Iso 17511 2020

INTERNATIONAL ISO
STANDARD 17511
Second edition
2020-04
In vitro diagnostic medical devices —

Requirements for establishing
metrological traceability of values
assigned to calibrators, trueness
control materials and human samples
Dispositifs médicaux de diagnostic in vitro — Exigences pour
iTeh STANDARD PREVIEW
l'établissement d'une traçabilité métrologique des valeurs attribuées
aux étalons, aux matériaux de contrôle de la justesse et aux
(standards.iteh.ai)
échantillons humains
ISO 17511:2020
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5f3d2884ac47/iso-17511-2020
Reference number
ISO 17511:2020(E)
© ISO 2020
ISO 17511:2020(E)


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ISO 17511:2020
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ISO 17511:2020(E)

Contents Page
Foreword......................................................................................................................................................................................................................................... vi
Introduction............................................................................................................................................................................................................................. viii
1 Scope.................................................................................................................................................................................................................................. 1
2 Normative references....................................................................................................................................................................................... 2
3 Terms and definitions, symbols and abbreviated terms............................................................................................. 2
4 General requirements to be fulfilled by a manufacturer for establishing, validating
and documenting metrological traceability of human sample values determined
with a specified IVD MD..............................................................................................................................................................................19
4.1 Requirements for documenting metrological traceability of measured quantity values..... 19
4.2 Definition of the measurand...................................................................................................................................................... 19
4.3 Specifications for maximum allowable expanded measurement uncertainty, Umax(y)...... 20
4.3.1 General requirements................................................................................................................................................ 20
4.3.2 Scope of the specification....................................................................................................................................... 20
4.4 Defining the calibration hierarchy....................................................................................................................................... 20
4.4.2 Measured quantity....................................................................................................................................................... 21
4.4.3 Highest level of metrological traceability................................................................................................. 21
4.4.4 Traceability to SI............................................................................................................................................................ 21
4.4.5 Non-SI traceable IVD MDs...................................................................................................................................... 21
4.5
4.4.6 iTeh STANDARD PREVIEW
Number of levels in the specified hierarchy........................................................................................... 21
Selection and requirements for RMs and calibrators.......................................................................................... 21
4.5.1 (standards.iteh.ai)
General requirements................................................................................................................................................ 21
4.5.2 Characteristics to be documented.................................................................................................................. 21
4.5.3 Higher order RMs that conform with ISO 15194............................................................................... 22
ISO 17511:2020
4.5.4 https://standards.iteh.ai/catalog/standards/sist/d85d1739-6f01-4d6c-aff0-
RMs not conforming to ISO 15194................................................................................................................. 22
4.5.5 Commutability of RMs............................................................................................................................................... 22
5f3d2884ac47/iso-17511-2020
4.5.6 Exception to commutability assessment requirements............................................................... 23
4.5.7 Application of a non-commutable CRM..................................................................................................... 23
4.5.8 Alternative RMs.............................................................................................................................................................. 23
4.5.9 Augmentation of alternative RMs.................................................................................................................... 23
4.5.10 Non-commutable end-user IVD MD calibrators................................................................................. 24
4.6 Selection and requirements for MPs.................................................................................................................................. 24
4.6.1 Rationale for selection of MPs and documentation responsibility..................................... 24
4.6.2 Metrological status of MPs.................................................................................................................................... 24
4.6.3 Reference measurement laboratories......................................................................................................... 24
4.6.4 Impact of influence quantities........................................................................................................................... 25
4.6.5 Changes in the measured quantity within a calibration hierarchy.................................... 25
4.7 Estimating uncertainty of assigned values for end-user IVD MD calibrators................................. 25
4.7.2 Documentation for method of estimating ucal .................................................................................... 26
4.7.3 Statistical considerations and scope of ucal estimates................................................................... 26
4.7.4 Expression of ucal .......................................................................................................................................................... 26
4.7.5 Product modifications............................................................................................................................................... 27
4.7.6 Information to be provided to the end-user.......................................................................................... 28
4.8 Validation of metrological traceability of values assigned to an IVD MD calibrator................. 28
4.8.1 General validation requirements..................................................................................................................... 28
4.8.2 Validation strategies................................................................................................................................................... 28
4.8.3 Test design considerations and acceptance criteria....................................................................... 29
4.8.4 Calibration hierarchies with an available RMP................................................................................... 29
4.8.5 Calibration hierarchies with no available RMP................................................................................... 29
4.8.6 Calibration hierarchies with no RMPs and no CRMs...................................................................... 29
4.8.7 Validation of design changes to an end-user IVD MD calibrator.......................................... 30
4.9 Additional calibration hierarchy documentation responsibilities........................................................... 30
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ISO 17511:2020(E)

