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SIST EN ISO 15193:2009
01-julij-2009
'LDJQRVWLþQLPHGLFLQVNLSULSRPRþNLLQYLWUR0HUMHQMHNROLþLQYY]RUFLKELRORãNHJD
L]YRUD=DKWHYH]DYVHELQRLQSUHGVWDYLWHYUHIHUHQþQLKPHULOQLKSRVWRSNRY ,62
In vitro diagnostic medical devices - Measurement of quantities in samples of biological
origin - Requirements for content and presentation of reference measurement
procedures (ISO 15193:2009)
In-vitro-Diagnostika - Messung von Größen in Proben biologischen Ursprungs -
Anfor¬derungen Inhalt und Aufbereitung von Referenzmessverfahren (ISO 15193:2009)
Dispositifs médicaux de diagnostic in vitro - Mesurage des grandeurs dans des
échantillons d'origine biologique - Exigences relatives au contenu et a la présentation
des modes opératoires de mesure de référence (ISO 15193:2009)
Ta slovenski standard je istoveten z: EN ISO 15193:2009
ICS:
11.100.10 'LDJQRVWLþQLSUHVNXVQL In vitro diagnostic test
VLVWHPLLQYLWUR systems
SIST EN ISO 15193:2009 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 15193:2009
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SIST EN ISO 15193:2009
EUROPEAN STANDARD
EN ISO 15193
NORME EUROPÉENNE
EUROPÄISCHE NORM
May 2009
ICS 11.100.10
English Version
In vitro diagnostic medical devices - Measurement of quantities
in samples of biological origin - Requirements for content and
presentation of reference measurement procedures (ISO
15193:2009)
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 - Anforderungen an den Inhalt und
Exigences relatives au contenu et à la présentation des die Darstellung von Referenzmessverfahren (ISO
procédures de mesure de référence (ISO 15193:2009) 15193:2009)
This European Standard was approved by CEN on 16 April 2009.
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 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 Management Centre has the same status as the
official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2009 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 15193:2009: E
worldwide for CEN national Members.
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SIST EN ISO 15193:2009
EN ISO 15193:2009 (E)
Contents Page
Foreword .3
Annex ZA (informative) Relationship between this International Standard and the Essential
Requirements of EU Directive 98/79 .4
2
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SIST EN ISO 15193:2009
EN ISO 15193:2009 (E)
Foreword
This document (EN ISO 15193:2009) 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 shall be given the status of a national standard, either by publication of an identical
text or by endorsement, at the latest by November 2009, and conflicting national standards shall be withdrawn
at the latest by November 2009.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
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 EC Directive.
For relationship with EC Directive, see informative Annex ZA, which is an integral part of this document.
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, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
3
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SIST EN ISO 15193:2009
EN ISO 15193:2009 (E)
Annex ZA
(informative)
Relationship between this International Standard and the Essential Requirements
of EU Directive 98/79
This International Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide one means of conforming to Essential Requirements of
the New Approach Directive 98/79.
Once this standard is cited in the Official Journal of the European Communities under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the normative
clauses of this standard confers, within the limits of the scope of this standard, a presumption of conformity
with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
WARNING: Other requirements and other EU Directives may be applicable to the products falling within the
scope of this standard.
