prEN ISO 15194

SLOVENSKI STANDARD
01-marec-2024
Nadomešča:
SIST EN ISO 15194:2009
Diagnostični medicinski pripomočki in vitro - Zahteve za certificirane referenčne
materiale in vsebino podporne dokumentacije (ISO/DIS 15194:2023)
In vitro diagnostic medical devices - Requirements for certified reference materials and
the content of supporting documentation (ISO/DIS 15194:2023)
In-vitro-Diagnostika - Messung von Größen in Proben biologischen Ursprungs -
Anforderungen an zertifizierte Referenzmaterialien und an den Inhalt der
Begleitdokumentation (ISO/DIS 15194:2023)
Dispositifs médicaux de diagnostic in vitro Mesurage des grandeurs dans les
échantillons d'origine biologique Exigences relatives aux matériaux de référence
certifiés et au contenu de la documentation associée (ISO/DIS 15194:2023)
Ta slovenski standard je istoveten z: prEN ISO 15194
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

DRAFT INTERNATIONAL STANDARD
ISO/DIS 15194
ISO/TC 212 Secretariat: ANSI
Voting begins on: Voting terminates on:
2023-12-26 2024-03-19
In vitro diagnostic medical devices — Requirements for
certified reference materials and the content of supporting
documentation
ICS: 11.100.10
This document is circulated as received from the committee secretariat.
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
ISO/CEN PARALLEL PROCESSING
THEREFORE SUBJECT TO CHANGE AND MAY
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ISO/DIS 15194:2023(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
PROVIDE SUPPORTING DOCUMENTATION. © ISO 2023

ISO/DIS 15194:2023(E)
DRAFT INTERNATIONAL STANDARD
ISO/DIS 15194
ISO/TC 212 Secretariat: ANSI
Voting begins on: Voting terminates on:

In vitro diagnostic medical devices — Requirements for
certified reference materials and the content of supporting
documentation
ICS: 11.100.10
This document is circulated as received from the committee secretariat.
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
© ISO 2023
ISO/CEN PARALLEL PROCESSING
THEREFORE SUBJECT TO CHANGE AND MAY
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NATIONAL REGULATIONS.
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NOTIFICATION OF ANY RELEVANT PATENT
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ii
PROVIDE SUPPORTING DOCUMENTATION. © ISO 2023

ISO/DIS 15194:2023(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Intended use, production and characterization of a Certified Reference Material
(CRM) . 9
4.1 Intended Use . 9
4.2 Production and certification . 9
4.3 Commutability . 9
5 Content of supporting documentation . 9
5.1 Supporting documentation. 9
5.2 Label . 10
5.3 Reference Material Certificate. 10
5.4 Certification Report . 11
5.4.1 General . 11
5.4.2 Warning and safety precautions .12
5.4.3 Introduction . 12
5.4.4 Scope of application for the CRM .12
5.4.5 Terms and Definitions .12
5.4.6 General properties .13
5.4.7 Specific properties . 13
5.4.8 Assignment of certified values . 15
5.4.9 Intended use . 16
5.4.10 Instructions for use. 16
5.4.11 Reference material Producer . 17
5.4.12 Bibliography . 17
5.4.13 Annexes . 18
5.4.14 Dates of authorization and revision . 18
Annex A (informative) Certified reference materials with nominal properties or ordinal
quantities .19
Annex ZA (informative) Relationship between this European Standard the General Safety
and Performance Requirements of Regulation (EU) 2017/746 aimed to be covered .20
Bibliography .23
iii
ISO/DIS 15194:2023(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).
ISO draws attention to the possibility that the implementation of this document may involve the use
of (a) patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed
patent rights in respect thereof. As of the date of publication of this document, ISO had not received
notice of (a) patent(s) which may be required to implement this document. However, implementers are
cautioned that this may not represent the latest information, which may be obtained from the patent
database available at www.iso.org/patents. ISO shall not be held responsible for identifying any or all
such patent rights.
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of 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
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 third edition cancels and replaces the second edition (ISO 15194:2009), which has been technically
revised.
