EN ISO 15194:2026

• Abstract:

  This document specifies requirements for certified reference materials (CRMs) of higher metrological order and the content of the supporting documentation and the calibration hierarchies as described in ISO 17511:2020, 5.2.1, 5.3.1, 5.4.1, 5.5.1, 5.6.1, 5.7.1. It is applicable to CRMs intended for use as either primary reference materials (PRMs), secondary calibrators or international conventional calibrators within calibration hierarchies appropriate for measurands used in laboratory medicine, or for applications as trueness controls. It also specifies requirements for determining the certified value of a CRM, including evaluation, and reporting of the assigned uncertainty.; This document is applicable 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 ISO 17511:2020, Clause 1.; When a CRM includes multiple measurands, this document is applied to each of the certified quantity values present in the CRM.; Although intended to be applicable to producers of CRMs, this document is also useful for reference materials (RMs) that are not in conformity with the full metrological requirements of CRMs. For example, this document does not apply to an RM created by an in vitro diagnostic medical device (IVD MD) manufacturer for use as working calibrator or end-user calibrator within a calibration hierarchy traceable to a CRM, although some content can be useful in assessing its performance.

• Status: Published
• Publication Date: 21-Jul-2026
• ICS: 11.100.10 - In vitro diagnostic test systems
• Technical Committee: CEN/TC 140 - In vitro diagnostic systems
• Drafting Committee: CEN/TC 140/WG 3 - Quality management in the medical laboratory
• Current Stage: 6060 - Definitive text made available (DAV) - Publishing
• Start Date: 22-Jul-2026
• Completion Date: 22-Jul-2026
• Directive: Harmonized Standard2017/746 - Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU
• Mandate: M/575 - Medical devices in support of Regulation (EU) 2017/745 and in vitro diagnostic medical devices in support of Regulation (EU) 2017/746
• Mandate: M/575 Amd 1 - Medical devices in support of Regulation (EU) 2017/745 and in vitro diagnostic medicial devices in support of Regulation (EU) 2017746
• Mandate: M/575 Amd 2 - Medical devices in support of Regulation (EU) 2017/745 and in vitro diagnostic medicial devices in support of Regulation (EU) 2017746
• Ref Project: SIST EN ISO 15194:2026 - In vitro diagnostic medical devices - Requirements for certified reference materials and the content of supporting documentation (ISO 15194:2026)

• Replaces: EN ISO 15194:2009 - In vitro diagnostic medical devices - Measurement of quantities in samples of biological origin - Requirements for certified reference materials and the content of supporting documentation (ISO 15194:2009)
• Effective Date: 18-Jan-2023
• Referred By: CEN/TS 15968:2010 - Determination of extractable perfluorooctanesulphonate (PFOS) in coated and impregnated solid articles, liquids and fire fighting foams - Method for sampling, extraction and analysis by LC-qMS or LC-tandem/MS
• Effective Date: 29-Jul-2026
• Consolidated By: ISO 15194:2026 - In vitro diagnostic medical devices — Requirements for certified reference materials and the content of supporting documentation
• Effective Date: 12-Feb-2026

Overview

EN ISO 15194:2026 sets out the essential requirements for certified reference materials (CRMs) used in in vitro diagnostic (IVD) medical devices, with a focus on higher metrological order CRMs and their supporting documentation. This standard was developed by CEN, adopting the content of ISO/FDIS 15194:2026, and aligns closely with ISO 17511:2020, which details calibration hierarchies and traceability structures in laboratory medicine. The updated 2026 edition clarifies definitions, strengthens requirements for documentation, and standardizes how certified reference values, uncertainties, and intended uses are reported.

The goal is to assure accuracy and traceability in IVD measurement results, which is vital for patient safety, clinical decision-making, and regulatory compliance. The standard guides CRM producers and users in laboratory medicine, ensuring that reference materials deliver reliable, consistent, and harmonized results across diverse analytical systems.

