FprEN ISO 17511

In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples (ISO/FDIS 17511:2019)

This document specifies technical requirements and documentation necessary to establish metrological traceability of values assigned to calibrators, trueness control materials and human samples for quantities measured by IVD MDs. The human samples are those intended to be measured, as specified for each IVD MD. Metrological traceability of values for quantities in human samples extends to the highest available reference system component, ideally to RMPs and certified reference materials (CRMs).
All parties having a role in any of the steps described in a calibration hierarchy for an IVD MD are subject to the requirements described. These parties include but are not limited to manufacturers (of IVD MDs), RMP developers (see ISO 15193), RM producers (see ISO 15194), and reference/calibration laboratories (see ISO 15195) supporting calibration hierarchies for IVD MDs.
NOTE 1 Producers of RMs intended for use in standardization or calibration of IVD MDs include commercial and non-commercial organizations producing RMs for use by many end-users of IVD MDs and/or calibration laboratories, or for use by a single end-user medical laboratory, as in the case of a measurement standard (calibrator) intended to be used exclusively for calibration of a laboratory-developed MP.
This document is applicable to:
a) all IVD MDs that provide measurement results in the form of numeric values, i.e. rational (ratio) and/or differential (interval) scales, and counting scales.
b) IVD MDs where the measurement result is reported as a qualitative value established with a ratio of two measurements (i.e. the signal from a specimen being tested and the signal from a RM with a specified concentration or activity at the cut-off), or a counting scale, with corresponding decision threshold(s). This also includes IVD MDs where results are categorized among ordinal categories based on pre-established quantitative intervals for a quantity.
c) RMs intended for use as trueness control materials for verification or assessment of calibration of IVD MDs, i.e. some commutable CRMs and some external quality assessment (EQA) materials (if so indicated in the RM's intended use statement).
d) IVD MD-specific calibrators and trueness control materials with assigned values, intended to be used together with a specified IVD MD.
e) IVD MDs as described in a) and b), where no end-user performed calibration is required (i.e. when the manufacturer performs a factory calibration of the IVD MD).
This document is not applicable to:
a) calibrators and trueness control materials for IVD MDs which, due to their formulation, are known to have zero amount of measurand;
b) control materials that are used only for internal quality control purposes in medical laboratories to assess the imprecision of an IVD MD, either its repeatability or reproducibility, and/or for assessing changes in IVD MD results compared to a previously established calibration condition;
c) control materials that are used only for internal quality control purposes in medical laboratories and which are supplied with intervals of suggested acceptable values that are not metrologically traceable to higher order reference system components;
d) properties reported as nominal scales and ordinal scales, where no magnitude is involved.
NOTE 2 Nominal scales are typically used to report e.g. identity of blood cell types, microorganism types, identity of nucleic acid sequences, identity of urine particles.
NOTE 3 Ordinal s

In-vitro-Diagnostika - Anforderungen an die Ermittlung metrologischer Rückführbarkeit von Werten, die Kalibratoren, Richtigkeitskontrollmaterialien und Humanproben zugeordnet sind (ISO/FDIS 17511:2019)

