265

In preparing the guidance docu-

LEGISLATION AND NORMS ment, the Working Group re-
viewed a variety of different manu-
facturers’ own procedures and pro-
Relevant legislation, legislation plans and related initiatives in different countries tocols, papers and articles pub-
and continents
lished in the open literature, and
the requirements of the ISO 9000
Accred Qual Assur (1996) 1 : 265–274 However, these Standards are series of Standards, Good Labora-
deliberately written in broad terms, tory Practice and ISO Guide 25.
P. Bedson so as to be as widely applicable as The guidance sets out an approach
M. Sargent possible, and they do not go into to EQ based on four stages of
detail on many issues. All stipulate qualification; design qualification
The development and ap- general requirements such as in- (DQ), installation qualification
plication of guidance on struments must be fit for purpose, (IQ), operational qualification
properly maintained and calibrated (OQ) and performance qualifica-
equipment qualification to national or international stand- tion (PQ). Additional sections cov-
of analytical instruments ards, but are not specific as to er the requirements for and pro-
what is actually required or how it vide advice on documentation, cali-
Abstract This paper describes the should be achieved. It is also un- bration and traceability, and re-
development of guidance for the clear as to where and when formal qualification. There are also sec-
equipment qualification (EQ) of EQ is appropriate and of how it tions on NAMAS accreditation,
analytical instruments. EQ is a for- should be documented. A key ob- GLP compliance, and ISO 9000
mal process that provides docu- jective in developing the guidance certification, which highlight the
mented evidence that an instru- was, therefore, to provide users specific requirements and emphasis
ment is fit for its intended purpose and suppliers of analytical instru- of each Standard.
and kept in a state of maintenance ments, as well as those responsible The Working Group identified
and calibration consistent with its for the assessment, certification several aspects of EQ which caused
use. and monitoring of analytical labo- particular problems. DQ is seen as
ratories, with a clear and consistent primarily for manufacturers of in-
Key words approach for the qualification of struments. Clearly this is true in re-
Equipment qualification (EQ) 7 analytical instruments. The guid- lation to the design of the instru-
Design qualification (DQ) 7 ance has been prepared with the ment itself, but an important as-
Installation qualification (IQ) 7 primary aim of assisting the inter- pect of the guidance has been to
Operational qualification (OQ) 7 pretation of formal quality Stand- emphasise the role that users of in-
Performance qualification (PQ) ards in order to satisfy regulatory struments have in considering the
and accreditation requirements. intended use of the instrument and
An important consideration in agreeing appropriate specifications
Introduction preparing the guidance was that it with manufacturers and suppliers
should be widely accepted and prior to its purchase. There is also
EQ is becoming increasingly im- take account of current practice. In confusion regarding the distinction
portant to analytical laboratories. order to achieve this, the Labora- between OQ and PQ. The Work-
For many laboratories it is no tory of the Government Chemist ing Group attempted to resolve
longer sufficient to just do things (LGC) established an Instrumenta- this issue by focusing on what each
right; they must also provide docu- tion Working Group under the stage is trying to achieve, rather
mented evidence to demonstrate auspices of Eurachem-UK with than the activities carried out in
the integrity of their data and val- support from the DTI VAM Initia- order to achieve it. The aim of OQ
idity of their results. Many labora- tive [5]. The working group has is to provide evidence that an in-
tories achieve this through formal brought together a wide cross-sec- strument performs according to the
quality systems which are generally tion of instrument manufacturers, key performance characteristics
implemented in accordance with representatives of accreditation agreed between the user and sup-
one or more of the three main in- bodies and regulatory authorities, plier at the time of purchase,
ternationally recognised quality and users of analytical instruments. whereas PQ is concerned with pro-
Standards: the ISO 9000 series of A full list of those individuals and viding evidence that the instrument
Standards [1], Good Laboratory organisations represented on the performs according to a specifica-
Practice (GLP) [2,3] and ISO working group is given in Annex 2. tion appropriate for its routine use.
Guide 25 [4]. If the key performance characteris-
266

tics agreed at the time of purchase 1.4 Operational specification the key
are the same as those appropriate
References performance characteristics of the
instrument and ranges over which
for routine use, then the checks 1. “Quality Systems – Model for quality the instrument is required to operate
and tests carried out may be the assurance in design, development, pro- and consistently perform, as agreed
same for both OQ and PQ. duction, installation and servicing”; BS between the user and supplier.
In view of the wide variety of EN ISO 9001 : 1994 1.5 Functional specification The func-
2. “Good Laboratory Practice – The Uni- tional specification defines the over-
analytical instrumentation, the all requirements of the instrument
ted Kingdom Compliance Pro-
Working Group decided to adopt a gramme”; UK Department of Health including the operational specifica-
modular approach to the prepara- 1989 tion (see above) and other critical
tion of the guidance document. 3. “Good Laboratory Practice for Non- factors relating to its use (e.g. level
The first module offers general clinical Laboratory Studies”; Food and of training/expertise required by op-
Drug Administration (FDA); 21 CFR erators).
guidance applicable to a wide Ch.1 Part 58 1.6 Equipment Qualification (EQ) the
range of analytical instruments. A 4. “General requirements for the compe- overall process of ensuring that an
draft of this module is attached at tence of calibration and testing labora- instrument is appropriate for its in-
Annex 1 and it will be supple- tories”; ISO/IEC Guide 25, 3rd Ed., tended use and that it performs ac-
1990. (note new version in draft stage) cording to specifications agreed by
mented by modules offering more 5. Further information on the DTI Valid the user and supplier. EQ is often
detailed guidance for specific types Analytical Measurement (VAM) Ini- broken down into Design, Installa-
of instruments. Modules for gas tiative can be obtained from the VAM tion, Operation and Performance
chromatography, high performance Helpdesk at the Laboratory of the qualification:-
Government Chemist, Queens Road, 1.7 Design Qualification (DQ) covers all
liquid chromatography and capilla- procedures prior to the installation
Teddington, Middlesex, TW11 0LY,
ry electrophoresis are in prepara- UK (tel. 0181 943 7393) of the system in the selected envi-
tion and these will be published in ronment. DQ defines the functional
due course. The Working Group and operational specifications of the
instrument and details the conscious
would welcome comments on these decisions in the selection of the sup-
modules. Following any revision, it Annex 1: Guidance on equipment
qualification of analytical plier.
