EN ISO 17511:2003

SLOVENSKI STANDARD
01-november-2003
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In vitro diagnostic medical devices - Measurement of quantities in biological samples -
Metrological traceability of values assigned to calibrators and control materials (ISO
17511:2003)
In-vitro-Diagnostika - Messung von Größen in Proben biologischen Ursprungs -
Metrologische Rückführbarkeit von Werten, die Kalibriermaterialien und
Kontrollmaterialien zugeordnet sind (ISO 17511:2003)
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 17511:2003)
Ta slovenski standard je istoveten z: EN ISO 17511:2003
ICS:
11.100.10 'LDJQRVWLþQLSUHVNXVQL In vitro diagnostic test
VLVWHPLLQYLWUR systems
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 17511
NORME EUROPÉENNE
EUROPÄISCHE NORM
August 2003
ICS 07.100.10
English version
In vitro diagnostic medical devices - Measurement of quantities
in biological samples - Metrological traceability of values
assigned to calibrators and control materials (ISO 17511:2003)
Dispositifs médicaux de diagnostic in vitro - Mesurage des In-vitro-Diagnostika - Messung von Größen in Proben
grandeurs dans des échantillons d'origine biologique - biologischen Ursprungs - Metrologische Rückführbarkeit
Traçabilité métrologique des valeurs attribuées aux agents von Werten, die Kalibriermaterialien und Kontrollmaterialien
d'étalonnage et aux matériaux de contrôle (ISO zugeordnet sind (ISO 17511:2003)
17511:2003)
This European Standard was approved by CEN on 11 March 2003.
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 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 Management Centre has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Luxembourg, Malta, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, Switzerland and United
Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2003 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 17511:2003 E
worldwide for CEN national Members.

Contents
page
Foreword.3
Introduction .4
1 Scope .6
2 Normative references .6
3 Terms and definitions.6
4 Metrological traceability chain and calibration hierarchy .12
4.1 Principles.12
4.2 Structure and nomenclature.13
4.3 Considerations in establishing metrological traceability.17
4.4 Functions of reference materials .18
5 Calibration transfer protocols .18
5.1 Availability and structure.18
5.2 Cases with primary reference measurement procedure and primary calibrator(s) giving
metrological traceability to SI.19
5.3 Cases with international conventional reference measurement procedure (which is not
primary) and international conventional calibrator(s) without metrological traceability to SI.20
5.4 Cases with international conventional reference measurement procedure (which is not
primary) but no international conventional calibrator and without metrological traceability to
SI.21
5.5 Cases with international conventional calibrator (which is not primary) but no international
conventional reference measurement procedure and without metrological traceability to SI .22
5.6 Cases with manufacturer's selected measurement procedure but neither international
conventional reference measurement procedure nor international conventional calibrator and
without metrological traceability to SI.23
5.7 Trueness control materials.24
6 Expression of uncertainty of measurement.24
7 Validation of metrologically traceable calibration.25
8 Information on metrological traceability to be given in the instructions for use of an in vitro
diagnostic medical device .26
Annex ZA (informative) Clauses of this European Standard addressing essential requirements or other
provisions of EU Directives .27
Bibliography .28
Foreword
This document (EN ISO 17511:2003) has been prepared by Technical Committee CEN/TC 140 "In vitro diagnostic
medical devices", the secretariat of which is held by DIN, in collaboration with Technical Committee ISO/TC 212
"Clinical laboratory testing and in vitro diagnostic test systems".
This European Standard EN ISO 17511:2003 including the Amendment shall be given the status of a national
standard, either by publication of an identical text or by endorsement, at the latest by February 2004, and
conflicting national standards shall be withdrawn at the latest by February 2004.
This document has been prepared under a 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.
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), the European Confederation of
Laboratory Medicine (ECLM), and the European Diagnostic Manufacturers Association (EDMA) have contributed to
its preparation.
This standard includes a Bibliography.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Czech Republic, Denmark, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxembourg, Malta, Netherlands, Norway, Portugal,
Slovakia, Spain, Sweden, Switzerland and the United Kingdom.
