SIST ISO/DGuide 80:2013

Guidance for in-house production of reference materials for quality control (QCMs)

ISO Guide 80 outlines the essential characteristics of reference materials for quality control (QC) purposes, 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 transportation conditions is avoided). The content of this Guide also applies to inherently stable materials, which can be transported to other locations without risk of any significant change in the property values of interest.
The primary audience for this Guide is laboratory staff 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, such as laboratory sites at different locations or for proficiency testing schemes, should conform to the relevant requirements of ISO Guides 34 and 35.
The description of the production of reference materials (RMs), as detailed in ISO Guide 34 and ISO Guide 35 is also applicable to the preparation of quality control materials (QCMs). However, the requirements for "in-house" QCMs are less demanding than those for a certified reference material (CRM). The preparation of QCMs should involve homogeneity and stability assessments, and a limited characterization of the material to provide an indication of its relevant property values and their variation, prior to use. This document 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 is not included in this Guide.
The layout and structure of this 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.

Lignes directrices pour la production interne des matériaux de référence utilisés pour contrôle qualité (QCMs)

Navodilo za ???

General Information

• Status: Not Published
• ICS: 71.040.30 - Chemical reagents
• Technical Committee: REM - Reference materials
• Current Stage: 4020 - Public enquire (PE) (Adopted Project)
• Start Date: 17-Sep-2012
• Due Date: 04-Feb-2013
• Completion Date: 13-Nov-2012
• Ref Project: ISO Guide 80:2014 - Guidance for the in-house preparation of quality control materials (QCMs)

Standards Content (sample)

GUIDE 80
First edition
2014-08-15
Guidance for the in-house preparation
of quality control materials (QCMs)
Lignes directrices pour la préparation interne des matériaux de
référence utilisés pour le contrôle qualité
Reference number
ISO GUIDE 80:2014(E)
ISO 2014
---------------------- Page: 1 ----------------------
ISO GUIDE 80:2014(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2014

All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form

or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior

written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of

the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail [e-mail]
Web www.iso.org
Published in Switzerland
ii © ISO 2014 – All rights reserved
---------------------- Page: 2 ----------------------
ISO GUIDE 80:2014(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Quality control materials (QCMs) ....................................................................................................................................................... 2

5 Applications of quality control materials (QCMs) ............................................................................................................. 2

6 Steps in the in-house preparation of quality control materials (QCMs) .....................................................3

7 Material specification ...................................................................................................................................................................................... 4

7.1 Matrix type, matching and commutability ...................................................................................................................... 4

7.2 Properties and property values ................................................................................................................................................ 4

7.3 Unit size ......................................................................................................................................................................................................... 4

7.4 Total bulk amount of material ................................................................................................................................................... 4

8 Preparation of quality control materials (QCMs) ............................................................................................................... 5

8.1 Sourcing of bulk material ............................................................................................................................................................... 5

8.2 Material processing ............................................................................................................................................................................. 5

8.3 Sub-division and packaging ......................................................................................................................................................... 7

9 Homogeneity ............................................................................................................................................................................................................ 9

9.1 Overview ...................................................................................................................................................................................................... 9

9.2 Analytical approach ............................................................................................................................................................................ 9

9.3 Statistical treatment of homogeneity data ...................................................................................................................10

10 Characterization and value assignment ....................................................................................................................................12

11 Stability .......................................................................................................................................................................................................................12

11.1 Overview ...................................................................................................................................................................................................12

11.2 Assessing stability .............................................................................................................................................................................12

11.3 Assigning an expiry date to a QCM......................................................................................................................................13

12 Transportation

....................................................................................................................................................................................................13

13 Documentation for quality control materials (QCMs) ................................................................................................13

13.1 General ........................................................................................................................................................................................................13

13.2 Information to be available with quality control materials (QCMs) ......................................................13

13.3 Labelling of QCM units ..................................................................................................................................................................14

13.4 Useful information to be retained .......................................................................................................................................14

14 Storage .........................................................................................................................................................................................................................15

14.1 General ........................................................................................................................................................................................................15

14.2 Monitoring of storage conditions .........................................................................................................................................15

15 Using quality control materials (QCMs) ....................................................................................................................................15

15.1 General ........................................................................................................................................................................................................15

15.2 Minimum sample size ....................................................................................................................................................................15

15.3 Mixing procedure ...............................................................................................................................................................................15

15.4 Dry mass correction ........................................................................................................................................................................16

15.5 Storing opened containers of QCMs ..................................................................................................................................16

