EN ISO 5649:2024

SLOVENSKI STANDARD
01-februar-2025
Medicinski laboratoriji - Koncepti in specifikacije za oblikovanje, razvoj, izvajanje
in uporabo laboratorijsko razvitih testov (ISO 5649:2024)
Medical laboratories - Concepts and specifications for the design, development,
implementation, and use of laboratory-developed tests (ISO 5649:2024)
Medizinische Laboratorien - Konzepte und Spezifikationen für den Entwurf, die
Entwicklung, die Herstellung und den Einsatz hauseigener In‑vitro-Diagnostika
(laborentwickelte Tests) (ISO 5649:2024)
Laboratoires médicaux - Concepts et spécifications relatifs à la conception, au
développement, à la mise en œuvre et à l’utilisation des tests développés en laboratoire
(ISO 5649:2024)
Ta slovenski standard je istoveten z: EN ISO 5649:2024
ICS:
11.100.01 Laboratorijska medicina na Laboratory medicine in
splošno general
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 5649
EUROPEAN STANDARD
NORME EUROPÉENNE
December 2024
EUROPÄISCHE NORM
ICS 11.100.10
English Version
Medical laboratories - Concepts and specifications for the
design, development, implementation, and use of
laboratory-developed tests (ISO 5649:2024)
Laboratoires médicaux - Concepts et spécifications Medizinische Laboratorien - Konzepte und
relatifs à la conception, au développement, à la mise en Spezifikationen für den Entwurf, die Entwicklung, die
œuvre et à l'utilisation des tests développés en Herstellung und den Einsatz hauseigener In-vitro-
laboratoire (ISO 5649:2024) Diagnostika (laborentwickelte Tests) (ISO 5649:2024)
This European Standard was approved by CEN on 6 December 2024.

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
© 2024 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5649:2024 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 5649:2024) 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 June 2025, and conflicting national standards shall be
withdrawn at the latest by December 2027.
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.
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 5649:2024 has been approved by CEN as EN ISO 5649:2024 without any modification.

International
Standard
ISO 5649
First edition
Medical laboratories — Concepts
2024-11
and specifications for the design,
development, implementation and
use of laboratory-developed tests
Laboratoires médicaux — Concepts et spécifications relatifs
à la conception, au développement, à la mise en œuvre et à
l’utilisation des tests développés en laboratoire
Reference number
ISO 5649:2024(en) © ISO 2024
ISO 5649:2024(en)
© ISO 2024
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 5649:2024(en)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General requirements . 16
4.1 Rationale for laboratory-developed tests (LDTs) .16
4.2 Feasibility assessment .17
4.3 Management system .17
4.3.1 General .17
4.3.2 Transfer of laboratory-developed tests (LDTs) .18
4.3.3 Control of subcontractors .18
5 Requirements for the design and development of laboratory-developed tests (LDTs) .18
5.1 Determination of LDT performance specifications .18
5.1.1 General .18
5.1.2 Intended use .19
5.1.3 Scientific validity . 20
5.1.4 Scientific literature . 20
5.2 Risk management . 20
5.2.1 Risk management system . 20
5.2.2 Risk differentiation for the LDT.21
5.3 Essential principles for safety and performance .21
5.4 Preliminary and pilot testing . 22
6 Requirements for the performance evaluation of laboratory-developed tests (LDTs) .22
6.1 Performance evaluation . 22
6.2 Validation master plan . 23
6.3 Analytical performance . 23
6.3.1 General . 23
6.3.2 Measurement uncertainty (MU) .24
6.4 Clinical performance .24
6.5 Excluded performance characteristics . 25
6.6 Software verification and validation . 25
6.7 Validation documentation and final acceptance criteria . 25
6.8 Post validation activities of verification . 26
7 Implementation, monitoring and retirement of laboratory-developed tests (LDTs) .27
7.1 Transfer into routine use .27
7.2 Result reporting and interpretation .27
7.3 Maintenance .27
7.4 Monitoring and review activities .27
7.5 Change management . 28
7.6 Retirement of laboratory-developed tests (LDTs) . 28
Annex A (informative) Example workflow for a laboratory-developed test (LDT) lifecycle .29
Bibliography .31

iii
ISO 5649:2024(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).
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 5649:2024(en)
Introduction
Medical laboratory testing is carried out to an appropriate standard and all work is performed with a high
level of skill and competence so as not to produce unreliable results which can lead to patient harm.
