See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/297688862

The new ISO Guide 80: Guidance for the in-house preparation of quality
control materials (QCMs)

Article  in  Accreditation and Quality Assurance · December 2014

DOI: 10.1007/s00769-014-1084-1

CITATIONS READS

5 4,364

2 authors, including:

Angelique Botha
National Metrology Institute of South Africa
47 PUBLICATIONS   83 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Test and Measurement Conference View project

APMP.QM-K41 View project

All content following this page was uploaded by Angelique Botha on 14 October 2017.

The user has requested enhancement of the downloaded file.

The new ISO Guide 80: Guidance for the
in-house preparation of quality control
materials (QCMs)

Steve Wood & Angelique Botha

Accreditation and Quality Assurance

Journal for Quality, Comparability and
Reliability in Chemical Measurement

ISSN 0949-1775
Volume 19
Number 6

Accred Qual Assur (2014) 19:477-480

DOI 10.1007/s00769-014-1084-1

1 23
Your article is protected by copyright and
all rights are held exclusively by Springer-
Verlag Berlin Heidelberg. This e-offprint is
for personal use only and shall not be self-
archived in electronic repositories. If you wish
to self-archive your article, please use the
accepted manuscript version for posting on
your own website. You may further deposit
the accepted manuscript version in any
repository, provided it is only made publicly
available 12 months after official publication
or later and provided acknowledgement is
given to the original source of publication
and a link is inserted to the published article
on Springer's website. The link must be
accompanied by the following text: "The final
publication is available at link.springer.com”.

1 23
 Author's personal copy
Accred Qual Assur (2014) 19:477–480
DOI 10.1007/s00769-014-1084-1
INTERNATIONAL BODIES
The new ISO Guide 80: Guidance for the in-house preparation
of quality control materials (QCMs)
Steve Wood • Angelique Botha
Received: 26 August 2014 / Accepted: 6 October 2014 / Published online: 16 October 2014
 Springer-Verlag Berlin Heidelberg 2014
Abstract Reference materials (RMs) are widely used in
measurement laboratories for a variety of purposes, and it is
important to recognise that the material most appropriate for a
particular application should be used. Certified reference
materials (CRMs) are used for method validation, the cali-
bration of a measurement system and all other aspects of the
evaluation of the measurement system where the trueness of
the measurement result is required. For other aspects, such as
quality control, precision studies, the checking of the vari-
ability between operators, where the results are compared
relatively, any suitable reference material can be used. ISO/
REMCO, the ISO Committee on Reference Materials, has
prepared ISO Guide 80, a guidance document for the in-house
preparation of quality control materials (QCMs). QCMs are
mostly used to monitor the performance of laboratory meth-
ods that have already been validated over time to be able to
detect change or when a method goes out of statistical control.
QCMs are RMs and as such have to be sufficiently homoge-
neous and stable for the intended use. QCMs are usually
prepared in-house by laboratory staff for in-house use only,
and therefore, the requirements for ‘‘in-house’’ QCMs are less
demanding than those for a CRM. For example, transport
issues are not of concern. The quality assessment of QCMs
should involve homogeneity and stability assessments, and a
limited characterisation of the material to provide an indica-
tion of its relevant property values and their variation, prior to
use.
S. Wood
LGC, Queens Road, Teddington, Middlesex TW11 0LY, UK
A. Botha (&)
National Metrology Institute of South Africa (NMISA), CSIR,
Building 5, Meiring Naudé Road, Brummeria, Pretoria 0001,
South Africa
e-mail: abotha@nmisa.org
Keywords ISO Guide 80
In-house preparation