4.9.1 Obligation to end-users............................................................................................................................................ 30

4.9.2 Maintaining documentation................................................................................................................................. 30
4.9.3 Third party manufacturers of IVD MD calibrators........................................................................... 30
4.9.4 Modifications introduced by independent entities.......................................................................... 30
4.9.5 Calibration hierarchies supporting IVD MDs developed by a single entity
for its own use.................................................................................................................................................................. 31
4.9.6 RMs other than end-user IVD MD calibrators...................................................................................... 31
4.9.7 EQA and PT materials with claims of metrologically traceable target values........... 31
5 Model calibration hierarchies for metrological traceability................................................................................31
5.1 Elements of the description of a calibration hierarchy...................................................................................... 31
5.2 Cases with RMPs and primary RMs.................................................................................................................................... 32
5.2.1 General considerations............................................................................................................................................. 32
5.2.2 Definition of the measurand................................................................................................................................ 33
5.2.3 Selecting RMPs................................................................................................................................................................ 34
5.2.4 Primary RMPs................................................................................................................................................................... 34
5.2.5 Primary calibrators..................................................................................................................................................... 35
5.2.6 Assigning a value to a secondary RM or calibrator.......................................................................... 35
5.2.7 Commutability of secondary RMs................................................................................................................... 35
5.2.8 Manufacturer’s Selected MP................................................................................................................................ 35
5.2.9 Working calibrators..................................................................................................................................................... 35
5.2.10 Manufacturer’s standing MP................................................................................................................................ 36
5.2.11 Manufacturer's end-user calibrator.............................................................................................................. 36
5.2.12 ucal of the assigned value of the end-user calibrator...................................................................... 36
5.2.13 End-user IVD MD........................................................................................................................................................... 36
5.3 iTeh STANDARD PREVIEW
Cases with a primary RMP that defines the measurand................................................................................... 36
5.3.1 General Considerations............................................................................................................................................ 36
5.3.2 (standards.iteh.ai)
Definition of the measurand................................................................................................................................ 38
5.3.3 Higher order RMP that defines the measurand.................................................................................. 38
5.3.4 The primary RMP and definition ISO 17511:2020 of the measurand....................................................................... 38
5.3.5 Documentation of the primary RMP............................................................................................................. 38
5.3.6 Assignment of values5f3d2884ac47/iso-17511-2020
to secondary RMs................................................................................................... 39
5.3.7 Manufacturer’s selected MP................................................................................................................................. 39
5.3.8 Manufacturer's working calibrator................................................................................................................ 39
5.3.10 Manufacturer's end-user calibrator.............................................................................................................. 40
5.3.11 End-user IVD MD........................................................................................................................................................... 40
5.4 Cases for measurands defined by a RMP calibrated with a particular primary calibrator.40
5.4.2 Definition of the measurand................................................................................................................................ 41
5.4.3 Value assignment of the primary RM........................................................................................................... 42
5.4.4 Value assignment of the primary calibrator........................................................................................... 42
5.4.5 Selection and intended use of the RMP in the calibration hierarchy................................ 42
5.4.6 Manufacturer's selected MP................................................................................................................................. 42
5.4.7 Manufacturer’s working calibrator................................................................................................................ 42
5.4.9 End-user IVD MD calibrator................................................................................................................................. 43
5.4.10 End-user IVD MD........................................................................................................................................................... 43
5.5 Cases with an international conventional calibrator that defines the measurand.................... 43
5.5.2 The international conventional calibrator — Material description.................................. 45
5.5.3 Value assignment of an international conventional calibrator.............................................. 45
5.5.4 Commutability of an international conventional calibrator..................................................... 45
5.5.5 Calibration and selection of the manufacturer’s selected MP................................................ 46
5.5.6 Characteristics and value assignment of the manufacturer’s working calibrator.46
5.5.8 End-user IVD MD calibrator................................................................................................................................. 46
5.5.9 End-user IVD MD........................................................................................................................................................... 46
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ISO 17511:2020(E)