Annex A (informative) Case study 1 — Preparation of a QCM from coal ......................................................................17

Annex B (informative) Case study 2 — Preparation of geological or metallurgical quality control

materials (QCMs) ..............................................................................................................................................................................................19

Annex C (informative) Case study 3 — Preparation of a wheat flour fortified with folic acid quality

control material (QCM) ...............................................................................................................................................................................26

© ISO 2014 – All rights reserved iii
---------------------- Page: 3 ----------------------
ISO GUIDE 80:2014(E)

Annex D (informative) Case study 4 — Bauxite quality control material (QCM) .................................................32

Annex E (informative) Case study 5 — Pharmaceutical reference standards ........................................................37

Annex F (informative) Case study 6 — Preparation of testing materials for “bromate in water” ......42

BIBLIOGRAPHY ......................................................................................................................................................................................................................49

iv © ISO 2014 – All rights reserved
---------------------- Page: 4 ----------------------
ISO GUIDE 80:2014(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of any

patent rights identified during the development of the document will be in the Introduction and/or on

the ISO list of patent declarations received (see www.iso.org/patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation on the meaning of ISO specific terms and expressions related to conformity

assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers

to Trade (TBT) see the following URL: Foreword - Supplementary information

The committee responsible for this document is ISO/REMCO, Committee on reference materials (which

has the task to prepare guidance documents for the preparation, characterization, certification and use

of reference materials (RMs) and the competence assessment of reference material producers.

© ISO 2014 – All rights reserved v
---------------------- Page: 5 ----------------------
ISO GUIDE 80:2014(E)
Introduction

Reference materials (RMs) are widely used in measurement laboratories for a variety of purposes and it

is important to recognize that the material most appropriate for a particular application should be used.

Certified reference materials (CRMs), i.e. those which have property values and associated uncertainties

assigned by metrologically valid procedures are primarily used for method validation and calibrations

providing metrological traceability.

The preparation of reference materials for metrological quality control (i.e. control of the quality of

measurements not products) is an important activity which provides materials suitable for the day-to-

day demonstration that a particular (part of a) measurement system is under statistical control. Such

materials do not require characterization by metrologically valid procedures, and can be prepared “in-

house”, i.e. by laboratory staff familiar with their behaviour, to fulfil specific quality control requirements.

Reference materials which are sufficiently homogeneous and stable are necessary for metrological

quality control purposes, such as demonstrating a measurement system is under statistical control,

performs as expected and provides reliable results; where the trueness of the measurement result is

not critical. Different industries use various terminologies to describe such materials (e.g. in-house

reference materials, quality control materials, check samples, etc.). For the purposes of this Guide, the

term “Quality Control Materials” (QCMs) will be used to simplify repeated citation.

While CRMs are produced by established reference material producers and are commercially available,

QCMs are often prepared by a laboratory for its own internal use. Frequently, QCMs are characterized

only for a limited scope (a limited number of property values) and for specific laboratory applications.

The rationale for preparing quality control materials can be one or a combination of the following factors:

— to have an RM representing as closely as possible routine samples, suitable for quality control;

— to have a suitable day-to-day RM to complement a commercially available CRM;
— no suitable CRM exists;

— the application does not require a material having the full characteristics of a CRM (e.g. traceability

and uncertainty for specified property values).
[1]

QCMs are RMs and as such the requirements of ISO Guide 34 for the production of RMs apply. However,

if the material is only used in-house by the preparing laboratory, some requirements (e.g. for transport

stability) can be relaxed. The preparation of a QCM is related to that of a CRM and those preparing QCMs

[1] [2]

may wish to consult ISO Guides 34 and 35 for further guidance. Where appropriate, this Guide will

refer to relevant parts of these Guides.

It is recognized that the aim of many laboratories requiring QCMs is to minimize the time and effort

needed to prepare the materials. To this end, many laboratories use samples of real products for which

there is a body of analytical data available. A number of case studies are included as annexes of this

guidance document to provide examples of how such data may be processed to confirm fitness for

purpose of the materials.
vi © ISO 2014 – All rights reserved
---------------------- Page: 6 ----------------------
GUIDE ISO GUIDE 80:2014(E)
Guidance for the in-house preparation of quality control
materials (QCMs)
1 Scope

This Guide outlines the essential characteristics of reference materials for quality control (QC) purposes,

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 transportation conditions is avoided). The content

of this Guide also applies to inherently stable materials, which can be transported to other locations

without risk of any significant change in the property values of interest.

