SIST EN ISO 18704:2026

SLOVENSKI STANDARD
01-april-2026
Nadomešča:
SIST-TS CEN/TS 17811:2022
Molekularne diagnostične preiskave in vitro - Zahteve in priporočila za
predpreiskovalne procese pregleda urina in drugih telesnih tekočin - Izolirana
brezcelična DNK (ISO 18704:2026)
Molecular in vitro diagnostic examinations - Requirements and recommendations for pre-
examination processes for urine and other body fluids - Isolated cell-free DNA (ISO
18704:2026)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für Urin und andere Körperflüssigkeiten - Isolierte zellfreie DNA
(ISO 18704:2026)
Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus
préanalytiques pour l’urine et d’autres liquides corporels - ADN libre extrait (ISO
18704:2026)
Ta slovenski standard je istoveten z: EN ISO 18704:2026
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 18704
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2026
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 17811:2022
English Version
Molecular in vitro diagnostic examinations - Requirements
and recommendations for pre-examination processes for
urine and other body fluids - Isolated cell-free DNA (ISO
18704:2026)
Analyses de diagnostic moléculaire in vitro - Exigences Molekularanalytische in-vitro-diagnostische Verfahren
et recommandations relatives aux processus - Spezifikationen für präanalytische Prozesse für Urin
préanalytiques pour l'urine et d'autres liquides und andere Körperflüssigkeiten - Isolierte zellfreie
corporels - ADN libre extrait (ISO 18704:2026) DNA (ISO 18704:2026)
This European Standard was approved by CEN on 13 February 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 18704:2026 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 18704:2026) 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 August 2026, and conflicting national standards shall
be withdrawn at the latest by February 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 CEN/TS 17811:2022.
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 18704:2026 has been approved by CEN as EN ISO 18704:2026 without any modification.

International
Standard
ISO 18704
First edition
Molecular in vitro diagnostic
2026-02
examinations — Requirements
and recommendations for pre-
examination processes for urine
and other body fluids — Isolated
cell-free DNA
Analyses de diagnostic moléculaire in vitro — Exigences et
recommandations relatives aux processus préanalytiques pour
l’urine et d’autres liquides corporels — ADN libre extrait
Reference number
ISO 18704:2026(en) © ISO 2026
ISO 18704:2026(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
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Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii
ISO 18704:2026(en)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General requirements . 6
5 Outside the laboratory . 7
5.1 Specimen collection .7
5.1.1 Information about the patient or specimen donor .7
5.1.2 Selection of the body fluid collection device by the laboratory .7
5.1.3 Urine and other body fluid specimen collection from the patient or donor and
stabilization procedures .8
5.1.4 Information about the specimen storage requirements at the body fluid
collection facility .9
5.2 Transport requirements .11
5.2.1 General .11
5.2.2 Transport using urine and other body fluid collection devices with cfDNA
stabilizers .11
5.2.3 Transport using urine and other body fluid collection devices without cfDNA
stabilizers . 12
6 Inside the laboratory .12
6.1 Specimen or sample reception . 12
6.2 Specimen or sample storage after transport and reception . 12
6.3 Urine and other body fluid specimen or sample processing prior to cfDNA isolation . 13
6.4 Storage requirements for urine and other body fluid samples after processing . 13
6.5 Isolation of urine and other body fluid cfDNA .14
6.5.1 General .14
6.5.2 Using a commercial cfDNA isolation kit approved for diagnostic use .14
6.5.3 Using a laboratory developed cfDNA isolation procedure .14
6.6 Quantity and quality assessment of isolated cfDNA . 15
6.6.1 General . 15
6.6.2 Quantity assessment of cfDNA . 15
6.6.3 Quality assessment of cfDNA . 15
6.7 Storage of isolated urine and other body fluid cfDNA.16
6.7.1 General .16
6.7.2 Storage of isolated urine and other body fluid cfDNA, isolated with a
commercially available kit . .16
6.7.3 Storage of isolated urine and other body fluid cfDNA, isolated with the
laboratory’s own procedure.17
Annex A (informative) Effects of pre-examination storage of unstabilized urine on cfDNA .18
Annex B (informative) Effects of pre-examination storage of unstabilized and stabilized urine
on the amount of a specific cfDNA target sequence.22
Bibliography .24

iii
ISO 18704:2026(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).