5.6 Cases with metrological traceability supported by an international harmonisation

protocol....................................................................................................................................................................................................... 46
5.6.1 General Considerations............................................................................................................................................ 46
5.6.2 International harmonisation protocol........................................................................................................ 47
5.6.3 Assignment of values to harmonisation RMs........................................................................................ 48
5.6.4 Application of harmonisation RMs................................................................................................................ 48
5.6.5 End-user IVD MD........................................................................................................................................................... 48
5.7 Cases for measurands with metrological traceability only to manufacturer’s
internal arbitrarily defined RM(s)....................................................................................................................................... 48
5.7.2 Selection of RMs............................................................................................................................................................. 49
5.7.3 Manufacturer’s Selected MP................................................................................................................................ 50
5.7.4 Manufacturer’s Standing MP............................................................................................................................... 50
5.7.5 End-user IVD MD calibrators.............................................................................................................................. 50
5.7.6 End-user IVD MD........................................................................................................................................................... 50
5.7.7 Documentation of the calibration hierarchy.......................................................................................... 50
6 Labelling information to be provided to end-users by the manufacturer..............................................51
Bibliography.............................................................................................................................................................................................................................. 52

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ISO 17511:2020
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ISO 17511:2020(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).
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. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on 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 the following
URL: www.iso.org/iso/foreword.html.
(standards.iteh.ai)
This document was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in
vitro diagnostic test systems. ISO 17511:2020
This second edition cancels and replaces the first edition (ISO 17511:2003), which has been technically
5f3d2884ac47/iso-17511-2020
revised. The main changes compared to the previous edition are as follows:
— incorporation of the special requirements for metrologically traceable calibration hierarchies for
measurement of catalytic concentration of enzymes (previously covered in ISO 18153:2003);
— to clarify that final reported values on human samples shall be metrologically traceable to the highest
order available reference, the title and scope were modified to include metrological traceability of
values assigned to human samples;
— updated normative references to remove International Vocabulary of Basic and General Terms
in Metrology, 2nd edition, ISO, Geneva (1993) and ISO Guide 35:1989, Certification of reference
materials — General and statistical principles;
— revision of Clause 4 to clearly define requirements of a manufacturer of an in vitro diagnostic
medical device in establishing and documenting metrological traceability of assigned values (for
calibrators, trueness controls and human samples), while incorporating requirements previously
addressed in Clauses 6, 7 and 8 (thus eliminating those sections);
— revision of Clause 5 to incorporate additional models of metrologically traceable calibration
hierarchies, especially 5.3 for measurement of catalytic concentration of enzymes (where the
measurand is defined by a primary RMP; previously addressed in ISO 18153:2003), and 5.6 for
an overview of the concept of assigned values of materials for measurands with metrological
traceability to international harmonisation protocols (addressed in detail in ISO 21151).
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.
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ISO 17511:2020(E)


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ISO 17511:2020
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ISO 17511:2020(E)

Introduction
In laboratory medicine, the objective of examining a measurand in a human sample is to produce
laboratory results that will enable a clinician to assess the risk of a disease, or to diagnose and make
treatment decisions for a medical condition. To be clinically useful, the results obtained from a given
human sample examined by different laboratories or among different in vitro diagnostic medical devices
(IVD MDs) within a single laboratory should be equivalent, regardless of the measurement procedure
employed. Equivalent results allow uniform application of medical decision limits and reference
intervals, which can reduce the risk of harm caused by medical decisions based on non-equivalent
examination results. Equivalence of results among different IVD MDs for the same measurand is also
important for the analysis of results in medical records for the purpose of supporting clinical decisions
and for conducting epidemiological investigations.
Equivalent results for human samples for a measurand can be achieved by establishing metrological
traceability of the values assigned to the calibrators for a measurement procedure (MP) to the highest
available reference system component for the measurand. Metrological traceability describes the
calibration hierarchy and the sequence of value assignments, demonstrating an unbroken linkage
between the measurement result for a human sample up to the highest available reference system
component in the calibration hierarchy. The point at which metrological traceability begins (i.e. the
highest level of metrological traceability in the calibration hierarchy) depends on the availability of
higher order reference measurement procedures (RMPs), reference materials (RMs) or harmonisation
protocols for the stated measurand.
Limitations in implementing metrologically traceable calibrations occur when different IVD MDs
intended for the same measurand do not measure the same or very closely related measurable quantities.
Some measurands of medical interest may be well-defined elements or molecules. An increasing number
(standards.iteh.ai)
of medical decisions depend on measurands that consist of complex and variable mixtures of chemical
structures, molecular species and molecular complexes in varying proportions, e.g. glycoproteins with
multiple isoforms, variant amino acid sequences,ISO nucleic acid sequences, and other complex molecular
17511:2020
forms. When the selectivity of an IVD MD is not fit-for-purpose, sample-specific influence quantities
in human samples due to factors including5f3d2884ac47/iso-17511-2020
disease, drugs or other pathological conditions may lead to
erroneous values for the intended measured quantity. Even with metrological traceability to higher
order reference system components, the selectivity of MPs at all levels in the calibration hierarchy for
a given IVD MD can influence its ability to achieve results for human samples that are equivalent to the
results obtained with other IVD MDs for the same measurand.
This document presents requirements for manufacturers of IVD MDs in documenting the calibration
hierarchy for a measured quantity in human samples using a specified IVD MD. The document includes
various model calibration hierarchies offering potential technical solutions for different kinds of
measurands in establishing metrological traceability of assigned values for human samples, calibrators
and trueness control materials. Use of this document as part of a broadly-based risk management
program for manufacturers of IVD MDs is consistent with the requirements of ISO 14971 and is
expected to assist in the reduction of the risk of harm to patients due to non-equivalence of results
among different IVD MDs.
viii © ISO 2020 – All rights reserved