The primary audience for this Guide is laboratory staff 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, such as laboratory sites at different locations or for proficiency testing

[1] [2]
schemes, should conform to the relevant requirements of ISO Guides 34 and 35.
[1]

The description of the production of reference materials (RMs), as detailed in ISO Guide 34 and

[2]

ISO Guide 35 is also applicable to the preparation of quality control materials (QCMs). However, the

requirements for “in-house” QCMs are less demanding than those for a certified reference material

(CRM). The preparation of QCMs should involve homogeneity and stability assessments, and a limited

characterization of the material to provide an indication of its relevant property values and their

variation, prior to use. This document 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

[3] [4] [5] [6]
, , , and is not included in this Guide.

The layout and structure of this 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.

2 Normative references

The following documents, in whole or in part, are normatively referenced in this document and are

indispensable for its application. For dated references, only the edition cited applies. For undated

references, the latest edition of the referenced document (including any amendments) applies.

ISO Guide 30, Reference materials — Selected terms and definitions

ISO/IEC Guide 99, International vocabulary of metrology — Basic and general concepts and associated

terms (VIM)

ISO 3534-1, Statistics — Vocabulary and symbols — Part 1: General statistical terms and terms used in

probability
3 Terms and definitions
[7] [8]

For the purposes of this document, the terms and definitions in ISO Guide 30 ISO/IEC Guide 99 and

[9]
ISO 3534-1 and the following apply.
© ISO 2014 – All rights reserved 1
---------------------- Page: 7 ----------------------
ISO GUIDE 80:2014(E)
3.1
indicative value

value of a quantity or property, included in the certificate of a CRM or otherwise supplied, which is

provided for information only (i.e. is not certified by the producer or the certifying body)

Note 1 to entry: Values assigned to quality control materials (QCMs) can only be indicative in that they have no

[7]

metrological traceability. ISO Guide 30:1992 uses the term “uncertified value” to describe a value of a quantity

provided for information only.
4 Quality control materials (QCMs)

The term “quality control material” or “QCM” has been devised for the purposes of this Guide solely to

simplify repeated reference to materials used routinely to assess the precision of test procedures. It is

not intended to define a new class of reference materials. Such materials are variously referred to in the

open literature as “in-house reference materials”, “quality control samples”, “check samples”, “set up

samples”, etc.

Where no suitable CRM exists, laboratories may use QCMs to provide an assessment of the repeatability

/ intermediate precision / reproducibility of a measurement result. QCMs cannot be used to establish

metrological traceability or trueness of a measurement result.

QCMs should always comply with the basic requirements of any reference material, i.e. they should be

sufficiently homogeneous and stable with respect to the properties of interest. The level of heterogeneity

should be less than the expected standard deviation of the measurement process or an established

criterion value against which the assessment of laboratory performance or the “normalization” of

results is acceptable. The QCM should be stable for a period of time that is at least as long as that during

which it is intended to be used.
5 Applications of quality control materials (QCMs)

The principal function of QCMs is to provide laboratories with an economical means of checking their

routine test procedures for precision on a regular basis (e.g. daily, weekly or monthly).

While CRMs can in all cases replace QCMs, QCMs are not replacements for CRMs; they are complementary

to them having a specific, limited purpose in the measurement process. CRMs produced according to

[1]

the principles of ISO Guide 34 are essential to establish the concept of metrological traceability in a

meaningful manner, and provide the highest standard with respect to reference materials. There is no

requirement for QCMs to have metrologically traceable assigned values; consequently, QCMs cannot

be used to establish metrological traceability or to estimate uncertainty. For method validation and

uncertainty estimation, QCMs may be used to a limited extent (e.g. for establishment of a precision

estimate as part of the total measurement uncertainty).
Uses of QCMs include (but are not limited to):

— preparation of QC charts – to demonstrate control of a measurement process within a laboratory or

to confirm the effectiveness of a laboratory’s quality control process or to demonstrate control of a

measurement process over a period of time;

— comparison of results (e.g. from two or more series of related samples either in a short period of

time or over an extended period of time when a measurement process is known to vary);

— method development – to establish consistency (for validation a certified reference material should

be used);
— instrument performance checks;

— repeatability and reproducibility studies – repeated use over an extended period of time,

instruments, operators, etc., to estimate long-term reproducibility or robustness of a measurement

process or laboratory;
2 © ISO 2014 – All rights reserved
---------------------- Page: 8 ----------------------
ISO GUIDE 80:2014(E)

— as check samples – for example, to confirm the degree of equivalence of measurement results from

two or more laboratories (e.g. provider and user), where the materials are inherently stable;

— operator variability;

— impact of any changes to the environmental conditions (e.g. temperature, humidity).