Diese Internationale Norm spezifiziert die technischen Anforderungen und die erforderliche Dokumentation, um die metrologische Rückführbarkeit von Werten zu etablieren, die Kalibratoren, Richtigkeitskontrollmaterialien und Humanproben hinsichtlich der mithilfe von In-vitro-Diagnostika gemessenen Größen zugeordnet wurden. Die Humanproben sind dabei die zu messenden Proben, so wie dies für das jeweilige In-vitro-Diagnostikum festgelegt ist. Die metrologische Rückführbarkeit von Werten für Messgrößen in Humanproben erstreckt sich bis auf die verfügbare Referenzsystemkomponente der höchstmöglichen Ordnung, idealerweise auf Referenzmessverfahren und zertifizierte Referenzmaterialien (ZRMs).
Alle Parteien, die eine Funktion in einer beschriebenen Kalibrierhierarchie für ein In-vitro-Diagnostikum übernehmen, unterliegen den beschriebenen Anforderungen. Zu diesen Parteien gehören, ohne darauf beschränkt zu sein: Hersteller (von In-vitro-Diagnostika), Entwickler von Referenzmessverfahren (siehe ISO 15193), Hersteller von Referenzmaterialien (siehe ISO 15194) und Referenz-/Kalibrierlaboratorien (siehe ISO 15195), die Kalibrierhierarchien für In-vitro-Diagnostika abstützen bzw. nutzen.
ANMERKUNG   Hersteller von Referenzmaterialien, die für die Verwendung bei der Normalisierung oder Kalibrierung von In-vitro-Diagnostika vorgesehen sind, sind sowohl kommerzielle Unternehmen als auch nicht kommerzielle Organisationen, die Referenzmaterialien zum Gebrauch durch viele Endanwender von In-vitro-Diagnostika produzieren. Dazu zählen auch Kalibrierlaboratorien oder ein medizinisches Laboratorium als alleiniger Endanwender, beispielsweise im Falle eines Normals (Kalibrator), der ausschließlich für die Kalibrierung eines vom Laboratorium entwickelten Messverfahrens vorgesehen ist.
Diese Internationale Norm gilt für:
a)   alle In-vitro-Diagnostika, die Messergebnisse als Zahlenwerte liefern, d. h. in Form von rationalen (Verhältniszahl) und/oder differenziellen (Intervall-)Skalen und Zählskalen;
b)   In-vitro-Diagnostika, bei denen das Messergebnis als qualitativer Wert ausgewiesen wird, der als Verhältniszahl aus zwei Messungen (d. h. aus dem Verhältnis eines aus einer analysierten Probe erhaltenen Messsignals und dem bei Analyse eines Referenzmaterials erhaltenen Signal bei einer spezifizierten Konzentration oder Aktivität an der Ausschlussgrenze) oder mit einer Zählskala mit entsprechenden Entscheidungsgrenzwerten ermittelt wird. Dies schließt auch In-vitro-Diagnostika mit ein, bei denen die Ergebnisse als Kategorien auf einer Ordinalskala auf der Grundlage von zuvor etablierten quantitativen Intervallen für eine Messgröße angegeben werden;
c)   Referenzmaterialien, die als Richtigkeitskontrollmaterialien für die Verifizierung oder Beurteilung der Kalibrierung von In-vitro-Diagnostika vorgesehen sind, d. h. einige kommutable (austauschbare) zertifizierte Referenzmaterialien und einige externe Qualitätskontrollmaterialien (sofern dies in den Angaben zum vorgesehenen Verwendungszweck des Referenzmaterials so angegeben ist);
d)   für das In-vitro-Diagnostikum spezifische Kalibratoren und Richtigkeitskontrollmaterialien mit zugeordneten Werten, die für die Verwendung zusammen mit einem festgelegten In-vitro-Diagnostikum vorgesehen sind;
e)   In-vitro-Diagnostika wie unter a) und b) beschrieben, bei denen keine vom Endanwender durchgeführte Kalibrierung erforderlich ist (d. h. wenn vonseiten des Herstellers eine Kalibrierung des In-vitro-Diagnostikums erfolgt).

Dispositifs médicaux de diagnostic in vitro - Exigences pour l'établissement d'une traçabilité métrologique des valeurs attribuées aux étalons, aux matériaux de contrôle de la justesse et aux échantillons humains (ISO/FDIS 17511:2019)

