scientist, US
Pharmacopeial Convention, 12601 Twinbrook Parkway, Rockville,
MD 20852-1790; email:
exb@usp.org.

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ABSTRACT

All analytical instruments and systems for compendial use must be qualified
to be "fit for intended use" using the guidance provided in the

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currently official
general chapter Analytical Instrument Qualification 〈1058〉.
Qualifying the operation and performance of an analytical instrument
or system
is a
critical part of a robust quality management system and is required in a current
good
manufacturing practice (CGMP) environment.
In pharmacopeial applications, the
performance of an instrument or system directly impacts the data reported by
establishing the reportable value
of an analytical test characteristic specified
in a
monograph.

In an earlier Stimuli article, Analytical Instrument and System (AIS) Qualification to Support Analytical
Procedure Validation over the Life Cycle (1),
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the overall aims and objectives of the Analytical Instrument and System
Qualification Joint Subcommittee (AISQ JSC) to enhance 〈1058〉 were
described (2). The purpose of this article is to explore in more detail the AIS life
cycle process published as Figure 5 of that article (republished
here as Figure 1). The process presented in this
article is not a formal proposal for revision of 〈1058〉, but
rather a deeper dive into the current
thinking and position of the AISQ JSC on
analytical instrument qualification and its relationship to the analytical procedure
life cycle management
framework. As with the previous articles published in PF on this topic (2–3), USP seeks stakeholder feedback on the concepts presented within.
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INTRODUCTION

The AIS qualification process provides the procedural and metrological performance
framework for an instrument or system with a maintained
qualified state of control
and calibration over its life cycle, as shown in Figure 1, in accordance with the operational ranges of
measurement as
specified in the user requirement specifications (URS). The framework
in Figure 1 also gives guidance on the roles and responsibilities
of vendors
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and users. However, the ultimate responsibility for assuring "fitness

for
use" of an AIS remains with the user. Various stakeholders throughout the
AIS
qualification process need to be identified and should be selected so that the
process is appropriately designed and controlled. Glossaries of
AIS qualification
abbreviations and terms, including definitions for the vendor
and user, are given at the end of this article.
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Figure 1. An illustrative AIS life cycle qualification process.

At the heart
of this process flow is the risk assessment and traceability matrix. A traceability
matrix, which forms part of the final qualification
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report, is the mapping of
each
requirement in the URS to an operational procedure, document, or test with
acceptance criteria so that all
qualification activities are completed. It is
clear
that the extent of the qualification effort required to assure "fitness for use"
depends both on the
complexity of the AIS and, critically, the use to which it
is
being put within a specific laboratory environment. There is no "one size fits
all"
approach
and some examples across the range of AIS are illustrated in Figure 2.
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Figure 2. Examples of Qualification Activities for Different AIS Groups

(1). Green, Orange, Red—differentiation between apparatus, instrument,
system AIS groups. Blue, Yellow, Gray—differentiation between applicable
qualification activities for each AIS group.
 Once a risk assessment has been completed, a detailed qualification
process flow, as shown in Figure 3, can be defined for the AIS risk
category. It is important to note that not all stages of the life cycle need to
be
undertaken and the identified stages should map to the risk
assessment matrix
shown
in Figure 2.

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Figure 3. Extension of the AIS qualification life cycle process.

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LIFE CYCLE PROCESS
DESCRIPTIONS

The approach of sequential activities in the qualification stages

described below is a means of organizing the activities to ensure an instrument
is
fit for intended use, from its first release for use to its retirement from service.
However, specific tests and elements described in each stage
may be shifted between
the qualification stages. What is important is that the appropriate tests are
performed at the time required as captured in
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the traceability matrix and during an
instrument’s routine use. A risk analysis and control strategy can support the
development of the qualification
phases and the specific tests that fall within each
qualification stage below. Risk analysis can be facilitated by identifying the
uncertainty
components of the AIS that may pose a risk to the performance of the
analytical procedure as described in Measurement Uncertainty
Evaluation
Relevant to Analytical Instrument and System (AIS)
Qualification (2). The risk analysis and control strategy principles are described in
Analytical
Procedure Life Cycle 〈1220〉.
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User Requirement
Specifications

