BRIEFING

1058 Analytical Instrument Qualification, USP 39 page 1055 and PF 41(3) [MayJune
2015]. In response to comments received after the proposal published in PF 41(3), the
General ChaptersChemical Analysis Expert Committee is proposing additional changes to
this general information chapter.

Additionally, minor editorial changes have been made to update the chapter to current USP
style.

(GCCA: H. Pappa.)
Correspondence NumberC163764; C164094; C164095; C164329; C164330; C164331;
C164342; C164343; C164910

Comment deadline: July 31, 2016

1058 ANALYTICAL INSTRUMENT QUALIFICATION

Change to read:

INTRODUCTION

A large variety of laboratory equipment, instruments, and computerized analytical systems,

ranging from simple nitrogen evaporators to complex multiple-function technologies (see
Instrument Categories), are used in the pharmaceutical industry to acquire data to help
ensure that products are suitable for their intended use. An analyst's objective is to
consistently obtain reliable and valid data suitable for the intended purpose. Depending on
the applications, users validate their procedures, calibrate their instruments, and perform
additional instrument checks, such as system suitability tests and analysis of in-process
quality control check samples to help ensure that the acquired data are reliable. With the
increasing sophistication and automation of analytical instruments, an increasing demand has
been placed on users to qualify their instruments.

Unlike method validation and system suitability activities, analytical instrument qualification
(AIQ) currently has no specific guidance or procedures. Competing opinions exist regarding
instrument qualification and validation procedures and the roles and responsibilities of those
who perform them. Consequently, various approaches have been used for instrument
qualification, approaches that require varying amounts of resources and generate widely
differing amounts of documentation. This chapter provides a scientific approach to AIQ and
considers AIQ as one of the major components required for generating reliable and consistent
data. Note that the amount of rigor applied to the qualification process will depend on the
complexity and intended use of the instrumentation. This approach emphasizes AIQ's place in
the overall process of obtaining reliable data from analytical instruments.

Validation versus Qualification

In this chapter, the term validation is used for manufacturing processes, analytical
procedures, and software procedures and the term qualification is used for instruments.
Thus, the phrase analytical instrument qualification (AIQ) is used for the process of
ensuring that an instrument is suitable for its intended application.
 A large variety of analytical instruments, ranging from a simple apparatus to complex
computerized systems, is used in the pharmaceutical industry to acquire data that will help
ensure that products meet their specifications. The majority
Many 1S (USP40)
of these instruments combine a metrological function with software control. There are many
ways of demonstrating that an instrument is qualified and under control, and these can
include qualification, calibration, validation, and maintenance. In order to ensure fitness for
purpose, an integrated approach, based upon a risk assessment, is recommended. For the
purposes of this chapter, the term instrument includes any apparatus, equipment,
instrument, or instrument system used in the laboratory.

This chapter provides a scientific approach for carrying out an analytical instrument
qualification (AIQ); it is left to each laboratory to justify and document their specific
approaches.

The instrument owner/user and their management are accountable for the qualification and
validation work outlined in this chapter.

This chapter outlines the principles and frame work of risk-based instrument qualification to
ensure fitness for the intended use in pharmacopeial analysis. The detailed operating
parameters to be qualified are found in the respective general chapters for specific
instrument types.

The risk assessment begins with the classification of the instrument to determine the
extent of qualification needed to demonstrate fitness for purpose. Generally, the more
complex the instrument, or the higher the criticality of the measurement, the greater the
amount of work that is required to ensure that quality data will be generated. In addition,
attention must be paid to ensuring that data integrity and security are maintained.

Instruments can generally be classified as belonging to Groups A, B, or C. It should be

noted that the same type of instrument can fit into one or more categories, depending on its
intended use. Therefore, no specific examples are provided.

Group A includes the least complex, standard instruments that are used without
measurement capability or user requirement for calibration, such as a magnetic stirrer or
vortex mixer. Proper function is ensured by observation, and no further qualification activities
are needed for this group.

Group B includes instruments that may provide a measurement or a quantitative condition

that can affect a measurement. Examples include a pH meter or an oven. Proper function of
instruments in this group may require only some elements of qualification, such as routine
calibration, maintenance, or performance checks. The level of qualification will also depend
on the criticality of the application. Generally, these instruments may have firmware but not
software that is updated by the user.