In many medical laboratories, the majority of routine clinical samples are processed and analysed using
commercially available tests on automated instrumentation purchased from various manufacturers of in
vitro diagnostic (IVD) medical devices. The marketing of medical devices is usually regulated by national
bodies, and devices must undergo stringent assessment before they can be placed on the market and put
into service.
However, there are clinical indications for which there are no commercially available IVD medical devices
for the specific intended use or there is a requirement for adding additional specification/approach(es) to a
commercial IVD medical device. Such tests are referred to as laboratory-developed tests (LDTs). LDTs can
be defined as tests developed (or modified) and used within a laboratory to carry out testing on specimens,
such as blood, body fluids and tissues, and samples derived from human specimens, such as bacterial isolates,
where the results are intended to assist in clinical diagnosis or be used in making decisions concerning
clinical management.
Due to technological development, advanced examinations are continuously introduced in the medical
laboratory. These can include, but are not limited to liquid chromatography-tandem mass spectrometry
(LC-MS/MS), time-of-flight/mass spectrometry (TOF/MS), nuclear magnetic resonance (NMR), molecular
diagnostic testing (e.g. polymerase chain reaction (PCR) based and next generation sequencing (NGS)),
in situ hybridization (ISH), immunohistochemistry (IHC), whole slide scanning and imaging, algorithm-
based analyses and other emerging technologies. These techniques may be developed in a clinical research
laboratory, transferred to the medical laboratory, and placed into routine use as diagnostic tests without
going through the same standard approval processes as commercially available IVD medical devices. These
tests are also considered to be LDTs.
LDTs have become more complex because of available technology and are increasingly being used to
diagnose high-risk conditions such as cancer, genetic disorders, rare diseases, etc., which in turn highlights
the need to ensure that the results obtained are accurate and reproducible to safeguard the health and well-
being of patients. While many laboratories can perform validation studies of these tests, there is currently
no international standard by which to assess the rationale for their intended use, design, development,
performance, quality, and reliability.
This document is intended to be used to provide additional guidance to laboratories using LDTs. Accreditation
to ISO 15189 is not a pre-requisite for laboratories to use this document.
Conceptually, the lifecycle of an LDT involves sequential phases that extend from the feasibility assessment
to the final retirement of the examination procedure. The main phases of a typical LDT lifecycle described
in this document, therefore, include the feasibility assessment, the design and development phase, the
preliminary/pilot testing followed by the performance evaluation phase, including validation and the
verification phases, the monitoring and review activities during LDT use, and the final retirement of the LDT.
The illustration shown in Figure 1 below demonstrates these different phases and indicates which clauses
of this document cover the corresponding lifecycle phases for an LDT. The arrows back to previous phases
within Figure 1 indicate an iterative, dynamic process which can include look-backs, rework or revalidation
for improvement of the LDT.
v
ISO 5649:2024(en)
Figure 1 — Possible lifecycle phases of an LDT
The rationale for the use of an LDT and the feasibility assessment consider the demand for an LDT and
determine whether analytical and clinical performance of the new LDT can meet requirements for adequate
measurement procedure results (refer to 4.1 and 4.2 of this document).
Design and development include the planning and definition of formal specifications for LDT performance
including iterative improvement of all LDT components according to the intended use of the LDT. This can
include redesign and reassessment of feasibility and the formal specifications of the LDT as a dynamic
process covering all aspects of the LDT development (refer to 5.1 to 5.3 of this document).
Preliminary testing precedes the performance evaluation phase and determines the technical aspects of
the LDT by demonstrating that the LDT meets the design and development requirements (refer to 5.4 of this
document).
Performance evaluation includes the collection, analysis and assessment of performance data typically
generated from validation and verification studies, but also includes activities of risk management and
supports the demonstration of the conformity of the LDT to applicable principles of safety and performance.
Validation is a defined process to confirm and control that the finally designed and developed LDT is
suitable for its intended use and fulfils all analytical and clinical performance claims (refer to 6.2 to 6.7 of
this document).
vi
ISO 5649:2024(en)
LDT specifications are verified, where relevant aspects of the LDT procedure deviate between the phase of
validation and routine use of the LDT (refer to 6.8 of this document for verification).
LDTs are continuously monitored and periodically reviewed to ensure conformity with the original
performance specifications. Significant changes of the LDT require a restart of the processes affected by the
modification including revalidation (refer to 7.1 to 7.5 of this document for implementation and monitoring).
