EN ISO 23118:2021

SLOVENSKI STANDARD
01-september-2021
Nadomešča:
SIST-TS CEN/TS 16945:2016
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese metabolomike v urinu, serumu in plazmi venske krvi (ISO 23118:2021)
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes
in metabolomics in urine, venous blood serum and plasma (ISO 23118:2021)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für Metabolomuntersuchungen in Urin, venösem Blutserum und
-plasma (ISO 23118:2021)
Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus
préanalytiques pour l'analyse du métabolome dans l'urine et le sang veineux (sérum et
plasma) (ISO 23118:2021)
Ta slovenski standard je istoveten z: EN ISO 23118:2021
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 23118
EUROPEAN STANDARD
NORME EUROPÉENNE
June 2021
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 16945:2016
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes in metabolomics in urine,
venous blood serum and plasma (ISO 23118:2021)
Analyses de diagnostic moléculaire in vitro - Molekularanalytische in-vitro-diagnostische Verfahren
Spécifications relatives aux processus préanalytiques - Spezifikationen für präanalytische Prozesse für
pour l'analyse du métabolome dans l'urine et le sang Metabolomuntersuchungen in Urin, venösem
veineux (sérum et plasma) (ISO 23118:2021) Blutserum und -plasma (ISO 23118:2021)
This European Standard was approved by CEN on 20 May 2021.

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, Turkey 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
© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 23118:2021 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 23118:2021) has been prepared by Technical Committee ISO/TC 212 "Clinical
laboratory testing and in vitro diagnostic test 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 December 2021, and conflicting national standards
shall be withdrawn at the latest by June 2024.
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 CEN/TS 16945:2016.
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, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 23118:2021 has been approved by CEN as EN ISO 23118:2021 without any modification.

INTERNATIONAL ISO
STANDARD 23118
First edition
2021-05
Molecular in vitro diagnostic
examinations — Specifications
for pre-examination processes in
metabolomics in urine, venous blood
serum and plasma
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour l'analyse du métabolome dans
l'urine et le sang veineux (sérum et plasma)
Reference number
ISO 23118:2021(E)
©
ISO 2021
ISO 23118:2021(E)
© ISO 2021
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.
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Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved

ISO 23118:2021(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3  Terms and definitions . 1
4 General considerations . 3
5 Urine . 4
5.1 Outside the laboratory . 4
5.1.1 Urine collection . 4
5.1.2 Transport requirements . 5
5.2 Inside the laboratory . 5
5.2.1 Specimen reception . 5
5.2.2 Storage requirements . 6
5.2.3 Urine sample processing . 6
5.2.4 Long-term storage requirements for urine samples. 6
5.2.5 Urine thawing . 6
6 Blood . 7
6.1 Outside the laboratory . 7
6.1.1 Primary collection . 7
6.1.2 Transport of pre-processed specimens to laboratory . 8
6.2 Inside the laboratory . 8
6.2.1 Specimen reception . 8
6.2.2 Sample processing . 9
6.2.3 Transport of processed samples to a laboratory for metabolomics analysis
or transport to a biobank . 9
6.2.4 Long-term storage requirements . 9
6.2.5 Serum and plasma thawing and use .10
Annex A (informative) Instability of the metabolome.11
Bibliography .17
ISO 23118:2021(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, 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 2021 – All rights reserved