Group C comprises the majority of analytical instruments and normally includes a

significant degree of computerization and complexity,
such as high-pressure liquid chromatographs and mass spectrometers. 1S (USP40)
All elements of qualification, including software validation, must be considered to ensure
proper functioning of instruments in this group. 1S (USP40)

Change to read:
 COMPONENTS OF DATA QUALITY

There are four critical components involved in the generation of reliable and consistent data
(quality data). Figure 1 shows these components as layered activities within a quality
triangle. Each layer adds to the overall quality. AIQ forms the base for generating quality
data. The other components essential for generating quality data are analytical method
validation, system suitability tests, and quality control check samples. These quality
components are described below.

Figure 1. Components of data quality.

Analytical Instrument Qualification

AIQ is the collection of documented evidence that an instrument performs suitably for its
intended purpose. Use of a qualified instrument in analyses contributes to confidence in the
validity of generated data.

Analytical Method Validation

Analytical method validation is the collection of documented evidence that an analytical

procedure is suitable for its intended use. Use of a validated procedure with qualified
analytical instruments provides confidence that the procedure will generate test data of
acceptable quality. Additional guidance on validation of compendial procedures may be found
in Validation of Compendial Procedures 1225.

System Suitability Tests

System suitability tests verify that the system will perform in accordance with the criteria
set forth in the procedure. These tests are performed along with the sample analyses to
ensure that the system's performance is acceptable at the time of the test. Chromatography
621 presents a more detailed discussion of system suitability tests as related to
chromatographic systems.

Quality Control Check Samples

Many analysts carry out their tests on instruments standardized

that have been standardized by 1S (USP40)
using reference materials and/or calibration standards. Some analyses also require the
inclusion of quality control check samples to provide an in-process or ongoing assurance of
the test's suitable performance. In this manner, AIQ and analytical method validation
contribute to the quality of analysis before analysts conduct the tests. System suitability tests
and quality control checks help ensure the quality of analytical results immediately before or
during sample analysis.

Change to read:

ANALYTICAL INSTRUMENT QUALIFICATION PROCESS

The following sections address the AIQ process in detail. The other three components of
building quality into analytical dataanalytical method validation, system suitability tests,
and quality control check samplesare not within the scope of this chapter.

Qualification Phases

Instrument qualification is not a single continuous process, but instead results from several
discrete activities over the lifetime of the instrument. 1S (USP40) For convenience, these
activities can be grouped into four phases: design qualification (DQ), installation qualification
(IQ), operational qualification (OQ), and performance qualification (PQ).

Some AIQ activities cover more than one qualification phase, and analysts could potentially
perform them during more than one of the phases. (see Table 1).
1S (USP40)
However, in many instances there is need for a 1S (USP40) specific order to the AIQ
activities; for example, IQ must occur first in order to initiate other qualification activities.
The AIQ activities will be defined and documented. All AIQ activities should be defined and
documented. 1S (USP40) Routine analytical tests do not constitute OQ testing. OQ tests are
specifically designed to verify the instrument's operation according to specifications in the
user's environment as documented in the DQ, 1S (USP40) and repeating the testing at
regular intervals may not be required. However, when the instrument undergoes major
repairs or modifications, relevant OQ and/or PQ tests should be repeated to verify whether
the instrument continues to operate satisfactorily. If an instrument is moved to another
location, an assessment should be made of what, if any, OQ test
qualification stage 1S (USP40)
should be repeated.
Table 1. Timing, Applicability, and Activities for Each Phase of Analytical Instrument
a
Qualification
Design Installation Operational Performance
Qualification Qualification Qualification Qualification
Timing and Applicability
At installation
of each Periodically at
Prior to instrument specified
purchase of a (new, old, or After installation or intervals for
new model of existing major repair of each
instrument unqualified) each instrument instrument
Activities
Assurance of Preventive
manufacturer's maintenance
DQ Description Fixed parameters and repairs
Establish
practices to
Assurance of address
adequate operation,
support calibration,
availability maintenance,
from Instrument and change
manufacturer delivery control
Utilities/facility Environment
Assembly and
installation
Network and Secure data
data storage storage, backup,
and archive
Instrument's Installation Instrument function
fitness for use verification tests and software Performance
in laboratory validation 1S (USP40) checks
a Activities under each phase are usually performed as given in the table. However, in
some cases, it may be more appropriate to perform or combine a given activity with
another phase. Such activities spanning more than one qualification phase are shown as
connected by double arrows. If an activity listed under a given phase is performed under
another phase, it is not necessary to repeat the activity under the phase where the
activity is listed. Performing the activity is far more important than the phase under which
the activity is performed.
1S (USP40)