LDTs that need replacement shall be retired (refer to 7.6 of this document for retirement).
An example for how this lifecycle can be applied to a workflow is presented in Annex A of this document.

vii
International Standard ISO 5649:2024(en)
Medical laboratories — Concepts and specifications for the
design, development, implementation and use of laboratory-
developed tests
1 Scope
This document establishes requirements for assuring quality, safety, performance and documentation
of laboratory-developed tests (LDTs) as per their intended use for the diagnosis, prognosis, monitoring,
prevention or treatment of medical conditions.
It outlines the general principles and assessment criteria by which an LDT shall be designed, developed,
characterized, manufactured, validated (analytically and clinically) and monitored for internal use by
medical laboratories.
The scope includes regulatory authority approved IVD medical devices that are used in a manner differing
from approved labelling or instructions for use for that device (e.g. use of a sample type not included in the
intended use, use of instruments or reagents not included in the labelling).
While this document follows a current best practice and state-of-the art approach, it does not provide
specific details on how to achieve these requirements within specific disciplines of the medical laboratory
nor specific technology platforms.
This document does not specify requirements for examination procedures developed by research or
academic laboratories developing and using testing systems for non-IVD purposes. However, the concepts
presented in this document can also be useful for these laboratories.
This document does not apply to the design, development and industrial production of commercially used
IVD medical devices.
2 Normative references
There are no normative references in this document.
3 Terms and definitions
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
analyte
component represented in the name of a measurable quantity
EXAMPLE In “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 (3.28)
[SOURCE: ISO 17511:2020, 3.1]
ISO 5649:2024(en)
3.2
analytical performance
analytical performance of an LDT
ability of a laboratory-developed test (LDT) (3.25) to detect or measure a particular analyte (3.1)
Note 1 to entry: Clinical evidence (3.7) of an LDT is composed of three elements: scientific validity (3.51), analytical
performance and clinical performance (3.8).
[20]
[SOURCE: IMDRF/GRRP WG/N47:2018, 3.2 , modified — “IVD medical device” was replaced by “LDT”.]
3.3
analytical sensitivity
sensitivity of a measurement procedure
quotient of the change in a measurement indication and the corresponding change in a value of a quantity
being measured
Note 1 to entry: The analytical sensitivity can depend on the value of the quantity being measured.
Note 2 to entry: The change considered in the value of the quantity being measured shall be large compared with the
resolution.
Note 3 to entry: The analytical sensitivity of a measuring system is the slope of the calibration curve.
Note 4 to entry: Analytical sensitivity should not be used to mean detection limit (3.13) or quantitation limit (3.43) and
should not be confused with diagnostic sensitivity (3.15).
[SOURCE: ISO 18113-1:2022, 3.2.4]
3.4
analytical specificity
selectivity of a measurement procedure
capability of a measuring system, using a specified measurement procedure (3.31), to provide measurement
results for one or more measurands (3.28) which do not depend on each other nor on any other quantity in
the system undergoing measurement
EXAMPLE Capability of a measuring system to measure the concentration of creatinine in blood plasma by the
alkaline picrate procedure without interference from the glucose, urate, ketone, or protein concentrations.
Note 1 to entry: Lack of analytical specificity is called analytical interference.
Note 2 to entry: Lack of analytical specificity in immunochemistry measurement procedures can be due to cross-
reactivity (3.11).
Note 3 to entry: Specificity of a measurement procedure should not be confused with diagnostic specificity (3.16).
Note 4 to entry: ISO/IEC Guide 99:2007 uses the term selectivity for this concept instead of specificity.
[SOURCE: ISO 18113-1:2022, 3.2.5]
3.5
bias
measurement bias
estimate of a systematic measurement error
Note 1 to entry: See also ISO/IEC Guide 99:2007, 2.17, systematic measurement error.
Note 2 to entry: This definition applies to quantitative measurements only.
[SOURCE: ISO 15189:2022, 3.1, modified — a new Note 1 to entry was added and former Note 1 to entry is
Note 2 to entry.]
ISO 5649:2024(en)
3.6
biological reference interval
reference interval
specified interval of the distribution of values taken from a biological reference population
Note 1 to entry: A biological reference interval is commonly defined as the central 95 % interval. Another size or an
asymmetrical location of the biological reference interval can be more appropriate in particular cases.