INTERNATIONAL STANDARD ISO 17511:2020(E)
In vitro diagnostic medical devices — Requirements for

establishing metrological traceability of values assigned to
calibrators, trueness control materials and human samples
1 Scope
This document specifies technical requirements and documentation necessary to establish metrological
traceability of values assigned to calibrators, trueness control materials and human samples for
quantities measured by IVD MDs. The human samples are those intended to be measured, as specified
for each IVD MD. Metrological traceability of values for quantities in human samples extends to the
highest available reference system component, ideally to RMPs and certified reference materials (CRMs).
All parties having a role in any of the steps described in a calibration hierarchy for an IVD MD are
subject to the requirements described. These parties include but are not limited to manufacturers (of
IVD MDs), RMP developers (see ISO 15193), RM producers (see ISO 15194), and reference/calibration
laboratories (see ISO 15195) supporting calibration hierarchies for IVD MDs.
NOTE 1 Producers of RMs intended for use in standardization or calibration of IVD MDs include
commercial and non-commercial organizations producing RMs for use by many end-users of IVD MDs
and/or calibration laboratories, or for use by a single end-user medical laboratory, as in the case of
a measurement standard (calibrator) intended to be used exclusively for calibration of a laboratory-
developed MP. (standards.iteh.ai)
This document is applicable to:
ISO 17511:2020
a) all IVD MDs that provide measurement results in the form of numeric values, i.e. rational (ratio)
and/or differential (interval) scales, and counting scales.
5f3d2884ac47/iso-17511-2020
b) IVD MDs where the measurement result is reported as a qualitative value established with a ratio
of two measurements (i.e. the signal from a specimen being tested and the signal from a RM with a
specified concentration or activity at the cut-off), or a counting scale, with corresponding decision
threshold(s). This also includes IVD MDs where results are categorized among ordinal categories
based on pre-established quantitative intervals for a quantity.
c) RMs intended for use as trueness control materials for verification or assessment of calibration of
IVD MDs, i.e. some commutable CRMs and some external quality assessment (EQA) materials (if so
indicated in the RM’s intended use statement).
d) IVD MD-specific calibrators and trueness control materials with assigned values, intended to be
used together with a specified IVD MD.
e) IVD MDs as described in a) and b), where no end-user performed calibration is required (i.e. when
the manufacturer performs a factory calibration of the IVD MD).
This document is not applicable to:
a) calibrators and trueness control materials for IVD MDs which, due to their formulation, are known
to have zero amount of measurand;
b) control materials that are used only for internal quality control purposes in medical laboratories to
assess the imprecision of an IVD MD, either its repeatability or reproducibility, and/or for assessing
changes in IVD MD results compared to a previously established calibration condition;
c) control materials that are used only for internal quality control purposes in medical laboratories
and which are supplied with intervals of suggested acceptable values that are not metrologically
traceable to higher order reference system components;
© ISO 2020 – All rights reserved 1