---

Key Topics

• Certified Reference Materials (CRMs):

  • CRMs are highly characterized materials with specified property values and uncertainties, supporting traceability to recognized measurement standards.
  • They serve as primary reference materials, secondary calibrators, or trueness controls in calibration hierarchies.

• Supporting Documentation:

  • The standard details the required content for reference material certificates and certification reports.
  • Required documentation includes information on material source, processing, characterization, measurement results, traceability, certified values, uncertainty calculations, safety information, and instructions for use.

• Calibration Hierarchies:

  • CRMs act as anchor points in calibration hierarchies, ensuring metrological traceability of routine laboratory measurements to higher-order references described in ISO 17511:2020.
  • Descriptions must clarify a CRM’s place and role within these hierarchies.

• Commutability and Intended Use:

  • The commutability of CRMs (their ability to behave like patient samples across measurement systems) is critically assessed and documented.
  • Intended clinical use, matrix properties, and any limitations in application are to be clearly reported.

• Certified Value Assignment & Uncertainty:

  • Outlines rigorous procedures for establishing certified values for each measurand, including methods for evaluation and reporting of measurement uncertainty.
  • Ensures results are accurate and reliable for calibration and trueness assessment purposes.

---

Applications

EN ISO 15194:2026 is vital for:

• Producers of Certified Reference Materials:

  • Guidance on the design, production, value assignment, and documentation of CRMs for IVD applications.
  • Standardizes evaluation of homogeneity, stability, traceability, and uncertainty.

• Clinical Laboratories & Diagnostic Manufacturers:

  • Ensures that calibration systems and trueness controls used in lab medicine meet international requirements.
  • Supports compliance with European regulations, such as the In Vitro Diagnostic Regulation (IVDR - Regulation (EU) 2017/746).

• Regulatory Authorities & Assessors:

  • Provides a harmonized baseline for assessment of CRM quality, documentation, and traceability claims in conformity assessment and market surveillance processes.

• End Users & Quality Managers:

  • Assures laboratory professionals that reference materials used for calibration, proficiency testing, or method validation meet recognized benchmarks for reliability and support valid medical decisions.

---

Related Standards

• ISO 17511:2020
  In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples
  (Defines calibration hierarchies and traceability concepts referenced by EN ISO 15194:2026)

• ISO 17034
  General requirements for the competence of reference material producers

• ISO 15193
  In vitro diagnostic medical devices - Measurement procedures for quantities in biological samples

• ISO/IEC Guide 99:2007
  International vocabulary of metrology - Basic and general concepts and associated terms

These standards collectively ensure global harmonization, reliability, and safe application of reference materials in IVD medical testing environments. By adhering to EN ISO 15194:2026, organizations can demonstrate commitment to best practices in clinical measurement, traceability, and documentation integrity.

SLOVENSKI STANDARD
01-september-2026
Nadomešča:
SIST EN ISO 15194:2009
Diagnostični medicinski pripomočki in vitro - Zahteve za certificirane referenčne
materiale in vsebino podporne dokumentacije (ISO 15194:2026)
In vitro diagnostic medical devices - Requirements for certified reference materials and
the content of supporting documentation (ISO 15194:2026)
In-vitro-Diagnostika - Messung von Größen in Proben biologischen Ursprungs -
Anforderungen an zertifizierte Referenzmaterialien und an den Inhalt der
Begleitdokumentation (ISO 15194:2026)
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 15194:2026)
Ta slovenski standard je istoveten z: EN ISO 15194:2026
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.

EN ISO 15194
EUROPEAN STANDARD
NORME EUROPÉENNE
July 2026
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes EN ISO 15194:2009
English Version
In vitro diagnostic medical devices - Requirements for
certified reference materials and the content of supporting
documentation (ISO 15194:2026)
Dispositifs médicaux de diagnostic in vitro - Exigences In-vitro-Diagnostika - Anforderungen an zertifizierte
relatives aux matériaux de référence certifiés et au Referenzmaterialien und an den Inhalt der
contenu de la documentation associée (ISO Begleitdokumentation (ISO 15194:2026)
15194:2026)
This European Standard was approved by CEN on 21 June 2026.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2026 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 15194:2026 E
worldwide for CEN national Members.

Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard the General Safety
and Performance Requirements of Regulation (EU) 2017/746 aimed to be covered . 4
European foreword
This document (EN ISO 15194:2026) has been prepared by Technical Committee ISO/TC 212 "Medical
laboratories and in vitro diagnostic 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 January 2027, and conflicting national standards shall
be withdrawn at the latest by July 2029.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 15194:2009.
This document has been prepared under a standardization request addressed to CEN by the European
Commission. The Standing Committee of the EFTA States subsequently approves these requests for its
Member States.
For the relationship with EU Legislation, see informative Annex ZA, which is an integral part of this
document.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN website.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO 15194:2026 has been approved by CEN as EN ISO 15194:2026 without any modification.

Annex ZA
(informative)
Relationship between this European Standard the General Safety and
Performance Requirements of Regulation (EU) 2017/746 aimed to be
covered
This European standard has been prepared under M/575 to provide one voluntary means of
conforming to the General Safety and Performance Requirements of Regulation (EU) 2017/746 of 5
April 2017 concerning in vitro diagnostic medical devices [OJ L 117] and to system or process
requirements including those relating to quality management systems, risk management, post-market
surveillance systems, performance studies, clinical evidence or post-market performance follow-up.
Once this standard is cited in the Official Journal of the European Union under that Regulation,
compliance with the normative clauses of this standard given in Tables ZA.1, ZA.3, ZA.4 and application
of the edition of the normatively referenced standards as given in Table ZA.2 confers, within the limits
of the scope of this standard, a presumption of conformity with the corresponding General Safety and
Performance Requirements of that Regulation, and associated EFTA Regulations.
Where a definition in this standard differs from a definition of the same term set out in Regulation (EU)
2017/746, the differences shall be indicated in the Annex ZA. For the purpose of using this standard in
support of the requirements set out in Regulation (EU) 2017/746, the definitions set out in this
Regulation prevail.
Where the European standard is an adoption of an International Standard, the scope of this standard
can differ from the scope of the European Regulation that it supports. As the scope of the applicable
regulatory requirements differ from nation to nation and region to region, the standard can only
support European regulatory requirements to the extent of the scope of the In vitro Diagnostic
Regulation (EU) 2017/746).
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Regulation (EU) 2017/746. This means that risks have to be
‘reduced as far as possible’, ‘reduced to a level as low as reasonably practicable’, ‘reduced to the lowest possible
level’, ‘reduced as far as possible and appropriate’, ‘removed or reduced as far as possible’, ‘eliminated or reduced
as far as possible’, ‘prevented’ or ‘minimized’, according to the wording of the corresponding General Safety and
Performance Requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety
and Performance Requirements 1, 2, 3, 4, 5, 8, 10, 11, 13, 15, 16, 17, 18 and 19 of the Regulation.
NOTE 3 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European Standard and Annex I of Regulation (EU)
2017/746 [OJ L 117] and to system or process requirements including those relating to quality
management systems, risk management, post-market surveillance systems, clinical
investigations, clinical evaluation or post-market clinical follow-up
General Safety and Clause(s) / sub-
Performance Requirements clause(s) Remarks / Notes
of Regulation (EU) 2017/746 of this EN
9.3 4, 5 Covered with respect to
—  properties and characterization of a
certified reference material
—  identification of a suitable certified
reference material through its supporting
documentation that describes its fitness
for the intended application
20.4.1. (u) 5.3 Covered with respect to the information
in the reference material certificate that