is intended to combine the general 1.8 Installation Qualification (IQ) co-
and supplementary guidance and instruments vers all procedures relating to the
publish them as a consolidated installation of the instrument in the
Contents selected environment. IQ establishes
guide. It is also envisaged that in- 1. Glossary of Terms that the instrument is received as
strument manufacturers will adopt 2. Introduction designed and specified, that it is
aspects of the guidance as part of 3. The Equipment Qualification (EQ) properly installed in the selected en-
their own EQ documentation. Process vironment, and that this environ-
4. Documentation ment is suitable for the operation
Comments on the guidance, or 5. Design Qualification (DQ) and use of the instrument.
views on the equipment qualifica- 6. Installation Qualification (IQ) 1.9 Operational Qualification (OQ) is
tion of analytical instruments, 7. Operational Qualification (OQ) the process of demonstrating that an
should be sent to the authors of 8. Performance Qualification (PQ) instrument will function according to
9. Calibration and Traceability its operational specification in the
this paper at LGC. 10. Requalification selected environment.
11. NAMAS Accreditation 1.10 Performance Qualification (PQ) is
Acknowledgements The development of 12. GLP Compliance defined as the process of demon-
the guidance was supported under con- 13. ISO 9000 Certification strating that an instrument consis-
tract with the United Kingdom Depart- 14. References tently performs according to a speci-
ment of Trade and Industry as part of the 15. Bibliography fication appropriate for its routine
National Measurement System Valid use.
Analytical Measurement Programme. The 1. Glossary of terms 1.11 Validation is the process of evaluat-
guidance has been drafted by the Labora- Many of the terms in this document ing the performance of a specific
tory of the Government Chemist with as- are currently used in different ways measuring procedure and checking
sistance from the Eurachem-UK Instru- to convey a variety of meanings. that the performance meets certain
mentation Working Group. The members The following descriptions explain pre-set criteria. Validation estab-
of this working group have played a ma- how these terms should be inter- lishes and provides documented evi-
jor role in developing the guidance and preted in this document: dence that the measuring procedure
their help is gratefully acknowledged to- 1.1 Instrument all types of measuring is fit for a particular purpose.
gether with those who commented infor- equipment ranging from simple 1.12 System Suitability Checking (SSC)
mally on the guidance during the drafting stand-alone instruments through to A series of tests to check the per-
process. complex multi-component instru- formance of a measurement process.
ment systems. SSC may form part of the process of
1.2 User the organisation purchasing the validation when applied to a particu-
instrument including its management lar measuring procedure. SSC estab-
and staff. lishes that the operational conditions
1.3 Supplier the instrument manufactur- required for a specific measurement
er, vendor, lessor or approved agent. process are being achieved.
 267

1.13 Calibration The set of operations ment will be supplemented by more offer varying levels of support for
which establish, under specified con- detailed guidance on the qualifica- EQ and, at present, there is no uni-
ditions, the relationship between val- tion of specific types of instruments. form acceptance of what is covered
ues indicated by a measuring instru- 2.5 The requirements set out in this by each stage nor what each stage
ment or process and the correspond- document are not intended to be a will be called.
ing known values of the measurand. compulsory series of tests that must 3.3 The EQ process described in this
1.14 Traceability The property of a result be carried out. Users of this guide document is summarised in Figure 1
of a measurement whereby it can be should exercise their professional and is based on four stages of “qual-
related to appropriate standards, judgement as to the extent to which ification”: design qualification (DQ);
generally national or international individual requirements are applica- installation qualification (IQ); opera-
standards, through an unbroken ble and the level of detail required tional qualification (OQ); and per-
chain of comparisons. for proper qualification of instru- formance qualification (PQ). Subse-
ments. quent sections of this guidance docu-
2 Introduction 2.6 Although the approach, and many ment describe, individually, these
2.1 Formal quality systems and/or regul- of the requirements, may be applica- four stages of qualification in more
atory requirements require various ble to other equipment, e.g. that detail and provide broad guidance
levels and combinations of equip- used for sample preparation or that as to what each stage should in-
ment qualification, calibration, verif- which forms part of a manufacturing clude.
ication of performance, and system process, this equipment is outside 3.4 The applicability of each stage of
suitability checking. The standards the scope of this guide. EQ will vary during the lifetime of
and other documents which specify 2.7 Most instruments have varying com- an instrument. All four stages will
these requirements are mostly gen- binations of computer or micropro- be applicable to the purchase of a
eral purpose and do not go into de- cessor hardware and software. The new instrument. Aspects of DQ and
tail on many issues. They are, there- formal validation of these compo- IQ may need to be repeated follow-
fore, open to varying interpretation. nents is outside the scope of this ing major changes (see Section 10).
Good Laboratory Practice document. Where necessary, users PQ, and many aspects of OQ,
(GLP)[1,2] deliberately puts an onus must ascertain and seek documented should be carried out throughout
on the laboratory to set and justify evidence from suppliers that such the entire life of the instrument and
its own level of compliance. Howev- components have been developed provide a reference against which
er, in some cases, guidance is pro- and manufactured to appropriate the instrument’s continued perform-
vided to indicate specific require- Standards and formally validated ance can be judged.
ments in certain areas (e.g. the NIS during production. Guidance on the 3.5 The EQ process and the require-
documents provided by UKAS for validation of computerised systems ments of each qualification stage are
use with the NAMAS M10 Stand- is available elsewhere [6,7,8,9,10,11]. generic and therefore applicable to
ard[3]). This general lack of detail 2.8 The terms “validation” and “qualifi- both complex and simple instru-
leads to differences in interpretation cation” are used widely and often to ments. However, specific operational
between different regulatory bodies, convey the same meaning. The ap- tests carried out during qualification
different countries, different asses- proach taken in this guidance docu- will, of course, vary according to the
sors and different professional advi- ment is that validation is application type of instrument (e.g. the tests to
sors. The result is frequently confu- orientated and relates to a specific demonstrate that a HPLC auto-
sion and misunderstanding amongst measurement method or process, sampler is performing to specifica-
those who have to meet the require- whereas qualification is instrument tion are quite different from those
ments and decide what is necessary orientated and relates primarily to employed in testing a UV/VIS spec-
in order “to comply”. the operational specification of the trometer).