ISO 23118:2021(E)
Introduction
Metabolomics is the "-omic" science that deals with the characterization of the metabolome, in turn
defined as the whole set of small molecules (molecular mass <2 000 Da) in a certain biological system
[1]
such as a cell, a tissue, an organ, or an entire organism . The analyses are mainly performed via two
major analytical techniques, namely mass spectrometry (MS) and nuclear magnetic resonance (NMR)
[2][3][4]
. The former has a sensitivity that can be as low as picomolar, requires sample separation and
multiple experimental runs targeted to specific classes of compounds. The latter measures metabolites
present at concentration above 1 µM and is mainly used for untargeted analyses, where all metabolites
above the detection limit are observed simultaneously, independent of their chemical nature, without
any separation procedure.
The metabolome is dynamic and quite sensitive to perturbations. The metabolome can change
drastically during primary sample collection, transport, storage, and processing. As a result, the
outcome from the diagnostic and research measurements could become an unreliable representation
of the specific targeted physiological state or point in time, but instead describes an artificial profile
generated during the pre-examination process. Pre-analytical variations have been identified to
originate from two main sources:
a) enzymatic activity in the samples, mainly related to the presence of cells;
b) chemical reactions (e.g. redox reactions) among metabolites or between metabolites and oxygen,
see References [5] to [11].
Moreover, the analyses can be influenced by the use of additives or by the introduction of contaminants,
and therefore the selection of appropriate collection tubes and plasticware is also a critical aspect of
the pre-examination phase.
Studies have been undertaken to establish the best pre-examination procedures in terms of
maintenance of the original sample metabolome by identifying the critical steps and parameters
affecting the metabolome composition. Additionally, standardization of the entire pre-examination
workflow is needed to ensure comparability in multicentre studies. At the present state of the art, there
are no defined pre-examination procedures for metabolomic samples. As a consequence, the procedures
adopted by the various centres differentially influence the metabolome of the samples, making their
comparison unreliable. The adoption of the present requirements for the pre-examination phase make
it possible to compare and evaluate the results obtained from metabolic analysis.
This document draws upon such studies to codify and standardize the steps for urine, serum and
plasma metabolomics analysis in what is referred to as the pre-analytical phase.
INTERNATIONAL STANDARD ISO 23118:2021(E)
Molecular in vitro diagnostic examinations —
Specifications for pre-examination processes in
metabolomics in urine, venous blood serum and plasma
1 Scope
This document specifies requirements and gives recommendations for the handling, documentation
and processing of urine, venous blood plasma and serum intended for metabolomics analysis in the pre-
examination processes. This document is applicable to metabolomics examinations and can be used by
biomedical laboratories, customers of laboratories, in vitro diagnostics developers and manufacturers,
institutions and companies performing biomedical research, biobanks, and regulatory authorities.
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 15189, Medical laboratories — Requirements for quality and competence
ISO 15190, Medical laboratories — Requirements for safety
3  Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 15189 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
biofluid
biological fluid which can be excreted (such as urine or sweat), secreted (such as breast milk, saliva
or bile), obtained with a needle (such as blood or cerebrospinal fluid), or produced as a result of a
pathological process (such as blister or cyst fluid)
3.2
examination
set of operations having the object of determining the value or characteristics of a property
Note 1 to entry: Processes that start with the isolated analyte and include all kinds of parameter testing or
chemical manipulation for quantitative or qualitative examination.
Note 2 to entry: For metabolomic analysis, analyte isolation is not necessarily required.
[SOURCE: ISO 20166-1:2018, 3.10, modified — admitted term “analytical test” has been deleted and
Note 2 entry has been added.]
3.3
fasting
abstinence from any solid or liquid food excluding water for at least 8 hours
ISO 23118:2021(E)
3.4
mass spectrometry
MS
method used to analyse chemical compounds on the basis of their mass to charge ratio
3.5
metabolic profiling
use of analytical platforms to simultaneously measure the ensemble of metabolites (3.6) in biological
systems that can be measured by the employed (or selected) technique
EXAMPLE Examples for such techniques are NMR and MS.
3.6
metabolites
small molecules (≤ 2 000 Da) that are intermediates and/or products of metabolism of the host
organisms, of its microflora, deriving from food, drinks, drugs or pollutants.
Note 1 to entry: For further information see Reference [1].
3.7
metabolome
complete set of metabolites (3.6) to be found within an organism or a biological sample
Note 1 to entry: For further information see Reference [1]
3.8
metabolomics
comprehensive analysis of the metabolome (3.7) of a biological specimen (3.14) (e.g., organism, cell,
tissue or biofluids (3.1))
3.9
MS-based metabolomics
use of mass spectrometry (3.4) to measure metabolites (3.6) in biological samples
3.10
nuclear magnetic resonance spectroscopy
NMR
method based on the selective absorption of high frequency radio waves by atomic nuclei subjected to a
stationary magnetic field
Note 1 to entry: NMR provides chemical and structural properties of molecules.
3.11
NMR-based metabolomics
use of NMR spectroscopy (3.10) to measure metabolites (3.6) in biological samples
3.12
plasma
liquid part of unclotted blood
Note 1 to entry: Plasma samples can contain anti-coagulants.
3.13
pre-examination processes
preanalytical phase
preanalytical workflow
processes that start, in chronological order, from the clinician’s request and include the examination
(3.2) request, preparation and identification of the patient, collection of the primary sample(s),
temporary storage, transportation to and within the analytical laboratory, aliquoting, retrieval
Note 1 to entry: The preanalytical phase can include preparative processes that can influence the outcome of the
intended examination (3.2).
2 © ISO 2021 – All rights reserved