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 18704:2026(en)
Introduction
Molecular in vitro diagnostics has enabled significant progress in medicine. Further progress has been
achieved and is still expected by new technologies used to examine profiles of nucleic acids, proteins, and
metabolites in human tissues and body fluids (e.g. genomic, epigenomic, transcriptomic, proteomic and
metabolomic profiling). However, the profiles of these molecules can change drastically during specimen
collection, transport, storage and processing. This can make the outcome from diagnostics or research
unreliable or even result in failure because the subsequent examination will not measure the genuine profile
of nucleic acids, proteins or metabolites as it was in the patient, but a profile altered by the pre-examination
process. Therefore, specifying, developing, verifying and validating preanalytical workflows has become an
[21]
essential part of examination development.
Most of the DNA in the body is located within cells, but small amounts of DNA originating from cells can
also be found outside of cells (extracellular DNA). In case of circulating body fluids such as blood, this DNA
is called circulating cell-free DNA (ccfDNA) and in case of non-circulating body fluids such as urine, saliva,
cerebrospinal fluid, pleural effusion, ascites, and synovial fluid, the DNA is called cell-free DNA (cfDNA).
cfDNA is of specific interest, as for example cfDNA in urine originates from cells from the genitourinary
[22]
tract or from ccfDNA passing through glomerular filtration. cfDNA from cancerous or malignant cells in
[23],[24]
urine have been associated with cancer specific sequences, epigenetic and structural changes. Urine
is currently the most frequently used non-circulating body fluid for cfDNA examination because it is easily
obtained from patients. Although urine is often described as the major specimen type, in this document the
term body fluid is used for urine and other body fluids as defined in Clause 3.
Standardization of the entire workflow from specimen collection to the cfDNA examination is needed to
minimize post-collection release of DNA from cells into the fluid and degradation of cfDNA in the specimen,
which can change the original native cfDNA profile in the body fluid. Post collection microbial growth in
the specimen can further enhance the degradation of the cfDNA, e.g. in urine and saliva. Furthermore, the
isolation of cfDNA can lead to a cfDNA profile bias. Different methods to determine cfDNA yield and quality
can lead to additional variations and impacts.
Studies have been undertaken to determine the pre-examination sources of these and other variables,
as they can impact the cfDNA examination. The variables can compromise the specified examination
performance characteristics, such as sensitivity, specificity, linearity and reproducibility. They can also
impact the examination reliability which could lead to an erroneous examination result and misdiagnosis.
This document draws upon such work to codify and standardize the steps prior to cfDNA examination from
body fluids in what is referred to as the pre-examination process.
In this document, the following verbal forms are used:
— “shall” indicates a requirement;
— “should” indicates a recommendation;
— “may” indicates a permission;
— “can” indicates a possibility or a capability.

v
International Standard ISO 18704:2026(en)
Molecular in vitro diagnostic examinations — Requirements
and recommendations for pre-examination processes for
urine and other body fluids — Isolated cell-free DNA
1 Scope
This document specifies requirements and provides recommendations for the pre-examination process
of cell-free DNA (cfDNA) from body fluid specimens other than blood, including but not limited to the
collection, handling, storage, transport, processing and documentation of human body fluids, such as urine,
pleural effusions, ascites, cerebrospinal fluid (CSF), and saliva, intended for cfDNA examination. Processing
includes multiple steps, such as centrifugation for specimen purification and isolation of cfDNA.
This document does not cover dedicated measures for cytohistological analysis of nucleated cells derived
from body fluid, nor measures for preserving and handling of pathogens, and other bacterial or whole
microbiome DNA in body fluids described.
Dedicated measures for preserving circulating cell-free DNA (ccfDNA) from blood are covered in ISO 20186-3.
This document is applicable to medical laboratories, health institutions including facilities collecting and
handling specimens, laboratory customers, in vitro diagnostic examination developers and manufacturers,
biobanks, institutions and organizations performing biomedical research, and regulatory authorities.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in
this document.
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 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 15189, ISO 13485 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
aliquot
portion of a larger amount of homogenous material, assumed to be taken with negligible sampling error
Note 1 to entry: The term is usually applied to fluids that are uniform in structure and composition. Tissues are
heterogeneous and therefore cannot be aliquoted.