DESIGN QUALIFICATION

Design qualification (DQ) is the documented collection of activities that define the
functional and operational specifications of the instrument and criteria for selection of the
vendor, based on the intended purpose of the instrument. Design qualification (DQ) may be
performed not only by the instrument developer or manufacturer but also may be performed
by the user. The manufacturer is generally responsible for robust design and maintaining
information describing how the analytical instrument is manufactured (design specifications,
functional requirements, etc.) and tested before shipment to users. Nonetheless, the user
should ensure that commercial off-the-shelf (COTS) instruments are suitable for their
intended application and that the manufacturer has adopted a quality system that provides
for reliable equipment. Users should also determine the manufacturer's capability for support
installation, services, and training. This determination might be aided by the user's previous
interaction with the manufacturer.

Design qualification (DQ) is the documented collection of activities that define the
functional and operational specifications of the instrument, including the criteria for selection
of the supplier, based on the intended purpose of the instrument.
DQ is the documented collection of activities that define the functional and operational
specifications and intended purpose of the instrument. 1S (USP40)
DQ states what the laboratory wants the instrument to do and shows that the selected
instrument is suitable. DQ may be performed by the instrument manufacturer or the user. It
is expected that DQ requirements will be minimal for commercial, off-the-shelf instruments.
Verification that the instrument specifications meet the desired functional requirements may
suffice.

The supplier is generally responsible for robust design and maintaining documentation
describing how the analytical instrument and any associated controlling software are
manufactured (for example, design specifications, functional requirements, and others) and
tested, sometimes called factory acceptance tests. Nonetheless, the user should ensure that
instruments are suitable for their intended application and that
may evaluate whether 1S (USP40)
the supplier has adopted a quality system that provides for reliable instrumentation,
software, and network connectivity. Users should also determine the supplier's capability to
support installation, services, and training. This determination might be aided by the user's
previous interaction with the supplier.

When use of an instrument changes or it is subject to a major upgrade, it may be

necessary to review and/or update the user's DQ documentation. 1S (USP40)

INSTALLATION QUALIFICATION

IQ is the documented collection of activities necessary to establish that an instrument is

delivered as designed and specified, is properly installed in the selected environment, and
that this environment is suitable for the instrument. IQ applies to an instrument that is new
or was pre-owned. or to any instrument that exists on site but has not been previously
qualified. For any instrument that exists on site but has not been previously qualified,
or not qualified to current industry standards, 1S (USP40)
existing documents should be collated and a risk assessment should be undertaken to
determine the best course of action. 1S (USP40)

Relevant parts of IQ would also apply to a qualified instrument that has been transported
to another location or is being reinstalled for other reasons, such as prolonged storage.

The activities and documentation typically associated with IQ are as follows.

DescriptionProvide a description of the instrument or the collection of instrument

components, including its manufacturer, model, serial number, software version, and
location. Use drawings and flow charts where appropriate.

1S (USP40)

Instrument delivery: Ensure that the instrument, software, manuals, supplies, and any
other instrument accessories arrive as specified in the purchase order by the user 1S (USP40)
and that they are undamaged. For a pre-owned or existing instrument, manuals and
documentation should be obtained.
 Description: Document information about the instrument and all components, including
supplier(s), model(s), serial number(s), software version(s), and location. 1S (USP40)

Utilities/Facility/Environment: Verify that the installation site satisfactorily meets

manufacturer supplier 1S (USP40) -specified environmental requirements.

Assembly and InstallationAssemble and install the instrument, and perform any
preliminary diagnostics and testing. Assembly and installation may be done by the
manufacturer, vendor, specialized engineers, or qualified in-house personnel. Manufacturer-
established installation tests and guides provide a valuable baseline reference for determining
instrument acceptance. Any abnormal event observed during assembly and installation
merits documenting. Installation packages purchased from the manufacturer or the vendor
may, however, need to be supplemented with user-specific criteria.

Assembly and installation: Assemble and install the instrument, and perform any
preliminary diagnostics and testing. Assembly and installation may be done by the supplier,
service agents, specialized engineers, or qualified in-house personnel. Supplier-established
installation tests provide a valuable baseline reference for determining instrument
acceptance. Any abnormal event observed during assembly and installation merits
documenting. IQ documentation packages purchased from a supplier should be reviewed to
ensure that they are acceptable to the user before and after execution. 1S (USP40)

Network and Data StorageSome analytical systems require users to provide network
connections and data storage capabilities at the installation site. When required, connect the
instrument to the network, and check its functionality.