The main changes are as follows:
— incorporated requirements, concepts and definitions for consistency with ISO 17511:2020;
— removed or reduced text regarded as redundant or of limited relevance. As a result Section 4 in the
second edition - Systematic designation of CRM properties - has been deleted;
— expanded and clarified the Scope statement to specify requirements for higher-order CRMs whose
intended for use is to underpin routine measurements in laboratory medicine;
— added requirements regarding description of the intended use and commutability of the CRM; and
— strengthened the documentation requirements for both the certificate and the certification report
accompanying a CRM.
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.
iv
ISO/DIS 15194:2023(E)
Introduction
Reference measurement systems are needed to enable the results produced by end user measurement
procedures to be metrologically traceable to measurement standards and/or measurement procedures
of the highest metrological level. Such systems exist within a traceability chain/calibration hierarchy as
described in ISO 17511:2020. In the context of in vitro diagnostic (IVD) medical devices, they mitigate
the risk of harm to patients by avoiding inconsistent results from different measurement systems.
Substances that are used to establish and maintain this metrological traceability of measurement
results - over time within one location, between different physical locations or with the application
of different measurement procedures - are Reference Materials (RMs). Certified Reference Materials
(CRMs) are a category of RMs required at the higher metrological levels of a calibration hierarchy or
that underpin the metrological traceability of measurement results.
A given CRM is supported by documentation describing the sources of the material, its processing and
production, measurement results, metrological traceability, instructions for use, homogeneity and
stability data, commutability data when applicable, and storage conditions, as well as health and safety
warnings. When the intended application of the CRM is as a secondary calibrator in the calibration
hierarchy of IVD devices, the commutability of the CRM is a critical property to be reported.
This Standard specifies the quality requirements for such materials and the recommended content of
their supporting documentation.
CRMs are used for one of three main purposes:
a) calibration of quantity values indicated by a measurement system or assigned to another RM;
b) assessment of measurement trueness of quantity values obtained in a given laboratory, or in a
group of laboratories;
c) assessment of measurement trueness of quantity values obtained using a new measurement
procedure.
NOTE “Measurement trueness” (ISO 17511:2020 3.47) is the closeness of agreement between the average of
an infinite number of replicate measured quantity values and a reference quantity value. It is inversely related to
systematic measurement error but is not related to random measurement error.
“Measurement precision” (ISO 17511:202 3.34) is the closeness of agreement between measured
quantity values obtained by replicate measurements on the same or similar objects under specified
conditions. It is usually expressed numerically by measures of imprecision, such as standard deviation,
variance, or coefficient of variation under the conditions of measurement. “Measurement precision” is a
measure of random measurement error.
The combined uncertainty of the assigned value of a CRM is determined by the combined uncertainty
of the steps above the CRM in the calibration hierarchy and the CRM uncertainties associated with its
homogeneity and stability. Suitability of its measurement uncertainty is determined by its intended use
in the calibration hierarchy.
Since the proper use of a CRM depends on the provision of detailed information, it is important to apply
rules for the documentation of CRMs.
In this Standard, defined concepts are indicated by italicized text.
v
DRAFT INTERNATIONAL STANDARD ISO/DIS 15194:2023(E)
In vitro diagnostic medical devices — Requirements for
certified reference materials and the content of supporting
documentation
1 Scope
This standard specifies requirements for producers of CRMs of higher metrological order and the
content of their supporting documentation that comply with the requirements of ISO 17511 and the
calibration hierarchies described therein. It is applicable to CRMs intended for use as either primary
reference materials, secondary calibrators or international conventional calibrators within calibration
hierarchies appropriate for measurands used in laboratory medicine, or for applications as trueness
controls. Requirements for determining the certified value of a CRM, including evaluation and reporting
of the assigned uncertainty, are specified.
This standard applies primarily to CRMs with assigned property values where the property has a
magnitude that can be expressed as a quantitative scalar number or ratio to a reference or refers to a
counting scale as also described in the scope of ISO 17511:2020. Annex A provides information on CRMs
for qualitative nominal properties and ordinal quantities, to provide guidance on important quality
attributes for such CRMs, whilst recognizing that they are not within the metrological traceability
schemes described in ISO 17511:2020.
When a CRM includes multiple measurands, this Standard is applied to each of the certified quantity
values present in the CRM.
