Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 2: Isolated genomic DNA (ISO 20186-2:2019)

This document gives guidelines on the handling, storage, processing and documentation of venous whole blood specimens intended for genomic DNA examination during the pre-examination phase before a molecular examination 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 cell free circulating DNA, which are not described in this document.
NOTE Circulating cell free DNA in blood is covered in ISO 20186-3.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing capillary blood as well as for collecting and storing blood by paper based technologies or other technologies generating dried blood. These are not described in this document.
This document does not cover the isolation of specific blood cells and subsequent isolation of genomic DNA therefrom.
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 2: Isolierte genomische DNA (ISO 20186-2:2019)

Diese Internationale Norm gibt Empfehlungen zur Handhabung, Dokumentation, Lagerung und Verarbeitung von Proben venösen Vollbluts, die für die Untersuchung genomischer DNA vorgesehen sind, während der präanalytischen Phase vor der Durchführung einer molekularen Untersuchung. Diese Internationale Norm betrifft Proben, die mit Blutentnahmeröhrchen für venöses Vollblut entnommen wurden.
Diese Internationale Norm ist anwendbar auf alle molekularen in vitro diagnostischen Untersuchungen, die in medizinischen Laboratorien durchgeführt werden. Sie ist darüber hinaus für die Verwendung durch Kunden von Laboratorien, Entwickler und Hersteller von In vitro Diagnostika, durch Institutionen und kommerzielle Organisationen, die biomedizinische Forschungen durchführen, sowie durch Biobanken und Arzneimittelagenturen bestimmt.
Zur Stabilisierung von blutzellfreier zirkulierender DNA sind andere spezielle Maßnahmen erforderlich, die in dieser Internationalen Norm nicht beschrieben werden. Zellfrei im Blut zirkulierende DNA wird behandelt in ISO 20186 3, Molecular in vitro diagnostic examinations — Specifications for pre-examination processes for venous whole blood — Part 3: Isolated circulating cell free DNA from plasma.
Auch bei der Abnahme, Stabilisierung, dem Transport und der Lagerung von Kapillarblut sowie für die Gewinnung und Lagerung von Blut mithilfe von papierbasierten Techniken sowie anderen Techniken zur Herstellung von getrocknetem Blut sind verschiedene spezielle Maßnahmen nötig. Diese werden in dieser Internationalen Norm ebenfalls nicht beschrieben.
Diese Internationale Norm behandelt nicht die Isolierung von bestimmten Blutzellen und die anschließende Präparation von genomischer DNA aus diesen Zellen.
Auch DNA von im Blut vorliegenden Pathogenen wird in dieser Internationalen Norm nicht behandelt.
ANMERKUNG   Internationale, nationale oder regionale Regelungen bzw. Anforderungen können ebenfalls für bestimmte Themen in dieser Internationalen Norm gelten.

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus préanalytiques pour le sang total veineux - Partie 2: ADN génomique extrait (ISO 20186-2:2019)

Le présent document fournit des lignes directrices pour la manipulation, le stockage, le traitement et la documentation des prélèvements de sang total veineux destinés à l'analyse de l'ADN génomique durant la phase préanalytique précédant la réalisation d'une analyse moléculaire. 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 à prendre pour stabiliser l'ADN libre circulant dans le sang.
NOTE L'ADN libre circulant dans le sang est traité dans l'ISO 20186‑3.
Des mesures spécifiques différentes sont prises pour prélever, stabiliser, transporter et stocker le sang capillaire, et pour prélever et stocker le sang par des technologies à base de support papier ou d'autres technologies produisant du sang séché. Ces mesures ne sont pas décrites dans le présent document.
Le présent document ne traite ni de l'extraction de cellules sanguines spécifiques ni de l'extraction de l'ADN génomique qu'elles contiennent.
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 - 2. del: Iz genoma izolirana DNK (ISO 20186-2:2019)

