SIST EN ISO 15195:2003

SLOVENSKI STANDARD
SIST EN ISO 15195:2003
01-december-2003
/DERUDWRULMVNDPHGLFLQD±=DKWHYH]DUHIHUHQþQHPHULOQHODERUDWRULMH,62

Laboratory medicine - Requirements for reference measurement laboratories (ISO
15195:2003)
Laboratoriumsmedizin - Anforderungen an Referenzmesslaboratorien (ISO 15195:2003)
Médecine de laboratoires - Exigences pour les laboratoires réalisant des mesurages de
référence (ISO 15195:2003)
Ta slovenski standard je istoveten z: EN ISO 15195:2003
ICS:
11.100.01 Laboratorijska medicina na Laboratory medicine in
splošno general
SIST EN ISO 15195:2003 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 15195:2003

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SIST EN ISO 15195:2003
EUROPEAN STANDARD
EN ISO 15195
NORME EUROPÉENNE
EUROPÄISCHE NORM
October 2003
ICS 11.100
English version
Laboratory medicine - Requirements for reference measurement
laboratories (ISO 15195:2003)
Médecine de laboratoires - Exigences pour les laboratoires Laboratoriumsmedizin - Anforderungen an
réalisant des mesurages de référence (ISO 15195:2003) Referenzmesslaboratorien (ISO 15195:2003)
This European Standard was approved by CEN on 24 July 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 15195:2003 E
worldwide for CEN national Members.

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SIST EN ISO 15195:2003
EN ISO 15195:2003 (E)
Foreword
This document (EN ISO 15195:2003) 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 April 2004, and conflicting national
standards shall be withdrawn at the latest by April 2004.
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.
Endorsement notice
The text of ISO 15195:2003 has been approved by CEN as EN ISO 15195:2003 without any
modifications.
NOTE Normative references to International Standards are listed in Annex ZA (normative).
2

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SIST EN ISO 15195:2003
EN ISO 15195:2003 (E)
Annex ZA
(normative)
Normative references to international publications
with their relevant European publications
This European Standard incorporates by dated or undated reference, provisions from other
publications. These normative references are cited at the appropriate places in the text and the
publications are listed hereafter. For dated references, subsequent amendments to or revisions of
any of these publications apply to this European Standard only when incorporated in it by
amendment or revision. For undated references the latest edition of the publication referred to
applies (including amendments).
NOTE Where an International Publication has been modified by common modifications, indicated
by (mod.), the relevant EN/HD applies.
Publication Year Title EN Year
ISO 17511 2003 In vitro diagnostic medical devices - EN ISO 17511 2003
Measurement of quantities in biological
samples - Metrological traceability of
values assigned to calibrators and
control materials
ISO 18153 2003 In vitro diagnostic medical devices - EN ISO 18153 2003
Measurement of quantities in biological
samples - Metrological traceability of
values for catalytic concentration of
enzymes assigned to calibrators and
control materials
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SIST EN ISO 15195:2003

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SIST EN ISO 15195:2003

INTERNATIONAL ISO
STANDARD 15195
First edition
2003-10-01


Laboratory medicine — Requirements for
reference measurement laboratories
Médecine de laboratoires — Exigences pour les laboratoires réalisant
des mesurages de référence





Reference number
ISO 15195:2003(E)
©
ISO 2003

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SIST EN ISO 15195:2003
ISO 15195:2003(E)
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ii © ISO 2003 — All rights reserved

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SIST EN ISO 15195:2003
ISO 15195:2003(E)
Contents Page
Foreword. iv
Introduction . v
1 Scope. 1
2 Normative references . 1
3 Terms and definitions. 2
4 Management system requirements. 4
4.1 Organization and management . 4
4.2 Quality management system . 5
4.3 Personnel. 6
4.4 Measurement documentation and records . 6
4.5 Contracting . 6
5 Technical requirements. 7
5.1 Premises and environmental conditions. 7
5.2 Handling of samples . 7
5.3 Equipment. 7
5.4 Reference materials . 8
5.5 Reference measurement procedures. 8
5.6 Metrological traceability — Uncertainty of measurement . 8
5.7 Quality assurance . 9
5.8 Reporting results . 9
Annex A (informative) Cross-references to ISO/IEC 17025:1999. 11
Bibliography . 12

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SIST EN ISO 15195:2003
ISO 15195:2003(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 15195 was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in vitro
diagnostic test systems.
iv © ISO 2003 — All rights reserved