ISO 18704:2026(en)
[SOURCE: ISO 20166-1:2018, 3.1, modified — “that are uniform in structure and composition ” was added in
Note 1 to entry.]
3.2
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2020, 3.1, modified — The example was removed.]
3.3
ascites
abnormal buildup of fluid in the abdomen that can cause swelling
Note 1 to entry: In late-stage cancer, tumour cells can be found in the fluid in the abdomen.
Note 2 to entry: Ascites also occurs in patients with liver disease.
Note 3 to entry: This definition was adapted from Reference [28].
3.4
body fluid
natural fluid or secretion that is produced by the body including, but not limited to, urine (3.26), saliva,
semen, mucus, vaginal secretions, breast milk, amniotic fluid, cerebrospinal fluid, synovial fluid, ascites
(3.3), pleural effusions and pericardial fluid
Note 1 to entry: For the purpose of this document blood and faeces are not included.
[SOURCE: ISO/TR 19591:2018, 3.23, modified — Blood and faeces were deleted from the definition, and
saliva, ascites and pleural effusion were added; Note 1 to entry was added.]
3.5
body fluid collection device
tube or other container in which the body fluid (3.4) (e.g. urine (3.26)) specimen (3.23) is collected
3.6
cfDNA
cell-free DNA
extracellular human DNA (3.12) present in non-circulating body fluids (3.4) such as urine (3.26)
[29]
Note 1 to entry: cfDNA can include DNA present in vesicles such as exosomes.
3.7
cfDNA profile
cell-free DNA profile
amount of different cell-free DNA (cfDNA) (3.6) molecules, present in a body fluid (3.4) that can be measured
in the absence of any losses, inhibition and interference
3.8
cfDNA stabilizer
cell-free DNA stabilizer
compound, solution or mixture that is designed to minimize degradation and fragmentation of cell-free DNA
(cfDNA) (3.6) as well as release of genomic DNA (3.16) from nucleated cells
3.9
closed system
non-modifiable system provided by the vendor including all necessary components for the analysis (i.e.,
hardware, software, procedures and reagents)
3.10
collection device manufacturer
entity that manufactures in vitro diagnostic or research devices, intended for the collection of specimens
(3.23)
ISO 18704:2026(en)
3.11
collection facility
area where a human specimen (3.23) is collected, such as physician’s office, patient’s home, hospital and clinic
3.12
DNA
deoxyribonucleic acid
polymer of deoxyribonucleotides occurring in a double-stranded (dsDNA) or single-stranded (ssDNA) form
[SOURCE: ISO 22174:2024, 3.1.6]
3.13
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”.
Note 4 to entry: For the purpose of this document, examination starts with the isolated cell-free DNA (cfDNA) (3.6).
[SOURCE: ISO 15189:2022, 3.8 — Note 4 to entry was added.]
3.14
examination manufacturer
entity that manufactures in vitro diagnostic or research examination devices, including measurement
systems, instruments, reagents, and instructions for use for a specific examination (3.13)
Note 1 to entry: Adapted from ISO 20166-4:2021, 3.16.
3.15
examination performance
analytical test performance
analytical performance
accuracy, precision, specificity, sensitivity and limit of detection of a test to examine the analyte (3.2) of
interest
Note 1 to entry: Other test performance characteristics such as robustness may apply as well.
Note 2 to entry: Examination performance is determined from examination performance studies used to assess the
ability of an in vitro diagnostic examination (3.13) procedure to measure or detect a particular analyte.
Note 3 to entry: Examination performance includes such characteristics as analytical sensitivity, detection limit,
analytical specificity (interference and cross-reactivity), trueness, precision and linearity.
Note 4 to entry: Adapted from ISO 20184-1:2018, 3.4.
3.16
genomic DNA
gDNA
DNA (3.12) from the nuclear and mitochondrial genomes containing all coding (exon) and non-coding (intron
and other) sequences
[SOURCE: ISO 20186-2:2019, 3.12, modified — Note 1 to entry was removed.]

ISO 18704:2026(en)
3.17
interfering substance
endogenous or exogenous substance that can be present in specimens (3.23) and that can alter an examination
(3.13) result
EXAMPLE Stabilization solution.