Ta mednarodni standard vsebuje priporočila za obravnavo, dokumentiranje, shranjevanje in obdelavo vzorcev venske polne krvi, namenjenih za analizo iz genoma izolirane DNA 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 na primer izvajajo v medicinskih laboratorijih. Uporabljali naj bi ga tudi uporabniki laboratorijev, razvijalci in proizvajalci diagnostike in vitro, nanaša pa se tudi na institucije in komercialne organizacije, ki izvajajo biomedicinske raziskave, biobanke ter regulativne organe. Krvna genomska DNA lahko po odvzemu krvi razpade ali se razkroji. Zato je treba uporabiti posebne ukrepe za pridobivanje vzorcev krvi dobre kakovosti za analizo genomske DNA. To je še posebej pomembno za analitične preskusne postopke, ki zahtevajo DNA z veliko molekularno težo. Za ohranjanje cirkulirajoče brezcelične DNA je treba uporabiti drugačne namenske ukrepe, ki niso opisani v tem mednarodnem standardu. Cirkulirajoča brezcelična DNA je opisana v standardu ISO 20091-3, Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese za vensko polno kri - 3. del: Iz plazme izolirana cirkulirajoča brezcelična DNA Za zbiranje, stabiliziranje, prevoz in shrambo kapilarne krvi ter za zbiranje in shrambo krvi s tehnologijami, ki temeljijo na papirju, ali drugimi tehnologijami, pri katerih nastaja posušena kri, je treba uporabiti drugačne namenske ukrepe. Ti niso opisani v tem mednarodnem standardu. Patogena DNA v krvi ni zajeta 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
26-Mar-2019
Current Stage
6060 - Definitive text made available (DAV) - Publishing
Due Date
27-Mar-2019
Completion Date
27-Mar-2019

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SLOVENSKI STANDARD
SIST EN ISO 20186-2:2019
01-julij-2019
Nadomešča:
SIST-TS CEN/TS 16835-2:2015
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za vensko polno kri - 2. del: Iz genoma izolirana DNK (ISO 20186-2:2019)

Molecular in vitro diagnostic examinations - Specifications for pre-examination processes

for venous whole blood - Part 2: Isolated genomic DNA (ISO 20186-2:2019)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für

präanalytische Prozesse für venöse Vollblutproben - Teil 2: Isolierte genomische DNA

(ISO 20186-2:2019)

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus

préanalytiques pour le sang total veineux - Partie 2: ARN cellulaire extrait (ISO 20186-

2:2019)
Ta slovenski standard je istoveten z: EN ISO 20186-2:2019
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
11.100.30 Analiza krvi in urina Analysis of blood and urine
SIST EN ISO 20186-2:2019 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 20186-2:2019
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SIST EN ISO 20186-2:2019
EN ISO 20186-2
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2019
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 16835-2:2015
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for venous whole blood -
Part 2: Isolated genomic DNA (ISO 20186-2:2019)

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 2: ADN génomique venöse Vollblutproben - Teil 2: Isolierte genomische

extrait (ISO 20186-2:2019) DNA (ISO 20186-2:2019)
This European Standard was approved by CEN on 2 February 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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,

Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, 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 20186-2:2019 E

worldwide for CEN national Members.
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SIST EN ISO 20186-2:2019
EN ISO 20186-2:2019 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

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SIST EN ISO 20186-2:2019
EN ISO 20186-2:2019 (E)
European foreword

This document (EN ISO 20186-2:2019) 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 September 2019, and conflicting national standards

shall be withdrawn at the latest by March 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 16835-2:2015.

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, Former Yugoslav Republic of Macedonia,

France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,

Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,

Turkey and the United Kingdom.
Endorsement notice

The text of ISO 20186-2:2019 has been approved by CEN as EN ISO 20186-2:2019 without any

modification.
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SIST EN ISO 20186-2:2019
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SIST EN ISO 20186-2:2019
INTERNATIONAL ISO
STANDARD 20186-2
First edition
2019-02
Molecular in vitro diagnostic
examinations — Specifications for
pre-examination processes for venous
whole blood —
Part 2:
Isolated genomic DNA
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour le sang total veineux —
Partie 2: ADN génomique extrait
Reference number
ISO 20186-2:2019(E)
ISO 2019
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(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