4
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SIST EN ISO 15193:2009
INTERNATIONAL ISO
STANDARD 15193
Second edition
2009-05-01
In vitro diagnostic medical devices —
Measurement of quantities in samples of
biological origin — Requirements for
content and presentation of reference
measurement procedures
Dispositifs médicaux de diagnostic in vitro — Mesurage des grandeurs
dans des échantillons d'origine biologique — Exigences relatives au
contenu et à la présentation des procédures de mesure de référence
Reference number
ISO 15193:2009(E)
©
ISO 2009
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
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ii © ISO 2009 – All rights reserved
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
Contents Page
Foreword. iv
Introduction . v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions. 2
4 Presentation of a reference measurement procedure . 4
4.1 Elements of a reference measurement procedure . 4
4.2 Warning and safety precautions . 4
4.3 Introduction . 5
4.4 Scope . 5
4.5 Terms, definitions, symbols and abbreviated terms. 5
4.6 Measurement principle and measurement method. 6
4.7 Check list . 6
4.8 Reagents and materials . 7
4.9 Apparatus . 9
4.10 Sampling and sample. 9
4.11 Preparation of measuring system and analytical portion . 9
4.12 Operation of measuring system. 11
4.13 Data processing. 11
4.14 Analytical reliability . 12
4.15 Special cases . 15
4.16 Validation of a reference measurement procedure. 15
4.17 Reporting . 15
4.18 Quality assurance. 16
4.19 Bibliography . 16
4.20 Dates of authorization and revision. 16
Annex A (informative) Reference procedures for properties other than differential and rational
quantities . 17
Bibliography . 18
© ISO 2009 – All rights reserved iii
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SIST EN ISO 15193:2009
ISO 15193:2009(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 15193 was prepared by the European Committee for Standardization (CEN) Technical Committee
CEN/TC 140, In vitro diagnostic medical devices, in collaboration with Technical Committee ISO/TC 212,
Clinical laboratory testing and in vitro diagnostic test systems, in accordance with the Agreement on technical
cooperation between ISO and CEN (Vienna Agreement).
This second edition cancels and replaces the first edition (ISO 15193:2002), which has been technically
revised.
iv © ISO 2009 – All rights reserved
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
Introduction
Reference measurement systems are needed to produce useful and reliable measurement results, whether in
science, technology or routine service, so as to be comparable and ultimately metrologically traceable to
measurement units and/or measurement standards and/or measurement procedures of the highest
metrological level. Reference measurement procedures play a crucial role in this metrological system because
they can be used for the following:
a) in assessing performance properties of measuring systems – comprising measuring instruments, auxiliary
equipment as well as reagents,
b) in demonstrating if there is a functional interchangeability of different routine measurement procedures
purporting to measure the same quantity,
c) in assigning quantity values to reference materials that are then used for purposes of calibration or
trueness control of routine measurement procedures, and
d) in detecting analytical influence quantities in patient samples.
For medical laboratory measurements, in particular, it is vitally important to both patient care and health
screening that the measurement results reported to the physicians and patients are adequately comparable,
reproducible and accurate. In some cases, it is advisable that a reference measurement procedure be given in
the form of a standard, namely when it is related to technical requirements:
⎯ that are specified in standards, technical specifications, or technical regulations, etc.,
⎯ for which quantity values are to be stated by the supplier, and
⎯ that have a direct relationship to the performance of a product or process.
The advantages of having such a standard are listed in ISO/IEC Guide 15.
In Clause 3 of this International Standard, concepts are indicated by italicized text.
© ISO 2009 – All rights reserved v
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SIST EN ISO 15193:2009
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SIST EN ISO 15193:2009
INTERNATIONAL STANDARD ISO 15193:2009(E)
In vitro diagnostic medical devices — Measurement of
quantities in samples of biological origin — Requirements for
content and presentation of reference measurement procedures
1 Scope
This International Standard specifies requirements for the content of a reference measurement procedure for
in vitro diagnostic medical devices and medical laboratories.
NOTE 1 It is intended that an experienced laboratory worker who follows a measurement procedure written in
accordance with this International Standard can be expected to produce measurement results with a measurement
uncertainty not exceeding the stipulated interval.
This International Standard applies to reference measurement procedures providing values of differential or
rational quantities. Annex A provides information on nominal properties and ordinal quantities.
This International Standard is valid for any person, body or institution involved in one of the various branches
of laboratory medicine whose intention is to write a document to serve as a reference measurement procedure.
Full descriptions of measurement methods are usually published in scientific literature, in which methods are
described in sufficient detail that they can be used as the basis of a documented measurement procedure.
NOTE 2 In this International Standard, “international measurement standard” designates a material standard. The term
“international standard” is used by WHO for reference materials.
2 Normative references
The following referenced documents are indispensable for the application 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 15194, In vitro diagnostic medical devices — Measurement of quantities in samples of biological origin —
Requirements for certified reference materials and the content of supporting documentation
ISO/IEC Guide 98-3:2008, Guide to the expression of uncertainty in measurement (GUM:1995)
ISO/IEC Guide 99:2007, International vocabulary of metrology — Basic and general concepts and associated
terms (VIM)
© ISO 2009 – All rights reserved 1
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO/IEC Guide 99 and
ISO/IEC Guide 98-3 and the following apply.