ISO 17511:2020(E)

d) properties reported as nominal scales and ordinal scales, where no magnitude is involved.
NOTE 2 Nominal scales are typically used to report e.g. identity of blood cell types, microorganism types,
identity of nucleic acid sequences, identity of urine particles.
NOTE 3 Ordinal scales are often applied to results differentiated into dichotomous groupings (e.g. ‘sick’
vs. ‘healthy’), and occasionally to results differentiated into non-dichotomous categories where the result
categories are rank-ordered but the rank-ordered categories cannot be differentiated in terms of relative
degree of difference, e.g. negative, +1, +2, +3 for grading of presence of haemoglobin in urine specimens by visual
observation.
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 18113-2, In vitro diagnostic medical devices — Information supplied by the manufacturer (labelling) —
Part 2: In vitro diagnostic reagents for professional use
ISO 15193, In vitro diagnostic medical devices — Measurement of quantities in samples of biological
origin — Requirements for content and presentation of reference measurement procedures
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
3 Terms and definitions, symbols and abbreviated terms
(standards.iteh.ai)
For the purposes of this document, the following terms and definitions apply.
ISO 17511:2020
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
5f3d2884ac47/iso-17511-2020
— ISO Online browsing platform: available at https://w ww.iso.org/obp
— IEC Electropedia: available at http://w ww.electropedia.org/
3.1
analyte
component represented in the name of a measurable quantity (3.38)
EXAMPLE In the type of quantity (3.38) "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 long phrase represents the
measurand (3.26).
3.2
analytical selectivity
selectivity of a measuring system
selectivity
property of a measuring system (3.29), used with a specified MP (3.27), whereby it provides measured
quantity (3.38) values for one or more measurands (3.26) such that the values of each measurand (3.26)
are independent of other measurands (3.26) or other quantities (3.38) in the phenomenon, body, or
substance being investigated
EXAMPLE Capability of a measuring system (3.29) to measure the amount-of-substance concentration of
creatinine in blood plasma without being influenced by the other components present in the sample.
Note 1 to entry: In chemistry, selectivity of a measuring system (3.29) is usually obtained for quantities (3.38)
with selected components in concentrations within stated intervals.
Note 2 to entry: Selectivity as used in physics is a concept close to specificity as it is sometimes used in chemistry.
2 © ISO 2020 – All rights reserved

ISO 17511:2020(E)

[SOURCE: ISO/IEC Guide 99:2007 4.13, modified — ‘analytical selectivity’ added as the preferred term.
Included only Example 5 with abbreviated text and NOTES 3 and 4.]
3.3
measurement bias
bias
estimate of a systematic measurement error
Note 1 to entry: See ISO/IEC Guide 99:2007 2.17, systematic measurement error.
Note 2 to entry: This definition applies to quantitative measurements only.
[SOURCE: ISO/IEC Guide 99:2007 2.18, modified — Note 1 and 2 to entry have been added.]
3.4
calibration
operation that, under specified conditions, in a first step, establishes a relation between the quantity
(3.38) values with measurement uncertainties (3.48) provided by measurement standards (3.28) and
corresponding indications with associated measurement uncertainties (3.48) and, in a second step, uses
this information to establish a relation for obtaining a measurement result from an indication
Note 1 to entry: A calibration may be expressed by a statement, calibration function, calibration diagram,
calibration curve, or calibration table. In some cases, it may consist of an additive or multiplicative correction of
the indication with associated measurement uncertainty (3.48).
Note 2 to entry: Calibration should not be confused with adjustment of a measuring system (3.29), often
mistakenly called “self-calibration”, or with verification (3.50) of calibration.
Note 3 to entry: Often, the first step(standards.iteh.ai)

alone in the above definition is perceived as being calibration.
[SOURCE: ISO/IEC Guide 99:2007 2.39]

ISO 17511:2020
3.5 https://standards.iteh.ai/catalog/standards/sist/d85d1739-6f01-4d6c-aff0-
calibration hierarchy 5f3d2884ac47/iso-17511-2020
sequence of calibrations (3.4) from a reference to the final measuring system (3.29), where the outcome
of each calibration (3.4) depends on the outcome of the previous calibration (3.4)
Note 1 to entry: Measurement uncertainty (3.48) necessarily increases along the sequence of calibrations (3.4).
Note 2 to entry: The elements of a calibration hierarchy are one or more measurement standards (3.28) and
measuring systems (3.29) operated according to MPs (3.27).
Note 3 to entry: A comparison between two measurement standards (3.28) may be viewed as a calibration (3.4) if
the comparison is used to check and, if necessary, correct the quantity (3.38) value and measurement uncertainty
(3.48) attributed to one of the measurement standards (3.28).
Note 4 to entry: In this document, a calibration hierarchy is defined as a detailed description of the process for
assigning a value of a measurand (3.26) to a sample using a specified sequence of MPs (3.27) and RMs (3.39)
(calibrated by higher order RMs (3.39) and/or MPs (3.27) for the same type of quantity (3.38), where available).
Note 5 to entry: For purposes of this definition, a sample includes human samples as well as calibration materials
(3.6), EQA materials or other RMs (3.39).
[SOURCE: ISO/IEC Guide 99:2007 2.40, modified — excludes original Note 3. Note 3 to entry is Note 4
and Note 5 has been added.]