Software installation, network, and data storage: Some analytical systems require the
installation of software onto a qualified computer and to be connected to a network for
communications and data storage at the installation site. Information technology involvement
is often required with computerized laboratory systems. 1S (USP40)

Installation verification: Perform the initial diagnostics and testing of the instrument after
installation. When required, connect the instrument to the network, and check its
functionality. 1S (USP40)

Software configuration and/or customization: Any configuration or customization of

instrument software should occur before the OQ and documented. Unless changes are
needed for specific component tests, the OQ should be performed using the software
configuration that will be used for routine analysis. 1S (USP40)

1S (USP40)

OPERATIONAL QUALIFICATION

After a successful IQ, the instrument is ready for OQ testing. Operational qualification (OQ)
is the documented collection of activities necessary to demonstrate that an instrument will
function according to its operational specification in the selected environment. Testing
activities in the OQ phase may consist of these test parameters.

OQ is the documented collection of activities necessary to demonstrate that an instrument

will function according to its operational specification testing in the selected environment. OQ
demonstrates fitness for purpose for the user's ways of working, and should reflect the
contents of the DQ document. Testing activities in the OQ phase may consist of the following
test parameters. 1S (USP40)
Fixed parameters: These tests measure the instrument's non-changing parameters such as
length, height, weight, voltage inputs, acceptable pressures, and loads. If the manufacturer-
supplied specifications for these parameters satisfy the user, the test requirements may be
waived. However, if the user wants to confirm the parameters, testing can be performed at
the user's site. Fixed parameters do not change over the life of the instrument, and therefore
never need redetermination to be retested. 1S (USP40) [NOTEThese tests could also be
performed during the IQ phase; (see Table 1)
1S (USP40)
if so, fixed parameters need not be retested as part of OQ testing.]

Software functions: Where applicable, OQ testing should include critical elements of the
configured application software to show that the whole system works as intended. Functions
to test would be those applicable to data capture, analysis of data, and reporting results
under actual conditions of use as well as security, access control, and audit trail. The user
can apply risk assessment methodologies and can leverage the supplier's software testing to
focus the OQ testing effort. 1S (USP40)

Secure data storage, backup, and archiving: When applicable, test secure data handling,
such as storage, backup, audit trails, and archiving at the user's site, according to written
procedures.

Instrument function tests: Instrument functions required by the user should be tested to
verify that the instrument operates as intended by the manufacturer. Manufacturer-supplied
Supplier 1S (USP40) information is useful in identifying specifications for these parameters and
in designing tests to evaluate the identified parameters. Users, or their qualified designees,
should perform these tests to verify that the instrument meets manufacturer or user
specifications in the user's environment. verify that the instrument meets the supplier or
user specifications in the user's environment. 1S (USP40)

The extent of OQ testing that an instrument undergoes depends on its intended

applications, Therefore, no specific OQ tests for any instrument or application are offered in
this chapter. therefore, no specific OQ tests for any instrument or application are offered in
this chapter. Parameters to qualify are described in the general chapters pertaining to a
specific analytical technique. 1S (USP40)

OQ tests can be modular or holistic. Modular testing of individual components of a system

may facilitate interchanging of such components without requalification Holistic tests, which
involve the entire system, are also acceptable. but requires a risk assessment to justify it.
Holistic tests, which involve the entire system, demonstrate that the whole system works
against
complies with 1S (USP40)
user specifications in the DQ. 1S (USP40)

For OQ test suites

packages 1S (USP40)
purchased from a service provider or supplier, the user must review the material to assure
themselves of the scientific soundness of the tests and compliance with applicable
regulations. The user should review the documents before execution and approve the tests
after execution to ensure completeness and accuracy of the completed document and the
test data generated. 1S (USP40)

Software configuration and/or customization: Any configuration or customization of

instrument software should occur before the OQ and documented. Unless changes are
needed for specific component tests, the OQ should be performed using the software
configuration that will be used for routine analysis. 1S (USP40)

PERFORMANCE QUALIFICATION

Performance qualification (PQ) is the documented collection of activities necessary to

demonstrate that an instrument consistently performs according to the specifications defined
by the user, and is appropriate for the intended use. After IQ and OQ have been performed,
the instrument's continued suitability for its intended use is demonstrated through
performance qualification. The PQ phase may include the following parameters.

