EN ISO 18153:2003
(Main)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 (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 (ISO 18153:2003)
ISO 18153:2003 specifies how to assure the metrological traceability of values assigned to calibrators and control materials intended to establish or verify trueness of measurement of the catalytic concentration of enzymes.
The calibrators and control materials are those provided by the manufacturers as part of, or to be used together with, in vitro diagnostic medical devices.
The following subjects are outside the scope of ISO 18153:2003: requirements for the design or selection of a reference measurement procedure; quantities involving mass of enzyme or immunoreactivity of enzymes; control materials that do not have an assigned value and are used only for assessing the precision of a measurement procedure, either its repeatability or reproducibility (precision control materials); control materials intended for intralaboratory quality control purposes and supplied with intervals of suggested acceptable values, each interval obtained by interlaboratory consensus with respect to one specified measurement procedure, and with limiting values that are not metrologically traceable; metrological traceability of routine results to the product calibrator and their relations to any medical discrimination limit; properties involving nominal and ordinal scales.
In-vitro-Diagnostika - Messung von Größen in Proben biologischen Ursprungs - Metrologische Rückführbarkeit von Werten der katalytischen Konzentration von Enzymen, die Kalibratoren und Kontrollmaterialien zugeordnet sind (ISO 18153: 2003)
Diese Europäische Norm legt fest, wie die metrologische Rückführbarkeit der Kalibratoren und Kontrollmaterialien zugeordneten Werte sichergestellt wird, die ihrerseits dafür vorgesehen sind, die Richtigkeit einer Messung der katalytischen Konzentration von Enzymen zu etablieren oder zu verifizieren. Kalibratoren und Kontrollmaterialien sind solche Materialien, die von den Herstellern als Teil der In-vitro-Diagnostika oder zur gemeinsamen Verwendung mit diesen geliefert werden.
Nicht zum Anwendungsbereich dieser Norm gehören
a) Anforderungen an die Entwicklung oder die Auswahl eines Referenzmessverfahrens;
b) Größen, welche die Masse oder die Immunreaktivität von Enzymen betreffen;
c) Kontrollmaterialien, die keinen Zielwert besitzen und nur zur Bewertung der Präzision eines Messverfahrens, entweder von dessen Wiederholpräzision oder dessen Vergleichpräzision, verwendet werden (Präzisionskontrollmaterialien);
d) Kontrollmaterialien, die zu Qualitätskontrollzwecken innerhalb eines Laboratoriums vorgesehen sind und mit Akzeptanzbereichen bereitgestellt werden, wobei jeder Bereich durch Übereinkunft zwischen verschiedenen Laboratorien in Bezug auf ein festgelegtes Messverfahren erhalten wurde, und mit Grenzwerten, die nicht metrologisch rückführbar sind;
e) die metrologische Rückführbarkeit von Routineergebnissen auf den Produktkalibrator und deren Bezug zu medizinischen Entscheidungsgrenzen;
f) Eigenschaften, die mit Nominal- und Ordinalskalen beschrieben werden.
Dispositifs médicaux de diagnostic in vitro - Mesurage des grandeurs dans des échantillons d'origine biologique - Traçabilité métrologique des valeurs de concentration catalytique des enzymes attribuées aux agents d'étalonnage et aux matériaux de contrôle (ISO 18153:2003)
La présente Norme européenne spécifie la manière dont on garantit la traçabilité métrologique des valeurs attribuées aux agents d'étalonnage et aux matériaux de contrôle destinés à établir ou vérifier la justesse de mesurage de la concentration catalytique des enzymes. Ces agents d'étalonnage et ces matériaux de contrôle sont fournis par les fabricants en tant que parties intégrantes des dispositifs médicaux de diagnostic in vitro ou comme éléments à utiliser conjointement avec ces derniers.