3.18
microorganism
entity of microscopic size, encompassing bacteria, fungi, protozoa and viruses
[SOURCE: ISO 11139:2018, 3.176]
3.19
pre-examination process
pre-analytical phase
pre-analytical workflow
pre-examination phase
process that starts, in chronological order, from the user’s request and includes the examination (3.13)
request, preparation and identification of the patient, collection of the specimen(s) (3.23), transportation to
and within the laboratory, ending when the examination begins
Note 1 to entry: For the purpose of this document, pre-examination process ends with the isolated cell-free DNA
(cfDNA) (3.6).
[SOURCE: ISO 15189:2022, 3.24, modified — The preferred terms “pre-analytical phase”, “pre-analytical
workflow” and “pre-examination phase” were added; Note 1 to entry was added.]
3.20
proficiency test
evaluation of participant performance against pre-established criteria by means of interlaboratory
comparisons
[SOURCE: ISO/IEC 17043:2023, 3.7, modified — The term was changed from “proficiency testing” to
“proficiency test”; Note 1 to entry was removed.]
3.21
room temperature
temperature in the range of 18 °C to 25 °C
Note 1 to entry: Local or national regulations can have different definitions.
[SOURCE: ISO 20166-1:2018, 3.22]
3.22
sample
one or more parts taken from a specimen (3.23)
[SOURCE: ISO 15189:2022, 3.28]
3.23
specimen
primary sample
discrete portion of a body fluid (3.4) or tissue or other sample (3.22) associated with the human body taken
for examination (3.13), study or analysis of one or more quantities or characteristics to determine the
character of the whole
[SOURCE: ISO 15189:2022, 3.25, modified — Note 1 to entry was removed.]

ISO 18704:2026(en)
3.24
stability
ability of a sample (3.22) material, when stored under specified conditions, to maintain a stated property
value within specified limits for a specified period of time
Note 1 to entry: The measurand constituent for the purpose of this document is isolated DNA (3.12).
[SOURCE: ISO Guide 30:2015, 2.1.15, modified — In the definition, “characteristic” was changed to “ability”;
“specified property value” was changed to “stated property value”; Note 1 to entry was removed and a new
note was added.]
3.25
storage
prolonged interruption of the pre-examination process (3.19) of a sample (3.22) or analyte (3.2) respectively,
or of their derivatives, under appropriate conditions in order to preserve their properties
Note 1 to entry: Long-term storage typically occurs in laboratory archives or in biobanks.
[SOURCE: ISO 20184-1:2018, 3.22, modified — The examples of derivatives “stained sections or tissue
blocks” were removed from the definition.]
3.26
urine
liquid product of the human excretory system produced by the kidneys and expelled through the urethra via
urination
[SOURCE: ISO 30500:2025, 3.1.2.3, modified — Note 1 to entry was removed.]
3.27
validation
confirmation of plausibility for a specific intended use or application through the provision of objective
evidence that specified requirements have been fulfilled
Note 1 to entry: Objective evidence can be obtained through observation, measurement, examination (3.23) or by
other means.
Note 2 to entry: The word “validated” is used to designate the corresponding status.
[SOURCE: ISO 15189:2022, 3.31, modified — Note 3 to entry was removed.]
3.28
verification
confirmation of truthfulness, through the provision of objective evidence, that specified requirements have
been fulfilled
EXAMPLE 1 Confirmation that design input specifications of a measuring system are achieved.
EXAMPLE 2 Confirmation that a target measurement uncertainty can be met.
Note 1 to entry: Verification is the process that intends to confirm that the established performance claims of a
measuring system, e.g. trueness, precision, reportable range, can be replicated in the laboratory before human sample
examination (3.23) is performed.
Note 2 to entry: The objective evidence needed for a verification can be the result of a regulatory authority assessment,
an inspection or other forms of determination, such as performing alternative calculations or reviewing documents.
Note 3 to entry: The word “verified” is used to designate the corresponding status.
[SOURCE: ISO 15189:2022, 3.32, modified — In Example 1 “performance” was changed to “design input”;
Notes 1 and 2 to entry have been revised; Note 3 to entry has been removed.]

ISO 18704:2026(en)
3.29
workflow
series of activities necessary to complete a task
[SOURCE: ISO 20166-1:2018, 3.30]
4 General requirements
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
and ISO/IEC 17020 or ISO/IEC 17025. ISO 20658 and ISO 20387 (for biobanking) may also apply. The
requirements on laboratory equipment, reagents, and consumables according to ISO 15189 shall be followed;
ISO/IEC 17020 and ISO/IEC 17025 may also apply. For IVD developers and manufacturers ISO 13485 may
apply instead.
