EN ISO 20186-3:2019

Molecular in-vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 3: Isolated circulating cell free DNA from plasma (ISO 20186-3:2019)

This document provides recommendations and requirements on the handling, storage, processing and documentation of venous whole blood specimens intended for circulating cell free DNA (ccfDNA) examination during the pre-examination phase before an analytical test is performed. This document covers specimens collected in venous whole blood collection tubes.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for stabilizing blood genomic DNA, which are not described in this document. Blood genomic DNA is covered in ISO 20186-2.
Different dedicated measures are taken for preserving DNA in circulating exosomes, which are not described in this document.
NOTE    ccfDNA obtained from blood by the procedures cited in this document can contain DNA originally present in exosomes[8][9].
DNA in pathogens present in blood is not covered by this document.

Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für präanalytische Prozesse für venöse Vollblutproben - Teil 3: Aus Plasma isolierte zirkulierende zellfreie DNA (ISO 20186-3:2019)

Dieses Dokument enthält Empfehlungen und Anforderungen für die Handhabung, Lagerung, Verarbeitung und Dokumentation von venösen Vollblutproben, die für die Untersuchung zirkulierender zellfreier DNA (ccfDNA) vorgesehen sind, während der präanalytischen Phase vor Beginn einer analytischen Prüfung. Dieses Dokument behandelt Untersuchungsmaterial, das in Blutentnahmeröhrchen für venöses Vollblut entnommen wurde.
Dieses Dokument gilt für alle molekularen in vitro diagnostischen Untersuchungen, die in medizinischen Laboren durchgeführt werden. Es ist außerdem auch für die Verwendung durch Labor Kunden, Entwickler und Hersteller von In vitro Diagnostika, Biobanken, Einrichtungen und kommerzielle Organisationen, die in der biomedizinischen Forschung tätig sind, sowie durch Aufsichtsbehörden vorgesehen.
Zur Stabilisierung genomischer DNA aus Blut werden andere spezielle Maßnahmen getroffen, die nicht in diesem Dokument beschrieben sind. Genomische DNA aus Blut wird in ISO 20186 2 behandelt.
Zur Erhaltung der DNA in zirkulierenden Exosomen werden andere zweckbestimmte Maßnahmen ergriffen, die in diesem Dokument nicht beschrieben werden.
ANMERKUNG   ccfDNA, die mit den in diesem Dokument vorgeschlagenen Verfahren aus Blut gewonnen wurde, kann DNA enthalten, die ursprünglich in Exosomen vorlag [8], [9].
Nicht durch dieses Dokument abgedeckt ist DNA, die in Krankheitserregern im Blut vorhanden ist.

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus préanalytiques pour le sang total veineux - Partie 3: ADN libre circulant extrait du plasma (ISO 20186-3:2019)

Le présent document fournit des recommandations et des exigences sur la manipulation, le stockage, le traitement et la documentation des prélèvements de sang total veineux destinés à l'analyse de l'ADN libre circulant (ADNlc) durant la phase préanalytique précédant la réalisation d'un essai analytique. Le présent document concerne les échantillons primaires prélevés dans des tubes de prélèvement de sang total veineux.
Le présent document s'applique aux analyses de diagnostic moléculaire in vitro réalisées par des laboratoires de biologie médicale. Il est également destiné à être utilisé par des clients de laboratoires, des développeurs et fabricants de l'industrie du diagnostic in vitro, ainsi que par des biobanques, des institutions et des organismes commerciaux spécialisés en recherche biomédicale, de même que des autorités de réglementation.
Des mesures spécifiques différentes, non décrites dans le présent document, sont prises pour stabiliser l'ADN génomique sanguin. L'ADN génomique sanguin est couvert par l'ISO 20186-2.
Des mesures spécifiques différentes, non décrites dans le présent document, sont prises pour préserver l'ADN des exosomes circulants.
NOTE       L'ADNlc extrait du sang à l'aide des protocoles cités dans le présent document est susceptible de contenir de l'ADN présent à l'origine dans les exosomes[8][9].
L'ADN des pathogènes présents dans le sang n'est pas couvert par le présent document.

Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese za vensko polno kri - 3. del: Iz plazme izolirana cirkulirajoča brezcelična DNK (ISO 20186-3:2019)

Ta mednarodni standard vsebuje priporočila za obravnavo, dokumentiranje, shranjevanje in obdelavo vzorcev venske polne krvi, namenjenih za analizo cirkulirajoče brezcelične DNK (ccfDNA) med predpreiskovalno fazo, preden se izvede molekularni preskus. Ta mednarodni standard zajema vzorce, ki so zbrani s cevkami za zbiranje venske polne krvi. Ta mednarodni standard se uporablja za molekularne diagnostične preiskave in vitro, vključno z laboratorijsko razvitimi preskusi, ki jih izvajajo v medicinskih laboratorijih. Uporabljali naj bi ga tudi uporabniki laboratorijev, razvijalci in proizvajalci diagnostike in vitro, navezuje pa se tudi na institucije in komercialne organizacije, ki izvajajo biomedicinske raziskave, biobanke ter regulativne organe. Profili cirkulirajoče brezcelične DNK se lahko znatno spremenijo po odvzemu krvi od darovalca (npr. sprostitev genomske DNK iz belih krvnih celic, razpad ali sprememba količine cirkulirajoče brezcelične DNK). Zato je treba sprejeti posebne ukrepe za pridobivanje vzorcev krvi dobre kakovosti za analizo in shrambo cirkulirajoče brezcelične DNK. Za ohranjanje krvne genomske DNK je treba uporabiti drugačne namenske ukrepe, ki niso opisani v tem mednarodnem standardu. Krvna genomska DNK je opisana v standardu ISO 20185-2, Molekularne diagnostične preiskave in vitro – specifikacije za predpreiskovalne procese za vensko polno kri - 2. del: Iz genoma izolirana DNK OPOMBA: cirkulirajoča brezcelična DNK iz krvi, pridobljena s postopki, ki jih predlaga ta dokument, lahko vsebuje DNK iz eksosomov. Patogena DNK v krvi ni zajeta v tem mednarodnem standardu. Za ohranjanje DNK v cirkulirajočih eksosomih je treba uporabiti drugačne namenske ukrepe, ki niso opisani v tem mednarodnem standardu. OPOMBA: Za določene teme, ki so zajete v tem mednarodnem standardu, lahko veljajo tudi mednarodni, nacionalni ali regionalni predpisi ali zahteve.

General Information

• Status: Published
• Publication Date: 22-Oct-2019
• Withdrawal Date: 30-Oct-2022
• ICS: 11.100.10 - In vitro diagnostic test systems
• Technical Committee: CEN/TC 140 - In vitro diagnostic systems
• Drafting Committee: CEN/TC 140/WG 3 - Quality management in the medical laboratory
• Current Stage: 6060 - Definitive text made available (DAV) - Publishing
• Start Date: 23-Oct-2019
• Due Date: 11-Aug-2018
• Completion Date: 23-Oct-2019
• Ref Project: SIST EN ISO 20186-3:2020 - Molecular in-vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 3: Isolated circulating cell free DNA from plasma (ISO 20186-3:2019)

Relations

• Replaces: CEN/TS 16835-3:2015 - Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 3: Isolated circulating cell free DNA from plasma
• Effective Date: 05-Sep-2018

Standards Content (Sample)