PQ is the documented collection of activities necessary to demonstrate that an instrument

consistently performs according to the specifications defined by the user, and is appropriate
for the intended use. The PQ verifies the fitness for purpose of the instrument under actual
conditions of use. After IQ and OQ have been performed, the instrument's continued
suitability for its intended use is demonstrated through continued PQ.

The user must define the PQ plans, including test procedures, acceptance criteria, and
frequency. Preventive maintenance plans and documentation of repairs and other changes
are also a necessary part of the overall instrument qualification.

PQ may include the following activities. 1S (USP40)

Performance checks: Set up a A 1S (USP40) test or series of tests to verify the acceptable
performance of the instrument for its intended use. PQ tests are usually based on the
instrument's typical on-site applications and may consist of analyzing known components or
standards. The tests should be based on good science and reflect the general intended use of
the instrument. Some system suitability tests or quality control checks that are performed
concurrently with the test samples can be used to demonstrate that the instrument is
performing suitably. PQ tests may resemble those performed during OQ, but the
specifications for PQ results may be set differently if required. Nevertheless, user
specifications for PQ tests should demonstrate trouble-free instrument operation for the
intended applications. As is the case with OQ testing, PQ tests may be modular or holistic.

Testing frequency depends on the ruggedness of the instrument and the criticality of the
tests performed.
Testing frequency depends on the ruggedness of the instrument and the criticality of the
analytic method. 1S (USP40)
Testing may be unscheduled; for example, each time the instrument is used. It may also be
scheduled for regular intervals. Experience with the instrument can influence this decision,
which should be documented. 1S (USP40) It may be useful to repeat the same PQ tests each
time the instrument is used so that a history of the instrument's performance can be
compiled. Alternatively, the instrument may be incorporated into an integrated support
system to ensure that it remains continually qualified. Some system suitability tests or
quality control checks that are performed concurrently with the test samples also imply that
the instrument is performing suitably. System suitability tests that are performed
concurrently with the test preparations may also ensure that the instrument is performing
suitably. 1S (USP40)

Preventive maintenance and repairs: When an instrument fails to meet PQ test

specifications, it requires maintenance or repair. A periodic preventive maintenance may also
be recommended for many instruments. The relevant PQ test(s) should be repeated after the
needed maintenance or repair to ensure that the instrument remains qualified. Periodic
preventive maintenance activities are required for many instruments. This may include
calibration. Document the preventive maintenance plans, including procedures and frequency
as part of the AIQ package. When an instrument fails to meet PQ criteria or otherwise
malfunctions, the cause of the failure must be investigated and documented. The instrument
may require maintenance or repair. The relevant OQ or PQ test(s) should be repeated after
the needed maintenance or repair to ensure that the instrument remains qualified. 1S (USP40)

Practices for Operation, Calibration, Maintenance, and Change ControlEstablish

practices to maintain and calibrate the instrument. Each maintenance and calibration activity
should be documented.

Practices for performance qualification, change control, and periodic review: Each
PQ, maintenance, and calibration activity should be documented. Change control should be
established to control changes to the instrument configuration, including firmware and
software. Critical instruments should have a periodic review to ensure that the system is still
under control. Typical areas for review can include qualification/validation status, currency of
user procedures, change control records, correctness and completeness of records produced
by the system, backup and recovery of electronic records, and review and sign-off of test
results.

The instrument owner/user and their management are responsible for this work, although
portions can be carried out on his/her behalf by internal staff or external suppliers or service
providers. 1S (USP40)

Change to read:

ROLES AND RESPONSIBILITIES

Users

Users are ultimately responsible for instrument operations and data quality. The user's
group encompasses analysts, their supervisors, instrument specialists, and organization
management. Users are ultimately responsible for specifying their needs and ensuring that a
selected instrument meets them, and that data quality and integrity are maintained. The
user's group encompasses analysts, their supervisors, instrument specialists, and
organization management. 1S (USP40) Users should be adequately trained in the instrument's
use, and their training records should be maintained as required by the regulations.