Introduction
For measurements of quantities in laboratory medicine, it is essential that the quantity is adequately defined and
that the results reported to the physicians or other health care personel and patients are adequately accurate (true
and precise) to allow correct medical interpretation and comparability over time and space.
NOTE In this European Standard the concept "accuracy of measurement" (see 3.1) is related to both "trueness of
measurement" (see 3.33) and "precision of measurement" (see 3.23) whereas the Directive 98/79/EC on in vitro diagnostic
medical devices uses the term ‘’accuracy'’ instead of ‘'trueness’'.
To allow 'correct medical interpretation' involves more than the metrological (analytical) aspects of the traceability
chain. As the measurement results are eventually used by the physician for the benefit of the patients, the
physician should gather information on a number of other aspects, such as knowledge about the pre- and post-
analytical phase, the diagnostic sensitivity and specificity, and relevant reference interval(s). The present European
Standard deals only with the analytical aspects of measurements in Laboratory Medicine (see also 1 e)).
The measurement of quantities in biological samples requires reference measurement systems including:
- the definition of the analyte in the biological sample with regard to the intended clinical use of the measurement
results;
- a reference measurement procedure for the selected quantity in human samples;
- suitable reference materials for the selected quantity, e.g. primary calibrators and secondary matrix-based
calibrators that are commutable.
The trueness of measurement of a value assigned to a defined quantity of a calibrator or trueness control material,
depends on the metrological traceability of the value through an unbroken chain of alternating measurement
procedures and measurement standards (calibrators), usually having successively decreasing uncertainties of
measurement (see Figure 1). The uncertainty of the value assigned to a given calibrator or trueness control
material depends on the stated metrological traceability chain and the combined uncertainties of its links.
The ideal end-point of a metrological traceability chain is the definition of the relevant unit of the International
System of Units (SI), but the selection of steps and the level at which metrological traceability for a given value
stops, depend on the availability of higher order measurement procedures and calibrators. In many cases, at
present, there is no metrological traceability above the manufacturer's selected measurement procedure or the
manufacturer's working calibrator. In such cases, trueness is referred to that level of the calibration hierarchy until
an internationally agreed reference measurement procedure and/or calibrator becomes available.
The objective of a chosen metrologically traceable calibration is to transfer the degree of trueness of a reference
material, and/or reference measurement procedure, to a procedure that is of a lower metrological order, e.g. a
routine procedure. Metrological traceability of calibration requires that the reference and routine measurement
procedures measure the same measurable quantity with an analyte of the same pertinent characteristics.
In this context, it is important to recognize that different procedures purporting to measure the same quantity may in
fact give different results when applied to a particular sample or reference material. This may arise, for example,
when two or more immunoprocedures purporting to measure the concentration of a hormone such as thyrotropin
(thyroid stimulating hormone, TSH) are applied to a reference material of the hormone, because the respective
reagents recognize and react to different extents with various epitopes in the material, thus leading to results for
different although related quantities.
Laboratory medicine routinely provides results for 400 to 700 types of quantity. For most of these, the metrological
traceability of the assigned value for a product calibrator stops after only one metrologically higher step consisting
of a (reference) measurement procedure, or after two steps consisting of a measurement procedure and a
(reference) calibrator. The reason is that many of such quantities are related to mixtures of molecular species with
clinically relevant properties in common, but with different structures and molecular masses in varying proportions,
e.g. glycoproteins.
Depending on the possibility of metrological traceability to SI and on the availability of various metrological levels of
measurement procedures and calibrators, the following five typical upper ends of the metrological traceability chain
can be identified.
a) Quantities for which results of measurements are metrologically traceable to SI.
A primary reference measurement procedure and one or more (certified) primary reference materials (used as
calibrators) are available. These levels exist for approximately 25 to 30 types of quantity having well defined
components, e.g. some electrolytes, metabolites, steroid hormones, and some thyroid hormones. These types
of quantity cover a large proportion of the routine results provided by medical laboratories (see 4.2.2, 5.2,
Figures 1 and 2).
b) Quantities for which results of measurements are not metrologically traceable to SI.
1)
...