Les points suivants ne relèvent pas du domaine d'application de la présente Norme :
a) les exigences relatives à la conception ou à la sélection d'un mode opératoire de référence ;
b) les grandeurs ayant un rapport avec la masse de l'enzyme ou l'immunoréactivité des enzymes ;
c) les matériaux de contrôle qui n'ont pas une valeur attribuée et qui sont utilisés uniquement pour l'évaluation de la fidélité d'un mode opératoire de mesure, en termes de répétabilité ou de reproductibilité (matériaux de contrôle de la fidélité) ;
d) les matériaux de contrôle destinés à la maîtrise de la qualité intralaboratoire et fournis avec des intervalles de valeurs acceptables proposées, chaque intervalle ayant fait l'objet d'un consensus interlaboratoire pour un mode opératoire de mesure spécifié avec des valeurs limites sans traçabilité métrologique ;
e) la traçabilité métrologique de résultats de routine par rapport au matériau d'étalonnage produit par un fabricant et leurs relations à une limite de décision clinique ,
f) les propriétés qui impliquent des échelles nominales et ordinales.
Diagnostični medicinski pripomočki in vitro - Merjenje količin v vzorcih biološkega izvora – Meroslovna sleddljivost vrednosti za katalitične koncentracije encimov, dodeljenih kalibratorjem in kontrolnim materialom (ISO 18153:2003)
General Information
Standards Content (Sample)
SLOVENSKI STANDARD
01-november-2003
'LDJQRVWLþQLPHGLFLQVNLSULSRPRþNLLQYLWUR0HUMHQMHNROLþLQYY]RUFLKELRORãNHJD
L]YRUD±0HURVORYQDVOHGGOMLYRVWYUHGQRVWL]DNDWDOLWLþQHNRQFHQWUDFLMHHQFLPRY
GRGHOMHQLKNDOLEUDWRUMHPLQNRQWUROQLPPDWHULDORP ,62
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 (ISO 18153:2003)
In-vitro-Diagnostika - Messung von Größen in Proben biologischen Ursprungs -
Metrologische Rückführbarkeit von Werten der katalytischen Konzentration von
Enzymen, die Kalibratoren und Kontrollmaterialien zugeordnet sind (ISO 18153: 2003)
Dispositifs médicaux de diagnostic in vitro - Mesurage des grandeurs dans des
échantillons d'origine biologique - Traçabilité métrologique des valeurs de concentration
catalytique des enzymes attribuées aux agents d'étalonnage et aux matériaux de
contrôle (ISO 18153:2003)
Ta slovenski standard je istoveten z: EN ISO 18153:2003
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 18153
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 for
catalytic concentration of enzymes assigned to calibrators and
control materials (ISO 18153:2003)
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 de concentration von Werten der katalytischen Konzentration von Enzymen,
catalytique des enzymes attribuées aux agents die Kalibratoren und Kontrollmaterialien zugeordnet sind
d'étalonnage et aux matériaux de contrôle (ISO (ISO 18153: 2003)
18153:2003)
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 18153:2003 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 .8
4.1 Principles.8
4.2 Structure .9
5 Validation of metrologically traceable calibration.11
5.1 Principles.11
5.2 Analytical specificity of measurement procedures.11
5.3 Commutability of calibrators .12
5.4 Commutability of control materials.12
Annex A (informative) List of IFCC primary reference measurement procedures .13
Annex B (informative) List of certified reference materials (CRM).14
Annex ZA (informative) Clauses of this European Standard addressing essential requirements or other
provisions of EU Directives .15
Bibliography .16
Foreword
This document (EN ISO 18153:2003) 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 18153:2003 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.
Annexes A and B are informative.
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
The Directive 98/79/EC on in vitro diagnostic medical devices requires that the metrologically traceability of values
assigned to calibrators and control materials be assured through available reference measurement materials and
reference measurement procedures of higher order. Following this concept, the European Standard
prEN ISO 17511 on "traceability" has been elaborated which describes a hierarchical order of measurement
procedures and calibration materials. The general rules expressed in that standard also apply to quantities
involving catalytic activity. Whenever possible, metrological traceability should be demonstrated to the SI unit which
forms the top of the calibration hierarchy.
For the measurement of the catalytic activity concentration of enzymes (hereafter called 'catalytic concentration'), a
hierarchy of calibrators and measurement procedures is described in the present standard. For enzyme
measurements, the definition of the derived coherent SI unit "mole per second cubic metre", given the special
name "katal per cubic metre" by the General Conference on Weights and Measures, is the top of the hierarchy
followed by a primary reference measurement procedure to which lower level measurement procedures,
calibrators, and control materials should be traced whenever possible.
