SIST EN ISO 17511:2021
(Main)In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples (ISO 17511:2020)
In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples (ISO 17511:2020)
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
In-vitro-Diagnostika - Anforderungen an die Ermittlung metrologischer Rückführbarkeit von Werten, die Kalibratoren, Richtigkeitskontrollmaterialien und Humanproben zugeordnet sind (ISO 17511:2020)
Dieses Dokument 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.
[...]
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 17511:2020)
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,
In vitro diagnostični medicinski pripomočki - Zahteve za vzpostavitev meroslovne sledljivosti vrednosti, dodeljenih kalibratorjem, kontrolnim materialom in vzorcem človeškega izvora (ISO 17511:2020)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-september-2021
Nadomešča:
SIST EN ISO 17511:2003
In vitro diagnostični medicinski pripomočki - Zahteve za vzpostavitev meroslovne
sledljivosti vrednosti, dodeljenih kalibratorjem, kontrolnim materialom in vzorcem
človeškega izvora (ISO 17511:2020)
In vitro diagnostic medical devices - Requirements for establishing metrological
traceability of values assigned to calibrators, trueness control materials and human
samples (ISO 17511:2020)
In-vitro-Diagnostika - Anforderungen an die Ermittlung metrologischer Rückführbarkeit
von Werten, die Kalibratoren, Richtigkeitskontrollmaterialien und Humanproben
zugeordnet sind (ISO 17511:2020)
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 17511:2020)
Ta slovenski standard je istoveten z: EN ISO 17511:2021
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
17.020 Meroslovje in merjenje na Metrology and measurement
splošno in general
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
EN ISO 17511
EUROPEAN STANDARD
NORME EUROPÉENNE
June 2021
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes EN ISO 17511:2003
English Version
In vitro diagnostic medical devices - Requirements for
establishing metrological traceability of values assigned to
calibrators, trueness control materials and human samples
(ISO 17511:2020)
Dispositifs médicaux de diagnostic in vitro - Exigences In-vitro-Diagnostika - Anforderungen an die
pour l'établissement d'une traçabilité métrologique Ermittlung metrologischer Rückführbarkeit von
des valeurs attribuées aux étalons, aux matériaux de Werten, die Kalibratoren,
contrôle de la justesse et aux échantillons humains Richtigkeitskontrollmaterialien und Humanproben
(ISO 17511:2020) zugeordnet sind (ISO 17511:2020)
This European Standard was approved by CEN on 4 February 2020.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 17511:2021 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the General
Safety and Performance Requirements of Regulation (EU) 2017/746 aimed to be
covered. 5
European foreword
This document (EN ISO 17511:2021) has been prepared by Technical Committee ISO/TC 212 "Clinical
laboratory testing and in vitro diagnostic test systems" in collaboration with Technical Committee
CEN/TC 140 “In vitro diagnostic medical devices” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by December 2021, and conflicting national standards
shall be withdrawn at the latest by June 2024.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 17511:2003.
This document has been prepared under a standardization request/mandate given to CEN by the
European Commission and the European Free Trade Association, and supports essential requirements
of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this
document.
NOTE In this European Standard the concept "accuracy of measurement" is not equivalent to "trueness of
measurement" (see 3.47) nor to the "precision of measurement" (see 3.34) alone. Instead, accuracy is commonly
used as a combination of trueness and precision, which is also used as a concept in the Regulation 2017/746/EU
on in-vitro diagnostic medical devices.
The following referenced documents are indispensable for the application of this document. For
undated references, the latest edition of the referenced document (including any amendments) applies.
For dated references, only the edition cited applies. However, for any use of this standard ‘within the
meaning of Annex ZA’, the user should always check that any referenced document has not been
superseded and that its relevant contents can still be considered the generally acknowledged state-of-
art.
When an IEC or ISO standard is referred to in the ISO standard text, this should be understood as a
normative reference to the corresponding EN standard, if available, and otherwise to the dated version
of the ISO or IEC standard as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the
extent (in whole or in part) to which they apply.
Table – Correlation between normative references and dated EN and ISO standards
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 18113-2:2009 EN ISO 18113-2:2011 ISO 18113-2:2009
ISO 15193 EN ISO 15193:2009 ISO 15193:2009
ISO 15194 EN ISO 15194:2009 ISO 15194:2009
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 17511:2020 has been approved by CEN as EN ISO 17511:2021 without any modification.