Although intended to be applicable to producers of CRMs, this Standard will also be useful for RMs
that do not comply with the full metrological requirements of CRMs. For example, this International
Standard does not apply to a RM created by IVD MD manufacturers for use as working calibrator or
end-user calibrator within a calibration hierarchy traceable to a CRM, although some content may be
useful in assessing its performance.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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 80000 (all parts), Quantities and units
ISO 17511, In vitro diagnostic medical devices — Requirements for establishing metrological traceability of
values assigned to calibrators, trueness control materials and human samples
ISO 17034, General requirements for the competence of reference material producers
ISO/IEC Guide 99:2007, International vocabulary of metrology — Basic and general concepts and
associated terms (VIM)
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO/IEC Guide 99 and ISO 17511
and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
ISO/DIS 15194:2023(E)
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
analyte
component represented in the name of a quantity (3.22)
EXAMPLE In the type of quantity (3.22) "mass of protein in 24-hour urine", "protein" is the analyte. In
"amount of substance of glucose in plasma", "glucose" is the analyte. In both cases the full phrase describes the
measurand (3.13).
[SOURCE: ISO 17511:2020, 3.1]
3.2
calibrator
CRM (3.3) or a RM (3.23) with a traceable assigned quantity (3.22) value used in calibration of a
measurement system (3.16) according to a specified measurement procedure (3.15)
[SOURCE: ISO 17511:2020, 3.6, modified – “CRM or a RM with a traceable assigned quantity value”
replaced “measurement standard”]
3.3
certified reference material (CRM)
reference material (3.23), accompanied by documentation issued by an authoritative body and providing
one or more specified property values with associated uncertainty (3.29) and traceability (3.17) using
valid procedures
Note 1 to entry: “Documentation” is given in the form of a reference material certificate (3.24) and a certification
report (3.4).
Note 2 to entry: Requirements for the production of a CRM are given in ISO 17034. ISO Guide 35 provides technical
guidance on the characterization and the assessment of the homogeneity and stability of a CRM.
Note 3 to entry: In this definition, “uncertainty” covers both ‘measurement uncertainty’ (3.29) and ‘uncertainty
associated with the value of a nominal property’, such as for identity or sequence. “Traceability” covers both
‘metrological traceability (3.17) of a quantity (3.22) value’ and ‘traceability of a nominal property value’.
Note 4 to entry: Specified quantity (3.22) values of CRMs require metrological traceability (3.17) with associated
measurement uncertainty (3.29).
Note 5 to entry: ISO 17034 has an analogous definition.
Note 6 to entry: Specific additional requirements for CRMs and the content of supporting documentation required
in the field of IVD medical devices (3.11) are given in this Standard.
Note 7 to entry: For a specified material, a calibration certificate provided by an accredited calibration laboratory
is not by itself sufficient to confer the status of CRM on these types of materials.
EXAMPLE Human serum with an assigned quantity (3.22) value and associated measurement uncertainty
(3.29) for concentration (amount of substance per unit volume) of cholesterol inherently present in the serum
and used as a calibrator (3.2) or as a trueness control material (3.28) is an example of a CRM.
See also primary calibrator (3.18) and secondary calibrator (3.27).
[SOURCE: ISO 17511: 2020, 3.9 – modified. Note 1 to entry includes a certification report in addition
to a reference material certificate as “documentation” required for a CRM to meet the Scope of this
Standard]
3.4
certification report
additional information on a CRM (3.3), supplementary to that contained in a reference material
certificate (3.24) that describes the production, characterization and certification of a CRM (3.3)
intended for use in laboratory medicine and with IVD devices (3.11)
ISO/DIS 15194:2023(E)
3.5
commutability of a reference material
commutability
property of a reference material (3.23), demonstrated by the closeness of agreement between the relation
among the measurement results for a stated quantity (3.22) in this material, obtained according to at
least two measurement procedures (3.15), and the relation obtained among the measurement results for
other specified materials
Note 1 to entry: The RM (3.23) is usually a secondary calibrator (3.27) and the other materials are usually clinical
samples (3.26).
Note 2 to entry: For the commutability assessment of a CRM (3.3) it is desirable to measure the clinical samples
(3.26) with as many measurement procedures (3.15) as feasible.
Note 3 to entry: Closeness of agreement is defined in terms of fitness for purpose as appropriate for the intended
use of the RM (3.23).
Note 4 to entry: The validity of a commutability statement is restricted to the measurement procedures (3.15)
specified in a particular comparison.
