ISO 17593:2022

INTERNATIONAL ISO
STANDARD 17593
Second edition
2022-03
Clinical laboratory testing and in vitro
medical devices — Requirements for
in vitro monitoring systems for self-
testing of oral anticoagulant therapy
Laboratoires d'analyses de biologie médicale et dispositifs
médicaux de diagnostic in vitro — Exigences relatives aux systèmes
d'autosurveillance des traitements par anti-coagulant oraux
Reference number
ISO 17593:2022(E)
© ISO 2022

---------------------- Page: 1 ----------------------
ISO 17593:2022(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2022
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: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii
  © ISO 2022 – All rights reserved

---------------------- Page: 2 ----------------------
ISO 17593:2022(E)
Contents Page
Foreword .v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Design and development .8
4.1 General requirements . 8
4.2 Measuring interval . 8
4.3 Safety. 8
4.4 Risk management . 8
4.4.1 Identification of hazards . 8
4.4.2 Risk management . 9
4.5 Ergonomic and human factor aspects . 9
4.6 Quality assurance and risk controls . 10
4.6.1 General . 10
4.6.2 Measurement verification . 10
4.6.3 Control of system performance . 10
4.6.4 Verification of self-testing performance . 10
4.7 Metrological traceability . 10
5 Information supplied by the manufacturer .11
5.1 General requirements . 11
5.2 Instructions for use of the oral-anticoagulation monitoring system .12
5.3 Labels for the reagents and control(s) . 13
5.4 Instructions for use of reagents and control materials . 14
6 Safety and reliability testing .14
6.1 General requirements . 14
6.1.1 Protocol . 14
6.1.2 Instruments and reagents . 15
6.1.3 Acceptance criteria .15
6.2 Protection against electric shock . 15
6.3 Protection against mechanical hazards. 15
6.4 Electromagnetic compatibility.15
6.5 Resistance to heat . 15
6.6 Resistance to moisture and liquids . 15
6.7 Protection against liberated gases, explosion, and implosion . 15
6.8 Instrument components . 15
6.9 Performance test . 15
6.10 Mechanical resistance to shock, vibration, and impact . 16
6.10.1 Vibration test protocol . 16
6.10.2 Drop test protocol . 16
6.11 Temperature exposure limits . . 16
6.11.1 High-temperature test protocol . 16
6.11.2 Low-temperature protocol . 17
6.12 Humidity-exposure test protocol . 17
6.13 Reagent and storage and use testing . 17
7 Training and education programs .18
7.1 Training of healthcare providers . 18
7.2 Education of lay persons . 18
7.3 Evaluation of user conformance in following the manufacturer’s and the
physician’s instructions . 19
8 System performance validation .19
iii
© ISO 2022 – All rights reserved

---------------------- Page: 3 ----------------------
ISO 17593:2022(E)
8.1 General . 19
8.2 Contributors to measurement uncertainty. 19
8.3 System performance validation study . 19
8.4 Validation of measurement precision . 20
8.4.1 General .20
8.4.2 Validation of measurement repeatability . 21
8.4.3 Validation of intermediate precision . 21
8.4.4 Data analysis .23
8.5 Validation of system accuracy .26
8.5.1 General requirements .26
8.5.2 Study population . 26
8.5.3 Samples/Specimen. 27
8.5.4 Instruments and reagents .28
8.5.5 Comparator measurement procedure .28
8.5.6 Study design .28
8.5.7 Procedure .29
8.5.8 Data analysis .30
8.6 Minimum acceptable system accuracy . 33
8.6.1 System accuracy requirement . 33
8.6.2 System accuracy assessment .34
8.6.3 Data presentation .34
9 Lay person performance evaluation .35
9.1 General . 35
9.2 Study overview . 35
9.3 Study sites . 37
9.4 Subjects . 37
9.5 Instruments and materials . 37
9.6 Evaluation of lay person proficiency . 37
9.6.1 Initial evaluation . 37
9.6.2 Home use .38
9.6.3 Mid and final evaluation .38
9.7 Evaluation of instructions for use .38
9.8 Acceptance criteria and data assessment . 39
Annex A (normative) Additional requirements for electromagnetic compatibility .40
Annex B (informative) Traceability chain examples .42
Annex C (informative) Examples of an uncertainty calculation for a prothrombin INR
determination using an oral anticoagulation monitoring system .46
Annex D (informative) Elements of quality assurance of oral-anticoagulation monitoring
systems .50
Bibliography .51
iv
  © ISO 2022 – All rights reserved