Le présent document spécifie les exigences techniques et la documentation nécessaire pour établir la traçabilité métrologique des valeurs assignées aux étalons, aux matériaux de contrôle de la justesse et aux échantillons humains pour des grandeurs mesurées par des dispositifs médicaux de DIV. Les échantillons humains sont les échantillons destinés à être mesurés, tel que spécifié pour chaque dispositif médical de DIV. La traçabilité métrologique des valeurs pour les grandeurs dans des échantillons humains s'étend jusqu'au composant du système de référence le plus élevé disponible, dans l'idéal jusqu'aux PMR et aux matériaux de référence certifiés (MRC).
Toutes les parties impliquées dans l'une des étapes décrites dans une hiérarchie d'étalonnage pour un dispositif médical de DIV sont soumises aux exigences décrites. Ces parties comprennent, de manière non exhaustive, les fabricants (des dispositifs médicaux de DIV), les concepteurs des PMR (voir l'ISO 15193), les fabricants de MR (voir l'ISO 15194) et les laboratoires d'étalonnage/de référence (voir l'ISO 15195) qui mettent en place des hiérarchies d'étalonnage pour les dispositifs médicaux de DIV.
NOTE 1 Parmi les fabricants de MR destinés à être utilisés dans le cadre de la normalisation ou de l'étalonnage de dispositifs médicaux de DIV figurent des organisations commerciales et non commerciales qui produisent des MR à l'attention de nombreux utilisateurs finaux de dispositifs médicaux de DIV et/ou de laboratoires d'étalonnage ou d'un seul laboratoire de biologie médicale, comme dans le cas d'un étalon destiné à être utilisé exclusivement à des fins d'étalonnage d'une PM développée par un laboratoire.
Le présent document s'applique à:
a) tous les dispositifs médicaux de DIV qui fournissent des résultats de mesure sous forme de valeurs numériques, c'est-à-dire des échelles rationnelles (rapport) et/ou différentielles (intervalle) et des échelles de dénombrement;
b) les dispositifs médicaux de DIV dont le résultat de mesure est présenté sous forme de valeur qualitative établie à l'aide d'un rapport entre deux mesurages (c'est-à-dire le signal d'un échantillon soumis à essai et le signal d'un MR présentant une concentration spécifiée ou une activité à la valeur seuil) ou d'une échelle de dénombrement avec des seuils de décision correspondants. Cela comprend également les dispositifs médicaux de DIV dont les résultats sont classés par catégories ordinales à partir d'intervalles quantitatifs préétablis pour une grandeur;
c) des MR destinés à être utilisés comme matériaux de contrôle de la justesse pour la vérification ou l'évaluation de l'étalonnage de dispositif médical de DIV, c'est-à-dire certains MRC commutables et certains matériaux d'évaluation externe de la qualité (EEQ) (si indiqué dans la déclaration d'usage prévu du MR);
d) des étalons et des matériaux de contrôle de la justesse spécifiques aux dispositifs médicaux de DIV dont les valeurs sont assignées, destinés à être utilisés conjointement avec un dispositif médical de DIV spécifié;
e) les dispositifs médicaux de DIV, tels que décrits en a) et b), qui ne requièrent pas la réalisation d'un étalonnage par l'utilisateur final (c'est-à-dire lorsque le fabricant procède à un étalonnage d'un dispositif médical de DIV en usine).
Le présent document ne s'applique pas:
a) aux étalons et aux matériaux de contrôle de la justesse pour les dispositifs médicaux de DIV dont il est établi, en raison de leur formulation, qu'ils cont

Diagnostični medicinski pripomočki in vitro - Zahteve za vzpostavitev meroslovne sledljivosti vrednosti, dodeljenih kalibratorjem, kontrolnim materialom in človeškim vzorcem (ISO/DIS 17511:2019)

Standards Content (sample)

SLOVENSKI STANDARD
oSIST prEN ISO 17511:2019
01-maj-2019
'LDJQRVWLþQLPHGLFLQVNLSULSRPRþNLLQYLWUR=DKWHYH]DY]SRVWDYLWHYPHURVORYQH
VOHGOMLYRVWLYUHGQRVWLGRGHOMHQLKNDOLEUDWRUMHPNRQWUROQLPPDWHULDORPLQ
þORYHãNLPY]RUFHP,62',6
In vitro diagnostic medical devices - Requirements for establishing metrological

traceability of values assigned to calibrators, trueness control materials and human

samples (ISO/DIS 17511:2019)
In-vitro-Diagnostika - Messung von Grössen in Proben biologischen Ursprungs -