Note 2 to entry: A biological reference interval can depend upon the type of primary sample and the examination
(3.17) procedure used.
Note 3 to entry: In some cases, only one biological reference limit is important, usually an upper limit, “x”, so that the
corresponding biological reference interval would be less than or equal to “x”.
Note 4 to entry: Terms such as ‘normal range’, ‘normal values’, and ‘clinical range’ are ambiguous and therefore
discouraged.
[SOURCE: ISO 15189:2022, 3.2]
3.7
clinical evidence
information that supports the clinical utility (3.9) of a laboratory-developed test (LDT) (3.25) for its intended
use (3.22), including scientific validity (3.51), analytical performance (3.2), and clinical performance (3.8)
3.8
clinical performance
clinical performance of a laboratory-developed test (LDT)
ability of a laboratory-developed test (LDT) (3.25) to yield results that are correlated with a particular clinical
condition/physiological state in accordance with target population and intended user
Note 1 to entry: Clinical performance can include diagnostic sensitivity (3.15) and diagnostic specificity (3.16) based on
the known clinical or physiological state of the individual, and negative predictive values (3.37) and positive predictive
values (3.42) based on the prevalence of the disease.
Note 2 to entry: The clinical performance of an LDT is also referred to as the ability of a test to discriminate between
the target condition and health.
[20]
[SOURCE: IMDRF/GRRP WG/N47:2018, 3.11 , modified — “IVD Medical Device” was replaced by “LDT”
and Note 2 was replaced.]
3.9
clinical utility
usefulness of the results obtained from testing and the value of the information to either the individual
being tested or the broader population, or both
Note 1 to entry: Aside from scientific validity (3.51), analytical performance (3.2), and clinical performance (3.8), a laboratory
is not required to demonstrate any other elements of the clinical utility of a laboratory-developed test (LDT) (3.25).
[23]
Note 2 to entry: Adapted from GHTF/SG5/N6:2012, 4.7 .
3.10
competence
demonstrated ability to apply knowledge and skills to achieve intended results
[SOURCE: ISO 15189:2022, 3.5]
3.11
cross-reactivity
degree to which a substance other than the analyte (3.1) intended to be measured affects an examination
(3.17) procedure
EXAMPLE Antibody binding to metabolites of the analyte, structurally similar drugs, etc.
Note 1 to entry: Analytical specificity (3.4) is a related concept.

ISO 5649:2024(en)
Note 2 to entry: Cross-reactivity of metabolites can be a desirable attribute of certain examination procedures, such
as for screening for the presence of illegal drugs.
Note 3 to entry: It is important to calculate cross-reactivity on the basis of moles per litre. For guidelines in calculating
cross-reactivity, see Reference [54].
[SOURCE: ISO 18113-1:2022, 3.2.14, modified — “binds to a reagent in a competitive binding immunochemical
measurement procedure” was replaced by “intended to be measured affects an examination procedure”.]
3.12
design and manufacture
activities that may include specification development, production, assembly, processing, sterilization,
installation of a laboratory-developed test (LDT) (3.25) or putting a collection of devices, and possibly other
products, together for a medical purpose as specified by the laboratory
[20]
[SOURCE: IMDRF/GRRP WG/N47:2018, 3.25 NOTE 3, modified — “medical device” was replaced by “LDT”.]
3.13
detection limit
limit of detection
measured quantity value, obtained by a given measurement procedure (3.31), for which the probability of
falsely claiming the absence of a component in a material is β, given a probability α of falsely claiming its
presence
Note 1 to entry: IUPAC recommends default values for α and β equal to 0,05.
Note 2 to entry: The abbreviation LoD is sometimes used.
Note 3 to entry: The term “sensitivity” is discouraged for ‘detection limit’.
[19]
[SOURCE: JCGM 200:2012, 4.18 ]
3.14
diagnostic accuracy
extent of agreement between the information from the test under evaluation and applicable performance
attributes as measured by a reference method
Note 1 to entry: Diagnostic accuracy can be expressed in different ways, including sensitivity-specificity pairs,
likelihood ratio pairs, and the area under a receiver operating characteristic curve.
Note 2 to entry: Diagnostic accuracy shall be interpreted in context with the condition of interest and the combination
of specific criteria and methods used.
Note 3 to entry: Diagnostic accuracy is not the same as measurement accuracy (3.29), which is the closeness of a single
result of a measurement and a true value.