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
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2  Normative references ...................................................................................................................................................................................... 1

3  Terms and definitions ..................................................................................................................................................................................... 1

4 General considerations .................................................................................................................................................................................. 5

5 Outside the laboratory ................................................................................................................................................................................... 6

5.1 Specimen collection ............................................................................................................................................................................ 6

5.1.1 Information about the specimen donor/patient .................................................................................. 6

5.1.2 Selection of the venous whole blood collection tube by the laboratory .......................... 6

5.1.3 Venous whole blood specimen 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 ................................................................................................................................................................. 8

6 Inside the laboratory ....................................................................................................................................................................................... 8

6.1 Specimen reception ............................................................................................................................................................................ 8

6.2 Storage requirements ........................................................................................................................................................................ 8

6.3 Isolation of the genomic DNA ..................................................................................................................................................10

6.3.1 General...................................................................................................................................................................................10

6.3.2 Examination provider's instructions available ...................................................................................10

6.3.3 Examination provider's instructions not available .........................................................................10

6.4 Quantity and quality assessment of isolated genomic DNA ..........................................................................11

6.5 Storage of isolated genomic DNA .........................................................................................................................................11

6.5.1 General...................................................................................................................................................................................11

6.5.2 Genomic DNA isolated with commercially available kits .................. .........................................11

6.5.3 Genomic DNA isolated with the laboratory's own protocols .................................................12

Annex A (informative) Impact of pre-examination process steps on venous whole blood

genomic DNA quality .....................................................................................................................................................................................13

Bibliography .............................................................................................................................................................................................................................19

© ISO 2019 – All rights reserved iii
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(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.

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.
A list of all parts in the ISO 20186 series can be found on the ISO website.
iv © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
Introduction

Molecular in vitro diagnostics has enabled significant progress in medicine. Further progress is

expected by new technologies analysing profiles of nucleic acids, proteins, and metabolites in human

tissues and body fluids. However, the profiles of these molecules can change drastically during the

pre-examination process, including the specimen collection, transport, storage and processing.

Consequently, this makes the outcome from diagnostics or research unreliable or even impossible,

because the subsequent examination might not determine the real situation in the patient but an

artificial profile generated during the pre-examination processes.

Genomic DNA can fragment or degrade after blood collection. Therefore, special measures need to be

taken to secure good quality specimens for genomic DNA examination. This is particularly relevant for

examination test procedures requiring high molecular weight DNA (HMW DNA).

Standardization of the entire workflow from specimen collection to the genomic DNA examination is

needed due to genomic DNA degradation and fragmentation after blood collection. Studies have been

undertaken to determine the important influencing factors. This document draws upon such work to

codify and standardize the steps for venous whole blood genomic DNA examination in what is referred

to as the pre-examination phase.
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.
© ISO 2019 – All rights reserved v
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SIST EN ISO 20186-2:2019
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SIST EN ISO 20186-2:2019
INTERNATIONAL STANDARD ISO 20186-2:2019(E)
Molecular in vitro diagnostic examinations —
Specifications for pre-examination processes for venous
whole blood —
Part 2:
Isolated genomic DNA
1 Scope

This document gives guidelines on the handling, storage, processing and documentation of venous

whole blood specimens intended for genomic DNA examination during the pre-examination phase

before a molecular examination 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 cell free circulating DNA, which are not

described in this document.
NOTE Circulating cell free DNA in blood is covered in ISO 20186-3.

Different dedicated measures are taken for collecting, stabilizing, transporting and storing capillary

blood as well as for collecting and storing blood by paper based technologies or other technologies

generating dried blood. These are not described in this document.