Users should also be responsible for qualifying their instruments, because their training and
expertise in the use of instruments make them the best-qualified group to design the
instrument test(s) and specification(s) necessary for a successful AIQ. Consultants,
equipment manufacturer or vendors, validation specialists, and quality assurance (QA)
personnel can advise and assist as needed, but the final responsibility for qualifying
instruments lies with the users. The users must also maintain the instrument in a qualified
state by routinely performing PQ. Consultants, instrument manufacturers or suppliers,
validation specialists, and quality assurance personnel can advise and assist as needed, but
the final responsibility for qualifying instruments and validating systems lies with the users,
1S (USP40) The users must also maintain the instrument in a qualified state by routinely
performing PQ.
who must ensure that the instrument is maintained in a qualified state through routine
performance of PQ. 1S (USP40)
 Quality Unit

The role of the quality unit in AIQ remains the same as for any other regulated activity.
Quality personnel are responsible for ensuring that the AIQ process meets compliance
requirements, that processes are being followed, and that the intended use of the equipment
is supported by instrument is supported by complete, 1S (USP40) valid, and documented data.

The role of the Quality Unit in AIQ remains the same as for any other regulated activity.
1S (USP40)
Quality personnel are responsible for ensuring that the AIQ process meets compliance
requirements, that processes are being followed, and that the intended use of the equipment
is supported by valid and documented data.

Manufacturers, Suppliers, Service Agents, and Consultants 1S (USP40)

Manufacturers and developers are responsible for DQ when designing the instrument. They
are also responsible for validation of relevant processes used in manufacturing and assembly
of the instrument. Manufacturers should test the assembled instruments before shipping
them to users.

Manufacturers are responsible for designing and manufacturing the instrument, and
ensuring the quality of relevant processes used in manufacturing and assembly of the
instrument. Manufacturers should test the assembled instruments before shipping them to
users. To aid the user, vendors
suppliers 1S (USP40)
are responsible for developing meaningful specifications for the users to compare with their
needs and aid selection. as shown in Figure 1.
1S (USP40)

Where used, software should be developed and tested using a defined life cycle and should
have evidence of work performed to support major and minor revisions. Release notes should
accompany each version of software released. 1S (USP40)

Finally, it is desirable that manufacturers and vendors suppliers 1S (USP40) should notify all
known users about hardware
or software 1S (USP40)
defects discovered after a product's release; offer user training, service, repair, and
installation support; and invite user audits as necessary.

There should be a quality or technical agreement between the user organization and
manufacturers, suppliers, service agents, or consultants who supply calibration,
maintenance, qualification, or validation services; the agreement should define the scope of
work and the responsibilities of the two parties. 1S (USP40)

Change to read:

SOFTWARE VALIDATION

There is an increasing inability to separate the hardware and software parts of modern
analytical instruments. In many instances, the software is needed to qualify the instrument,
and the instrument operation is essential when validating the software. Therefore, to avoid
overlapping and potential duplication, software validation and instrument qualification can be
integrated into a single activity. 1S (USP40)
 Software used for analytical work can be classified into three categories: firmware;
instrument control, data acquisition, and processing software; and stand-alone software.
Although software validation is not the primary focus of this chapter, the following sections
describe in which cases this activity is under the scope of the analytical instrument
qualification.

Software used for analytical work

instruments 1S (USP40)
can be classified into four categories
groups: 1S (USP40)
firmware, instrument control software, data acquisition software, and processing software.
and standalone software.
1S (USP40)
Although software validation is not the primary focus of this chapter, the following sections
describe in which cases this activity is within the scope of the analytical instrument and
system qualification.

Authoritative guidance for the validation of software used in analytical instruments are the
Good Automated Manufacturing Practice (GAMP) guidelines and the GAMP Good Practice
Guide on Risk Based Validation of Laboratory Computerized Systems.
One source of the validation of software is the guide GAMP5: A Risk-Based Approach to
Compliant GxP Computerized Systems. 1S (USP40)
1S (USP40)

Firmware

Computerized analytical instruments contain integrated chips with low-level software

(firmware). Such instruments will not function without properly operating firmware, and in
most cases 1S (USP40) users generally cannot alter firmware design or 1S (USP40) function.
Firmware is therefore considered a component of the instrument itself. Indeed, the
qualification of hardware is not possible without operating it via its firmware.

Thus, when the hardware (that is, the analytical instrument) is qualified at the user's site,
the integrated
1S (USP40)
firmware is also essentially qualified. No separate on-site qualification of the firmware is
needed. Whenever possible, the firmware version should be recorded as part of the IQ
activities. Any changes made to firmware versions should be tracked through the change
control of the instrument (see Change Control, below).