This first step should lead to a preliminary scheme where the

appropriate instrument and the instrument specifications should be defined.
These specifications, along with the laboratory capabilities, current or
projected, may be used to write the user requirement specification (URS).
The
URS describes what the user wants the AIS to do and indicates the functional,
operational, and data requirements for the system.
URS should be taken as the foundation for design qualification (DQ),
and fitness for intended use is verified through operational qualification
(OQ)
testing.
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Vendor Contribution to the

Qualification Process

On basis of the URS, the user will select an appropriate vendor or

supplier that may provide an AIS with the functional and design specifications
(FS and DS) that will meet the URS. The user will also investigate the vendor
capabilities for an appropriate installation, qualification of the AIS,
training
of the user, and appropriate maintenance of the AIS. FS and DS describe how the
vendor will supply an AIS that will meet the URS for
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functionality, operation,
performance, data storage and processing, among other functions, while the DQ
evaluates the vendor capabilities for
post-installation support. The FS and DS
may take many forms, such as an instrument specification, manual, or
drawing.
Design Qualification

The DQ should document the review of AIS design documentation (e.g.,

specifications, requirements, component list, drawings) to demonstrate
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the
alignment of the URS, FS and DS, and other engineering technical documents, as
appropriate, as well as the compliance with critical ("good
practice"-relevant)
user requirements.
Purchase Order
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Once in agreement, the user will deliver a purchase order (PO), and
the vendor should provide, if appropriate, the site preparation requirements
for
the installation of the AIS. This site preparation should be completed before
the AIS is installed, according to a proper agreement between the
user and
vendor.
After purchase, the AIS is delivered with an AIS delivery note and,
if appropriate, a factory acceptance test (FAT) document.
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Installation Qualification

The vendor will manufacture the AIS, perform any necessary tests in
accordance with their quality system, and upon approval, deliver the AIS to
the
user in an appropriate manner. Start-up and commissioning may be done either
by
the vendor, a designated third party, or the user on the
installed AIS, and may
include system testing during installation. Data from commissioning may be
leveraged to support qualification activities if
the documentation practices
for
test generation, execution, and documentation meet CGMP.
AIS should be properly installed, and the installation qualification
(IQ) should be carried out and documented to verify that the AIS, as delivered,
complies with the approved DS. This may include initial adjustments,
calibration, preventive maintenance, training, and documentation.
Operational Qualification
 OQ is done to verify that, at the user's facility, the AIS meets its
specifications, focusing on the URS. In this way, OQ verifies that the AIS meets
the URS. OQ should be performed using appropriate holistic and modular AIS
functional tests.
For example, the following OQ functional tests can be adopted for a
near-infrared spectrometer, where the intended use of AIS is both
quantitative
and qualitative applications (Near-Infrared Spectroscopy 〈856〉):
Qualitative: Wavelength
accuracy using NIST SRM 2036, signal-to-noise ratios, or NIST SRM
2065 compliance
Quantitative: Same as
above, but also include standards for photometric linearity (e.g.,
Spectralon, or NIST SRMs 1928 and 1929)
Performance Qualification

Once the OQ is completed and approved by the user, the performance

qualification (PQ) is done to verify that the AIS and supporting systems,
when
connected together, can perform effectively and reproducibly, on the basis of
the approved process and procedure specifications and its
acceptance criteria.
PQ is the continued verification of "fitness for use" of an AIS confirming the
requirements of the URS throughout its life cycle.
This verification is usually
confirmed using a subset of the IQ and OQ testing as the basis of modular
performance combined with holistic testing
under actual conditions of use,
particularly for AIS with complex application software.
Qualification Summary
Report

A qualification summary report will comprise all AIS test data,

operating ranges, accuracy, limitations, and any other characteristic deemed
appropriate to recommend releasing the AIS for use if satisfactory.
Operational Use and System
Suitability Tests

After the qualification summary report is approved, the AIS can be

used to develop and validate procedures and to perform routine analytical
testing. The use of the AIS is limited to the ranges, computations, and
functionality that were qualified.

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New Analytical Procedures

Different analytical procedures may take advantage of existing

installed and qualified instruments provided that a formal comparison is done
between the new requirements and the consequent URS for that specific analytical
procedure and the existing FS and DS for the AIS.