ISO 17511:2020(E)

3.6
calibrator
calibration material
measurement standard (3.28) used in calibration (3.4) of a measuring system (3.29) according to a
specified MP (3.27)
[SOURCE: ISO/IEC Guide 99:2007 5.12, modified — “calibration material” has been added as an admitted
term, "of a measuring system according to a specified MP" has been added at the end of the definition,
NOTE has been deleted.]
3.7
catalytic activity
property of a component corresponding to the catalysed substance rate of conversion of a specified
chemical reaction, in a specified measuring system (3.29)
Note 1 to entry: In this document the "component" is an enzyme.
Note 2 to entry: The quantity (3.38) "catalytic activity" relates to an amount of active enzyme, not its
concentration; see 3.8.
Note 3 to entry: The coherent derived SI unit is "katal" (kat), equal to "mole per second" (mol s−1).
Note 4 to entry: The MP (3.27) is an essential element of the definition of the measurand (3.26).
Note 5 to entry: In many instances, instead of the conversion rate of the substrate ascribed in the short name
of the enzyme analyte (3.1), e.g. "creatine" in "creatine kinase", the conversion rate of an indicator substance as
substrate of a combined reaction is measured. Then the measurand (3.26) should be defined as 'catalytic activity
of the enzyme as measured by the conversion rate of an indicator substance in a specified system according to a
given MP (3.27)', e.g. 'catalytic activity of creatine kinase as measured by the rate of conversion of NADP+ in the
(standards.iteh.ai)
IFCC reference procedure in human serum'.
[SOURCE: ISO 18153:2003, 3.2] ISO 17511:2020

3.8 5f3d2884ac47/iso-17511-2020
catalytic-activity concentration
catalytic concentration
catalytic activity (3.7) of a component divided by volume of the original system
Note 1 to entry: The coherent derived SI unit is "katal per cubic metre" or "mole per second cubic metre"
(kat m−3 = mol s−1 m−3). In laboratory medicine, the unit of volume can be chosen to be "litre" (L).
Note 2 to entry: In this document the "component" is an enzyme and the "original system" can be, for example,
the plasma of a blood sample.
[SOURCE: ISO 18153:2003, 3.3]

3.9
certified reference material
CRM
RM (3.39) accompanied by documentation issued by an authoritative body and providing one or more
specified property values with associated uncertainties (3.48) and traceabilities (3.31), using valid
procedures
EXAMPLE Human serum with assigned quantity (3.38) value for the concentration of cholesterol and
associated measurement uncertainty (3.48) stated in an accompanying certificate, used as a calibrator (3.6) or
measurement trueness control material (3.46).
Note 1 to entry: ‘Documentation’ is given in the form of a ‘certificate’ (see ISO Guide 31).
Note 2 to entry: Procedures for the production and CRM certification are given in ISO 17034:2016 and
ISO Guide 35:2017.

ISO 17511:2020(E)