[SOURCE: ISO 17511:2020 3.10]
Note 5 to entry: The IFCC Working Group Recommendations for Assessing Commutability and CLSI Document
EP30-A provide guidance on how to undertake a commutability study.
[SOURCE: Bibliography - Refs. 15, 16, 17, and 18]
3.6
control material
substance, material or artefact intended by its producer to be used to verify the performance of an IVD
medical device (3.11)
[SOURCE: ISO 17511: 2020, 3.11]
3.7
examination
set of operations having the objective of determining the numerical value, text value or characteristics
of a property
[SOURCE: ISO 15189: 2022, 3.8]
3.8
higher-order reference material
higher-order RM
CRM (3.3) that meets internationally accepted quality requirements and provides a common
metrological reference within a calibration hierarchy by which a manufacturer can establish
metrological traceability (3.17)
[SOURCE: ISO 17511: 2020, 3.14]
3.9
higher-order reference measurement procedure
higher-order RMP
RMP (3.25) meeting internationally accepted quality requirements and providing a common
metrological reference within a calibration hierarchy by which a producer can establish metrological
traceability (3.17) and accepted as providing measurement results fit for their intended use in assessing
measurement trueness
Note 1 to entry: Quality requirements for higher-order RMPs are defined in ISO 15193.
[SOURCE: ISO 17511:2020, 3.15 - modified]
ISO/DIS 15194:2023(E)
3.10
international conventional calibrator
international conventional calibrator material
calibrator (3.2) whose quantity (3.22) value is assigned by international agreement but does not have
metrological traceability (3.17) to the SI
Note 1 to entry: The quantity (3.22) is defined with respect to the intended clinical application.
[SOURCE: ISO 17511:2020, 3.17]
3.11
in vitro diagnostic medical device
IVD medical device
IVD MD
device, whether used alone or in combination, intended by the manufacturer for the in vitro examination
(3.7) of specimens derived from the human body solely or principally to provide information for
diagnostic, monitoring or compatibility purposes and including reagents, calibrators (3.2), control
materials (3.6), specimen receptacles, software, and related instruments or apparatus or other articles
[SOURCE: ISO 17511:2020, 3.21]
3.12
matrix
system matrix
components of a material, except the analyte (3.1)
Note 1 to entry: The biological system excluding the analyte (3.1) is the matrix of the material.
EXAMPLE In the measurand (3.13) "mass of protein in 24-hour urine", "24-hour urine" is the matrix. In the
measurand (3.13) "amount of substance of glucose in plasma", "plasma" is the matrix.
[SOURCE: ISO 17511:2020, 3.24]
3.13
measurand
quantity (3.22) intended to be measured
Note 1 to entry: Specification of a measurand requires knowledge of the kind of quantity (3.22), description of the
state of the phenomenon, body, or substance carrying the quantity (3.22), including any relevant component, and
the chemical entities involved.
Note 2 to entry: analyte (3.1) or the name of a substance or entity are terms sometimes erroneously used as
synonyms for measurand. This usage is erroneous because these terms do not refer to a quantity (3.22).
Note 3 to entry: In laboratory medicine description of the measurand includes the name of the quantity (3.22)
(e.g. amount of substance concentration), the analyte (3.1) (e.g. D-glucose), and the matrix (3.12) in which it is
found (e.g. plasma).
[SOURCE: ISO 17511:2020, 3.26]
3.14
measurement method
method of measurement
generic description of a logical organization of operations used in a measurement
[SOURCE: ISO 17511:2020, 3.30]
ISO/DIS 15194:2023(E)
3.15
measurement procedure (MP)
description of a measurement according to one or more measurement principles and to a given
measurement method (3.14), based on a measurement model and including any calculation to obtain a
measurement result. A measurement procedure refers to a written specification for how a measurement
is performed, including a technical description of reagents, calibrators (3.2), equipment, instrument,
and other details necessary to create and operate a measuring system (3.16) that implements those
specifications
Note 1 to entry: A MP is usually documented in sufficient detail to enable an operator to perform a measurement.
Note 2 to entry: A MP can include a statement concerning a target measurement uncertainty (3.29).
Note 3 to entry: A MP is sometimes called a standard operating procedure, abbreviated SOP.
Note 4 to entry: In medical laboratory measurements, a specific instance of a measurement procedure, an IVD
medical device (3.11), is used to make a measurement on a clinical sample (3.26) to produce a measurement result
which is used to inform medical decisions for a patient.