---------------------- Page: 4 ----------------------
ISO 17593:2022(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 of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to
the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in
vitro diagnostic test systems.
This second edition cancels and replaces the first edition (ISO 17593:2007), which has been technically
revised.
The main changes are as follows:
— Updated with more current state of the art information that has evolved over several years.
— Subclause 8.4 Validation of measurement precision: added a more robust study design.
— Subclause 8.5.8.2 and 8.5.8.3: updated examples were added to reflect changes in criteria.
— Subclause 8.6 Minimum acceptable system accuracy : Updated requirements/performance criteria.
— Clause 9 Lay person performance evaluation: added clarity, revised performance criteria and
increased sample size.
— Removed Annex F listing of publications.
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.
v
© ISO 2022 – All rights reserved

---------------------- Page: 5 ----------------------
ISO 17593:2022(E)
Introduction
Oral-anticoagulation monitoring systems are in vitro diagnostic (IVD) medical devices that measure
prothrombin time in fresh, untreated human blood specimens. Prothrombin time is an indicator of
the ability of blood to clot. IVD medical devices for self-testing of oral-anticoagulation therapy are
used predominantly by individuals who have heart valve replacements, or who are suffering from
atrial fibrillation or deep vein thrombosis and are receiving oral anticoagulant therapy with vitamin
K antagonist medicines (e.g. warfarin). Patients must maintain the level of anticoagulant in the blood
high enough to reduce thrombin formation, yet low enough to avoid excessive bleeding. An oral-
anticoagulation monitoring system allows the user to monitor anticoagulation therapy and take action
to control the level of anticoagulant present in the blood. This document applies to oral-anticoagulation
monitoring systems to be used by lay persons. The primary objectives are to establish requirements
for oral-anticoagulation monitoring systems that will enable lay persons to achieve acceptable
performance, and to specify procedures for manufacturers and other interested parties to demonstrate
conformance of such systems to the requirements stated in this document.
Performance criteria for oral-anticoagulation monitoring systems were established, based on the state-
[31]
of-the-art, which has been shown to offer significant benefit to patients . The criteria are given in
terms of “system accuracy”, because metrological terms commonly used in International Standards
(e.g. trueness and measurement uncertainty) would not be familiar to lay persons. System accuracy,
which is affected by systematic bias and random effects (and is inversely related to measurement
uncertainty), describes the degree to which the individual results produced by an oral-anticoagulation
monitoring system agree with correct international normalized ratio (INR) values when the system is
used as intended by lay persons. In setting the performance criteria, it is assumed that users will be
properly selected and will receive the necessary training and that operating and control procedures
will be followed in accordance with the manufacturer’s instructions for use. It is also assumed that
manufacturers will anticipate and mitigate the effects of reasonably foreseeable misuse, including
reasonably foreseeable deviations from recommended operating and control procedures by the
intended users.
Requirements that are unique to self-testing with oral anticoagulation monitoring systems, including
specific content of information supplied by the manufacturer, are addressed in this document.
General requirements that apply to all IVD medical devices and which are covered by other standards
(e.g. IEC 61010-1, IEC 61010-2-101, ISO 13485, ISO 14971, ISO 23640 and ISO 18113-1, ISO 18113-4,
ISO 18113-5) are incorporated by reference, when appropriate. While the goal is to standardize these
requirements, it is also recognized that current national and regional usage by patients and regulatory
authorities should be taken into consideration.
vi
  © ISO 2022 – All rights reserved