[49]
[SOURCE: CLSI Harmonized Terminology Database, Project: EP12, M55, modified — “diagnostic accuracy
criteria” has been replaced by “applicable performance attributes as measured by a reference method”.]
3.15
diagnostic sensitivity
ability of an examination (3.17) procedure to have positive results associated with a particular disease or
condition
Note 1 to entry: Also defined as percent positivity in samples where the target marker is known to be present. For
information regarding description of the diagnostic performance characteristics (3.39) of a laboratory-developed test
(LDT) (3.25), see Reference [55].
Note 2 to entry: Diagnostic sensitivity is expressed as a percentage (number fraction multiplied by 100), calculated as
100 × the number of true positive values (TP) divided by the sum of the number of true positive values (TP) plus the
number of false negative values (FN), or 100 × TP / (TP + FN). This calculation is based on a study design where only
one sample is taken from each subject.

ISO 5649:2024(en)
Note 3 to entry: The target condition is defined by criteria independent of the examination procedure under
consideration.
[SOURCE: ISO 18113-1:2022, 3.2.17]
3.16
diagnostic specificity
ability of an examination (3.17) procedure to have negative results associated with an absence of a particular
disease or condition
Note 1 to entry: Also defined as percent negativity in samples where the target marker is known to be absent. For
information regarding description of the diagnostic performance characteristics (3.39) of a laboratory-developed test
(LDT) (3.25), see Reference [55].
Note 2 to entry: Diagnostic specificity is expressed as a percentage (number fraction multiplied by 100), calculated as
100 × the number of true negative values (TN) divided by the sum of the number of true negative plus the number of
false positive (FP) values, or 100 × TN / (TN + FP). This calculation is based on a study design where only one sample
is taken from each subject.
Note 3 to entry: The target condition is defined by criteria independent of the examination procedure under
consideration.
[SOURCE: ISO 18113-1:2022, 3.2.18]
3.17
examination
set of operations having the objective of determining the numerical value, text value or characteristics of a
property
Note 1 to entry: An examination may be the total of a number of activities, observations or measurements required to
determine a value or characteristic.
Note 2 to entry: Laboratory examinations that determine a numerical value of a property are called “quantitative
examinations”; those that determine the characteristics of a property are called “qualitative examinations”.
Note 3 to entry: Laboratory examinations are also called “assays” or “tests”.
[SOURCE: ISO 15189:2022, 3.8]
3.18
expected service life
expected lifetime
service life
time period specified by the laboratory during which the laboratory-developed test (LDT) (3.25) is expected
to maintain safe and effective use
Note 1 to entry: The expected service life can be determined by stability (3.54).
Note 2 to entry: Maintenance, repairs, or upgrades, e.g. safety (3.50) or cybersecurity modifications, can be necessary
during the expected service life.
[20]
[SOURCE: IMDRF/GRRP WG/N47:2018, 3.13, , modified — “manufacturer” was replaced by “laboratory”
and “medical device or IVD medical device” was replaced by “LDT”.]
3.19
expiry date
expiration date
upper limit of the time interval during which the performance characteristics (3.39) of a material stored
under specified conditions can be assured
Note 1 to entry: Expiry dates are assigned to reagents, calibrators, control materials, and other components by the
laboratory, based on experimentally determined stability (3.54) properties.
Note 2 to entry: Guidelines for determining the stability are found in ISO 23640:2011.

ISO 5649:2024(en)
[SOURCE: ISO 18113-1:2022, 3.1.22, modified — in Note 1 to entry, “manufacturer” was replaced by
“laboratory”.]
3.20
feasibility assessment
initial part of the laboratory-developed test (LDT) (3.25) lifecycle (3.26) phases that includes consideration of
a potential examination (3.17) method, by the laboratory, concerning various issues that are relevant to the
decision of developing a new examination method (e.g. laboratory users’ (3.24) needs and expectations and
availability of scientific data)
[43]
Note 1 to entry: Adapted from CLSI EP 19 .
3.21
indications for use
general description of the disease or condition that the laboratory-developed test (LDT) (3.25) diagnoses,
helps prevent, or monitors, including a description of the patient population for which the LDT is intended
[20]
[SOURCE: IMDRF/GRRP WG/N47, 3.17 , modified — “medical device or IVD medical device” was replaced
by “LDT”.]