[SOURCE: ISO 17511:2020, 3.27, modified - Note 4 to entry has been added.]
3.16
measuring system
measurement system
set of one or more measuring instruments and often other devices, including any reagent and supply,
assembled and adapted to give information used to generate measured quantity values within specified
intervals for quantities of specified kinds
Note 1 to entry: A measuring system may consist of only one measuring instrument.
[SOURCE: ISO/IEC Guide 99:2007, 3.2]
3.17
metrological traceability
property of a measurement result whereby the result can be related to a reference through a
documented unbroken chain of calibrations, each contributing to the measurement uncertainty (3.29)
Note 1 to entry: For this definition, a ‘reference’ can be a definition of a measurement unit through its practical
realization, or a measurement procedure (3.15) including the measurement unit for a quantity (3.22) value, or a
calibrator (3.2).
Note 2 to entry: Metrological traceability requires an established calibration hierarchy.
Note 3 to entry: The abbreviated term “traceability” is commonly used to refer to other concepts, such as ‘sample
traceability’ or ‘document traceability’ or ‘instrument traceability’ or ‘material traceability’, where the history
(“trace”) of an item is meant. Therefore, the full term of “metrological traceability” is preferred if there is any risk
of confusion.
[SOURCE: ISO 17511:2020, 3.30 –Notes 1,2 and 9 (here note 3 to entry) are retained from the source]
3.18
primary calibrator
primary calibration material
calibrator (3.2) established using a primary reference measurement procedure (3.20), or created as
an artefact, chosen by convention. A primary calibrator serves as the anchor point for a calibration
hierarchy
EXAMPLE 1 Primary calibrator of amount-of-substance concentration prepared by dissolving a known
amount of substance of a primary reference material (3.19) for a chemical component into a known volume of
solution.
EXAMPLE 2 Primary calibrator for isotope amount-of-substance ratio measurements, prepared by mixing
known amounts-of-substance of specified isotopes.
ISO/DIS 15194:2023(E)
Note 1 to entry: ISO 17511:2020 further explains the role of a primary calibrator, defined as position m.2 within
a calibration hierarchy.
[SOURCE: ISO 17511:2020 3.37 – with “measurement standard” replaced by “calibrator”, “Note 1 to
entry” added and Examples 1 to 5 in the source text replaced by two Examples relevant to laboratory
medicine.]
3.19
primary reference material (PRM)
high purity CRM (3.3) of an analyte (3.1), certified for the mass fraction or mole fraction of the analyte
(3.1) and which constitutes the realization of the SI for the analyte (3.1)
Note 1 to entry: A PRM has its quantity (3.22) value assigned either directly by a primary RMP (3.20) or by
quantifying the impurities in the material by appropriate analytical methods (e.g. mass balance method).
Note 2 to entry: ISO 17511:2020 further explains the role of a primary reference material, defined as position m.1
within a calibration hierarchy.
[SOURCE: SOURCE: ISO 17511: 2020, 3.35]
3.20
primary reference measurement procedure
primary RMP
RMP (3.25) used to obtain a measurement result without relation to a calibrator (3.2) for a quantity
(3.22) of the same kind
[SOURCE: ISO 17511:2020, 3.36]
3.21
primary sample
specimen
discrete portion of a body fluid or tissue or other sample (3.26) associated with the human body taken
for examination (3.7), study or analysis of one or more quantities (3.22) or other properties to determine
the character of the whole
[SOURCE: ISO 15189:2022, 3.25]
3.22
quantity
property of a phenomenon, body, or substance, where the property has a magnitude that can be
expressed as a number and a reference
+
EXAMPLE 1 “Plasma (Blood) — Na ion; amount-of-substance concentration of 143 mmol/L in a given person
at a given time”.
EXAMPLE 2 Number concentration of erythrocytes in blood sample (Whole Blood) of 5 × 10 /μL in a given
person at a given time.
Note 1 to entry: quantity is not to be confused with analyte (3.1).
Note 2 to entry: A measurement procedure (3.15) for which the result is expressed in a qualitative manner (e.g.
nucleotide sequence for a DNA sample or “present” or “not present” against a ratio or counting scale with a pre-
determined decision threshold), is consistent with this definition of the term quantity.