[3] [4] [5] [6]

When confirming that a measurement process is under statistical control, , , , the acceptability

of laboratory performance is generally assessed by comparing either the standard deviation or the

range of the individual results for the QCM against a pre-established criterion. If a lack of control of the

measurement process is identified, the laboratory needs to take action. In the simplest case, this may

require repeating the “suspect” measurements, perhaps following a re-calibration of instruments.

[10]

A more in-depth discussion of the uses of quality control materials can be found in ISO Guide 33.

[11]

Regardless of the intended use, it is necessary to assess homogeneity and stability of a QCM.

6 Steps in the in-house preparation of quality control materials (QCMs)

The fundamental purpose of QCMs is to detect change. In general, more pragmatic and less rigorous

protocols can be used for stability and homogeneity steps to strike a balance between material

development costs on the one hand and the intended use of the material on the other.

The production of any reference material requires a level of technical and organizational competence.

It is acknowledged that in many cases “in-house” QCMs will be prepared by technically competent staff

that is knowledgeable about the materials/processes being used.

The key steps involved in the in-house preparation of a typical QCM are summarized in the flow chart

in Figure 1 and are described in more detail in References [12] and [13]. Materials can be sourced

from, processed, sub-divided and packaged by third parties, where they have specialized equipment

and/or expertise. Materials may even be products which are commercially available and meet the user’s

specification (e.g. food products available in appropriately sized units from a single production batch).

Figure 1 — Key steps in the preparation of a typical QCM

NOTE Any of these steps may be subcontracted to a technically competent subcontractor.

© ISO 2014 – All rights reserved 3
---------------------- Page: 9 ----------------------
ISO GUIDE 80:2014(E)
7 Material specification

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.
7.1 Matrix type, matching and commutability

In general terms, the uncertainties associated with a measurement result arise from the two main

stages of the measurement procedure:
— the preparation of a sample comprising digestion, extraction, clean-up, etc.;

— the measurement of the property in the prepared sample by a suitable technique.

The scope and applicability of a matrix reference material is an important consideration for both the

production and use of all reference materials.

The matrix of the QCM should be the same or as similar as possible to the matrix of the routine test

samples, so that a satisfactory result for the QCM is genuinely indicative of satisfactory results for the

test samples. This matrix matching requires some knowledge of the analytical procedure used on the

routine samples, so that a judgment can be made as to the degree of variation of the physical/chemical

properties of the sample and test matrices that may cause them to respond differently to a particular

measurement procedure. For example, a freeze-dried food matrix may behave differently during analysis

to a similar foodstuff with higher moisture content.

Generally, QCMs are prepared for specific purposes and the materials’ properties can be closely matched

to the samples under analysis.
[14]

Commutability has particular significance in clinical chemistry and has been described elsewhere.

In practice, the impetus for the preparation of a QCM may often be the fact that adequate matrix CRMs are

not available and therefore the QCM producer is likely to use the specific matrix/property combination

in question and matching is not an issue.
7.2 Properties and property values

As for any reference material, the QCM should be characterized for those properties that are of particular

importance in the measurement of the routine test samples. The properties of the QCM should be as

similar as possible to those expected in the test samples. This may require some preliminary screening

measurements to be carried out on a number of candidate materials, to enable the most appropriate to

be selected.
7.3 Unit size

Unit size is the amount of material that comprises a single bottled unit of the QCM. When preparing a

QCM, the size of individual units should be based on the likely use, i.e. the amount of material required

for the measurements concerned and whether the units are to contain sufficient material for a single

analysis or for multiple measurements.
7.4 Total bulk amount of material

An estimate is required of the total bulk amount of candidate material that should be sourced. In

principle, this may be estimated by considering
— the number of units per year required by the laboratory,
— the unit size,
— the preparation yield,
4 © ISO 2014 – All rights reserved
---------------------- Page: 10 ----------------------
ISO GUIDE 80:2014(E)
— the quantity of material that can readily be homogenized,

— the length of time the supply is to be maintained and the assumed stability of the material,

— the type and size of the required storage facility.
8 Preparation of quality control materials (QCMs)
8.1 Sourcing of bulk material

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;
— 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 preparation procedures required for a particular QCM will depend on the nature of the matrix

and the properties of interest.

In general, liquid matrix QCMs are much easier to produce than their solid counterparts. The main reason

for this is that homo
...