identifies the applied reference material
and reference measurement procedure to
be provided in the instructions for use of
the IVD
20.4.1. (w) 5.3 Covered with respect to the information
in the reference material certificate that
describes the intended use of the applied
reference material and reference
measurement procedure to be provided
in the instructions for use of the IVD
Table ZA.2 — Normative references from Clause 2 of this document and their corresponding
European publications
Column 1 Column 2 Column 3 Column 4
Reference in International Title Corresponding European
Clause 2 Standard Edition Standard Edition
ISO 17034 ISO 17034:2016 General requirements for the EN ISO 17034:2016
competence of reference
material producers
ISO 17511 ISO 17511:2020 In vitro diagnostic medical EN ISO 17511:2021
devices — Requirements for
establishing metrological
traceability of values assigned
to calibrators, trueness
control materials and human
samples.
ISO/IEC Guide ISO/IEC Guide International vocabulary of None
99 99:2007 metrology — Basic and
general concepts and
associated terms (VIM)
Table ZA.3 — Correspondence between this European standard and Annex II of Regulation (EU)
2017/746 [OJ L 117] and to requirements to the technical documentation
Clause(s) / sub-clause(s)
Annex II of (EU) 2017/746 Remarks / Notes
of this EN
6.1.2.1. a) 5.4.9 b) Covered with respect to
information about the intended
use of the certified reference
material as trueness control
material
Table ZA.4 — Correspondence between this European standard and Annex XIII of Regulation
(EU) 2017/746 [OJ L 117] and to requirements for the performance evaluation, performance
studies and post-market performance follow-up
Clause(s) / sub-clause(s)
Annex XIII of (EU) 2017/746 Remarks / Notes
of this EN
th
1.1. 5 bullet point 4, 5 Covered with respect to
properties and characterization of
a certified reference material
to show metrological
traceability
identification of a suitable (i.e.
allowing metrological
traceability) certified
reference material through its
supporting documentation
Table ZA.5 — Differences in definitions between this European standard and Regulation (EU)
2017/746 [OJ L 117]
Defined term used this Defined in Defined or Legally Differences
EN this EN legally relevant relevan
term used in t
(EU) 2017/746 Yes/No
in vitro diagnostic Yes, legally relevant by Yes IVDR refers to "in vitro
medical device clause no Art. 2 no. 2 of diagnostic medical devices”
3.11 IVDR also as systems and reagent
products.
The documents listed in the Column 1 of Table ZA.2, in whole or in part, are normatively referenced in
this document and are indispensable for its application. The achievement of the presumption of
conformity is subject to the application of the edition of Standards as listed in Column 4 or, if no
European Standard Edition exists, the International Standard Edition given in Column 2 of Table ZA.2.
WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European
standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of
this standard.
International
Standard
ISO 15194
Third edition
In vitro diagnostic medical
2026-06
devices — Requirements for
certified reference materials
and the content of supporting
documentation
Dispositifs médicaux de diagnostic in vitro — Exigences
relatives aux matériaux de référence certifiés et au contenu de la
documentation associée
Reference number
ISO 15194:2026(en) © ISO 2026
ISO 15194:2026(en)
© ISO 2026
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
ISO 15194:2026(en)
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 .10
4.3 Commutability .10
5 Content of supporting documentation .10
5.1 Supporting documentation.10
5.2 Label .10
5.3 RM certificate .11
5.4 Certification report . 12
5.4.1 General . 12
5.4.2 Warning and safety precautions . 12
5.4.3 Introduction to a certification report . 13
5.4.4 Scope of application for the CRM . 13
5.4.5 Terms and definitions used in the certification report . 13
5.4.6 General properties . 13
5.4.7 Specific properties .14
5.4.8 Assignment of certified values . 15
5.4.9 Intended use .16
5.4.10 Instructions for use.17
5.4.11 Reference material producer .18
5.4.12 Bibliography .18
5.4.13 Annexes .18
5.4.14 Dates of authorization and revision .18
Annex A (informative) Certified reference materials (CRMs) with nominal properties or
ordinal quantities . 19
Bibliography .20