All steps of the pre-examination, examination and post-examination processes (i.e. the entire workflow)
can influence the diagnosis or research study results, thus, this entire workflow shall be specified, verified
and validated during the development of the examination, including the development of in vitro diagnostic
(IVD) medical devices. This includes explicitly all pre-examination process steps such as the examination
request, preparation and identification of the patient, collection of the specimen(s), transport to and within
the laboratory, storage and isolation of analytes.
The stability of the cfDNA profile should be investigated throughout the complete pre-examination process.
The verification and validation shall account for the variability of the body fluid specimen’s quality. cfDNA
profiles can change significantly after body fluid collection. The post-collection release of genomic DNA from
cells in the body fluid can change the cfDNA profile (see Reference [31]). In some body fluids, such as urine,
post-collection growth of bacteria can cause additional changes to the cfDNA profile such as contaminating
the human cfDNA with bacterial DNA and causing degradation of target cfDNA. Post-collection conditions
such as large temperature variations and prolonged storage or transportation times, or both, can also result
in cfDNA degradation. Post-collection changes can vary individually in specimens from different donors
or patients, and they can also depend on pathophysiological conditions. This can impact the validity and
reliability of the examination results.
During the design and development of a cfDNA based examination, an appropriate risk assessment shall
be performed (see also ISO 14971, ISO 22367, ISO 35001). Mitigation measures for eliminating or reducing
identified risks shall be established where required for ensuring the performance of the examination. It shall
be investigated and ensured that any change to the cfDNA profile(s) introduced during the pre-examination
process does not lead to a change of the examination result. To ensure the cfDNA profile is not compromised,
it can be necessary to characterize whether or how, or both, the profile intended to be examined changes
during the pre-examination process steps (e.g. degradation of target cfDNA, and the post-collection release
of genomic DNA from present cells). This can be done, for example by applying the intended examination
to specimens or samples that have been subjected to pre-examination steps such as transport and storage
in time course studies (see Annex A). Measures can be implemented to prevent or reduce impacts by the
identified pre-examination variables, e.g. by using body fluid collection devices with cfDNA stabilizers (see
Annex B).
During the whole pre-examination process, precautions shall be taken to avoid cross contamination between
different specimens or samples (e.g. by using single-use material whenever feasible or appropriate cleaning
procedures between processing of different specimens or samples), and to avoid mixing up of specimens or
samples.
Safety instructions for the whole pre-examination process shall be in place and followed. Safety regulations
on specimen or sample transport and handling shall be considered (see ISO 15189, ISO 15190 and ISO 20658).
If transport is required over public areas, corresponding regulations or laws for packaging and transport
apply [e.g. International Air Transport Association (IATA) for air transport].
The manufacturer’s material safety data sheet shall be considered before first use of any potentially
hazardous material (e.g. chemicals in stabilizers).
For all pre-examination steps, the examination manufacturer’s instructions shall be followed, if provided.

ISO 18704:2026(en)
Where, for justified reasons (e.g. unmet patient needs), a commercial product is not used in accordance with
the manufacturer’s instructions, responsibility for its verification, validation, use and performance lies with
the laboratory.
5 Outside the laboratory
5.1 Specimen collection
5.1.1 Information about the patient or specimen donor
The documentation shall include the identity of the patient or specimen donor, which may be in the form of
the name or a code.
The documentation should include, but is not limited to:
a) the relevant health status (e.g. healthy, disease type, concomitant disease) and demographics of the
patient or specimen donor (e.g. age and sex);
b) the information about medical treatment and special treatment prior to body fluid collection (e.g.
anaesthetics, medications, fasting status, surgical or diagnostic procedures);
c) the type and the purpose of the examination requested;
d) the appropriate consent from the patient or specimen donor.
NOTE See ISO 15189 for further information. ISO 20658 provides additional general guidance on the entire
collection process.
5.1.2 Selection of the body fluid collection device by the laboratory
The cfDNA profile of body fluids can be influenced by e.g. inadequate collection procedures, inappropriate
storage or transport conditions, separation of contaminating cells as well as by cfDNA isolation procedures.