Annex ZA
(informative)
Relationship between this European Standard and the General Safety and
Performance Requirements of Regulation (EU) 2017/746 aimed to be
covered
This European standard has been prepared under a Commission’s standardisation request to provide
one voluntary means of conforming to the General Safety and Performance Requirements of Regulation
(EU) 2017/746 of 5 April 2017 concerning in vitro diagnostic medical devices [OJ L 117].
Once this standard is cited in the Official Journal of the European Union under that Regulation,
compliance with the normative clauses of this standard given in Table ZA.1 confers, within the limits of
the scope of this standard, a presumption of conformity with the corresponding General Safety and
Performance Requirements of that Regulation, and associated EFTA regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Regulation (EU) 2017/746. This means that risks have to be
‘reduced as far as possible’, ‘reduced to a level as low as reasonably practicable’, ‘reduced to the lowest possible
level’, ‘reduced as far as possible and appropriate’, ‘removed or reduced as far as possible’, ‘eliminated or reduced
as far as possible’, ‘prevented’ or ‘minimized’, according to the wording of the corresponding General Safety and
Performance Requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety
and Performance Requirements 1, 2, 3, 4, 5, 8, 10, 11, 13, 15, 16, 17, 18 and 19 of the Regulation.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
Foreword, replacing the references in the core text.
NOTE 4 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European standard and Annex I of Regulation (EU)
2017/746 [OJ L 117]
General Safety and Clause(s)/sub-clause(s) of Remarks/Notes
Performance Requirements this EN
of Regulation (EU) 2017/746
9.1 (a) 4.3, 4.6.2 Covered with respect to analytical
performance requirements resul-
ting from a calibration hierarchy,
and related uncertainty
9.3 4.1, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 5 Covered
10.1 4.2, 4.5.4, 4.5.5 Covered with respect to definition
of the measurand, corresponding
performance characteristics and
commutability during design and
manufacturing processes
13.4 4.7, 4.8 Covered with respect to
effectiveness and reliability of
calibration
13.5 4.5.4, 4.5.5, 4.8 Covered with respect to
commutability and traceability of
end-user calibrator
14.1 4.3, 4.6.2 Covered with respect to analytical
performance requirements resul-
ting from a calibration hierarchy,
and related uncertainty
20.1 (g) 4.3, 4.7.1 Covered with respect to uncer-
tainty as a limitation and
information to be provided by the
manufacturer
20.4.1 (g) 4.7.1 Covered with respect to uncer-
tainty of assigned values for end-
user calibrator and information to
be provided by the manufacturer
20.4.1 (u) 4.7.1, 4.9.1, 4.9.3 Partly covered with respect to
uncertainty and assigned values of
end-user calibrators and their
associated metrological traceability
as the kind of information to be
provided by the manufacturer, but
the requirement to provide this
information in the IFU is not
addressed by this European
standard.
20.4.1 (w) 4.6.2, 4.7.1, 4.9.1 Partly covered with respect to
analytical performance require-
ments resulting from a calibration
hierarchy, assigned values for end-
user calibrators and their
associated metrological traceability
as the kind of information to be
provided by the manufacturer, but
the requirement to provide this
information in the IFU is not
addressed by this European
standard.
WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European
Standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of
this standard.