This document does not cover the isolation of specific blood cells and subsequent isolation of genomic

DNA therefrom.
DNA in pathogens present in blood is not covered by 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 15189:2012, Medical laboratories — Requirements for quality and competence
3  Terms and definitions
For the purposes of this document, the following terms and definitions 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/
© ISO 2019 – All rights reserved 1
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.1
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2003, 3.2]
3.2
backflow
flow of a liquid opposite to the usual or desired direction
3.3
blood collection set

intravenous device specialized for venepuncture consisting of a stainless steel bevelled needle and tube

(tubing) with attached plastic wings and fitting connector

Note 1 to entry: The connector attaches to an additional blood collection device, e.g. a blood collection tube (3.4).

3.4
blood collection tube

tube used for blood collection, usually in a vacuum which forces blood from the vein through the needle

into the tube
3.5
blood genomic DNA stabilizers

compounds, solutions or mixtures that are designed to minimize degradation and fragmentation of

genomic DNA (3.12) in blood
3.6
closed system

non-modifiable system provided by the vendor including all necessary components for the examination

(i.e. hardware, software, procedures and reagents)
3.7
deoxyribonucleic acid
DNA

polymer of deoxyribonucleotides occurring in a double-stranded (dsDNA) or single-stranded

(ssDNA) form
[SOURCE: ISO 22174:2005, 3.1.2]
3.8
DNase
deoxyribonuclease
enzyme that catalyses the degradation of DNA into smaller components
3.9
examination
analytical test

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 (3.1) and include all kinds of parameter testing or

chemical manipulation for quantitative or qualitative examination.

[SOURCE: ISO 15189:2012, 3.7, modified — Term and definition are used here without the original

notes; an additional term was added.]
2 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.10
examination performance
analytical test performance
analytical performance

ability of an examination procedure to measure or detect a particular analyte (3.1)

Note 1 to entry: Analytical performance is determined from analytical performance studies used to assess the

ability of an in vitro diagnostic examination procedure to measure or detect a particular analyte.

Note 2 to entry: Analytical performance includes such characteristics as analytical sensitivity, detection limit,

analytical specificity (interference and cross-reactivity), trueness, precision and linearity.

[SOURCE: ISO/TS 17822-1:2014, 3.2, modified — Two terms have been added.]
3.11
examination provider
analytical test provider
entity that provides the specific analytical test
3.12
genomic DNA

DNA from the nuclear and mitochondrial genomes containing all coding (exon) and non-coding (intron

and other) sequences

Note 1 to entry: In this document, reference is only made to genomic DNA present in cells in blood, excluding

circulating cell free DNA.
3.13
high molecular weight DNA
HMW DNA

DNA with an average double strand size larger than 50 kb on a pulsed field electrophoresis gel for the

purpose of this document
3.14
interfering substances

endogenous or exogenous substances in clinical specimens (3.17)/samples (3.23) that can alter an

examination result

Note 1 to entry: Examples of endogenous substances are blood components and acidic polysaccharides.

Note 2 to entry: Examples of exogenous substances are talc and anticoagulant.
3.15
needle holder

barrel used in routine venepuncture procedures to hold the blood collection tube (3.4) in place and to

protect the phlebotomist from direct contact with blood
3.16
pre-examination processes
preanalytical phase
preanalytical workflow

processes that start, in chronological order, from the clinician’s request and include the examination

request, preparation and identification of the patient, collection of the primary sample(s) (3.17),

transportation to and within the medical laboratory, isolation of analytes, and end when the analytical

examination begins

Note 1 to entry: The pre-examination phase includes preparative processes, e.g. DNA isolation procedures, which

influence the outcome of the intended examination.

[SOURCE: ISO 15189:2012, 3.15, modified — An additional term has been added and more details have

been included.]
© ISO 2019 – All rights reserved 3
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.17
primary sample
specimen

discrete portion of a body fluid, breath, hair or tissue taken for examination, study or analysis of one or

more quantities or properties assumed to apply for the whole
[SOURCE: ISO 15189:2012, 3.16, modified — Notes to entry have been omitted.]
3.18
primary sample collection device

apparatus specifically intended by an IVD manufacturer to obtain, contain and preserve a body fluid or

tissue for in vitro diagnostic examination
[SOURCE: ISO 18113-1:2009, 3.55]

Note 1 to entry: Includes devices intended to store a specimen prior to examination.