iii
ISO 15194:2026(en)
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, Medical laboratories and in vitro diagnostic
systems, in collaboration with the European Committee for Standardization (CEN) Technical Committee
CEN/TC 140, In vitro diagnostic medical devices, in accordance with the Agreement on technical cooperation
between ISO and CEN (Vienna Agreement).
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 Clause 4 of the second edition;
— expanded and clarified the Scope to specify requirements for higher order certified reference materials
(CRMs) whose intended use is to underpin routine measurements in laboratory medicine;
— added requirements regarding description of the intended use and commutability of the CRM;
— 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 15194:2026(en)
Introduction
Reference measuring systems are needed to enable the results produced by end user measurement
procedures (MPs) to be metrologically traceable to either measurement standards or MPs of the highest
metrological level. Such systems exist within a metrological traceability chain/calibration hierarchy as
described in ISO 17511. In the context of in vitro diagnostic (IVD) medical devices, metrological traceability
to the highest metrological level mitigates the risk of harm to patients by avoiding inconsistent results from
different measuring systems.
Reference materials (RMs) are used to establish and maintain metrological traceability of measurement
results over time within one location, between different physical locations or with the application of
different measurement procedures. 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 document 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 measuring 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 MP.
NOTE 1 “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.
NOTE 2 “Measurement precision” (ISO 17511:2020, 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 measurement uncertainty of the assigned value of a CRM is the combined measurement
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 on its production,
characterization and intended use, it is important to apply rules for the documentation of CRMs.
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.

v
International Standard ISO 15194:2026(en)
In vitro diagnostic medical devices — Requirements for
certified reference materials and the content of supporting
documentation
1 Scope
This document specifies requirements for certified reference materials (CRMs) of higher metrological
order and the content of the supporting documentation and the calibration hierarchies as described
in ISO 17511:2020, 5.2.1, 5.3.1, 5.4.1, 5.5.1, 5.6.1, 5.7.1. It is applicable to CRMs intended for use as either
primary reference materials (PRMs), secondary calibrators or international conventional calibrators
within calibration hierarchies appropriate for measurands used in laboratory medicine, or for applications
as trueness controls. It also specifies requirements for determining the certified value of a CRM, including
evaluation, and reporting of the assigned uncertainty.
This document is applicable 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 ISO 17511:2020, Clause 1.
When a CRM includes multiple measurands, this document is applied to each of the certified quantity values
present in the CRM.
Although intended to be applicable to producers of CRMs, this document is also useful for reference materials
(RMs) that are not in conformity with the full metrological requirements of CRMs. For example, this
document does not apply to an RM created by an in vitro diagnostic medical device (IVD MD) manufacturer
for use as working calibrator or end-user calibrator within a calibration hierarchy traceable to a CRM,
although some content can 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 17034, General requirements for the competence of reference material producers
ISO 17511, In vitro diagnostic medical devices — Requirements for establishing metrological traceability of
values assigned to calibrators, trueness control materials and human samples
ISO/IEC Guide 99, 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 17511 and ISO/IEC Guide 99 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
— IEC Electropedia: available at https:// www .electropedia .org/