3.1
primary sample
collection of one or more parts initially taken from a system and intended to provide information about the
system, or to serve as a basis for a decision about the system
NOTE In some cases, the information provided also applies to a larger system or a set of systems, of which the
sampled system is an element.
3.2
laboratory sample
primary sample, or a subsample of it, as prepared for sending to or as received by the laboratory and intended
for measurement
3.3
analytical sample
sample prepared from the laboratory sample and from which analytical portions can be taken
NOTE The analytical sample can be subjected to various treatments before an analytical portion is taken.
3.4
analytical portion
portion of material taken from the analytical sample and on which the measurement is actually carried out,
either directly or following dissolution
NOTE The analytical portion is taken directly from the primary sample or laboratory sample if no preparation of these
is required. The analytical portion is sometimes dissolved to give an analytical solution before being exposed to the
measuring device.
3.5
analytical solution
solution prepared prior to measurement by dissolving an analytical portion in a liquid or solid material, with or
without reaction
3.6
matrix
〈material system〉 components of a material system, except the analyte
3.7
reference measurement procedure
measurement procedure accepted as providing measurement results fit for their use in assessing
measurement trueness of measured quantity values obtained from other measurement procedures for
quantities of the same kind, in calibration, or in characterizing reference materials
NOTE 1 Adapted from ISO/IEC Guide 99:2007, 2.7.
NOTE 2 The roles of reference measurement procedures are detailed in ISO 17511 and ISO 18153.
NOTE 3 In ISO terminology, trueness is related to bias, systematic effect and systematic error, whereas accuracy is
related to both trueness (with its relations) and precision, which itself is related to standard deviation, random effect and
random error.
NOTE 4 The term “reference measurement procedure” is intended to be understood as a measurement procedure of
higher order.
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
3.8
analytical sensitivity
quotient of the change in an indication and the corresponding change in the value of a quantity being
measured
NOTE 1 The term “analytical sensitivity” is not intended to be used as a synonym for “detection limit”.
NOTE 2 ISO/IEC Guide 99:2007 uses the term “sensitivity of a measuring system”.
3.9
analytical specificity
ability of a measurement procedure to determine solely the quantity it purports to measure
3.10
analytical interference
systematic effect on a measurement caused by an influence quantity which does not by itself produce an
indication, but which causes an enhancement or depression of the indication
3.11
influence quantity
quantity that, in a direct measurement, does not affect a quantity that is actually measured, but affects the
relation between the indication and the measurement result
NOTE Adapted from ISO/IEC Guide 99:2007, 2.52.
3.12
measurand
quantity intended to be measured
NOTE 1 Adapted from ISO/IEC Guide 99:2007, 2.3.
NOTE 2 The term “analyte” is not intended to be used for measurand. Analyte is a component of a measurand.
EXAMPLE In the designation “Blood—Glucose; amount-of-substance concentration”, the term “Glucose” designates
the analyte, equal to the component.
3.13
detection limit
limit of detection
measured quantity value, obtained by a given measurement procedure, for which the probability of falsely
claiming the absence of a component in a material is β, given a probability α of falsely claiming its presence
NOTE 1 IUPAC recommends default values for α and β equal to 0,05.
NOTE 2 The abbreviation LOD is sometimes used.
NOTE 3 The term “sensitivity” is discouraged for this concept.
NOTE 4 Adapted from ISO/IEC Guide 99:2007, 4.18.
3.14
calibrator
measurement standard used in calibration
NOTE Adapted from ISO/IEC Guide 99:2007, 5.12.
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
4 Presentation of a reference measurement procedure
4.1 Elements of a reference measurement procedure
The content of a reference measurement procedure shall comprise at least the elements listed as mandatory
in Table 1. The order of the elements may be changed and additional elements, such as an abstract, may be
added as appropriate.