Quality control materials
Homogeneity
Stability
Introduction and background
Reference materials (RMs) are widely used in measure-
ment laboratories for a variety of purposes, and it is
important to recognise that the material most appropriate
for a particular application should be used. Certified ref-
erence materials (CRMs), i.e. those which have property
values and associated uncertainties assigned by metrolog-
ically valid procedures are primarily used for calibrations
or method validation and control to assure the trueness of
the measurement results.
There are some instances where a CRM is not always
required for the partial evaluation of the measurement
process. For the purpose of quality control regarding con-
sistency, where it must be demonstrated that a
measurement system is under reproducibility control, per-
forms in the same manner and provides consistent results,
i.e. where the trueness of the measurement result is not
critical, the only requirements for the reference materials
are that they are sufficiently homogeneous and stable.
While CRMs are produced by established reference
material producers and are commercially available, these
quality control samples or check samples, as they are
sometimes called, are often prepared by a laboratory for its
own internal use.
ISO/REMCO, the ISO Committee on Reference Materi-
als, has prepared ISO Guide 80 [1], a guidance document for
the in-house preparation of these quality control materials
(QCMs). QCMs are RMs and as such the description of the
production of reference materials, as detailed in ISO Guide
123
 Author's personal copy
478
34 [2] and ISO Guide 35 [3], is also applicable to the
preparation of QCMs. However, the requirements for ‘‘in-
house’’ QCMs intended for in-house use only are less
demanding than those for a CRM, for example, in respect of
transport issues. The quality assessment of QCMs should
involve homogeneity and stability assessments, and a lim-
ited characterisation of the material to provide an indication
of its relevant property values and their variation, prior to
use. Establishment of metrological traceability, full uncer-
tainty estimation and extensive stability testing are not
required for this type of reference material, and these pro-
cesses are not described in ISO Guide 80 [1].
ISO Guide 80 [1] outlines the essential characteristics of
QCMs and describes the processes by which they can be
prepared by competent staff within the facility in which
they will be used (i.e. where instability due to transporta-
tion conditions is avoided). The content of the Guide also
applies to inherently stable materials, which can be trans-
ported to other locations without risk of any significant
change in the property values of interest.
The primary audience for ISO Guide 80 [1] is laboratory
staffs who are required to prepare and use materials for
specific in-house quality control applications. Preparation
of QCMs, where transportation is a necessary component
of the supply chain, for instance, between laboratories at
different locations, should conform to the relevant
requirements of ISO Guides 34 [2] and 35 [3]. The new
Guide provides the quality criteria that a material should
fulfil to be considered fit-for-purpose for demonstrating a
measurement system is under statistical control. Guidance
on uses of such materials, for example setting up a QC
chart, is adequately covered elsewhere [4–7] and is not
included in ISO Guide 80 [1].
The layout and structure of the Guide provides general
information on the preparation of QCMs in the main
chapters, with specific case studies covering a range of
sectors in the annexes. The case studies are not complete
‘‘process manuals’’ but are included to highlight some of
the key considerations when preparing QCMs. The case
studies vary in complexity and detail, including sector
specific terminology, but provide a range of information for
laboratory staff to draw from.
It is expected that those involved in QCM preparation
will have some knowledge of the type of material to be
prepared and be aware of any potential problems due to
matrix effects, contamination, etc.
An overview of the content of ISO Guide 80 [1]
The key criteria in the specification and selection of a QCM
are for the material to be as close as possible to real
samples and available in appropriate quantities (Fig. 1).
123
Accred Qual Assur (2014) 19:477–480
Material Material Material
Specificaon Sourcing Processing
Sub-division & Homogeneity
Characterizaon
/ Value
Packaging Assessment
Assignment
Stability Documentaon
Storage
Assessment / Informaon
Fig. 1 Key steps in the preparation of a typical QCM
Sourcing and processing of bulk materials for QCM
preparation may at first seem difficult especially in those
cases where large quantities of material are required.
However, there are a number of options that may be
available including:
• excess sample material and
• accurate gravimetric formulation.
Processing the bulk material can have significant cost
implications for the preparation of QCMs and simple,
straightforward processing methods should be used to
ensure cost-effective QCM preparation. The exact prepa-
ration procedures required for a particular QCM will
depend on the nature of the matrix and the properties of
interest.
Once the bulk material has been sourced, there are a
number of processing stages which may need to be carried
out to ensure the material has the appropriate homogeneity
and stability for its intended purpose. Some of the more
common processes include drying, milling and grinding,
sieving, mixing and blending, filtration, stabilisation,
sterilisation.
Once the bulk material has been processed, it will need
to be subdivided and packaged. The subclauses in this
section of ISO Guide 80 describe some of the key con-
siderations for the subdivision process, and choice of
containers to ensure the QCM is sufficiently homogeneous
and stable for its intended purpose.
For QCMs to be produced cost-effectively, one aspect
that needs careful consideration is the choice of appropriate
containers for the individual units. If unsuitable containers
are used, a material may quickly degrade to the extent that
time-consuming and expensive sourcing and preparation
work on the bulk material may have to be repeated. The
type of container used depends on the inherent stability of
the material and the length of time it is required to remain
stable. For particularly susceptible materials, two forms of
containment (e.g. a vial within a polyethylene bag) can
 Author's personal copy
Accred Qual Assur (2014) 19:477–480
provide additional protection against degradation and
contamination.
Once a homogeneous bulk material has been produced,
the essential requirement of any subdivision process is that
the homogeneity of the material is maintained. That is, the
subdivision process itself, or the time taken to complete the
subdivision of a bulk material, should not reintroduce
heterogeneity into the material. This may conceivably