[SOURCE: ISO 17511:2020 3.38]
3.23
reference material (RM)
material sufficiently homogeneous and stable with reference to specified properties, which has been
established to be fit for its intended use in measurement or in examination (3.7) of nominal properties
EXAMPLE 1 Examples of RMs embodying a quantity (3.22):
ISO/DIS 15194:2023(E)
a) water of stated purity, the dynamic viscosity of which is used to calibrate viscometers;
b) pooled human serum with an assigned quantity (3.22) value for the amount-of-substance
+
concentration of Na and used as a calibrator (3.2).
EXAMPLE 2 Example of an RM embodying nominal properties:
DNA compound containing a specified nucleotide sequence.
EXAMPLE 3 Spheres of uniform size mounted on a microscope slide.
Note 1 to entry: RMs with or without assigned quantity (3.22) values can be used as control materials (3.6)
whereas only CRMs (3.3) with metrological traceability (3.17) of quantity (3.22) values can be used as calibrators
(3.2) or as trueness control materials (3.28).
Note 2 to entry: RMs normally embody quantity (3.22) values but can also embody nominal properties.
Note 3 to entry: RMs can have assigned quantity (3.22) values that are traceable to a measurement unit outside
the International System of units (SI).
Note 4 to entry: An RM accompanied by documentation issued by an authoritative body and referring to valid
measurement procedures (3.15) used to assign a quantity (3.22) value with associated measurement uncertainty
(3.29) and metrological traceability (3.17) is referred to as a CRM (3.3).
[SOURCE: ISO 17511: 2020, 3.39 with modifications]
3.24
reference material certificate
document containing the essential information required for the use of a CRM (3.3), confirming that the
necessary procedures have been carried out to ensure the validity and metrological traceability (3.17)
of the stated quantity (3.22) or nominal property values
[SOURCE: ISO Guide 31:2015, 3.4 – modified]
3.25
reference measurement procedure (RMP)
measurement procedure (3.15) accepted as providing measurement results fit for their intended use in
assessing measurement trueness of measured quantity (3.22) values obtained from other measurement
procedures (3.15) for a quantity (3.22) of the same kind, in calibration, or in assigning a quantity (3.22)
value to a CRM (3.3)
Note 1 to entry: Requirements of RMPs (3.25) used in a calibration hierarchy supporting IVD devices (3.11) are
described in ISO 15193.
Note 2 to entry: Explanation of the role of a primary RMP (3.20) within a calibration hierarchy can be found in
ISO 17511.
[SOURCE: ISO 17511:2020, 3.40 - modified]
3.26
sample
one or more parts taken from a primary sample (3.21)
[SOURCE: ISO 15189:2012, 3.24]
3.27
secondary calibrator
secondary calibration material
calibrator (3.3) established through calibration with respect to a primary calibrator (3.18) or by a RMP
(3.25) that defines the measurand (3.13) or by a consensus of results obtained using measurement
procedures (3.15)
Note 1 to entry: Also called commutable reference material or secondary reference material.
ISO/DIS 15194:2023(E)
Note 2 to entry: Calibration may be obtained directly between a primary calibrator (3.18) and a secondary
calibrator or involve an intermediate measurement system (3.16) calibrated by the primary calibrator (3.18) and
used to assign a measurement result to the secondary calibrator.
Note 3 to entry: ISO 17511 further explains the role of a secondary calibrator, defined as position m.3 within a
calibration hierarchy.
[SOURCE: ISO 17511:2020 3.42. – modified with “measurement standard” replaced by “calibrator”]
3.28
trueness control material
trueness control
CRM (3.3) used to assess the bias of a measurement procedure (3.15) for a specified quantity (3.22) in a
specified measuring system (3.16)
Note 1 to entry: Trueness controls are often prepared in a matrix (3.12) that emulates clinical samples (3.26).
Note 2 to entry: Trueness control materials shall be evaluated for commutability (3.5) with clinical samples (3.26).
[SOURCE: ISO 17511: 2020, 3.46 – modified as follows: “CRM” replaced “RM”, text was revised for
consistency with definitions in this Standard, “clinical” replaced “human” in Notes 1 and 2 to entry and
“shall” replaced “should” in Note 2 to entry]
3.29
uncertainty of measurement
measurement uncertainty
non-negative parameter characterizing the dispersion of the quantity (3.22) values being attributed to
a measurand (3.13), based on the information used
Note 1 to entry: Measurement uncertainty includes components arising from systematic effects, as in the case of
corrections to the assigned quantity (3.22) values of measurement standards. Sometimes estimated systematic
effects are not corrected for, but instead, the associated measurement uncertainty components are incorporated.