Enzymes in blood or other biological fluids can be measured for diagnostic purposes in terms of their catalytic
concentrations. The analytical principle of the measurement of the catalytic rate of conversion of substrate has
considerable advantages of speed, low limit of detection, analytical specificity, and low cost. Results of catalytic
concentration measurements are only comparable if the enzyme activities are measured under the same
conditions. Therefore, an enzyme measurand cannot be described only by kind-of-quantity (e.g. catalytic
concentration), name of enzyme and of system, but requires also the specified measurement procedure and
especially the indicator component of the measured reaction. At the top of the calibration hierarchy, the
measurement procedure should be internationally agreed, e.g. 'creatine kinase measured by the conversion rate of
NADH in the IFCC reference measurement procedure'.
Thus, the primary reference measurement procedure is an integral part of the definition of the measurand and has
to be followed in all detail, e.g. as concerns:
kind of substrate (where the specificity of the enzyme allows this to be varied) and its concentration,
activators and their concentrations,
direction of catalysed reaction,
indicator component,
buffer system and pH,
temperature,
pre-incubation time,
material used for starting the reaction,
lag time,
reaction time.
The disadvantage of the procedure-dependence of the definition of the enzyme measurand and therefore of the
results of the measurements are well known: problems are caused in external quality assessment (EQA) and in
assessing the transferability of methods; a multiplicity of biological reference intervals exists with the consequent
risk of clinical misinterpretation of enzyme results. The standardization of routine enzyme measurements is
important to laboratory medicine, to improve the clinical utility and comparability of results through the elimination of
existing differences in biological reference intervals.
Two approaches can be considered:
a) the exclusive routine use of a recommended or standardized procedure for each enzyme;
b) calibration of one or more routine procedures by commutable enzyme calibration materials with values
assigned by a chosen reference measurement procedure.
The "recommended procedure" approach (a)) has been pursued vigorously for more than twenty years. It has had
considerable success in improving the quality and comparability of enzyme measurements and in discouraging the
use of analytically unsatisfactory procedures. However, the recommended-procedure-approach to standardization
appears to have reached the limits of its usefulness. Its disadvantages include: absence of a consensus of choice
among a number of differing recommendations; intentional or unintentional modification of recommended
procedures in routine use; unresponsiveness of recommended procedures to analytical and technical
improvement; and partly non-adaptability of recommended procedures to preferred automation. As a change in
routine enzyme procedures, whether recommended or not, inevitably entails a change of biological reference
values, it is understandably unwelcome to clinicians.
Improvement of the design and analytical performance of enzyme measurements will, and should, continue.
However, this should follow the normal practice of development and dissemination of scientific advances. Attempts
to develop and promote further standardized procedures for universal use are neither practicable nor desirable.
The "reference measurement procedure and calibration material" approach (b)) has, in contrast, received relatively
little attention. Among the objections that have been raised are:
1. lack of stable enzyme reference materials in appropriate matrices to serve as calibrators;
2. dissimilarity between candidate enzyme calibrators and the analyte enzymes in human samples, including
differences in isoforms;
3. absence of a constant inter-procedure ratio between a calibrating (reference) procedure and calibrated
(routine) procedure(s), for both the enzyme calibrator and patients' samples containing the analyte enzyme
(also described as a lack of commutability).
The converse of these objections constitutes a list of specifications, both for higher order enzyme reference
materials and for families of measurement procedures between which calibration is proposed. The calibrator should
be stable and have an analyte enzyme that is close in its catalytic properties within its matrix to those of the analyte
enzyme in the routine samples. The procedures themselves should have the same specificity for the catalytic
activity of the target enzyme.
Harmonization of the results of routine enzyme measurements can thus be achieved by selecting a reference
measurement procedure and identifying a family of related procedures for each clinically important enzyme.
Results obtained by any procedure included within such a family will be metrologically traceable to the chosen
reference measurement procedure.
1 Scope
This European Standard specifies how to assure the metrological traceability of values assigned to calibrators and
control materials intended to
...
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