2.2 This document provides guidance to instrument. 3.6 Each stage of the qualification proc-
users and suppliers of analytical in- ess involves the same general ap-
struments on best practice for un- 3 The equipment qualification (EQ) proach: the preparation of a qualifi-
dertaking the “qualification” of in- process cation plan defining the scope of
struments. It aims to explain the 3.1 The primary requirement for all qualification (e.g. the tests to be per-
qualification process and to provide equipment used in analytical labora- formed and the acceptance criteria
advice on what needs to be done at tories is that it must be fit for its in- to be used); the execution of the
each stage of an instrument’s qualifi- tended purpose. The equipment plan (during which the results of the
cation. qualification (EQ) process must tests are recorded as the tests are
2.3 The document sets out a general ap- therefore establish that an instru- performed); and the production of a
proach to the qualification of instru- ment’s operational specification is report (and, if required, a certifi-
ments. As far as possible, the advice appropriate for its intended use and cate) in which the results of EQ are
provided is compatible with the re- that the instrument performs accord- documented.
quirements of ISO Guide 25[4], the ing to that specification. EQ must 3.7 The user is responsible for the vali-
ISO 9000 series of Standards[5] and also establish that an instrument is, dation of the measurement process
Good Laboratory Practice (GLP). and will be, kept in a state of main- and for the quality and reliability of
The guidance will, therefore, also be tenance and calibration consistent the data produced. The user is
useful to those involved in the as- with its use. therefore responsible for ensuring
sessment, certification and monitor- 3.2 There is often confusion with regard that an instrument is suitable for its
ing of analytical laboratories. to what is included in the EQ proc- intended use and that it is operating
2.4 The document provides generic ess and, in particular, what is cov- satisfactorily. Thus, the user is re-
guidance which is applicable to a ered by the individual stages (DQ- sponsible for EQ.
wide range of analytical instrumen- IQ-OQ-PQ) of qualification. This 3.8 The user must establish the level of
tation. It is intended that the docu- can arise because different suppliers EQ required and what aspects of
268

It may also be useful to include a

brief description of instrument
and its role in the measurement
process.
b) State clearly the intervals at
which aspects of EQ and/or spe-
cific checks and tests should be
performed, and the responsibility
level of the operator required to
perform the tests;
c) Provide details of each check and
test to be performed, the specifi-
cation and acceptance criteria to
be used. This information should
be concise enough to allow the
operator to make an unambi-
guous judgement on the result of
the test;
d) Provide sufficient information on
the procedures and materials re-
quired to perform each check
and test. This should also advise
on where there is a need to
achieve traceability to national or
international standards and how
this can be achieved;
e) Where qualification of one part
Fig. 1 The equipment qualification process of the instrument is dependant
on the correct functioning of an-
other part, any assumptions
made must be recorded;
EQ will be done in-house and what dertake aspects of EQ, but accept f) State the date on which qualifica-
will be carried out by a third party, that such services will often incur a tion was performed and the re-
which may be the original supplier. charge. sult of qualification and each
The extent to which this is carried 3.13 Wherever maintenance and calibra- check or test;
out by the user will depend on the tion operations are necessary, they g) State the reason for performing
experience and competence of the must be carried out before EQ. qualification (e.g. following in-
user. stallation of a new instrument,
3.9 The supplier should provide clear 4 Documentation following routine service, or fol-
guidance on what can be carried out 4.1 This section provides guidance on lowing instrument malfunction);
by the user, what can be carried out requirements relating to documenta- h) Provide clear information on the
by either the user or the supplier, tion covering the EQ process. It is action to be taken in the event of
and what can only be undertaken by not intended to cover other docu- test or qualification failure;
the supplier. The supplier should mentation relating to operation or i) State the circumstances which
make available documents, tools and servicing (e.g. manuals) of the in- may or will necessitate re-qualifi-
services to assist EQ and, in particu- strument. cation of the instrument (e.g. fol-
lar, to provide clear instructions and 4.2 EQ must be documented. EQ docu- lowing service or re-calibration);
details of tests required to demon- mentation can be prepared and pro- j) Contain the name(s) and signa-
strate satisfactory performance. Such vided by the user, the supplier, or ture(s) of the person(s) who ac-
testing (an integral part of OQ/PQ) both. Where it is provided by the tually performed qualification
can be carried out by the supplier or supplier (e.g. in a qualification pro- and/or each individual check and
the user, but must remain under the tocol), it remains the responsibility test. Contain the name and signa-
control of the user (see section 8.5). of the user and should be written in ture of the user authorising com-
3.10 Where any aspect of EQ, and/or a such a way that it can be readily fol- pletion of qualification.
performance check or test, is under- lowed and understood by the user. 4.3 It is strongly recommended that log-
taken by the supplier or a third par- Documentation covering EQ should books are kept for all instruments.
ty, users must satisfy themselves that satisfy the following requirements: Quality Standards, particularly NA-
it has been carried out competently a) The instrument and all modules MAS M10 and GLP, place a heavy
and correctly (the installer’s training and accessories must be uniquely emphasis on keeping records of in-
record may provide basic evidence identified, particularly Reports strument history. Maintaining an up-
of competence). and Certificates, including: to-date log-book of the overall histo-
3.11 The success or failure of all EQ – The supplier’s name, instru- ry of an instrument provides a con-
checks and tests performed should ment name, model and serial venient mechanism for recording in-
be formally recorded and, where number; formation and can provide the basis
these have been carried out by the – Any identifying number allo- for satisfying the requirements of
supplier or a third party, the results cated by the user; NAMAS M10, GLP and ISO 9001.