Note 2 to entry: The parameter may be, for example, a standard deviation called standard measurement
uncertainty (or a specified multiple of it), or the half-width of an interval, having a stated coverage probability.
Note 3 to entry: Measurement uncertainty comprises, in general, many components. Some of these may be
evaluated by Type A evaluation of measurement uncertainty from the statistical distribution of the quantity (3.22)
values from a series of measurements and can be characterized by standard deviations. The other components,
which may be evaluated by Type B evaluation of measurement uncertainty, can also be characterized by standard
deviations, evaluated from probability density functions based on experience or other information.
Note 4 to entry: In general, for a given set of information, it is understood that the measurement uncertainty is
associated with a stated quantity (3.22) value attributed to the measurand (3.13). A modification of this value
results in a modification of the associated uncertainty.
Note 5 to entry: Type A evaluation of measurement uncertainty is defined as evaluation of a component of
measurement uncertainty by a statistical analysis of measured quantity (3.22) values obtained under defined
measurement conditions.
Note 6 to entry: Type B evaluation of measurement uncertainty is defined as evaluation of a component of
measurement uncertainty determined by means other than a Type A evaluation. This may include standard
deviations:
a) obtained from information associated with authoritative published quantity (3.22) values,
b) associated with quantity (3.22) values of CRMs (3.3),
c) obtained from a calibration certificate,
d) obtained from experience or other means.
[SOURCE: ISO/IEC Guide 99:2007, 2.26, modified – Notes to entry 5 and 6 have been added]
ISO/DIS 15194:2023(E)
4 Intended use, production and characterization of a Certified Reference
Material (CRM)
4.1 Intended Use
When used within a calibration hierarchy a CRM shall be classified in accordance with its position and
role in the reference measurement system for a specified quantity. As described in ISO 17511, a CRM
can be classified as a:
a) primary reference material;
b) primary calibrator;
c) secondary calibrator;
d) international conventional calibrator.
NOTE ISO 17511 further explains the roles of a primary reference material, primary calibrator and
secondary calibrator, designated respectively in Figure 3 of ISO 17511 as positions m.1, m.2 and m.3, within a
calibration hierarchy where the results obtained for the measurand in clinical samples are traceable to the SI
through a particular primary calibrator.
4.2 Production and certification
A CRM shall be produced and certified in accordance with the quality system requirements set out in
ISO 17034. Certification includes the assessment of the homogeneity and stability of the material, the
assignment of the quantity value for the CRM and the measurement uncertainty of this assignment.
4.3 Commutability
A primary reference material (PRM) does not require a commutability assessment because it consists
predominantly of a defined high-purity analyte.
A secondary calibrator is a commutable CRM typically used at position m.3 in a calibration hierarchy as
described in ISO 17511:2020.
Producing a large batch of commutable CRM can involve pooling single donations of clinical samples or
developing another matrix that provides equivalent measurement responses to those of clinical samples.
Also, modifications of the matrix such as adding exogenous substances, freezing or lyophilization can
affect commutability of the CRM and compromise its suitability. If a non-commutable CRM is used as
a calibrator for one or more measurement procedures, results obtained for a clinical sample may not
agree among the measurement procedures. Similarly, use of a non-commutable CRM as a trueness
control material will not make it possible to evaluate and validate results produced by the assessed
measurement procedures. Consequently, a CRM intended for use as a calibrator or as a trueness control
material shall include evaluation of its commutability, such that its performance is consistent with its
intended use. Clause 5.4.7.4 of this Standard provides information on the technical requirements for
performing a commutability assessment. Additional technical guidance for performing commutability
assessments is provided in Bibliography References 15 through 18.
5 Content of supporting documentation
5.1 Supporting documentation
A CRM shall have an identifying label securely attached and shall be accompanied by a reference
material certificate.
In addition, information on the production and processing and the studies performed as well as the
assessment data for the CRM, shall be made available to the end-user by the producer. When this
ISO/DIS 15194:2023(E)
information is provided as a certification report end-users can evaluate the fitness of a CRM for i
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