occur in a number of ways.
Assessment of homogeneity
Homogeneity is a relative concept. The required level of
homogeneity of a QCM is dependent on an understanding
of the expected variation of the amount of sample used in
the measurement process under investigation. In all cases,
the level of inhomogeneity should result in a smaller effect
on the measurement result than the expected variation of
the measurement process or should be below an established
criterion value.
Once a candidate QCM has been subdivided into indi-
vidual aliquots, it is important to establish whether there
are any variations in its property values between aliquots.
For certain QCM matrices, such as true solutions which
have been prepared by procedures such as filtration (to
remove particulates) and thorough mixing, formal homo-
geneity testing is, in principle, not necessary. Such
materials may be formally regarded as being inherently
homogeneous. Nevertheless, because of the risk of con-
tamination (e.g. introduced due to packaging) or imperfect
subdivision, it is recommended to carry out a simple
homogeneity study.
For more complex matrices such as foodstuffs, soils and
solid matrices that are inherently heterogeneous, a formal
experimental investigation of homogeneity is required. A
sufficient number of units, representative of the entire batch
of the QCM should be chosen and analysed for selected
properties [2]. In certain instances, one property can be
chosen to represent and quantify the homogeneity of sev-
eral properties of a similar general type. This should be
based on scientific evidence or on previous experience that
certain properties exhibit similar behaviour [8] or are
known to have a strong tendency to homogeneous distri-
bution in the sample (e.g. some metals in alloys).
A validated analytical method having a sufficient degree
of repeatability should be selected for the evaluation of the
homogeneity. The selected units should be representative
of the entire batch. The number of units is dictated by the
total number of units produced.
The principles of ISO Guide 35 [3] should be applied
with respect to the statistical evaluation of the results for
homogeneity.
479
When reviewing the homogeneity data, consideration
should be given to the nature of the material and whether
such variation is within acceptable limits. A useful first
step is to review the data graphically. This enables any
discordant features (such as outlying samples, trends or
other systematic effects) to be readily identified.
Characterisation
The purpose of QCMs is to monitor measurement pro-
cesses for change. In order to achieve this effectively, an
indication of the property values of the QCM used to
monitor the process is needed. It is also necessary to have
an indication of the likely variation in values due to het-
erogeneity between different aliquots.
An effective way of determining an indicative property
value is to use the overall mean derived from the homo-
geneity study. The range within which the property values
may reasonably be expected to lie can be estimated by the
deviation from this overall mean value. This deviation
from the mean can be used to establish control chart
warning limits. Conventionally, warning and action limits
(also described as lower and upper action limits) are
established at two and three times the standard deviation,
respectively.
Assessment of stability
Different materials will exhibit different types of (in)sta-
bility, some of which may be excluded from consideration
given long-term historic data and knowledge; some may be
undetectable but cannot be excluded from consideration;
some can be detected and should be assessed; and some
follow certain, well-established, chemical or physical
principles.
Full stability assessment for any reference material is a
costly, time-consuming and demanding process and is
inappropriate for QCMs, which are prepared in the labo-
ratory where they are intended to be used, as described in
ISO Guide 80 [1]. It is likely that the laboratory will have
previous experience of the stability of the types of matrix
and property values it is preparing as QCMs, or there may
be well-established background information from similar
materials.
However, the financial implications of using QCMs
whose property values have changed significantly can be
large (e.g. release of out-of-specification products or non-
release of in-specification products) and laboratories using
QCMs should have procedures in place which describe the
actions to be taken in the event of a QCM giving an
unexpected result.
123
 Author's personal copy
480
Concluding remarks
ISO Guide 80 [1] also provides information on issues
concerning the assignment of an expiry date to a QCM, the
labelling of a QCM and what information should be
available with the material and should be retained when the
material is no longer in use, as well as advice on the use
and storage of the material.
QCMs are an important part of the day-to-day opera-
tions of any analytical measurement system. It is common
practice for most analytical laboratories to prepare QCMs
in-house. The material is often sourced by the laboratory
from the sample materials that the laboratory analyses
routinely. The best way for a laboratory to ensure that a
measurement system is under statistical control is to
monitor whether the expected measurement results are
obtained for typical routine samples.
ISO Guide 80 [1] summarises the minimum require-
ments for the preparation of in-house reference materials
and provides some real-life examples in the case studies to
assist with the practical implementation of preparation
procedures.
123
View publication stats
Accred Qual Assur (2014) 19:477–480
References
1. ISO Guide 80 (2014) Guidance for the in-house preparation of
quality control materials (QCMs). International Standardisation
Organisation (ISO), Geneva, p 50
2. ISO Guide 34 (2009) General requirements for the competence of
reference material producers. International Standardisation Orga-
nisation (ISO), Geneva, p 32
3. ISO Guide 35 (2006) Reference materials—general and statistical
principles for certification. International Standardisation Organi-
sation (ISO), Geneva, p 64
4. ISO 7870-1 (2014) Control charts—Part 1: general guidelines.
International Standardisation Organisation (ISO), Geneva, p 16
5. ISO 7873 (1993) Control charts for arithmetic means with warning
limits. International Standardisation Organisation (ISO), Geneva,
p 13
6. ISO 7870-3 (2012) Control charts—Part 3: acceptance control
charts. International Standardisation Organisation (ISO), Geneva,
p 20
7. ISO 7870-2 (2013) Control charts—Part 2: Shewhart control
charts. International Standardisation Organisation (ISO), Geneva,
p 44
8. Lawn R, Roper R, Holcombe G, Stuart B (2001) Low-cost QC
laboratory reference materials—investigation of cost-effective
production procedures. Laboratory of the Government Chemist
(LGC), Teddington LGC/VAM/2001/009