ISO 15194:2026(en)
3.1
analyte
component represented in the name of a measurable quantity (3.22)
EXAMPLE In the type of quantity “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
certified reference material (CRM) (3.3) or reference material (RM) (3.23) with a traceable assigned quantity
(3.22) value used in calibration of a measuring system (3.16) according to a specified measurement procedure
(MP) (3.15)
[SOURCE: ISO 17511:2020, 3.6, modified — in the definition, “measurement standard” was changed to “CRM
or RM with a traceable assigned quantity value”.]
3.3
certified reference material
CRM
reference material (RM) (3.23) accompanied by documentation issued by an authoritative body and providing
one or more specified property values with associated uncertainty and traceability, using valid procedures
EXAMPLE Human serum with an assigned quantity (3.22) value and associated measurement uncertainty (3.18)
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).
Note 1 to entry: “Documentation” is given in the form of a RM certificate (3.24) and a certification report (3.4).
1)
Note 2 to entry: Requirements for the production of a CRM are given in ISO 17034. ISO 33405 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’ 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 value’ and ‘traceability of a nominal property value’.
Note 4 to entry: Specified quantity values of CRMs require metrological traceability with associated measurement
uncertainty.
Note 5 to entry: ISO 17034 has an analogous definition that uses the modifiers “metrological” and “metrologically”
to refer to both quantities and nominal properties. The text of the ISO 17511:2020, 3.9 definition, based on the text in
ISO/IEC Guide 99, is preferred as the basis for this term.
Note 6 to entry: Specific requirements for CRMs and the content of supporting documentation [in the field of in vitro
diagnostic (IVD) medical devices (3.11)] are given in this document.
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.
[SOURCE: ISO 17511:2020, 3.9, modified — in Note 1 to entry, “certification report” was added; Notes 2 and 5
to entry were changed; in Note 6 to entry, “ISO 15194” was changed to “this document”; in Note 7 to entry,
“does not confer” was changed to “is not by itself sufficient to confer”.]
3.4
certification report
additional information on a certified reference material (CRM) (3.3), supplementary to that contained in a RM
certificate (3.24) that describes the production, characterization and certification of a CRM intended for use
in laboratory medicine and with in vitro diagnostic (IVD) medical devices (3.11)
1)  Updated reference: ISO 33405 replaced ISO Guide 35, which has been withdrawn.

ISO 15194:2026(en)
3.5
commutability
property of a reference material (RM) (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 (MPs) (3.15), and the relation obtained among the measurement
results for other specified materials
Note 1 to entry: The reference material (RM) in question is usually a secondary calibrator (3.27) and the other specified
materials are usually clinical samples (3.26).
Note 2 to entry: For the commutability assessment of a certified reference material (CRM) (3.3) it is recommended to
measure the clinical samples with as many measurement procedures as feasible.
Note 3 to entry: Closeness of agreement of measurement results is defined in terms of fitness for purpose as
appropriate for the intended use of the RM.
Note 4 to entry: A commutability statement is restricted to the measurement procedures as specified in a particular
comparison.
Note 5 to entry: The recommendations of the IFCC Working Groups for Assessing Commutability and on Commutability
in Metrological Traceability, as well as a CLSI Document provide guidance on how to undertake a commutability
[16-20]
study .
[SOURCE: ISO 17511:2020, 3.10, modified — the preferred term “commutability of a reference material” was
removed; in Note 1 to entry, “calibrator” was replaced by “secondary calibrator” and “routine samples” was
replaced by “clinical samples”; Note 2 to entry was changed; Note 5 to entry was added.]
3.6
control material
substance, material or artefact intended by its producer to be used to verify the performance of a
measurement procedure (MP) (3.15)
Note 1 to entry: Reference materials (RMs) (3.23) with or without assigned quantity (3.22) values can be used as
control materials whereas only certified reference materials (CRMs) (3.3) with traceable quantity values can be used as
calibrators (3.2) or as trueness control materials (3.28)
[SOURCE: ISO 17511:2020, 3.11, modified — Note 1 to entry was added.]
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, modified — Notes 1 to 3 of entry were deleted.]
3.8
higher order reference material
higher order RM
certified reference material (CRM) (3.3) that meets internationally accepted quality requirements and
provides a common metrological reference within the calibration hierarchy to which a producer can
establish metrological traceability (3.17)
Note 1 to entry: Quality requirements for higher order RMs (3.23) are laid out in this document.
Note 2 to entry: Higher order RMs include primary reference materials (PRMs) (3.20), primary calibrators (3.19),
secondary calibrators (3.27) and international conventional calibrators (3.10).
Note 3 to entry: Pure substances constitute the PRM and ultimate source of higher order metrological traceability for
most traceability chains in chemistry, thermometry and calorimetry in general and for the certification of solution
and matrix (3.12) RMs in particular (see ISO 33405:2017).