Metrologische Rückverfolgbarkeit von Werten, die Kalibratoren und Kontrollmaterialien

zugeordnet sind (ISO/DIS 17511:2019)
Dispositifs médicaux de diagnostic in vitro - Mesurage des grandeurs dans des

échantillons d'origine biologique - Traçabilité métrologique des valeurs attribuées aux

agents d'étalonnage et aux matériaux de contrôle (ISO/DIS 17511:2019)
Ta slovenski standard je istoveten z: prEN ISO 17511
ICS:
11.100.10 'LDJQRVWLþQLSUHVNXVQL In vitro diagnostic test
VLVWHPLLQYLWUR systems
oSIST prEN ISO 17511:2019 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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oSIST prEN ISO 17511:2019
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oSIST prEN ISO 17511:2019
DRAFT INTERNATIONAL STANDARD
ISO/DIS 17511
ISO/TC 212 Secretariat: ANSI
Voting begins on: Voting terminates on:
2019-03-14 2019-06-06
In vitro diagnostic medical devices — Requirements for
establishing metrological traceability of values assigned to
calibrators, trueness control materials and human samples

Dispositifs médicaux de diagnostic in vitro — Mesurage des grandeurs dans des échantillons d'origine

biologique — Traçabilité métrologique des valeurs attribuées aux agents d'étalonnage et aux matériaux de

contrôle
ICS: 11.100.10
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 17511:2019(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
PROVIDE SUPPORTING DOCUMENTATION. ISO 2019
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oSIST prEN ISO 17511:2019
ISO/DIS 17511:2019(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2019

All rights reserved. Unless otherwise specified, or required in the context of its implementation, 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
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Published in Switzerland
ii © ISO 2019 – All rights reserved
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oSIST prEN ISO 17511:2019
ISO/DIS 17511:2019(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

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

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

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

3 Terms and definitions ..................................................................................................................................................................................... 2

4 General requirements to be fulfilled by a manufacturer for establishing, validating

and documenting metrological traceability of human sample values determined

with a specified IVD MD .............................................................................................................................................................................19

4.1 Requirements for documenting metrological traceability of measured quantity values ....19

4.2 Definition of the measurand .....................................................................................................................................................20

4.3 Specifications for maximum allowable expanded measurement uncertainty, Umax(y) .....20

4.4 Defining the calibration hierarchy – general requirements ..........................................................................21

4.5 Selection and requirements for RMs and calibrators .........................................................................................21

4.6 Selection and requirements for MPs .................................................................................................................................24

4.7 Estimating uncertainty of assigned values for end-user IVD MD calibrators ................................25

4.8 Validation of metrological traceability of values assigned to an IVD MD calibrator ................26

4.9 Additional manufacturer documentation responsibilities ............................................................................29

5 Model calibration hierarchies for metrological traceability ...............................................................................30

5.1 Elements of the description of a calibration hierarchy .....................................................................................30

5.2 Cases with RMPs and primary RMs ...................................................................................................................................30

5.3 Cases with a primary RMP that defines the measurand ..................................................................................34

5.4 Cases for measurands defined by a RMP calibrated with a particular primary calibrator 38

5.5 Cases with an international conventional calibrator that defines the measurand ...................41

5.6 Cases with metrological traceability supported by an international harmonisation

protocol ......................................................................................................................................................................................................44

5.7 Cases for measurands with metrological traceability only to manufacturer’s

internal arbitrarily defined RM(s).......................................................................................................................................46

6 Labelling information to be provided to end-users by the manufacturer .............................................49

Annex ZA (informative) Relationship between this International Standard and the Essential

Requirements of EU Directive 98/79 ...........................................................................................................................................50

Bibliography .............................................................................................................................................................................................................................52

© ISO 2019 – All rights reserved iii
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oSIST prEN ISO 17511:2019
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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 voluntary nature of standards, the meaning of ISO specific terms and

expressions related to conformity assessment, as well as information about ISO's adherence to the

World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following

URL: www .iso .org/iso/foreword .html.