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SIST EN ISO 15195:2003
ISO 15195:2003(E)
Introduction
The general requirements for the competence of calibration laboratories are laid down in ISO/IEC 17025 for
testing and calibration laboratories. This International Standard refers to the specific aspects of calibration
laboratories in the field of laboratory medicine where such “calibration laboratories” are usually denoted as
“reference measurement laboratories.”
The results produced by medical laboratories should be traceable to reference materials and/or reference
measurement procedures of higher order, whenever these are available. This is necessary in order to allow
transferability of measurement results in patient samples irrespective of the place and time of measurement.
In order to achieve this goal, the first and essential step is to define the quantity to be measured. Once the
quantity has been defined, a reference measurement system should be established, consisting of
• reference materials,
• reference measurement procedures, and
• reference measurement laboratories.
The reference measurement laboratories should be embedded in international (global) networks organized
under the auspices of, for example, International Federation of Clinical Chemistry and Laboratory Medecine
(IFCC) and International Committee of weights and Measures (CIPM).
Reference measurement laboratories must operate with a traceability to the highest metrological level
available and with a lower uncertainty than routine laboratories. The metrological level of the results provided
by reference measurement laboratories should be appropriate to enable routine laboratories to fulfil medical
requirements. The specific requirements of medical laboratories carrying out routine measurements are
addressed in ISO 15189.
The presentation of reference measurement procedures and the description of reference materials are the
subject of ISO standards (ISO 15193 and ISO 15194, respectively). This International Standard describes the
performance characteristics required for reference measurement laboratories in laboratory medicine. These
are highly specialized laboratories often attached to or subcontracted by entities such as national metrology
institutes, quality assessment/proficiency testing organizations, academic centres, or in vitro diagnostic
medical device manufacturers.
Reference measurement laboratories should implement reference measurement procedures and produce
results of measurement that are accurate and traceable to national or international primary reference
materials when such are available. Whenever possible, traceability should be established to a reference
material which forms an embodiment of the SI unit (ISO 17511).
In many instances, properties of biological materials cannot be expressed in SI units as the molecular
structure of their analytes is not exactly known and may be different in a reference material from that in a
native sample of human origin (e.g. state of glycosylation of a protein); then the traceability chain ends at a
lower level, e.g., at an arbitrary international unit (int. unit). However, the reference measurement laboratory
should provide traceable values on reference materials supplied by customers to the highest available level of
reference measurement procedures or reference materials.
Even if the value for a property of a biological material is not traceable to an SI unit, each step of a reference
measurement procedure (e.g. gravimetry, volumetry, temperature measurement) should have values that are
traceable to the respective SI unit.
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SIST EN ISO 15195:2003
ISO 15195:2003(E)
The traceability concept, its applicability and limitations are described in detail in the standard “Metrological
traceability of values assigned to calibrators and control materials” (ISO 17511).
Further tasks of reference measurement laboratories may include upon request:
 assisting in investigation of new or existing measurement procedures with regard to their trueness,
 providing accurate (true and precise) assigned values with stated uncertainty to materials for calibration,
internal quality control, and external quality assessment,
 acting as consultants to government, industry, and organizations conducting external quality assessment
schemes as well as to specialized individual laboratories.
The requirements described in this document and in ISO/IEC 17025 are prerequisites for reference
measurement laboratories to perform their tasks adequately. When the reference measurement laboratory is
integrated into a routine laboratory, the management system, personnel and equipment requirements of the
reference laboratory should comply with this International Standard and be independent of the routine
laboratory.
This International Standard should aid in establishing confidence in reference measurement laboratories that
are able to demonstrate their competence in accordance with the requirements laid down here.
This International Standard may form a basis for the accreditation of a reference measurement laboratory that
applies for official recognition of the performance of a reference measurement procedure. Reference
measurement laboratories are usually accredited by the national metrology institutes or national accrediting
bodies.
NOTE The requirements for recognition and operation are set out in ISO/IEC Guide 58. The International Laboratory
Accreditation Cooperation (ILAC) coordinates and supervises the regional organizations of national accrediting bodies,
such as the European Cooperation for Accreditation (EA), which ensures that member bodies recognize each other's
accreditation certificates.
This International Standard may furthermore facilitate collaboration between reference measurement
laboratories performing interlaboratory comparisons and encourage the highly desirable formation of
international networks of reference measurement laboratories.
It is understood that reference measurement procedures should be of high metrological order and the
analytical principle of measurement applied should allow an adequately low uncertainty. The results of
reference measurements should be traceable to reference materials or to a reference procedure of higher
order when available.
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SIST EN ISO 15195:2003
INTERNATIONAL STANDARD ISO 15195:2003(E)