of these checks and tests must be – The version and date of issue 4.4 Instrument log-books should identify
communicated to the user; of any computer hardware, the individual modules and accesso-
3.12 Users may expect suppliers to un- firmware and software; ries that constitute the instrument
 269

and be used to record the overall ied by version and date; proto- 5.7 Where instruments are made to
history of the instrument (e.g. the cols for IQ, OQ and PQ; model make measurements supporting reg-
date of purchase, the initial qualifi- SOPs etc.); ulatory studies, the user may also
cation and entry into service; the c) the level of skill required to op- need to seek confirmation that the
dates of when subsequent mainte- erate the instrument and details manufacturer is prepared, if re-
nance, calibration and qualification of any training necessary and quired, to allow regulatory authori-
have been performed and when courses provided by the supplier; ties access to detailed information
these are next due). In some circum- d) sample throughput, presentation and records relating to the instru-
stances it may be appropriate for all and introduction needs; ment’s manufacture and develop-
relevant information to be recorded e) data acquisition, processing and ment, for example: source codes; in-
in, or appended to, the instrument presentation needs; strument development records and
log-book (e.g. operating instructions f) requirements for, and expected procedures; calibration and qualifi-
and SOPs, maintenance and calibra- consumption of, services, utilities, cation documentation; batch test re-
tion records, and qualification and and consumables (e.g. electricity, cords and reports; hardware and
qualification protocols and reports). special gases); software qualification documenta-
In others, it may be more appro- g) environmental conditions within tion; and credentials of staff in-
priate to use the log-book as a sum- which, or range over which, the volved with the development of the
mary record of key information instrument must work; instrument.
which references where more de- h) suggested contents of, intervals
tailed procedures, reports and certif- between and procedures for 6 Installation Qualification (IQ)
icates can be accessed. maintenance and calibration of 6.1 There is a fine line between what is
4.5 Following qualification, the instru- the instrument, including the cost included in Installation Qualification
ment log-book must be updated with and availability of any service and what is included in Operational
the results of qualification. The in- contracts; Qualification. Indeed, the line may
strument itself should also be ‘la- i) the period for which support be drawn differently for different
belled’ to provide a clear indication (qualification, maintenance, parts manufacturers and/or different in-
of when the next qualification, cali- etc.) for the instrument can be struments. In this document IQ co-
bration or performance test is due. guaranteed; vers the installation of the instru-
j) information on health and safety ment up to and including its re-
5 Design Qualification (DQ) and environmental issues and/or sponse to the initial application of
5.1 Design Qualification is concerned requirements. power.
with what the instrument is required 5.5 In undertaking DQ, information and 6.2 IQ involves formal checks to con-
to do and links directly to fitness for knowledge of existing equipment firm that the instrument, its modules
purpose. DQ provides an opportuni- should be taken into account. If an and accessories have been supplied
ty for the user to demonstrate that instrument is mature in design and as ordered (according to specifica-
the instrument’s fitness for purpose has a proven track record, this may tions agreed between the user and
has been considered at an early provide a basic confidence and evi- supplier), and that the instrument is
stage and built into the procurement dence about its suitability for use. properly installed in the selected en-
process. For new techniques or instruments vironment. IQ must be formally doc-
5.2 DQ should, where possible, establish DQ may require more effort. umented (see Section 4) and should
the intended or likely use of the in- 5.6 The selection of the supplier and in- confirm the following:
strument and should define appro- strument is entirely at the discretion a) that the instrument (including all
priate operational and functional of the user. However, in selecting modules and accessories) has
specifications. This may be a com- the supplier and instrument, the user been delivered as ordered (de-
promise between the ideal and the should bear in mind that regulators livery note, purchase order,
practicalities of what is actually are likely to require evidence of: the agreed specifications), and that
available. Whilst it is the responsibil- use of rigorous design and specifica- the instrument has been checked
ity of the user to ensure that specifi- tion methods; fully documented and verified as undamaged;
cations exist, and that they are ap- quality control and quality assurance b) that all required documentation
propriate, they may be prepared by procedures; the use, at all times of has been supplied and is of cor-
the user, the supplier(s), or by dis- suitably qualified and experienced rect issue (e.g. operating manuals
cussion between the two. personnel; comprehensive, planned - which should also include their
5.3 The operational specification should testing of the system at all levels of issue number and date of issue;
define the key performance charac- the system; and the application of the supplier’s specification; and
teristics of the instrument and stringent change control, error re- details of all services and utilities
ranges over which the instrument is porting and corrective procedures. A required to operate the instru-
required to operate and consistently suitable questionnaire, third party ment);
perform. audit, or independent certification of c) that recommended service, main-
5.4 The functional specification should the supplier to an approved quality tenance, calibration and qualifi-
consider the overall requirements of scheme may provide the user with cation intervals and schedules
the instrument including the opera- evidence that regulatory require- have been provided. Where
tional specification (see above) and ments have been met. Where such maintenance can be carried out
other critical factors relating to its evidence is not available, it is the by the user, appropriate methods
use, for example: responsibility of the user to carry and instructions should be refer-
a) the overall business requirement; out more extensive qualification in enced along with contact points
b) documentation relating to the use order to provide the necessary assur- for service and spare parts;
of the instrument (e.g. clear, easy ance of the instrument’s fitness for d) that any required computer hard-
to use operating manuals, identif- use. ware, firmware and software has
270

been supplied and is of correct main under the control of the user. priate for a particular application.
issue; However, for complex instruments, SSC should be used before and dur-
e) that information on consumables it may only be possible for the sup- ing analysis to provide evidence of
required during the normal oper- plier to undertake OQ. satisfactory operation or to flag up
ation of the instrument system, 7.4 OQ should be carried out in accor- when performance is no longer ac-
and during start-up or shut-down dance with the supplier’s instruc- ceptable.
procedures, has been provided; tions and procedures, using suitable 8.5 Where a complete measuring system
f) that the selected environment for materials and protocols, and should is provided by the supplier, PQ can
the instrument system is suitable, satisfy the general requirements set be performed by the supplier, but
with adequate room for installa- out in Section 3 - Equipment Qualif- must remain under the control of
tion, operation and servicing, and ication. It is not possible to give fur- the user. In some circumstances, PQ
appropriate services and utilities ther general guidance on OQ requi- may also involve repeating many of
(electricity, special gases etc.) rements, because, at this stage, the the checks and tests carried out dur-
have been provided. (Note: sig- checks and tests necessary to de- ing OQ and, as such, these can also
nificant time and effort can be monstrate an instrument’s com- be performed by the supplier. How-
saved if these basic requirements pliance with its operational specifica- ever, wherever PQ is performed by
are checked prior to formal IQ tion are specific and vary depending the supplier, it is likely that the user
of the instrument); on the type of instrument undergo- will also have to undertake more
g) that health and safety and envi- ing qualification. However, OQ must frequent checks and tests to confirm
ronmental information relating to be formally documented in accor- the continued satisfactory perform-
the operation of the instrument dance with the general requirements ance of the instrument during rou-
has been provided. It is the re- set out in Section 4 - Documenta- tine use.