---------------------- Page: 6 ----------------------
INTERNATIONAL STANDARD ISO 17593:2022(E)
Clinical laboratory testing and in vitro medical devices —
Requirements for in vitro monitoring systems for self-
testing of oral anticoagulant therapy
1 Scope
This document specifies requirements for in vitro measuring systems for self-monitoring of vitamin-K
antagonist oral anticoagulation therapy, including performance, quality assurance and user training
and procedures for the validation of performance by the intended users under actual and simulated
conditions of use.
This document applies solely to prothrombin time measuring systems used by lay persons for
monitoring their own vitamin-K antagonist oral anticoagulation therapy, and which report results as
international normalized ratios (INR).
This document is applicable to manufacturers of such systems and those other organizations (e.g.
regulatory authorities and conformity assessment bodies) having the responsibility for assessing the
performance of these systems.
This document is not applicable to:
— in vitro measuring systems for coagulation quantities assessing vitamin-K antagonist oral
anticoagulation therapy used by physicians or healthcare providers;
— non-vitamin-K antagonist oral anticoagulation therapy (e.g. dabigatran);
— a comprehensive evaluation of all possible factors that can affect the performance of these systems;
— the medical aspects of oral-anticoagulation therapy.
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 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15198, Clinical laboratory medicine — In vitro diagnostic medical devices — Validation of user quality
control procedures by the manufacturer
ISO 17511, In vitro diagnostic medical devices — Requirements for establishing metrological traceability of
values assigned to calibrators, trueness control materials and human samples
ISO 18113-1, Clinical laboratory testing and in vitro diagnostic medical systems — Information supplied by
the manufacturer (labelling) — Part 1: Terms, definitions and general requirements
ISO 18113-4, Clinical laboratory testing and in vitro diagnostic medical systems — Information supplied by
the manufacturer (labelling) — Part 4: In vitro diagnostic reagents for self-testing
ISO 18113-5, Clinical laboratory testing and in vitro diagnostic medical systems — Information supplied by
the manufacturer (labelling) — Part 5: In vitro diagnostic instruments for self-testing
1
© ISO 2022 – All rights reserved

---------------------- Page: 7 ----------------------
ISO 17593:2022(E)
ISO 20916, In vitro diagnostic medical devices — Clinical performance studies using specimens from human
subjects — Good study practice
ISO 23640, In vitro diagnostic medical devices — Evaluation of stability of in vitro diagnostic reagents
IEC 60068-2-64:2008, Environmental testing — Part 2: Test methods — Test Fh: Vibration, broad-band
random (digital control) and guidance
IEC 60601-1-2, Medical electrical equipment - Part 1-2: General requirements for basic safety and essential
performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests
IEC 61000-4-2, Electromagnetic compatibility (EMC) — Part 4-2: Testing and measurement techniques —
Electrostatic discharge immunity test
IEC 61000-4-3, Electromagnetic compatibility (EMC) — Part 4-3: Testing and measurement techniques —
Radiated, radiofrequency, electromagnetic field immunity test
IEC 61010-1:2010, Safety requirements for electrical equipment for measurement, control and laboratory
use — Part 1: General requirements
IEC 61010-2-101:2015, Safety requirements for electrical equipment for measurement, control and
laboratory use — Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment
IEC 61326-1, Electrical equipment for measurement, control and laboratory use — EMC requirements –
Part 1: General requirements
IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use — EMC requirements –
Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment
EN 13532, General requirements for in vitro diagnostic medical devices for self-testing
WHO Technical Report Series, No. 889, 1999, Annex 3 — Guidelines for thromboplastins and plasma used
to control oral-anticoagulant therapy
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 18113-1 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/
3.1
accuracy
closeness of agreement between a measured quantity value and a true quantity value of a measurand
Note 1 to entry: For oral-anticoagulation monitoring systems, accuracy is measured by the extent to which
measurements of blood (3.3) specimens from different patients agree with the INR (3.11) values traceable to a
thromboplastin international reference preparation (IRP) (3.12).
[SOURCE: ISO/IEC Guide 99:2007, 2.13, modified — Notes 1, 2 and 3 to entry have been deleted, and a
new Note 1 to entry has been added.]
3.2
bias
difference between the expectation of the test results and an accepted reference value
[SOURCE: ISO 5725-1:1994, 3.8, modified — Note 1 to entry has been deleted.]
2
  © ISO 2022 – All rights reserved

---------------------- Page: 8 ----------------------
ISO 17593:2022(E)
3.3
blood
circulating intravascular tissue of the body, consisting of suspended formed elements and
...