Table 1 — Elements of the content of a reference measurement procedure
Subclause in this
Element Type
International Standard
Title page Mandatory —
Contents list Optional —
Foreword Optional —
Warning and safety precautions Mandatory 4.2
Introduction Optional 4.3
Title of reference measurement procedure Mandatory —
Scope Mandatory 4.4
Normative references Optional —
Terms, definitions, symbols, and abbreviated terms Optional 4.5
Measurement principle and method Mandatory 4.6
Check list Optional 4.7
Reagents Mandatory 4.8
Apparatus Mandatory 4.9
Sampling and sample Mandatory 4.10
Preparation of measuring system and analytical portion Mandatory 4.11
Operation of measuring system Mandatory 4.12
Data processing Mandatory 4.13
Analytical reliability Mandatory 4.14
Special cases Optional 4.15
Validation by inter-laboratory comparisons Mandatory 4.16
Reporting Mandatory 4.17
Quality assurance Mandatory 4.18
Bibliography (Annex) Optional 4.19
Dates of authorization and revision Mandatory 4.20
4.2 Warning and safety precautions
Attention shall be drawn to any danger associated with a type of sample, reagent, equipment or activity, and
all necessary precautions shall be described, including precautions for disposal. Regional, national and local
legislation and regulations may apply.
NOTE For a reference measurement procedure that is intended to be presented as an International Standard, refer
to ISO 78-2.
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
4.3 Introduction
The introduction shall comprise the following items, as appropriate, in any order:
a) description of the quantity measured by the reference measurement procedure, in terms of system,
component and kind-of-quantity, including any specifications to each;
b) brief statement of the role of the quantity in health care, if appropriate;
c) measurement method and rationale for its choice;
d) measurement model in terms of the measurand as a function of all input quantities;
e) place in a hierarchy of measurement procedures and calibrators;
f) metrological traceability.
4.4 Scope
The scope shall define the subject and aspect(s) covered, indicating any known limits of applicability. This
element shall not contain requirements.
The scope should include the following items:
a) objectives of measurement for which the reference measurement procedure is suited;
b) types of sample material to which the reference measurement procedure applies and whether limitations
exist;
c) interfering components, such as drugs, metabolites, additives, microbial growth;
d) mention of allowable modifications to the basic reference measurement procedure, e.g. as necessary to
eliminate an unusual and identifiable interference [details of modified procedure to be given in a separate
clause “Special cases” (see 4.15)];
e) measurement interval.
4.5 Terms, definitions, symbols and abbreviated terms
4.5.1 Concepts
If appropriate, this clause shall describe all elements essential for the understanding of the reference
measurement procedure.
NOTE These can include, for example:
a) a system of related concepts, e.g. isoenzymes of lactate dehydrogenase according to electrophoretic mobility,
b) a term that can be used with special meaning, unfamiliar to some potential readers, e.g. “quantity”, “property” or
“amount of substance” for the base kind-of-quantity with the unit mole, and
c) a current term that cannot be used for a given reason, e.g. “parts per million (ppm)” is avoided in favour of “mass
fraction, in milligram per kilogram” or “volume fraction, in cubic centimetre per cubic metre (or microlitre per litre)”
(see also 4.8.4).
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SIST EN ISO 15193:2009
ISO 15193:2009(E)
4.5.2 Nomenclature
The names of chemical compounds, biological components, quantities, units and symbols used shall be in
accordance with available International Standards (or European Standards if appropriate), or the latest
recommendations of the appropriate international organization(s). When more than one name is
recommended by authoritative sources, a single name may be chosen. The chosen name and synonyms shall
be listed with reference to the relevant standard or recommending organization.
4.5.3 Trivial names
If a trivial name of a reagent is to be used, it shall be given in parentheses following the systematic name the
first time the systematic name appears in the text.
4.6 Measurement principle and measurement method
4.6.1 The measurement principle shall be given, e.g. molecular absorption of visible light applied in a
procedure for measuring the amount-of-substance concentration of bilirubins in a liquid solution.
4.6.2 The measurement method shall be described. If appropriate, the reasons for the choice of a certain
step shall be given. Essential chemical reactions shall be indicated if they help in understanding the text or the
calculations. The reactions shall, if appropriate, be expressed in ionic form.
4.7 Check list
4.7.1 Appropriateness
If included, the checklist shall list the items and conditions that are required to perform the measurements.
NOTE A checklist is especially useful if the document is large. It is particularly applicable to reagents (see 4.8) and to
apparatus (see 4.9). The full descriptions and instructions for preparation of reagents would be given later in the text or as
an annex.
4.7.2 List of reagents and materials
If reagents are incorporated in the
...