ISO 15194:2026(en)
[21]
Note 4 to entry: According to the Joint Committee for Traceability in Laboratory Medicine (JCTLM), a higher order
RM is a CRM, meeting internationally accepted quality requirements, to which other measurement results can be
referenced, and its measurement uncertainty (3.18) is completely established. Metrologically, a higher order RM is
a RM deployed at a higher level in the calibration hierarchy. Certified, higher order RMs, where available, are used
by in vitro diagnostic medical device (IVD MD) (3.11) manufacturers to assign values to working calibrators. These
working calibrators are subsequently used by the manufacturer to assign values to measurands (3.13) in end-user
IVD MD calibrators and control materials (3.6) for use with IVD MDs in medical laboratories and other IVD testing
environments. Higher order RMs are most commonly produced and distributed by national metrology institutes
[21]
(NMIs). Some commercial sources also provide RMs listed by JCTLM .
[SOURCE: ISO 17511:2020, 3.14, modified — in the definition, “manufacturers ” was changed to “a producer”;
in Note 1 to entry, “ISO 15194” was changed to “this document”; in Note 4 to entry, the list of national
metrology institutes was removed.]
3.9
higher order reference measurement procedure
higher order RMP
reference measurement procedure (RMP) (3.25) meeting internationally accepted quality requirements
and providing a common metrological reference within the calibration hierarchy to 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.
Note 2 to entry: For reasons of higher cost, equipment complexity and operator training requirements, higher order
RMPs are typically performed in either national metrology institutes or accredited calibration (3.4) laboratories, or
both.
Note 3 to entry: In laboratory medicine, RMPs that meet the requirements of ISO 15193 are considered to be higher
order RMPs.
[21]
Note 4 to entry: According to JCTLM recommendations, higher order RMPs are well documented, high accuracy MPs
(3.15) used for assigning values to calibrator (3.2) materials. At the highest level these RMPs are frequently expensive
to develop, too complicated for routine use and not suitable for high throughput analysis.
[SOURCE: ISO 17511:2020, 3.15, modified — in the definition, “manufacturers ” was changed to “a producer”.]
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 International System of units (SI)
Note 1 to entry: The quantity is specified with respect to the intended clinical application.
[SOURCE: ISO 17511:2020, 3.17, modified — the preferred term “international measurement standard” was
removed.]
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 samples (3.26) 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), sample receptacles, software, and related instruments or apparatus or other articles
[SOURCE: ISO 17511:2020, 3.21, modified — in the definition, “specimen” was changed to “samples”.]

ISO 15194:2026(en)
3.12
matrix
system matrix
components of a material, except the analyte (3.1)
Note 1 to entry: The biological system excluding the analyte 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 “amount of substance of glucose in plasma”, “plasma” is the matrix.
[SOURCE: ISO 17511:2020, 3.24, modified — the Example was added.]
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, description of the state of the
phenomenon, body, or substance carrying the quantity, 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.
Note 3 to entry: In laboratory medicine, description of the measurand includes the name of the quantity (e.g. amount
of substance concentration), the analyte (e.g. D-glucose), and the matrix (3.12) in which it is found (e.g. plasma).
[SOURCE: ISO 17511:2020, 3.26, modified — the original Notes 2 and 3 to entry and the Example were
removed, and Notes 4 and 5 to entry were renumbered.]
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, modified — Note 1 to entry was removed.]
3.15
measurement procedure
MP
detailed 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 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
Note 1 to entry: An MP is usually documented in sufficient detail to enable an operator to perform a measurement.
Note 2 to entry: An MP can include a statement concerning a target measurement uncertainty (3.18).
Note 3 to entry: In medical laboratory measurements, a specific instance of a MP, an in vitro diagnostic (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 — in the definition, “including a technical description of reagents,
calibrators, equipment, instrument, and other details necessary to create and operate a measuring system”
was added; the original Note 3 to entry was removed and a new Note 3 to entry was added.]

ISO 15194:2026(en)
3.16
measuring 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 (3.22) values within
specified intervals for quantities of specified k
...