This document was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in

vitro diagnostic test systems.

This second edition cancels and replaces the first edition (ISO 17511:2003), which has been technically

revised. This new edition of ISO 17511 also cancels and replaces ISO 18153:2003, In vitro diagnostic

medical devices —Measurement of quantities in biological samples — Metrological traceability of values for

catalytic concentration of enzymes assigned to calibrators and control materials, by way of incorporation

of the special requirements for metrologically traceable calibration hierarchies for measurement of

catalytic concentration of enzymes into this new edition. The main changes compared to the previous

edition are as follows:

— inclusion of requirements for calibration hierarchies for catalytic concentration of enzymes

(previously covered in ISO 18153:2003)

— to clarify that final reported values on human samples shall be metrologically traceable to the highest

order available reference, the title and scope were modified to include metrological traceability of

values assigned to human samples

— updated normative references to replace International Vocabulary of Basic and General Terms in

Metrology, 2nd edition, ISO, Geneva (1993), with ISO/IEC Guide 99:2007,International vocabulary of

metrology – Basic and general concepts and associated terms (VIM ) and deleted ISO Guide 35:1989,

Certification of reference materials - General and statistical principles

— revision of clause 4 to clearly define requirements of a manufacturer of an in vitro diagnostic

medical device in establishing and documenting metrological traceability of assigned values (for

calibrators, trueness controls and human samples), while incorporating requirements previously

addressed in clauses 6, 7 and 8 (thus eliminating those sections)

— revision of clause 5 to incorporate additional models of metrologically traceable calibration

hierarchies, especially subclause 5.3 for measurement of catalytic concentration of enzymes

(previously addressed in ISO 18153:2003), and subclause 5.6 for an overview of the concept of

metrological traceability to international harmonisation protocols (addressed in detail in ISO

iv © ISO 2019 – All rights reserved
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oSIST prEN ISO 17511:2019
ISO/DIS 17511:2019(E)

21151, In vitro diagnostic medical devices — Measurement of quantities in samples of biological origin

— Requirements for international harmonisation protocols establishing metrological traceability of

values assigned to calibrators and human samples)
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oSIST prEN ISO 17511:2019
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Introduction

In laboratory medicine, the objective in examining a stated measurand in a human sample is to produce

equivalent results within medically relevant limits, irrespective of the measurement procedure (MP)

used or the laboratory performing the measurement. Equivalent results are important to support

clinical practice guidelines that use laboratory results to assess risk for disease, and/or to diagnose

or make treatment decisions for a medical condition. Equivalent results enable uniform application of

medical decision limits and reference intervals in a way that will reduce errors due to inappropriate

medical decisions and thus improve the quality of medical care for the people served by medical

laboratories and other users of in vitro diagnostic medical devices (IVD MDs). Equivalent results are

also important for analysing results in medical records for the purpose of supporting clinical decisions

and conducting epidemiological investigations.

Equivalent results for human samples can be achieved by establishing traceability of the calibration

of a MP to the highest available reference system component for a given measurand. Metrological

traceability describes the calibration hierarchy and the sequence of value assignments, demonstrating

an unbroken linkage between the measurement result for a human sample up to the highest available

reference system component in the calibration hierarchy. The point at which metrological traceability

begins (i.e. the highest level of metrological traceability in the calibration hierarchy) depends on the

availability of higher order reference measurement procedures (RMPs), reference materials (RMs) or

harmonisation protocols for the stated measurand.