Laboratory medicine — Requirements for reference
measurement laboratories
1 Scope
This International Standard gives the specific requirements for reference measurement laboratories in
laboratory medicine. Examinations of properties with results reported on a nominal or ordinal scale are not
included.
This International Standard is not applicable to routine medical laboratories.
NOTE 1 It is the laboratory’s responsibility to comply with the relevant legal health and safety requirements.
NOTE 2 Requirements for routine medical laboratories are specified in ISO 15189.
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 15193, In vitro diagnostic medical devices — Measurement of quantities in samples of biological origin —
Presentation of reference measurement procedures
ISO 15194:2002, In vitro diagnostic medical devices — Measurement of quantities in samples of biological
origin — Description of reference materials
ISO 17511, In vitro diagnostic medical devices — Measurement of quantities in biological samples —
Metrological traceability of values assigned to calibrators and control materials
ISO 18153, In vitro diagnostic medical devices — Measurement of quantities in biological samples —
Metrological traceability of assigned values for catalytic concentration of enzymes in calibrators and control
materials
International vocabulary of basic and general terms in metrology (VIM). BIPM, IEC, IFCC, ISO, IUPAC, IUPAP
1)
and OIML, 1993
Guide to the expression of uncertainty in measurement (GUM). BIPM, IEC, IFCC, ISO, IUPAC, IUPAP and
1)
OIML,1993