sponsibility of the supplier to tion. 8.6 PQ should be carried out in accor-
provide appropriate safety infor- dance with the general requirements
mation, on which the user must 8 Performance Qualification (PQ) set out in Section 3 - Equipment
act, and document the acceptance 8.1 The purpose of PQ is to ensure that Qualification. It is not possible to
of this guidance; the instrument functions correctly give further general guidance on PQ
h) that the response of the instru- and to a specification appropriate requirements, because, at this stage,
ment to the initial application of for its routine use. This specification the checks and tests necessary to de-
power is as expected or that any may be the original operational monstrate an instrument’s satisfacto-
deviations are recorded (if the specification or one more appro- ry performance are specific and de-
system is designed to perform priate for its current use. PQ pro- pendant on both the instrument type
any automatic diagnostic or start- vides the continuing evidence of and the analytical application. How-
up procedures the response to control and acceptable performance ever, PQ must be formally docu-
these should also be observed of the instrument during its routine mented in accordance with the gen-
and documented). use. eral requirements set out in Section
6.3 IQ may be carried out either by the 8.2 The frequency of, and need for, PQ 4 - Documentation.
supplier and/or the user. However, it should be specified in in-house oper-
should be noted that, in some cases, ating manuals or an SOP and should 9 Calibration and Traceability
the complexity of the instrument be based on need, type and previous 9.1 ISO Guide 25, the ISO 9000 series
alone may preclude the user per- performance of the instrument, in- of Standards and Good Laboratory
forming IQ and, in others, the un- cluding the time that the instrument Practice all require that, where rele-
packing of the equipment by the calibration has been found, in prac- vant and possible, calibrations
user may invalidate the warranty. tice, to remain within acceptable should be traceable to national or
6.4 IQ must be undertaken by a compe- limits. international standards. The impor-
tent individual and in accordance 8.3 Where possible, all operational tance of traceability to national and
with the supplier’s instructions and checks and tests should be perform- international standards is in estab-
procedures. The success or failure of ed using parameters as close as pos- lishing the accuracy of the data pro-
each of the IQ checks performed sible to those used during normal duced during the measurement proc-
should be formally recorded and, routine operation of the instrument. ess. Where this is not relevant or
where these have been carried out by For most analytical instruments possible, the basis for calibration or
the supplier, the results of these tests there will be a “grey” area between establishing the accuracy of results
must be communicated to the user. the optimum and unacceptable lev- must be documented.
els of performance. Wherever this is 9.2 Where instruments are used to de-
7 Operational Qualification (OQ) the case, the user must identify a termine absolute values of a param-
7.1 The purpose of Operational Qualifi- threshold below which the instru- eter (e.g. temperature, wavelength)
cation (OQ) is to demonstrate and ment’s performance is deemed to be the instrument should be calibrated
provide documented evidence that unacceptable and it should not be using reference materials or stand-
the instrument will perform accord- used until its performance is im- ards traceable to national or interna-
ing to the operational specification proved. tional standards. Most analytical in-
in the selected environment. 8.4 Aspects of performance qualification struments are not used in this way.
7.2 OQ normally takes place after the are often built into analytical meth- Instead, the parameter measured
IQ of a new instrument or after a ods or procedures. This approach is (e.g. mV) is compared with the val-
significant change to the instrument often called System Suitability ue for a known quantity of the de-
or a component such as repair or Checking (SSC) which demonstrates terminand of interest, in a calibrant,
service. that the performance of the measur- in a way which obeys definable laws.
7.3 OQ may be carried out either by the ing procedure (including instrumen- Thus, the traceability of the actual
supplier or the user, but must re- tal operating conditions) is appro- parameter measured (mV) is uni-
 271

mportant so long as the standard 10.2 Whenever such changes take place mented and describe the reasons
used to calibrate the measurement is it is essential to repeat relevant as- for, and differences, new features
traceable and the instrument re- pects of the original qualification and benefits of, the change. Users
sponse in relation to the concentra- process. This procedure is widely should ascertain and seek docu-
tion of the determinand is predicta- referred to as requalification. mented evidence from suppliers
ble. 10.3 The level of requalification re- that upgrades have been developed
9.3 For many applications, the accuracy quired will depend on the extent to and manufactured to appropriate
of the instrument’s operating param- which change has occurred and its Standards and formally validated
eters (e.g. mobile phase flow rates in impact on the instrument system. during production. Software up-
HPLC systems) is not critical and In many cases, requalification can grades should, as far as possible, be
hence the need for traceable calibra- be performed using the same EQ compatible with previous versions
tion to national or international protocols and checks and tests and, where this is not possible, the
standards is less important. In such which were undertaken prior to the supplier should offer a ‘validated’
circumstances, the accuracy of the routine use of the instrument. transfer of existing data to the up-
operating parameter is secondary 10.4 The nature of, and reason for, any graded system.
provided it remains consistently re- change to the instrument system, 10.10 Following installation of the up-
producible during the analysis of along with the results of all requal- grade, the instrument should be re-
both the sample and the standard, ification checks and tests perform- qualified using appropriate checks
and the satisfactory performance of ed, should be formally documented and tests. Where possible, the
the measuring system can be demon- according to the requirements set checks and tests used for requalifi-
strated (e.g. by System Suitability out in Section 4 - Documentation. cation should be designed so that
Checking). 10.5 Requalification may not necessarily the results can be compared with
9.4 However, in other circumstances, mean repeating the entire EQ those obtained using earlier ver-
the accuracy of an instruments oper- process. However, it must cover the sions, Any differences in the test
ating parameters and hence calibra- change and requalify those parts of results obtained from old and new
tion traceable to national or interna- the instrument system that are af- versions should be identified, docu-
tional standards will be more impor- fected by the change. mented and resolved.