3.22
intended use
intended purpose
objective intent regarding the use of a product, process or service as reflected in the specifications,
instructions and information regarding the laboratory-developed test (LDT) (3.25) provided by the laboratory
Note 1 to entry: The intended use can include the indications for use (3.21).
[20]
[SOURCE: IMDRF/GRRP WG/N47:2018, 3.13, , modified — “regarding the LDT” was added, “manufacturer”
was replaced by “laboratory”.]
3.23
in vitro diagnostic medical device
IVD medical device
medical device, whether used alone or in combination, intended for the in vitro examination (3.17) of
specimens derived from the human body solely or principally to provide information for diagnostic,
monitoring or compatibility purposes
Note 1 to entry: IVD medical devices include reagents, calibrators, control materials, specimen receptacles,
software, and related instruments or apparatus or other articles and are used, for example, for the following test
purposes: diagnosis, aid to diagnosis, screening, monitoring, predisposition, prognosis, prediction, determination of
physiological state.
Note 2 to entry: In some jurisdictions, certain IVD medical devices can be covered by other regulations.
[21]
[SOURCE: IMDRF/GRRP WG/N52, 3.18 , modified — “by the manufacturer” was deleted.]
3.24
laboratory user
individual or entity requesting services of the medical laboratory
Note 1 to entry: Users can include patients, clinicians, and other laboratories or institutions that send samples for
examination (3.17).
[SOURCE: ISO 15189:2022, 3.16]

ISO 5649:2024(en)
3.25
laboratory-developed test
LDT
laboratory-developed examination
in-house IVD
laboratory designed or developed method
test or examination (3.17) which is designed, developed, manufactured (or modified) and used within a
single laboratory or laboratory network to carry out testing on samples, where the results are intended to
assist in clinical diagnosis or be used in making decisions concerning clinical management
Note 1 to entry: There are four broad situations, as follows, where a laboratory is considered to have developed an LDT:
a) LDTs developed from first principles (de novo): this situation applies when a laboratory or laboratory network is
responsible for the design and production of the examination.
b) LDTs developed or modified from a published or any other source: these include tests produced by a laboratory
1) in accordance with scientific literature;
2) from the design specifications of an LDT manufactured by another laboratory; or
3) from the design specifications of any other source.
c) LDTs developed as assembly or combination of commercially authorized in vitro diagnostic medical devices (3.23)
and other, non-IVD products to a novel system for IVD purposes.
d) LDTs used for a purpose other than the intended use (3.22) assigned by the commercial manufacturer: IVD medical
devices become a laboratory-developed test (LDT) when
1) the intended use is different than the intended use claimed by the commercial manufacturer, for
example when a “laboratory product” (“for research use only”-product, “for laboratory use only”-
product, etc.) is used by the laboratory for IVD purposes;
2) a physical component of the commercial IVD medical device is modified, substituted, or removed; or
3) the test is not used in accordance with the manufacturer’s instructions for use, including significant
changes (3.53) of the intended use of the IVD medical device, such as, for example, the addition or
change of specimen type(s).
3.26
lifecycle
phases in the life of a laboratory-developed test (LDT) (3.25), from the initial feasibility assessment (3.20) to
final retirement
[20]
[SOURCE: IMDRF/GRRP WG/N47:2018, 3.24, modified — “medical device” was replaced by “LDT”.]
3.27
linearity
linearity of a measuring system
ability, within a given measuring interval (3.35), to provide results that are directly proportional to the
concentration (or amount) of the measurand (3.28) in the sample
Note 1 to entry: Linearity typically refers to overall system response (i.e. the final analytical answer rather than the
raw instrument output).
Note 2 to entry: The linearity of a system is measured by testing levels of a measurand that are known by formulation
or known relative to each other (not necessarily known absolutely).
Note 3 to entry: For some applications, users may choose to verify linearity using a linear equation that includes a
term for the y-intercept. In this less restrictive case, linearity is the ability of a testing system to provide results that
conform to a straight line of the form Y = AX + B within a given measuring interval. Additional information, e.g. from a
comparison study or calibration verification (3.57), should be provided to check whether the term for the y-intercept
is close to zero.
ISO 5649:2024(en)
Note 4 to entry: Nonlinearity is a contributor to systematic bias (3.5). There is no single statistic that can represent an
acceptable degree of nonlinearity.
[SOURCE: ISO 18113-1:2022, 3.2.24]
3.28
measurand
quantity intended to be m
...