1) This vocabulary has been prepared simultaneously in English and French by a joint working group consisting of
experts appointed by:
BIPM International Bureau of Weights and Measures
IEC International Electrotechnical Commission
IFCC International Federation of Clinical Chemistry and Laboratory Medicine
ISO International Organization for Standardization
IUPAC International Union of Pure and Applied Chemistry
IUPAP International Union of Pure and Applied Physics
OIML International Organization of Legal Metrology
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SIST EN ISO 15195:2003
ISO 15195:2003(E)
3 Terms and definitions
For the purposes of this document, the terms and definitions given in the International vocabulary of basic and
general terms in metrology (VIM) and the following apply.
3.1
accuracy of measurement
closeness of the agreement between the result of a measurement and a true value of the measurand
[VIM:1993, 3.5]
NOTE 1 According to ISO 5725-1, accuracy of measurement is related to both trueness of measurement and precision
of measurement.
NOTE 2 Accuracy cannot be given a numerical value in terms of the measurand, only descriptions such as “sufficient”
or “insufficient” for a stated purpose.
NOTE 3 An estimate of an inverse measure of accuracy is “deviation”, defined as “value minus a conventional true
value”.
NOTE 4 Instead of “a true value” in the definition above, ISO 3534-1 uses the concept “the accepted reference value”,
which can be a theoretical (true), assigned, consensus, or procedure-defined value.
NOTE 5 In this International Standard the concept “accuracy of measurement” is related to both trueness of
measurement (3.10) and precision of measurement (3.4) whereas the EU Directive on in vitro diagnostic medical
devices uses the term “accuracy” instead of “trueness”.
3.2
certified reference material
CRM
reference material, accompanied by a certificate, one or more of whose property values are certified by a
procedure which establishes its traceability to an accurate realization of the unit in which the property values
are expressed, and for which each certified value is accompanied by an uncertainty at a stated level of
confidence
[VIM:1993, 6.14]
3.3
measurable quantity
attribute of a phenomenon, body, or substance that may be distinguished qualitatively and determined
quantitatively
[VIM:1993, 1.1]
3.4
precision of measurement
closeness of agreement between independent results of measurement obtained under stipulated conditions
NOTE 1 Adapted from ISO 3534-1:1993, 3.14.
NOTE 2 “Precision of measurement” is a qualitative concept.
NOTE 3 The degree of precision is usually expressed numerically by statistical measures of imprecision of
measurement such as “standard deviation” and “coefficient of variation” that are inversely related to precision.
NOTE 4 “Precision” of a given measurement procedure is subdivided according to the specified precision conditions.
“Repeatability” relates to essentially unchanged conditions and is often termed “within-series precision” or “within-run
precision.” “Intermediate precision” refers to conditions where there is variation in one or more of the factors time,
calibration, operator, and equipment — usually within a laboratory. “Reproducibility” relates to change in conditions, i.e.,
different laboratories, operators, and measuring systems (including different calibrations and reagent batches) and is often
termed “interlaboratory precision”.
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SIST EN ISO 15195:2003
ISO 15195:2003(E)
NOTE 5 The definition used in this International Standard is consistent with related ISO standards. The definition for
precision of measurement as stated in ISO 3534-1:1993, 3.14, reads as follows: closeness of agreement between
independent test results obtained under stipulated conditions.
3.5
reference material
material or substance, one or more of whose property values are sufficiently homogeneous and well
established to be used for the calibration of a measuring system, the assessment of a measurement
procedure, or for assigning values to materials
[VIM:1993, 6.13; ISO Guide 30:1992, 2.1]
3.6
reference measurement laboratory
laboratory that performs a reference measurement procedure and provides results with stated uncertainties
NOTE ISO/IEC 17025 uses the term “calibration laboratory”.
3.7
reference measurement procedure
thoroughly investigated measurement procedure shown to have an uncertainty of measurement
commensurate with the intended use, especially in assessing the trueness of other measurement procedures
for the same quantity and in characterizing reference materials
NOTE 1 Adapted from ISO 15193.
NOTE 2 When several reference measurement procedures exist for a given measurable quantity, it can be possible to
arrange them in a hierarchy according to size of uncertainty of measurement. A primary reference measurement
procedure is sometimes termed a “definitive method of measurement”, but not by VIM:1993.
NOTE 3 The Consultative Committee on Amount of Substance (CCQM) of BIPM has defined a “primary method of
measurement” as a method having the highest metrological qualities, whose operation can be completely described and
understood, for which a complete uncertainty statement can be written down in terms of SI units, and whose results are,
therefore, accepted without reference to a standard of the quantity being measured. For amount of substance, the
following principles of measurement were identified as suitable for primary measurement procedures: isotope
dilution-mass spectrometry, coulometry, gravimetry, titrimetry, and determination of colligative properties such as freezing
point depression. BIPM, Comité Consultatif pour la Quantité de Matière, 1995.
NOTE 4 The Analytical Chemistry Division of IUPAC describes an allied concept, “absolute method”, wherein
calculations are based on universal quantities and fundamental physical constants only.
3.8
traceability
property of the result of a measurement or the value of a standard whereby it can be related to stated
references, usually national or International Standards, through an unbroken chain of comparisons all having
stated uncertainties
[VIM:1993, 6.10]
3.9
true value of a quantity
value consistent with the definition of a given particular quantity
NOTE 1 This is a value that would be obtained by a perfect measurement.
NOTE 2 True values are by nature indeterminate.
NOTE 3 The indefinite article “a,” rather than the definite article “the,” is used in conjunction with a “true value” because
there may be many values consistent with the definition of a given particular quantity.
[VIM:1993, 1.19]
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SIST EN ISO 15195:2003
ISO 15195:2003(E)
NOTE 4 ISO 3534-1:1993 instead of “a true value,” uses the concept “the accepted reference value,” which can be a
theoretical (true), assigned, consensus, or procedure-defined value.
3.10
trueness of measurement
closeness of agreement between the average value obtained from a large series of results of measurements
and a true value
NOTE 1 Adapted from ISO 3534-1:1993, 3.12.
NOTE 2 “Trueness of measurement” is a qualitative concept.
NOTE 3 The degree of trueness is usually expressed numerically by the statistical measure “bias” that is Inversely
related to trueness.
3.11
uncertainty of measurement
parameter, associated with the result of a measurement, that characterizes the dispersion of the values that
could reasonably be attributed to the measurand
[VIM:1993, 3.9, GUM:1993, B.2.18]
NOTE 1 The parameter may be, for example, a standard deviation (or a given multiple of it), or the half-width of an
interval having a stated level of confidence.
NOTE 2 “Uncertainty of measurement” comprises, in general, many components. Some of these components may be
evaluated from the statistical distribution of the results of series of measurements and can be characterized by
“experimental standard deviations”. The other components, which can also be characterized by standard deviations, are
evaluated from assumed probability distributions based on experience or other information.
NOTE 3 It is understood that the result of the measurement is the best estimate of the value of the measurand, and
that all components of uncertainty, including those arising from systematic effects, such as components associated with
corrections and reference standards, contribute to the dispersion.
3.12
validation
confirmation, through the provision of objective evidence, that the requirements for a specific intended use or
application have been fulfilled
[ISO 9000:2000, 3.8.5]
3.13
verification
confirmation, through the provision of objective evidence, that specified requirements have been fulfilled
[ISO 9000:2000, 3.8.4]
4 Management system requirements
4.1 Organization and management
The laboratory shall be organized and operated so that its independence of judgement and its integrity shall
not be influenced by commercial, financial, or other conflicts of interest.
The laboratory management shall specify the responsibility, authority,
...