tant, for example, where an analyti- 10.6 For example, the replacement of a
cal procedure developed in one la- detector source (e.g. deuterium 11 NAMAS Accreditation
boratory is to be transferred for rou- lamp) would require the detector This section has been prepared in
tine use in another laboratory or to be requalified using appropriate consultation with the United King-
where the accuracy of the parameter OQ/PQ procedures and protocols, dom Accreditation Service
may have a critical impact on the but would be unlikely to require (UKAS).
performance of the measurement the individual requalification of 11.1 NAMAS requirements are set out
process. other components of the instru- in the NAMAS M10 Standard and
9.5 Traceability to national and interna- ment (e.g. injector or pump). How- its Supplement[12]. Both the NA-
tional standards is usually, and often ever, because the change affected MAS Standard, its Supplement and
most efficiently, established through the instrument as a whole, it would other documentation produced by
the use of certified reference materi- also be necessary to carry out PQ UKAS (e.g. NIS documents) list
als or standards which are them- checks on the entire system to de- detailed requirements which are
selves traceable in this way. monstrate its satisfactory perform- relevant to the qualification of in-
9.6 Users should avoid over-specifying ance following the change. struments and it is not the inten-
calibration and/or traceability requi- 10.7 Similarly, for some ‘modular’ sys- tion to repeat these here.
rements (e.g. for parameters that are tems it is often possible to inter- 11.2 The basis of NAMAS accreditation
not critical to the method) because change components depending on is to provide users and their cus-
assessors will be justified in expect- the application and intended use of tomers with confidence in the qual-
ing users to demonstrate that any to- the instrument. Changes to the in- ity of the users testing activities,
lerances specified in procedures can strument system configuration (e.g. and in the technical and commer-
reasonably be met. replacing one detector with an- cial integrity of the user’s opera-
other) may not necessarily require tions. The philosophy of NAMAS
10 Requalification requalification of the individual is based around the “test”. Users
10.1 In general, an instrument will un- modules, but would require requal- are normally assessed and accre-
dergo a variety of change during its ification of the instrument system dited to perform specific tests in
life. This can vary from the routine as a whole. specific fields of measurement.
replacement of a single consumable 10.8 Significant changes to the instru- 11.3 As with other Standards, the basic
part, through to very significant ment system, for example, major requirement under NAMAS is that
changes affecting the entire instru- component or software upgrades, instruments must be fit for purpose
ment system. Examples of such cir- or enhancements which increase and suitable for their intended use.
cumstances include:- the instrument’s capabilities, will A primary consideration of NA-
– Movement or relocation of the normally require more extensive MAS assessors will be to assess the
instrument requalification. Indeed for such instrument’s fitness for purpose in
– Interruption to services or utili- substantial changes, there is often a the context of the test concerned
ties fine line between what is consid- and the accuracy required of re-
– Routine maintenance and re- ered to be requalification and what sults. In this respect, consideration
placement of parts constitutes qualification of a new must be given to the overall meas-
– Modification (e.g. instrument up- component. urement uncertainty, which will in-
grades or enhancements) 10.9 Upgrades to the instrument and/or clude a contribution from the in-
– A change of use its software should be fully docu- strument.
272

11.4 A difference between NAMAS and very many different tests which cility management to determine
other Standards is that NAMAS might be considered separately un- what maintenance and/or calibra-
explicitly states that instruments der other accreditation schemes, tion procedures are appropriate for
shall normally be owned by, or on for example, NAMAS. each item of equipment. However,
long-term lease to, the user and 12.3 The exact way in which the GLP if during an inspection there was
where, exceptionally, other instru- principles are applied in any parti- evidence of equipment malfunction,
ments are used, the user must have cular situation can vary. It is the poor performance etc., then this
evidence to show that the require- role of inspectors to assess wheth- would be taken as an indication
ments of the NAMAS M10 Stand- er, in their opinion (based on that existing procedures are inade-
ard are satisfied. knowledge of the types of proc- quate.
11.5 Instruments must be protected, as esses in use and the current indus- 12.8 Calibration should, where appro-
far as possible, from deterioration try norms), the basic GLP princi- priate, be traceable to national or
and abuse, and must be kept in a ples are being complied with. international standards. When this
state of maintenance and calibra- 12.4 The principles of Good Laboratory is not possible or applicable, in-
tion consistent with their use. They Practice and the operation of the spectors would expect that ade-
must be capable of achieving the United Kingdom Compliance Mon- quate procedures exist for estab-
accuracy required, and to comply itoring Programme are set out in lishing the accuracy and/or integrity
with any standard specifications rel- “Good Laboratory Practice - The of results. The level and frequency
evant to the tests concerned. Re- United Kingdom Compliance pro- of calibration will depend on the
cords of maintenance and calibra- gramme”(1) which is available from application. It is generally expected
tion must be kept. the UK Department of Health. The that instruments actually generating
11.6 Although the NAMAS M10 Stand- principles of GLP embodied in the study raw data are subject to high-
ard does not explicitly specify Compliance programme were first er levels of care than equipment
Equipment Qualification require- developed by the OECD and have used in a supporting role.
ments, it does necessitate that in- international acceptance. 12.9 There should be records of all in-
struments used are of established 12.5 Some test facilities operate quality strument operation, including rou-
design. Where other instruments management systems such as NA- tine and non-routine use, mainte-
are used, the user must demon- MAS or ISO 9000 in addition to nance and calibration. Any dam-
strate that they are suitable for GLP compliance. It is usually pos- age, malfunction, modification and
their intended purpose. New equip- sible to establish systems and pro- repair should be recorded. These
ment must be checked for com- cedures which satisfy the require- records should be to GLP stand-
pliance with appropriate specifica- ments of the different assessors and ards; although not raw data, these
tions, commissioned and calibrated inspectors. However, it must be re- data would be necessary to support
before use. membered that for certain activi- or allow reconstruction of com-
11.7 Instruments must only be operated ties, usually referred to as non-clin- pleted studies.
by authorised and competent staff, ical safety evaluation studies, GLP 12.10 There should be records demon-
and these must be named in the compliance is a mandatory regula- strating that personnel have been
appropriate procedures. Adequate, tory requirement. suitably trained (or have experi-
up-to-date, written instrument op- 12.6 The principles of GLP require that ence) to allow them to use the
erating instructions must be readily all equipment and apparatus are equipment correctly.
available for use by staff. suitable for their intended purposes 12.11 Under GLP, it is laboratory man-
and have adequate capacity to agement who is responsible for de-
12 GLP Compliance meet the requirements of the stud- monstrating that an instrument is
This sections has been prepared in ies and tests which will be carried suitable for its intended purpose
consultation with the United King- out. A complex validation exercise within the laboratory. Manufactur-
dom Department of Health Good would not necessarily be required, ers or suppliers can assist, but can-
Laboratory Practice Monitoring but Inspectors would expect to see not assume this responsibility.