SLOVENSKI STANDARD
01-januar-2020
Nadomešča:
SIST-TS CEN/TS 16835-3:2015
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za vensko polno kri - 3. del: Iz plazme izolirana cirkulirajoča brezcelična
DNK (ISO 20186-3:2019)
Molecular in-vitro diagnostic examinations - Specifications for pre-examination processes
for venous whole blood - Part 3: Isolated circulating cell free DNA from plasma (ISO
20186-3:2019)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für venöse Vollblutproben - Teil 3: Aus Plasma isolierte
zirkulierende zellfreie DNS (ISO 20186-3:2019)
Tests de diagnostic moléculaire in vitro - Spécifications relatives aux processus pré-
analytiques pour le sang - ARN cellulaire - Partie 3: ADN libre circulant extrait du plasma
(ISO 20186-3:2019)
Ta slovenski standard je istoveten z: EN ISO 20186-3:2019
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 20186-3
EUROPEAN STANDARD
NORME EUROPÉENNE
October 2019
EUROPÄISCHE NORM
ICS 11.100.10
English Version
Molecular in-vitro diagnostic examinations - Specifications
for pre-examination processes for venous whole blood -
Part 3: Isolated circulating cell free DNA from plasma (ISO
20186-3:2019)
Analyses de diagnostic moléculaire in vitro - Molekularanalytische in-vitro-diagnostische Verfahren
Spécifications relatives aux processus préanalytiques - Spezifikationen für präanalytische Prozesse für
pour le sang total veineux - Partie 3: ADN libre venöse Vollblutproben - Teil 3: Aus Plasma isolierte
circulant extrait du plasma (ISO 20186-3:2019) zirkulierende zellfreie DNA (ISO 20186-3:2019)
This European Standard was approved by CEN on 14 September 2019.

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
© 2019 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 20186-3:2019 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 20186-3:2019) 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 April 2020, and conflicting national standards shall be
withdrawn at the latest by October 2022.
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 16835-3:2015.
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 20186-3:2019 has been approved by CEN as EN ISO 20186-3:2019 without any
modification.
INTERNATIONAL ISO
STANDARD 20186-3
First edition
2019-09
Molecular in vitro diagnostic
examinations — Specifications for
pre-examination processes for venous
whole blood —
Part 3:
Isolated circulating cell free DNA
from plasma
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour le sang total veineux —
Partie 3: ADN libre circulant extrait du plasma
Reference number
ISO 20186-3:2019(E)
©
ISO 2019
ISO 20186-3:2019(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2019
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
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ISO copyright office
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Published in Switzerland
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ISO 20186-3:2019(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2  Normative references . 1
3  Terms and definitions . 1
4 General consideration . 5
5 Outside the laboratory . 5
5.1 Specimen collection . 5
5.1.1 Information about the specimen donor/patient . 5
5.1.2 Selection of the venous whole blood collection tube by the laboratory . 6
5.1.3 Venous whole blood collection from the donor/patient and stabilization
procedures . 6
5.1.4 Information about the specimen and storage requirements at the blood
collection facility . 7
5.2 Transport requirements . 7
6 Inside the laboratory . 8
6.1 Specimen reception . 8
6.2 Storage requirements for blood specimens . 8
6.3 Plasma preparation . 9
6.4 Storage requirements for plasma samples . 9
6.5 Isolation of the ccfDNA .10
6.5.1 General.10
6.5.2 Using blood collection tubes with stabilizers .10
6.5.3 Using blood collection tubes without stabilizers .11
6.6 Quantity and quality assessment of isolated ccfDNA .11
6.7 Storage of isolated ccfDNA .11
6.7.1 General.11
6.7.2 ccfDNA isolated with commercially available kits .12
6.7.3 ccfDNA isolated with the laboratory's own protocols .12
Annex A (informative) Impact of pre-examination process steps on circulating cell free DNA
profiles in venous whole blood plasma .13
Bibliography .16
ISO 20186-3:2019(E)
Foreword
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bodies (ISO member bodies). The work of preparing International Standards is normally carried out
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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
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on the ISO list of patent declarations received (see www .iso .org/patents).
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.org/iso/foreword .html.
This document was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in
vitro diagnostic test systems.
A list of all parts in the ISO 20186 series can be found on the ISO website.
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.
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