Limitations in implementing metrologically traceable calibrations occur when different IVD MDs

intended for the same measurand do not measure the same or very closely related measureable

quantities. Some measurands of medical interest may be well-defined elements or molecules. Other

measurands are complex and possibly variable mixtures of molecular species with medically relevant

properties in common, but with differences in chemical structures and molecular complexes in varying

proportions, e.g. glycoproteins with multiple isoforms, variant amino acid sequences, molecular

complexes. When the selectivity of an IVD MD is inadequate, sample-specific influence quantities in

human samples due to factors including disease, drugs or other pathological conditions may lead to

erroneous values for the intended measured quantity. Thus, the selectivity of MPs at all levels in the

calibration hierarchy for an IVD MD can influence the ability of a metrologically traceable calibration,

even with traceability to higher order reference system components, to achieve equivalent results

for human samples among different IVD MDs. Since measured values for complex molecular species

are important for medical decisions, calibration hierarchies for IVD MDs, regardless of the molecular

complexity of the measurand, need to be established with careful consideration and recognition of

MP selectivity limitations. To help ensure that metrologically traceable calibrations for IVD MDs with

claims of traceability to the same higher order reference system components are of practical value, the

selectivity of the applicable IVD MDs shall be fit-for-purpose to achieve equivalent results for human

samples among different IVD MDs.

This international standard presents requirements for documenting the calibration hierarchy for a

measured quantity in human samples using a specified IVD MD up to the highest available metrological

reference. This international standard includes models offering potential technical solutions to support

metrological traceability of measured values for measurands in human samples, calibrators and

trueness control materials.
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oSIST prEN ISO 17511:2019
DRAFT INTERNATIONAL STANDARD ISO/DIS 17511:2019(E)
In vitro diagnostic medical devices — Requirements for
establishing metrological traceability of values assigned to
calibrators, trueness control materials and human samples
1 Scope

This international standard specifies technical requirements and documentation necessary to establish

metrological traceability of values assigned to calibrators, trueness control materials and human

samples for quantities measured by IVD MDs. The human samples are those intended to be measured,

as specified for each IVD MD. Metrological traceability of values for quantities in human samples

extends to the highest available reference system component, ideally to RMPs and certified reference

materials (CRMs).

All parties having a role in any of the steps described in a calibration hierarchy for an IVD MD are

subject to the requirements described. These parties include but are not limited to manufacturers (of

IVD MDs), RMP developers (see ISO 15193), RM producers (see ISO 15194), and reference/calibration

laboratories (see ISO 15195) supporting calibration hierarchies for IVD MDs.

NOTE Producers of RMs intended for use in standardization or calibration of IVD MDs include

commercial and non-commercial organizations producing RMs for use by many end-users of IVD MDs

and/or calibration laboratories, or for use by a single end-user medical laboratory, as in the case of

a measurement standard (calibrator) intended to be used exclusively for calibration of a laboratory-

developed MP.
This international standard is applicable to:

a) all IVD MDs that provide measurement results in the form of numeric values, i.e. rational (ratio)

and/or differential (interval) scales, and counting scales

b) IVD MDs where the measurement result is reported as a qualitative value established with a ratio

of two measurements (i.e. the signal from a specimen being tested and the signal from a RM with a

specified concentration or activity at the cut-off), or a counting scale, with corresponding decision

threshold(s). This also includes IVD MDs where results are categorized among ordinal categories

based on pre-established quantitative intervals for a quantity.

c) RMs intended for use as trueness control materials for verification or assessment of calibration of

IVD MDs, i.e. some commutable CRMs and some external quality assessment (EQA) materials (if so

indicated in the RM’s intended use statement)

d) IVD MD-specific calibrators and trueness control materials with assigned values, intended to be

used together with a specified IVD MD.

e) IVD MDs as described in a) and b), where no end-user performed calibration is required (i.e. when

the manufacturer performs a factory calibration of the IVD MD).
This international standard is not applicable to:

a) calibrators and trueness control materials for IVD MDs which, due to their formulation, are known

to have zero amount of measurand.