Authority. evidence that new instruments were Computer software is a good exam-
12.1 Good Laboratory Practice (GLP) is subject to some form of evaluation ple: The supplier can carry out test-
concerned with the organisational before being approved for use on ing to show that the software func-
processes and the conditions under regulatory studies. It is important tions as expected, but the laborato-
which laboratory studies are plan- to remember that, however, most, ry must still show that the complete
ned, performed, monitored, re- if not all, items of automated instrument system and associated
corded and reported. GLP com- equipment will have microproces- software functions correctly in the
pliance is based upon the applica- sor/computer control. The princi- user environment.
tion and interpretation of a set of ples of GLP require that all com- 12.12 The principles and requirements of
principles rather than by means of puter systems are themselves sub- FDA GLP are set out in the Food
adherence to prescriptive regula- ject to a formal evaluation before and Drug Administration 21
tions, and that compliance with being used. CFR(2). Although the require-
these principles assures the quality 12.7 There should be documented pro- ments and principles of FDA GLP
and integrity of analytical data gen- cedures for the use, maintenance are inherently the same as those set
erated for regulatory purposes. and calibration of instruments. This down in the UK Compliance pro-
12.2 This approach is necessary because information might be in SOPs or in gramme, the FDA principles do ex-
of the very wide variety of study user manuals etc. In the latter case, pand and provide more detail on
types which are undertaken in ac- the user manuals must be refer- requirements relating to SOPs and
cordance with GLP. It should be enced in an appropriate SOP or records for instruments.
noted that GLP refers to studies Policy Document and handled in a 12.13 FDA GLP expands on the require-
where a single study can consist of controlled manner. It is for test fa- ments of SOPs necessitating that
 273

they set forth in sufficient detail gramme”; UK Department of Health ers, CJ Baijense, IJB Meuwsen, ML
the methods, materials and sched- 1989. Salm, EURACHEM Nederland Study
ules used in routine inspection, 2. “Good Laboratory Practice for Non- Group Harmonisation of Quality
cleaning, maintenance, calibration clinical Laboratory Studies”; Food Standard Systems.
and standardisation of instruments, and Drug Administration (FDA); 21 “Comparison of Standards with Require-
and, where appropriate, specify the CFR Ch.1 Part 58. ments on Calibration and Testing La-
remedial action to be taken in the 3. “General Criteria of Competence for boratories”; R Ohlon; Nordtest Techni-
event of instrument failure or mal- Calibration and Testing Laborato- cal Report No.179 April 1992.
function. SOPs also need to desig- ries”; NAMAS Accreditation Stand- “Good Laboratory Practice and the Role
nate the person responsible for ard M10; March 1989 Edition 1. of Quality Assurance”; GLP Advisory
each operation. 4. “General requirements for the com- Leaflet Number 3; UK Department of
12.14 Written records must include the petence of calibration and testing la- Health; 1991
date of inspection, maintenance, boratories”; ISO/IEC Guide 25, 3rd “The Quality Process in Instrument De-
calibration and standardisation op- Ed., 1990. (new version in draft sign, Development and Manufacture”;
erations and describe whether stage) J-M Varga; J. Clinical Immunoassay;
maintenance was routine and fol- 5. “Quality Systems - Model for quality 1994, Vol 17, Part 4, pp 243-248.
lowed the SOP. Written records assurance in design, development, “Validation of analytical methods by
must be kept of non-routine re- production, installation and servic- FDA laboratories”; J Guerra; Pharm.
pairs, performed as a result of fail- ing”; BS EN ISO 9001: 1994. Tech., March 1986, Vol 10, pp 74-84.
ure or malfunction, and these re- 6. “The Application of GLP Principles “A Suitable System for Chromatogra-
cords need to document the nature to Computer Systems”; GLP Adviso- phy”; R D McDowall; LC-GC Int., Vol
of the defect, how and when it was ry Leaflet Number 1; UK Depart- 8 No.4, April 1995.
discovered, and any remedial ac- ment of Health 1995. “Measuring Flow”; JV Hinshaw; LC-GC
tion taken in response to the de- 7. “GLP Consensus Document - The Int., Vol 8 No.3, March 1995.
fect. Application of the Principles of GLP “Automating method validation and sys-
to Computerised Systems” Environ- tem suitability testing in HPLC and
13 ISO 9000 Certification ment monograph No.116, OECD CE”; A Kohn; Am. Biotechnol. Lab.;
This section has been prepared in 1995. 1994, Vol 12 Part 11, pp 44-47.
consultation with the United King- 8. “Validating Computer-Controlled “Good Laboratory Practice, A primer for
dom Accreditation Service Analytical Systems for Pharmaceuti- HPLC, CE and UV-VIS Spectrosco-
(UKAS). cal Laboratories”; LC.GC Int.; Vol 8, py”; L Huber, Hewlett-Packard Com-
13.1 The requirements of the ISO 9000 No. 10, October 1995. pany, 1993.
series of Standards relating to in- 9. “Validation of Computerised Liquid “Spectrometry, Luminescence and Col-
strumental qualification are cov- Chromatographic Systems”; W B Fur- our; Science and Compliance”; Papers
ered by BS EN ISO 9001: 1994(2). man, T P Layoff and R F Tetzlaff presented at the second joint meeting
The philosophy behind ISO 9000 (US FDA); J. AOAC Int. Vol 77, of the UV Spectrometry Group of the
requirements is based on the estab- No. 5, 1994. UK and the Council for Optical Radia-
lishment of documented procedures 10. “A Guide to Managing the Configu- tion Measurements of the USA, June
and processes to ensure that instru- ration of Computer Systems (Hard- 1994; edited by C Burgess and DG
ments are adequately controlled. ware, Software & Firmware) used in Jones; Analytical Spectroscopy Library
ISO 9001 lists a number of require- NAMAS accredited laboratories” -Volume 6, Elsevier.