INTERNATIONAL ISO
STANDARD 17511
Second edition
2020-04
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 — Exigences pour
l'établissement d'une traçabilité métrologique des valeurs attribuées
aux étalons, aux matériaux de contrôle de la justesse et aux
échantillons humains
Reference number
ISO 17511:2020(E)
©
ISO 2020
ISO 17511:2020(E)
© ISO 2020
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
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Published in Switzerland
ii © ISO 2020 – All rights reserved
ISO 17511:2020(E)
Contents Page
Foreword .vi
Introduction .viii
1 Scope . 1
2 Normative references . 2
3 Terms and definitions, symbols and abbreviated terms . 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 .19
4.3 Specifications for maximum allowable expanded measurement uncertainty, Umax(y) .20
4.3.1 General requirements .20
4.3.2 Scope of the specification .20
4.4 Defining the calibration hierarchy .20
4.4.1 General requirements .20
4.4.2 Measured quantity .21
4.4.3 Highest level of metrological traceability .21
4.4.4 Traceability to SI .21
4.4.5 Non-SI traceable IVD MDs .21
4.4.6 Number of levels in the specified hierarchy .21
4.5 Selection and requirements for RMs and calibrators .21
4.5.1 General requirements .21
4.5.2 Characteristics to be documented .21
4.5.3 Higher order RMs that conform with ISO 15194 .22
4.5.4 RMs not conforming to ISO 15194 .22
4.5.5 Commutability of RMs . .22
4.5.6 Exception to commutability assessment requirements .23
4.5.7 Application of a non-commutable CRM .23
4.5.8 Alternative RMs.23
4.5.9 Augmentation of alternative RMs .23
4.5.10 Non-commutable end-user IVD MD calibrators .24
4.6 Selection and requirements for MPs .24
4.6.1 Rationale for selection of MPs and documentation responsibility .24
4.6.2 Metrological status of MPs .24
4.6.3 Reference measurement laboratories .24
4.6.4 Impact of influence quantities .25
4.6.5 Changes in the measured quantity within a calibration hierarchy .25
4.7 Estimating uncertainty of assigned values for end-user IVD MD calibrators .25
4.7.1 General requirements .25
4.7.2 Documentation for method of estimating u .26
cal
4.7.3 Statistical considerations and scope of u estimates .26
cal
4.7.4 Expression of u . . .26
cal
4.7.5 Product modifications .27
4.7.6 Information to be provided to the end-user .28
4.8 Validation of metrological traceability of values assigned to an IVD MD calibrator .28
4.8.1 General validation requirements .28
4.8.2 Validation strategies .28
4.8.3 Test design considerations and acceptance criteria .29
4.8.4 Calibration hierarchies with an available RMP.29
4.8.5 Calibration hierarchies with no available RMP .29
4.8.6 Calibration hierarchies with no RMPs and no CRMs .29
4.8.7 Validation of design changes to an end-user IVD MD calibrator .30
4.9 Additional calibration hierarchy documentation responsibilities .30
ISO 17511:2020(E)
4.9.1 Obligation to end-users .30
4.9.2 Maintaining documentation .30
4.9.3 Third party manufacturers of IVD MD calibrators .30
4.9.4 Modifications introduced by independent entities .30
4.9.5 Calibration hierarchies supporting IVD MDs developed by a single entity
for its own use .31
4.9.6 RMs other than end-user IVD MD calibrators .31
4.9.7 EQA and PT materials with claims of metrologically traceable target values .31
5 Model calibration hierarchies for metrological traceability .31
5.1 Elements of the description of a calibration hierarchy .31
5.2 Cases with RMPs and primary RMs .32
5.2.1 General considerations .32
5.2.2 Definition of the measurand .33
5.2.3 Selecting RMPs .34
5.2.4 Primary RMPs . .34
5.2.5 Primary calibrators.35
5.2.6 Assigning a value to a secondary RM or calibrator .35
5.2.7 Commutability of secondary RMs .35
5.2.8 Manufacturer’s Selected MP.35
5.2.9 Working calibrators . .35
5.2.10 Manufacturer’s standing MP .36
5.2.11 Manufacturer's end-user calibrator .36
5.2.12 u of the assigned value of the end-user calibrator .36
cal
5.2.13 End-user IVD MD .36
5.3 Cases with a primary RMP that defines the measurand .36
5.3.1 General Considerations .36
5.3.2 Definition of the measurand .38
5.3.3 Higher order RMP that defines the measurand .38
5.3.4 The primary RMP and definition of the measurand .38
5.3.5 Documentation of the primary RMP .38
5.3.6 Assignment of values to secondary RMs .39
5.3.7 Manufacturer’s selected MP .39
5.3.8 Manufacturer's working calibrator .39
5.3.9 Manufacturer’s standing MP .40
5.3.10 Manufacturer's end-user calibrator .40
5.3.11 End-user IVD MD .40
5.4 Cases for measurands defined by a RMP calibrated with a particular primary calibrator 40
5.4.1 General considerations .40
5.4.2 Definition of the measurand .41
5.4.3 Value assignment of the primary RM .42
5.4.4 Value assignment of the primary calibrator .42
5.4.5 Selection and intended use of the RMP in the calibration hierarchy .42
5.4.6 Manufacturer's selected MP .42
5.4.7 Manufacturer’s working calibrator .42
5.4.8 Manufacturer’s standing MP .43
5.4.9 End-user IVD MD calibrator .43
5.4.10 End-user IVD MD .43
5.5 Cases with an international conventional calibrator that defines the measurand .43
5.5.1 General considerations .43
5.5.2 The international conventional calibrator — Material description .45
5.5.3 Value assignment of an international conventional calibrator .45