b) control materials that are used only for internal quality control purposes in medical laboratories to

assess the imprecision of an IVD MD, either its repeatability or reproducibility, and/or for assessing

changes in IVD MD results compared to a previously established calibration condition;

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oSIST prEN ISO 17511:2019
ISO/DIS 17511:2019(E)

c) control materials that are used only for internal quality control purposes in medical laboratories

and which are supplied with intervals of suggested acceptable values that are not metrologically

traceable to higher order reference system components;

d) properties reported as nominal scales and ordinal scales, where no magnitude is involved

NOTE 1 Nominal scales are typically used to report e.g. identity of blood cell types, microorganism types,

identity of nucleic acid sequences, identity of urine particles.

NOTE 2 Ordinal scales are often applied to results differentiated into dichotomous groupings (e.g. ‘sick’ vs.

‘healthy’), and may also be applied to results differentiated into non-dichotomous categories where the result

categories are rank-ordered but the rank-ordered categories cannot be differentiated in terms of relative

degree of difference, e.g. negative, +1, +2, +3 for grading of presence of haemoglobin in urine specimens by visual

observation.
2 Normative references

The following document is referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

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

ISO/IEC Guide 99:2007, International vocabulary of metrology — Basic and general concepts and

associated terms (VIM)
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— IEC Electropedia: available at http: //www .electropedia .org/
— ISO Online browsing platform: available at https: //www .iso .org/obp
3.1
analyte
component represented in the name of a measurand
constituent of a sample with a measureable property

EXAMPLE In the measurand (measured quantity) "mass of total protein in 24-hour urine", "total protein" is

the analyte (and “mass” is the property.) In "amount of substance concentration of glucose in plasma", "glucose" is

the analyte (and “amount of substance concentration” is the property.)
[SOURCE: Adapted from ISO 18113-1:2009]
3.2
analytical selectivity
selectivity of a measuring system
selectivity

property of a measuring system, used with a specified MP, whereby it provides measured quantity

values for one or more measurands such that the values of each measurand are independent of other

measurands or other quantities in the phenomenon, body, or substance being investigated

EXAMPLE Capability of a measuring system to measure the amount-of-substance concentration of creatinine

in blood plasma without being influenced by the other components present in the sample.

Note 1 to entry: In chemistry, selectivity of a measuring system is usually obtained for quantities with selected

components in concentrations within stated intervals.

Note 2 to entry: Selectivity as used in physics is a concept close to specificity as it is sometimes used in chemistry.

[SOURCE: Adapted from VIM, 4.13]
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3.3
measurement bias
bias
estimate of a systematic measurement error
[SOURCE: VIM, 2.18]
Note 1 to entry: See VIM, 2.17, systematic measurement error
Note 2 to entry: This definition of applies to quantitative measurements only.
3.4
calibration

operation that, under specified conditions, in a first step, establishes a relation between the quantity

values with associated measurement uncertainties provided by measurement standards (calibrators)

and their corresponding indications and, in a second step, uses this relationship to establish a

measurement result from an indication (for an unknown sample).

Note 1 to entry: A calibration may be expressed by a statement, calibration function, calibration diagram,

calibration curve, or calibration table. In some cases, it may consist of an additive or multiplicative correction of

the indication with associated measurement uncertainty.

Note 2 to entry: Calibration should not be confused with adjustment of a measuring system, often mistakenly

called “self-calibration”, or with verification of calibration.

Note 3 to entry: Often, the first step alone in the above definition is perceived as being calibration.

[SOURCE: Adapted from VIM, 2.39]
3.5
calibration hierarchy

sequence of calibrations from a reference to the final measuring system, where the outcome of each

calibration depends on the outcome of the previous calibration.

Note 1 to entry: Measurement uncertainty necessarily increases along the sequence of calibrations.

Note 2 to entry: The elements of a calibration hierarchy are one or more measurement standards and measuring

systems operated according to MPs.