ments relating to the control of in- NAMAS NIS 37 Edition 1, October “Position paper on the Qualification of
spection, measuring and test equip- 1993. Analytical Equipment”; Paper agreed
ment and it is not intended to re- 11. “Validation of Computerised Analyti- by the Pharmaceutical Analytical
peat these here. cal Systems”; L Huber; Interpharm, Sciences Group (PASG); Pharm. Tech-
13.2 ISO 9001 requirements are very Buffalo Grove, IL, USA; 1995, 267 nol. Europe, November 1995.
similar to, but not generally as spe- pages, ISBN : 0-935184-75-9, Hewlett- “Quality Assurance and Instrumenta-
cific or detailed as those of NA- Packard partnumber 5959-3879. tion”; L Huber, J. Accred. Qual. Assur.
MAS. However, as with NAMAS 12. “Measurement and Calibration Sys- (1996) 1:24-34.
and GLP, there remains the same tems”; NAMAS Accreditation Stand-
basic requirement that instruments ard M10 Supplement; February 1993,
should be fit for purpose and kept Edition 1.
in a state of maintenance and cali-
bration consistent with their in- 15 Bibliography Annex 2: The Eurachem-UK
tended use. Perhaps the only differ- “International Guide to Quality in Analy- Instrumentation Working Group
ence, and only in application rather tical Chemistry”; 3rd draft, February
than in principle, is the emphasis 1995; CITAC Working Group. Dr Mike Sargent (Chairman)
that ISO 9000 places on design, “Accreditation for Chemical Laborato- Laboratory of the Government Chemist
and with this in mind, the broad ries: Guidance on the interpretation of
guidance provided under Section 5 the EN 45000 series of Standards and Dr Mike Ford
- Design Qualification should help ISO Guide 25”; EURACHEM Guid- VAM Working Group
users to demonstrate that adequate ance Document No.1 / WELAC Guid- Mr Steve Monk
design has been built into ensuring ance Document No. WGD 2; Edition 1, Department of Health GLP Monitoring
that instruments are fit for purpose. April 1993. Authority
“Quality Assurance in Analytical Chemi-
14 References cal Laboratories - A Comparison of Mr Andy Martin
1. “Good Laboratory Practice - The Current Standards in The Nether- United Kingdom Accreditation Service
United Kingdom Compliance Pro- lands”; HA van’t Klooster, HA Deck- (UKAS)
274

Dr David Rudd
Glaxo Wellcome Research and Develop- BOOK REVIEWS
ment
Mr Paul Yorke Accred Qual Assur (1996) 1 : 274 developing countries that are right-
Perkin Elmer Q Springer-Verlag 1996 ly concerned with their future and
Dr Gary Fenton are eager to learn what they
Waters Accreditation and quality should do. Well, this is the book
Mr Ian Vallance (replaced Ms Meraney assurance in analytical that they, too, need to study very
McCann and Dr Helge Schrenker) carefuly. If UNIDO still has some
Hewlett Packard chemistry funds to devote for real help, this
Mr Lars Lis
Helmut Günzler (ed.) monograph is the right choice.
Varian Send copies of it to analytical labo-
Springer, 1996
Mr John Hammond ratories in developing countries
Unicam and you will disseminate very use-
Dr Peter Smith ful information at modest cost.
Hilger Analytical The reader will be surprised to
Professor Peter Stockwell
This book, published in German in see in Prof. de Bièvre’s chapter on
P S Analytical 1994, is now available to a wider Traceability of Measurements of SI
public in English translation. (p. 185 Fig. 12 and p. 186 Fig. 13)
Mr Colin Andrews
GAMBICA Thanks to the editor, the text has the considerable number of unac-
been brushed up and updated in ceptable results presented by labo-
Mr Paul Winson accordance with the events and ratories – among which there could
Perkin Elmer
changes that have taken place be quite a few that have been in
Dr Grant Cameron since 1994. The authors of the dif- fact accredited! It follows from this
Anachem
ferent chapters are indeed the gu- that users of services of analytical
Dr Lyndon Davies rus of their specialities, and the laboratories cannot be sure that
Lyndon Davies Associates reader gets first-hand information the results of accredited laborato-
Mr Terence Duley on the broadest aspects of the sub- ries are necessarily in all cases free
Cecil Instruments ject in 266 pages. It is certainly in- of errors. Probably the confiden-
Mr Roy Lines teresting to read through the whole tiality of interlaboratory studies
Coulter Electronics book from start to finish (the chap- should be lifted – with the consen-
Mr Tony McGarrigle ters are in a logical sequence); sus of the laboratories – and made
Fisons Instruments however, it can also be used as a public. Until that time, in the case
Dr Steve Ellison
lexicon or reference book. of sensitive fields, e.g. clinical labo-
Laboratory of the Government Chemist There is no doubt that analyti- ratories, analysis of toxic elements
cal laboratories should devote ever in food, the environment etc.,
Mr David Holcombe
Laboratory of the Government Chemist more attention to assuring the clients of analytical laboratories
quality of their results. It is also should rather insist on their own
Mr Peter Bedson (Secretariat) true that in certain countries it is
Laboratory of the Government Chemist
assessment of their partners’ per-
still possible to get laboratory ac- formance.
creditation for very vaguely de- The reliable factual information
P. Bedson (Y) 7 M. Sargent fined fields of work without speci- in this book is its main asset. It can
Laboratory of the Government Chemist fying matrices, concentration limits be recommended to chemists of
Queens Road, Teddington, Middlesex
TW11 0LY or quality parameters of results. analytical laboratories that want to
United Kingdom The situation will change, and la- exist and prosper in years to come.
boratories should prepare them-
selves for this. The book gives
them all the basic information and
references needed for this prepara- M. Parkany
tion. The reviewer visited a consid- 10, ch. du Champ d’Anier
erable number of laboratories in CH-1209 Geneva, Switzerland