ISO 23118:2021(E)
[SOURCE: ISO 15189:2012, 3.15, modified — An additional term was added, and more details were
included.]
3.14
primary sample
specimen
discrete portion of a body fluid, breath, hair or tissue taken for examination (3.2), study or analysis of
one or more quantities or properties assumed to apply for the whole
[SOURCE: ISO 15189:2012, 3.16, modified — The term and definition are used here without the original
notes.]
3.15
room temperature
temperature which is defined as 18 °C to 25 °C for the purpose of this document
3.16
serum
liquid that can be separated from clotted blood
3.17
stability
characteristic of a reference material, when stored under specified conditions, to maintain a specified
property value within specified limits for a specified period of time
[SOURCE: ISO Guide 30:2015, 2.1.15 — The term and definition are used here without the original note.]
4 General considerations
For general statements on medical laboratory quality management systems and in particular on
specimen collection, reception, and handling (including avoidance of cross contaminations) see
ISO 15189 or ISO/IEC 17020. The requirements on laboratory equipment, reagents, and consumables
according to ISO 15189 shall be followed; ISO/IEC 17020 can also apply.
All steps of a diagnostic workflow can influence the final analytical test result and a risk assessment
shall be performed (see also ISO 14971). Mitigation measures for eliminating or reducing identified risks
shall be established where required for ensuring the performance of the examination. It shall especially
be investigated and ensured that the metabolites intended to be analysed are not compromised in a
manner impacting the examination performance. This can be done, e.g. by applying the intended
examination to specimens/samples which underwent time course studies reflecting the individual pre-
examination process steps such as transport and storage and by implementing measures to prevent or
reduce impacts by the identified pre-analytical variables.
In the absence of suitable specimen stabilization technologies, regarding the metabolome, the specimen
collection shall be carried out in hospital premises or institutions where there are immediate suitable
biofluid processing procedures available.
Specifically, for specimens intended to be analysed by metabolomics, the following steps shall be
considered:
a) patient pre-treatment (fasting, therapy, etc.);
b) the specimen collection from the patient;
c) the selection of collection containers and packages (e.g. collection tubes, cooling box, box for storing
and transportation);
d) the selection of stabilization procedures (e.g. any compounds added for stabilizing the specimen);
e) the recording of any additions or modifications to the specimen;
ISO 23118:2021(E)
f) the recording of types and quantity as well as description of specimens.
Safety requirements for facilities, transport and handling shall be considered in accordance with
ISO 15189 and ISO 15190. WHO Guidelines for the Safe Transport of Infectious Substances and
[14]
Diagnostic Specimens should be followed.
5 Urine
5.1 Outside the laboratory
5.1.1 Urine collection
5.1.1.1 General
For the collection of the specimen the requirements (e.g. disease condition, specimen size) for the
intended molecular examination shall be considered.
See also ISO 15189.
5.1.1.2 Information about the specimen donor/patient
The documentation shall include the ID of the specimen donor/patient, which can be in the form of a
code.
The documentation should include, but is not limited to:
a) the health status and relevant lifestyle factors of the urine donor [e.g. healthy, disease type,
concomitant disease(s)];
b) demographics (e.g., age, sex);
c) the information about medical treatment and any treatment prior to urine collection (e.g.
anaesthetics, medications, diagnostic procedures);
d) the collection time, including information about fasting, previous activities.
e) the appropriate consent from the specimen donor/patient.
5.1.1.3 Selection and labelling of collection containers
The laboratory shall define the container intended for urine collection.
Additives are usually not used, because they can interfere with the analytical method. If they are
required for specific purposes, their impact on the analytical performance and outcome shall be
analysed. Some additives in collection tubes could present a risk to patients (e.g. toxic or corrosive).
For the labelling (specimen identification) of the urine collection tube a routine procedure (see also
ISO 15189) or a procedure with additional information (e.g. 2D-barcode) shall be used.
5.1.1.4 Urine collection and reception from the specimen donor
5.1.1.4.1 General
Instruction for the urine collection shall be given to the donor, including any safety measures that need
to be followed while handling collection containers containing harmful additives. All urine collection
4 © ISO 2021 – All rights reserved

ISO 23118:2021(E)
devices should be checked for compatibility with metabolomics, e.g. avoiding any interference with the
metabolomics profile.
NOTE For non-toilet-trained children, the most popular non-invasive method used is the clean catch, which
National Institute for Health and Clinical Excellence (NICE), 2007 defines as a gold standard. This involves
catching a sample by holding a sterile specimen bottle in the urine stream. Urine collection bags and u
...