Note 3 to entry: In this definition, “uncertainty” covers both ‘measurement uncertainty’ (3.48) and ‘uncertainty
associated with the value of a nominal property’, such as for identity and sequence. “Traceability” covers both
‘metrological traceability (3.31) of a quantity value’ and ‘traceability of a nominal property value’.
Note 4 to entry: Specified quantity (3.38) values of CRMs require metrological traceability (3.31) with associated
measurement uncertainty (3.48)[25].
Note 5 to entry: ISO/REMCO has an analogous definition[25] but uses the modifiers “metrological” and
“metrologically” to refer to both quantities (3.38) and nominal properties.
Note 6 to entry: Specific requirements for CRMs and the content of supporting documentation (in the field of in
vitro diagnostic medical devices) are given in ISO 15194.
Note 7 to entry: For a specified material, a calibration (3.4) certificate provided by an accredited calibration (3.4)
laboratory does not confer the status of CRM on these types of materials.
[SOURCE: ISO/IEC Guide 99:2007 5.14, modified — Note 6 and 7 to entry have been added.]
3.10
commutability of a reference material
commutability
property of a RM (3.39), demonstrated by the closeness of agreement between the relation among the
measurement results for a stated quantity (3.38) in this material, obtained according to two MPs (3.27),
and the relation obtained among the measurement results for other specified materials
Note 1 to entry: The RM (3.39) in question is usually a calibrator (3.6) and the other specified materials are
usually routine samples.
Note 2 to entry: In commutability assessment of an RM (3.39), comparisons among all applicable MPs (3.27) is
desirable. (standards.iteh.ai)
Note 3 to entry: Closeness of agreement of measurement
ISO 17511:2020results is defined in terms of fitness for purpose as
appropriate for the intended use of the RM (3.39).
5f3d2884ac47/iso-17511-2020
Note 4 to entry: A commutability statement is restricted to the MPs (3.27) as specified in a particular comparison.
[SOURCE: ISO/IEC Guide 99:2007 5.15 modified — Note 2 and Note 3 have been deleted. Note 2 to entry
to Note 4 to entry have been added.]
3.11
control material
substance, material or article intended by its manufacturer (3.22) to be used to verify the performance
characteristics of an IVD MD (3.21)
[SOURCE: ISO 18113-1:2009, 3.13]
3.12
end-user IVD MD calibrator
end-user calibrator
RM (3.39) used as a measurement standard (3.28) intended for use with one or more IVD MD (3.21) MPs
(3.27) intended to examine a particular measurand (3.26) in human samples
Note 1 to entry: End user calibrators includes RMs (3.39) or calibrators (3.6) applied internally by the manufacturer
(3.22) to implement a final calibration (3.4) of the IVD MD (3.21), prior to the IVD MD’s (3.21) release and delivery
to the end-user, where end-user calibration is not required (i.e. 'factory calibration').
Note 2 to entry: Factory-generated calibrations (3.4) or calibration (3.4) functions include calibration (3.4)
information (equations, formula, functions, parameters, data) stored, e.g., in electronic format, for use with a
microprocessor as part of an IVD MD (3.21) measuring system (3.29) to transform “signal” generated in the course
of measuring unknown human samples to an amount of substance or other final measured value.

ISO 17511:2020(E)

3.13
equivalence of measured values
equivalent results
agreement of measured values among different IVD MDs (3.21) intended to measure the same
measurand (3.26), where the differences in measured values on the same human samples do not affect
clinical interpretation
Note 1 to entry: A conclusion of equivalence of measured values for the same human samples among two or more
MPs (3.27) is based on the differences in measured values being within a pre-defined margin or limit.
[SOURCE: Harmonization.net, modified — wording revised for clarity.]

3.14
higher order reference material
higher order RM
CRM (3.9) that meets internationally accepted quality requirement and provides a common metrological
reference within the calibration hierarchy (3.5) to which manufacturers (3.22) can establish metrological
traceability (3.31)
Note 1 to entry: Quality requirements for higher order RMs are laid out in ISO 15194.
Note 2 to entry: Higher order RMs include fit–for–purpose primary RMs (3.35), primary calibrators (3.37),
secondary calibrators (3.42) and international conventional calibrators (3.17).
Note 3 to entry: Pure substances constitute the primary measurement standard (3.37) and ultimate source
of higher-order metrological traceability (3.31) for most traceability chains in chemistry, thermometry
and calorimetry in general and for the certification of solution and matrix (3.24) RMs (3.39) in particular
(see ISO Guide 35:2017).
(standards.iteh.ai)
Note 4 to entry: According to Joint Committee for Traceability in Laboratory Medicine (JCTLM) FAQs [27], a higher
order RM is a CRM (3.9), meeting internationally accepted quality requirements, to which other measurement
results can be referenced, and its measurement uncertainty ISO 17511:2020
(3.48) is completely established. Metrologically, a
higher order RM is a RM (3.39) deployed at a higher level in the calibration hierarchy (3.5). Certified, highest order
RMs, where available, are used by IVD MD (3.21) manufacturers (3.22) to assign values to working calibrators
5f3d2884ac47/iso-17511-2020
(3.51). These working calibrators (3.51) are subsequently used by the manufacturer (3.22) to assign values to
measurands (3.26) in end-user IVD MD calibrators (3.12) and control materials (3.11) for use with IVD MDs (3.21)
in medical laboratories and other IVD testing environments. Higher order RMs are most commonly produced
and distributed by national metrology institutes (NMIs), e.g. U.S. National Institute of Standards and Technology
(NIST), European Commission Joint Research Centre (EU-JRC), LGC Standards (UK), World Health Organization
(WHO), National Institute for Biological Standards and Control (UK), National Institute of Metrology (CN),
National Metrology Institute of Japan (JP), Reference Material Institute for Clinical Chemistry Standards (JP),
Japanese Industrial Standards Committee (JISC), Centro Nacional de Metrología (MX), etc. Some commercial
sources also provide RMs listed by JCTLM[28].
3.15
higher order reference measurement procedure
higher order RMP
reference measurement procedure (RMP) (3.40) meeting internationally accepted quality requirements
and providing a common metrological reference within the calibration hierarchy (3.5) to which
manufacturers’ (3.22) can establish metrological traceability (3.31) and accepted as providing
measurement results fit for their intended use in assessing measurement trueness (3.47)
Note 1 to entry: Quality requirements for higher order RMPs (3.15) are defined in ISO 15193.
Note 2 to entry: For reasons of higher cost, equipment complexity and operator training requirements, higher
order RMPs are typically performed in national metrology (3.32) institutes and/or accredited calibration (3.4)
laboratories.
Note 3 to entry: In laboratory medicine, RMPs (3.40) that meet the requirements of ISO 15193 are considered to
be higher order RMPs.