Note 3 to entry: A comparison between two measurement standards may be viewed as a calibration if the

comparison is used to check and, if necessary, correct the quantity value and measurement uncertainty attributed

to one of the measurement standards.
[SOURCE: VIM, 2.40]

Note 4 to entry: In this document, a calibration hierarchy is defined as a detailed description of the process for

assigning a value of a measurand to a sample using a specified sequence of MPs and RMs (calibrated by higher

order RMs and/or MPs for the same type of quantity, where available.)

Note 5 to entry: For purposes of this definition, a sample includes human samples as well as calibration materials,

EQA materials or other RMs.
3.6
calibrator
measurement standard used in calibration
[SOURCE: VIM, 5.12]

Note 1 to entry: In this international standard, calibrator is synonymous with calibration material.

Note 2 to entry: A calibrator is a measurement standard used in the calibration of a measuring system according

to a specified MP.
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3.7
catalytic activity

property of a component corresponding to the catalysed substance rate of conversion of a specified

chemical reaction, in a specified measurement system
[SOURCE: Adapted from (26)]
Note 1 to entry: In this standard the "component" is an enzyme.

Note 2 to entry: The quantity "catalytic activity" relates to an amount of active enzyme, not its concentration, see

subclause 3.8.

Note 3 to entry: The coherent derived SI unit is "katal" (kat), equal to "mole per second" (mol s ).

Note 4 to entry: The MP is an essential element of the definition of the measurand for the quantity "catalytic

activity".

Note 5 to entry: In many instances, instead of the conversion rate of the substrate ascribed in the short name

of the enzyme analyte, e.g. "creatine" in "creatine kinase", the conversion rate of an indicator substance as

substrate of a combined reaction is measured. (In these circumstances) the measurand should be defined as

'catalytic activity of the enzyme as measured by the conversion rate of an indicator substance in a specified

system according to a given MP', e.g. 'catalytic activity of creatine kinase as measured by the rate of conversion of

NADP+ in the IFCC reference procedure in human serum'.
[SOURCE: Adapted from ISO 18153:2003, 3.2]
3.8
catalytic-activity concentration
catalytic concentration

catalytic activity of a component divided by volume of the original system[SOURCE: Adapted from [26]]

Note 1 to entry: The coherent derived SI unit is "katal per cubic metre" or "mole per second cubic metre" (kat m

-1 -3

= mol s m ). In laboratory medicine, the unit of volume can be chosen to be "litre" (L).

Note 2 to entry: In this standard the "component" is an enzyme and the "original system" can be, for example,

blood plasma.
[SOURCE: Adapted from ISO 18153:2003, 3.3]
3.9
certified reference material
CRM

RM accompanied by documentation issued by an authoritative body and providing one or more

specified property values with associated uncertainties and traceabilities, using valid procedures.

EXAMPLE Human serum with assigned quantity value for the concentration of cholesterol and associated

measurement uncertainty stated in an accompanying certificate, used as a calibrator or measurement trueness

control material.

Note 1 to entry: ‘Documentation’ is given in the form of a ‘certificate’ (see ISO Guide 31).

Note 2 to entry: Procedures for the production and certification of CRMs are given in ISO 17034:2016 and ISO

Guide 35:2017.

Note 3 to entry: In this definition, “uncertainty” covers both ‘measurement uncertainty’ and ‘uncertainty

associated with the value of a nominal property’, such as for identity and sequence. “Traceability” covers both

‘metrological traceability of a quantity value’ and ‘traceability of a nominal property value’.

Note 4 to entry: Specified quantity values of CRMs require metrological traceability with associated measurement

[27]
uncertainty .
[27]

Note 5 to entry: ISO/REMCO has an analogous definition but uses the modifiers “metrological” and

“metrologically” to refer to both quantities and nominal properties.
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[SOURCE: Adapted from VIM, 5.14]

Note 6 to entry: Specific requirements for CRMs and the content of supporting documentation (in the field of

...