Specifically, the post-collection degradation can significantly change the cfDNA profile in body fluids, e.g. in
[32],[33]
urine. This can impact the validity of the examination results.
In order to prevent cfDNA degradation, bacterial growth and, where required, release of genomic DNA from
cells and DNA from microorganisms, body fluid collection devices with cfDNA profile stabilizers, or devices
without stabilizers with immediate post-collection addition of stabilizers should be used. These stabilizers
should also allow the separation of nucleated cells from cfDNA in the body fluid, e.g. by centrifugation. Body
fluid collection devices without cfDNA profile stabilizers and workflows without immediate post-collection
addition of cfDNA stabilizers should only be used if the ordered examination specifications allow the non-
use of stabilizers.
The examination manufacturer’s instructions for use for the specimen collection shall be followed. Where
the cfDNA examination manufacturer requires usage of a dedicated body fluid collection device or body
fluid cfDNA stabilizer, these shall be used. This can include a transfer into a secondary container with a
stabilizer. The device’s and stabilizers’ catalogue and lot numbers shall be documented.
For specimens intended for extended storage in a biobank the individual human cfDNA examinations needed
are not always known in advance of extended storage. Therefore, body fluid collection devices with cfDNA
profile stabilizers or workflows with immediate post-collection addition of cfDNA stabilizers should be used
to enable the use of a wider range of examinations.

ISO 18704:2026(en)
5.1.3 Urine and other body fluid specimen collection from the patient or donor and stabilization
procedures
5.1.3.1 General
The examination manufacturer shall specify, verify and validate the body fluid collection device for the
examination and shall provide instructions for use for the specimen collection procedure, either with or
where appropriate without stabilizers.
NOTE In some countries it is not a requirement of the examination manufacturer to provide such instructions for
use and to specify, verify and validate the body fluid collection device for the examination.
A cfDNA stabilizer should be used, to prevent any cfDNA profile changes during the pre-examination
process. This may be a collection device prefilled with a stabilizer or an external stabilizer may be added to
the collected urine or body fluid, e.g. from a bulk solution.
Where the specimen collection device is intended for self-collection or home collection, or both, the collection
device manufacturer shall validate this device for these purposes. This shall include mitigating any potential
risks for the patient or donor from the cfDNA stabilizer where appropriate (see Clause 4).
The laboratory shall have written or visual instructions, or both, in place for body fluid collection. These
shall follow the examination manufacturer’s instructions for use where provided.
Where the examination manufacturer’s instructions are not provided (e.g. due to less stringent legal
frameworks), or where, for justified reasons (e.g. unmet patient needs), they require modifications, the
laboratory shall specify, verify and validate the body fluid collection device and collection procedure for
the intended examination and document this according to its quality management system requirements.
This shall include specifications for specimen storage and transport as required for the examination (see
5.1.4 and 5.2). Where the selected body fluid collection device manufacturer provides specified and verified
instructions (see 5.1.3.2 and 5.1.3.3) for the body fluid collection, these can serve as a basis for the laboratory
to verify this device for the examination.
Where the specifications given in the instructions for use of the selected body fluid collection device do not
meet the examination requirements during verification, they shall be modified to be fit for purpose, verified
and documented by the laboratory.
Where specimen self-collection is possible (e.g. saliva, urine), written or visual instructions, or both, either
from the body fluid collection device manufacturer or the laboratory shall be supplied to the patient or
donor. Laboratory instructions shall be based on the body fluid collection device manufacturer’s or the
examination manufacturer’s requirements, or both.
The instructions for body fluid specimen collection shall include:
a) Requirements and recommendations to follow before the collection, in particular related to e.g. drinking
or fasting, or both, before collection, or collection time (e.g. first midstream urine of the morning).
b) All requirements for patient identification, collection, storage and transport of the specimen to the
laboratory. For collection this shall include requirements:
1) to collect the specimen within the specified volume range;
2) to mix the specimen with the stabilizer(s) if required by the manufacturer, e.g. by immediate
shaking or inverting.
For self-collection, the patient or donor shall be provided with an appropriate body fluid collection device
(e.g. container, tube), identity tag(s) [(e.g. label, radio frequency identification (RFID)], and in general
anything needed for the specimen collection, preservation, storage and transport procedure for returning
the specimen to laboratory.
The patient or donor shall also be provided with an option to confirm compliance with the supplied
instructions for the body fluid specimen col
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