ISO 17511:2020(E)

Note 4 to entry: According to JCTLM FAQs[27], higher order RMPs are well documented, high accuracy (MPs) (3.27)
used for assigning values to calibration materials (3.6). At the highest level (these MPs) (3.27) are frequently
expensive to develop, too complicated for routine use and not suitable for high throughput analysis.
3.16
influence quantity
quantity (3.38) that, in a direct measurement, does not affect the quantity (3.38) that is actually
measured, but affects the relation between the indication and the measurement result
EXAMPLE Amount-of-substance concentration of bilirubin in a direct measurement of haemoglobin amount-
of-substance concentration in human blood plasma.
[SOURCE: ISO/IEC Guide 99:2007 2.52, modified — excludes 3 examples and 2 notes.]
3.17
international conventional calibrator
international conventional calibration material
international measurement standard
calibrator (3.6) whose quantity (3.38) value is not metrologically traceable (3.31) to the SI but is assigned
by international agreement
Note 1 to entry: The quantity (3.38) is defined with respect to the intended clinical application.
3.18
international conventional reference measurement procedure
international conventional RMP
MP (3.27) yielding values that are not metrologically traceable to the SI but which by international
agreement are used as reference values for a defined quantity (3.38)
(standards.iteh.ai)
Note 1 to entry: The quantity (3.38) is defined with respect to the intended clinical application.
3.19 ISO 17511:2020

international harmonisation protocol
description of a process implemented 5f3d2884ac47/iso-17511-2020
by an international body to achieve equivalence of measured values
(3.13) within medically acceptable limits among two or more IVD MDs (3.21) intended for examination
of the same measurand (3.26) for cases where there are no higher order RMPs (3.15) and no fit for
purpose CRMs (3.9) or international conventional calibrators (3.17)
Note 1 to entry: A harmonisation protocol can be used to achieve standardization of measured values for a stated
measurand (3.26) when there are no other higher order reference system components that are suitable for use.
3.20
international measurement standard
measurement standard (3.28) recognized by signatories to an international agreement and intended to
serve worldwide as the basis for assigning values to other standards for the same quantity (3.38)
EXAMPLE 1 The international prototype of the kilogram.
EXAMPLE 2 ERM®-DA470k/IFCC for the calibration (3.4) of immunoassay-based in-vitro diagnostic devices or
control products for the proteins certified. European Commission — Joint Research Centre (JRC), Geel, Belgium.
EXAMPLE 3 Triple point of water — the single combination of pressure and temperature at which liquid water,
solid ice, and water vapour coexist in a stable equilibrium, occurring at exactly 273,16 K (0,01 °C; 32,02 °F) at a
partial vapour pressure of 611,657 pascals (6,116 57 mbar; 0,006 036 59 atm).
[SOURCE: ISO/IEC Guide 99:2007 5.2, modified — Example 2 and Example 3 have been deleted. New
Example 2 and Example 3 have been added]

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In vitro diagnostic medical devices —

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4.9.1 Obligation to end-users............................................................................................................................................ 30

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5.6 Cases with metrological traceability supported by an international harmonisation

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In vitro diagnostic medical devices — Requirements for

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Note 2 to entry: This definition applies to quantitative measurements only.

Note 3 to entry: Often, the first step(standards.iteh.ai)

[SOURCE: ISO/IEC Guide 99:2007 2.39]

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[SOURCE: ISO 18153:2003, 3.2] ISO 17511:2020

[SOURCE: ISO 18153:2003, 3.3]

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[SOURCE: Harmonization.net, modified — wording revised for clarity.]

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