5.5.4 Commutability of an international conventional calibrator .45
5.5.5 Calibration and selection of the manufacturer’s selected MP.46
5.5.6 Characteristics and value assignment of the manufacturer’s working calibrator 46
5.5.7 Manufacturer’s standing MP .46
5.5.8 End-user IVD MD calibrator .46
5.5.9 End-user IVD MD .46
iv © ISO 2020 – All rights reserved
ISO 17511:2020(E)
5.6 Cases with metrological traceability supported by an international harmonisation
protocol .46
5.6.1 General Considerations .46
5.6.2 International harmonisation protocol .47
5.6.3 Assignment of values to harmonisation RMs .48
5.6.4 Application of harmonisation RMs .48
5.6.5 End-user IVD MD .48
5.7 Cases for measurands with metrological traceability only to manufacturer’s
internal arbitrarily defined RM(s).48
5.7.1 General considerations .48
5.7.2 Selection of RMs .49
5.7.3 Manufacturer’s Selected MP.50
5.7.4 Manufacturer’s Standing MP .50
5.7.5 End-user IVD MD calibrators .50
5.7.6 End-user IVD MD .50
5.7.7 Documentation of the calibration hierarchy .50
6 Labelling information to be provided to end-users by the manufacturer .51
Bibliography .52
ISO 17511:2020(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 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. The main changes compared to the previous edition are as follows:
— incorporation of the special requirements for metrologically traceable calibration hierarchies for
measurement of 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 remove International Vocabulary of Basic and General Terms
in Metrology, 2nd edition, ISO, Geneva (1993) and 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 5.3 for measurement of catalytic concentration of enzymes (where the
measurand is defined by a primary RMP; previously addressed in ISO 18153:2003), and 5.6 for
an overview of the concept of assigned values of materials for measurands with metrological
traceability to international harmonisation protocols (addressed in detail in ISO 21151).
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
vi © ISO 2020 – All rights reserved
ISO 17511:2020(E)
ISO 17511:2020(E)
Introduction
In laboratory medicine, the objective of examining a measurand in a human sample is to produce
laboratory results that will enable a clinician to assess the risk of a disease, or to diagnose and make
treatment decisions for a medical condition. To be clinically useful, the results obtained from a given
human sample examined by different laboratories or among different in vitro diagnostic medical devices
(IVD MDs) within a single laboratory should be equivalent, regardless of the measurement procedure
employed. Equivalent results allow uniform application of medical decision limits and reference
intervals, which can reduce the risk of harm caused by medical decisions based on non-equivalent
examination results. Equivalence of results among different IVD MDs for the same measurand is also
important for the analysis of results in medical records for the purpose of supporting clinical decisions
and for conducting epidemiological investigations.
Equivalent results for human samples for a measurand can be achieved by establishing metrological
traceability of the values assigned to the calibrators for a measurement procedure (MP) to the highest
available reference system component for the 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 measurable quantities.
Some measurands of medical interest may be well-defined elements or molecules. An increasing number
of medical decisions depend on measurands that consist of complex and variable mixtures of chemical
structures, molecular species and molecular complexes in varying proportions, e.g. glycoproteins with
multiple isoforms, variant amino acid sequences, nucleic acid sequences, and other complex molecular
forms. When the selectivity of an IVD MD is not fit-for-purpose, 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. Even with metrological traceability to higher
order reference system components, the selectivity of MPs at all levels in the calibration hierarchy for
a given IVD MD can influence its ability to achieve results for human samples that are equivalent to the
results obtained with other IVD MDs for the same measurand.
This document presents requirements for manufacturers of IVD MDs in documenting the calibration
hierarchy for a measured quantity in human samples using a specified IVD MD. The document includes
various model calibration hierarchies offering potential technical solutions for different kinds of
measurands in establishing metrological traceability of assigned values for human samples, calibrators
and trueness control materials. Use of this document as part of a broadly-based risk management
program for manufacturers of IVD MDs is consistent with the requirements of ISO 14971 and is
expected to assist in the reduction of the risk of harm to patients due to non-equivalence of results
among different IVD MDs.
viii © ISO 2020 – All rights reserved
INTERNATIONAL STANDARD ISO 17511:2020(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 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 reproducib
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