In some instruments, firmware can also be capable of fixed calculations on the acquired
data. These calculations need to be defined and verified by the user. Some instruments have
firmware that enables users to define programs for the instrument's operation; similarly,
these user-defined programs need to be defined and verified to demonstrate that they are fit
for the intended purpose. Any user-defined programs should be placed under change control
and, if possible, access should be restricted to authorized personnel. 1S (USP40)

Instrument Control, Data Acquisition, and Processing Software

Software for instrument control, data acquisition, and processing for many of today's
computerized instruments is loaded on a computer connected to the instrument. Operation of
the instrument is then controlled via the software, leaving fewer operating controls on the
instrument. Also, the software is needed for data acquisition and post-acquisition
calculations. Thus, both hardware and software, their functions inextricably intertwined, are
critical to providing analytical results.

The manufacturer should perform DQ, validate this software, and provide users with a
summary of validation. At the user site, holistic qualification, which involves the entire
instrument and software system, is more efficient than modular validation of the software
alone. Thus, the user qualifies the instrument control, data acquisition, and processing
software by qualifying the instrument according to the AIQ process.

The software in this group can be classified into three types: 1) non-configurable software
(the software cannot be modified to change the business process), 2) configurable software
(using tools from the supplier to modify the business process supported), and 3) configurable
software with custom additions (configurable software above with custom software or macros
to automate the business process).
that cannot be modified to change the business process; 2) configurable software that
includes tools from the supplier to modify the business process; and 3) configurable software
with custom additions, i.e., custom software or macros to automate the business process.
1S (USP40)

The supplier of the system should develop and test the software according to a defined life
cycle and provide users with a summary of the tests that were carried out. Ideally, this
software development should be carried out under a quality management system.

At the user site, integrated qualification of the instrument, in conjunction with validation of
the software, involves the entire system. This is more efficient than separating instrument
qualification from validation of the software. 1S (USP40)

Stand-Alone Software
1
An authoritative guide for validating stand-alone software, such as LIMS, is available. The
validation process is administered by the software developer, who also specifies the
development model appropriate for the software. Validation takes place in a series of
activities planned and executed through various stages of the development cycle.

1S (USP40)

Change to read:

CHANGE CONTROL

Changes to instruments, including software, become inevitable as manufacturers suppliers

1S (USP40) add new features and correct known defects. However, implementing all such
changes may not always benefit users. Users should therefore adopt changes they deem
useful or necessary and should also assess the effects of changes to determine what, if any,
requalification is required. The change control process enables them to do this.

Change control may follow the DQ/IQ/OQ/PQ classification process. For DQ, evaluate the
changed parameters, and determine whether need for the change warrants implementing it.
If implementation of the change is needed, install the changes to the system during IQ.
Evaluate which of the existing OQ and PQ tests need revision, deletion, or addition as a result
of the installed change. Where the change calls for additions, deletions, or revisions to the
OQ or PQ tests, follow the procedure outlined below.

Operational Qualification
Revise OQ tests as necessitated by the change. Perform the relevant tests affected by the
change. This ensures the instrument's effective operation after the change is installed.

Performance Qualification
Revise PQ tests as necessitated by the change. Perform the PQ testing after installation of
the change if similar testing was not already performed during OQ. In the future, perform the
revised PQ testing.

For changes to firmware and to software for instrument control, data acquisition, and
processing, change control is performed through DQ/IQ/OQ/PQ of the affected instrument.
Change control for stand-alone software requires user-site testing of changed functionality.
1S (USP40)

Change to read:

ANALYTICAL INSTRUMENT QUALIFICATION DOCUMENTATION

Documents obtained during instrument qualification qualification activities 1S (USP40)

should be retained in an accessible manner. Where multiple instruments of one kind exist,
documents common to all instruments and documents specific to an instrument may be
stored separately. During change control, additional documents may supplement those
obtained during the qualification process, and both sets of documents should be retained and
maintained in a suitable manner that allows for appropriate protection and access.

Delete the following:

INSTRUMENT CATEGORIES

Modern laboratories typically include a suite of instruments and equipment varying from
simple nitrogen evaporators to complex automated instruments. Therefore, applying a single
set of principles to qualifying such dissimilar instruments would be scientifically
inappropriate. Users are most capable of establishing the level of qualification needed for an
instrument. On the basis of the level needed, it is convenient to categorize instruments into
three groups: A, B, and C, as defined below. Examples of instruments in each group are
provided. Note that the list of instruments provided here is for illustration only and is not
meant to be exhaustive. It does not provide the exact category for an instrument at a user
site. That category should be determined by users for their specific instruments or
applications.