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If the comparison of the new URS to the existing AIS FS and DS shows
agreement, the AIS may be accepted for the new procedure. If the
comparison does
not show agreement for that specific analytical procedure, the instrument may
be
updated, upgraded, or a new instrument may
be considered for purchase. A risk
analysis should always be done to evaluate any impact on previously implemented
procedures using that AIS. If
use outside of the qualified conditions is needed,
the appropriate tests should be repeated at the new operating conditions.
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Ongoing Performance Verification
of the Qualified State

An appropriate plan should be defined to ensure the AIS continues to

operate as qualified. This may include preventive maintenance, calibration
strategies, change controls, logbooks, and other operations. A periodic
monitoring and review should be performed to assess the cumulative
impact of
changes, AIS operating history, calibrations, logbooks, technical deviations,
AIS performance, maintenance history (repairs,
discrepancies during
maintenances, etc.), security (access, data integrity, passwords, data storage
across interfaces, etc.), and other areas from
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the validation maintenance
programs.
Any changes in the AIS components, moves, repairs, or updates should
be done in accordance with the deviation management and change
control
procedures, which may require the repetition of IQ, OQ, and PQ testing before
a
return to routine operation. If the AIS fails to requalify, then
it should be
retired from operation.
Any reportable values generated by the AIS while it may not have been
operating in its qualified state should be investigated.
The necessary steps to remove the AIS from service—such as performing
a final calibration; archiving documents such as calibration records,
maintenance records, trainings, user manuals, electronic records, application
software, process data, and source code (if software is needed to
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read the
archived data); and AIS disposal—should be documented.

ABBREVIATIONS
AIS: Analytical Instrument and System
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DQ: Design Qualification

DS: Design Specifications
FAT: Factory Acceptance Test
FS: Functional Specifications
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IQ: Installation Qualification

OQ: Operational Qualification
PO: Purchase Order
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PQ: Performance Qualification

URS: User Requirement Specifications

CONFLICT OF INTEREST
DISCLAIMER

The authors did not declare any conflicts of interest related to the
subject matter of this Stimuli article.
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REFERENCES

1. Burgess C, Weitzel MLJ, Roussel J-M, Quattrocchi O,

Ermer J, Slabicky R, Martin GP, and Vivó-Truyols G. Analytical instrument
and system
(AIS) qualification to support analytical procedure validation
over the life cycle, PF 48(1), United States
Pharmacopeia, January 2022.
2. Weitzel MLJ, Roussel J-M, Burgess C, Quattrocchi O,
Ermer J, Slabicky R, and Vivó-Truyols G. Measurement uncertainty evaluation
relevant to
analytical instrument and system (AIS) qualification—the role of
measurement uncertainty concepts within the AIS. PF
48(2), United States
Pharmacopeia, March 2022.
3. Furman WB, Layloff TP, and Tetzlaff RF. Validation of
computerized liquid chromatographic systems. J AOAC Int.
1994;77(5):1314–1318.
doi:10.1093/jaoac/77.5.1314.
 4. Joint Committee for Guides in Metrology. International
vocabulary of metrology—basic and general concepts and associated terms
(VIM),
3rd edition. JCGM 200:2012.

a 
Burgess Analytical Consultancy
Limited, ‘Rose Rae’, The Lendings, Startforth, Barnard Castle, Co. Durham, DL12 9AB,
United Kingdom.

b 
SYRUS Solutions, Inc.,
Danbury, CT, United States.

c 
Training and Consultant at
D´Amico Sistemas S.A., Buenos Aires, Argentina.

d 
Independent Consultant,
Winnipeg, Manitoba, Canada.

e
 
Consultant, Macon,
France.

f
 
Ermer Quality Consulting,
Bensheim, Germany.

g
 
Tecnometrix, Ciutadella de
Menorca, Spain.

h
 
Gustavus Adolphus College,
Saint Peter, MN, United States

i
 
United States Pharmacopeia,
Rockville, MD, United States.

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Auxiliary Information
-
Please
check for your question in the FAQs
before contacting USP.

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Topic/Question Contact Expert Committee

ANALYTICAL INSTRUMENT AND SYSTEM Edmond Biba

GCMDQ2020 General Chapters -
(AIS) QUALIFICATION; THE QUALIFICATION Senior Scientific Liaison Measurement and Data Quality
LIFE CYCLE
PROCESS
Page Information:

Not Applicable
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