The exact grouping of an instrument must be determined by users for their specific
requirements. Depending on individual user requirements, the same instrument may
appropriately fall into one group for one user and another group for another user. Therefore,
a careful selection of groups by users is highly encouraged.

Group A

Group A includes standard equipment with no measurement capability or usual

requirement for calibration, where the manufacturer's specification of basic functionality is
accepted as user requirements. Conformance of Group A equipment with user requirements
may be verified and documented through visual observation of its operation. Examples of
equipment in this group are nitrogen evaporators, magnetic stirrers, vortex mixers, and
centrifuges.

Group B

Group B includes standard equipment and instruments providing measured values as well
as equipment controlling physical parameters (such as temperature, pressure, or flow) that
need calibration, where the user requirements are typically the same as the manufacturer's
specification of functionality and operational limits. Conformance of Group B instruments or
equipment to user requirements is determined according to the standard operating
procedures for the instrument or equipment, and documented during IQ and OQ. Examples
of instruments in this group are balances, melting point apparatus, light microscopes, pH
meters, variable pipets, refractometers, thermometers, titrators, and viscometers. Examples
of equipment in this group are muffle furnaces, ovens, refrigerator-freezers, water baths,
pumps, and dilutors.

Group C

Group C includes instruments and computerized analytical systems, where user

requirements for functionality, operational, and performance limits are specific for the
analytical application. Conformance of Group C instruments to user requirements is
determined by specific function tests and performance tests. Installing these instruments can
be a complicated undertaking and may require the assistance of specialists. A full
qualification process, as outlined in this document, should apply to these instruments.
Examples of instruments in this group include the following:

atomic absorption spectrometers

differential scanning calorimeters
dissolution apparatus
electron microscopes
flame absorption spectrometers
high-pressure liquid chromatographs
mass spectrometers
microplate readers
thermal gravimetric analyzers
X-ray fluorescence spectrometers
X-ray powder diffractometers
densitometers
diode-array detectors
elemental analyzers
gas chromatographs
IR spectrometers
near-IR spectrometers
Raman spectrometers
UV/Vis spectrometers
inductively coupled plasma-emission spectrometers

1S (USP40)

Add the following:

GLOSSARY
 [NOTEThe definitions of these terms may be different than in other USP general
chapters.]

Calibration: The set of operations that establish, under specified conditions, the relationship
between values of quantities indicated by a measuring instrument or values represented by a
material measure or a reference material, and the corresponding values realized by
standards.
An operation that, under specified conditions, in a first step, establishes a relation between
the quantity values, with measurement uncertainties provided by measurement standards,
and corresponding indications with associated measurement uncertainties and, in a second
step, uses this information to establish a relation for obtaining a measurement result from an
indication. Note that:

1. A calibration may be expressed by a statement, calibration function, calibration

diagram, calibration curve, or calibration table. In some cases, it may consist of an
additive or multiplicative correction of the indication with associated measurement
uncertainty.
2. Calibration should not be confused with adjustment of a measuring system, often
mistakenly called self-calibration, or with verification of calibration.
3. Often, the first step alone in the above definition is perceived as being calibration.

1S (USP40)

Maintenance: Actions performed to keep an analytical instrument in a state of proper

function so that it continues to operate within the boundaries set during qualification or
validation.

Qualification: Action of proving that any instrument works correctly and delivers the
expected results; demonstration of fitness for purpose.

Software configuration: Adaptation of software functions to a business process using tools

provided within the application by the supplier of the software.

Software customization: Changing the way software automates a business process by the
addition of externally custom-coded software modules using a recognized programming
language or the development of macros within the application software.

Software validation: Confirmation by examination and provision of objective evidence that

software conforms to user needs and intended uses, and that the particular requirements
implemented through software can be consistently fulfilled.

Supplier: This term is used generically and can mean the manufacturer, a vendor, a service
agent, or a consultant, depending on the circumstances. 1S (USP40)

1
General Principles of Software Validation: Final Guidance for Industry and FDA Staff, U.S. Department of Health and
Human Services, Food and Drug Administration, Rockville, MD, January 11, 2002.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085281.htm (accessed
December 2012.) 1S (USP40)

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

USP39NF34 Page 1055