Note 2 to entry: Includes both vacuum and non-vacuum specimen collection devices.

3.19
proficiency testing

evaluation of participant performance against pre-established criteria by means of inter-laboratory

comparisons

[SOURCE: ISO 17043:2010, 3.7, modified — Term and definition are used here without the original notes.]

3.20
RNA
ribonucleic acid

polymer of ribonucleotides occurring in a double-stranded or single-stranded form

[SOURCE: ISO 22174:2005, 3.1.3]
3.21
RNase
ribonuclease
enzyme that catalyses the degradation of RNA into smaller components
3.22
room temperature
temperature in the range of 18 °C to 25 °C
Note 1 to entry: Local or national regulations can have different definitions.
3.23
sample
one or more parts taken from a primary sample (3.17)
[SOURCE: ISO 15189:2012, 3.24, modified — The example has been omitted.]
3.24
stability

ability of a sample material, when stored under specified conditions, to maintain a stated property

value within specified limits for a specified period of time

[SOURCE: ISO Guide 30:2015, 2.1.15, modified — The words “reference material” were replaced by

“sample material”.]
4 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.25
validation

confirmation, through the provision of objective evidence, that the requirements for a specific intended

use or application have been fulfilled

Note 1 to entry: The term “validated” is used to designate the corresponding status.

[SOURCE: ISO 9000:2015, 3.8.13, modified — Note 1 and 3 have been omitted.]
3.26
venous whole blood

blood collected after directly puncturing a vein, usually with a needle and syringe, or other

collection device
3.27
verification

confirmation, through the provision of objective evidence, that specified requirements have been

fulfilled

Note 1 to entry: The term “verified” is used to designate the corresponding status.

[SOURCE: ISO 9000: 2015, 3.8.12, modified — Note 1 and Note 2 have been omitted.]

Note 2 to entry: Confirmation can comprise activities such as
— performing alternative calculations;

— comparing a new design specification with a similar proven design specification;

— undertaking tests and demonstrations; and
— reviewing documents prior to issue.
3.28
workflow
series of activities necessary to complete a task
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 15189:2012, 4.2, 5.4.4, 5.4.6 or ISO/IEC 17020:2012, 7.2 and Clause 8. The requirements on

laboratory equipment, reagents, and consumables according to ISO 15189:2012, 5.3 shall be followed;

ISO 15189:2012, 5.5.1.2 and 5.5.1.3 and ISO/IEC 17020:2012, 6.2 can also apply.

All steps of a diagnostic workflow can influence the final examination result. Thus, the entire workflow,

including specimen/sample storage and transport conditions, and its impact on the stability of

biomolecules intended to be examined shall be verified and validated. Workflow steps which cannot

always be controlled shall be documented and their impact on the examination performance shall

be investigated and mitigation measures shall be established to enable the required examination

performance. In these cases, risk assessment is recommended.

The stability of the genomic DNA should be investigated throughout the complete pre-examination

[8]

workflow. Additional post-collection effects can also occur, e.g. genomic DNA fragmentation .

Before or during the design of an examination, it should be investigated and ensured that the genomic

DNA minimum amount and size required for the examination are not affected by the envisioned entire

pre-examination workflow.

Safety procedures for handling and transport shall be in place. Safety regulations on transport and

handling shall be considered (see ISO 15189:2012, 5.2.3 and 5.4.5, and ISO 15190).

© ISO 2019 – All rights reserved 5
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)

During the whole pre-examination process, precautions shall be taken to avoid cross contamination

between different samples/specimens, e.g. by using single-use material whenever feasible or

appropriate cleaning procedures between processing of different specimens/samples.

If a commercial product is not used in accordance with the manufacturer's instructions, responsibility

for its validation, verification, use and performance lies with the user.

NOTE International, national or regional regulations or requirements can also apply to specific topics

covered in this document.
5 Outside the laboratory
5.1 Specimen collection
5.1.1  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 relevant health status of the specimen donor or patient [e.g. healthy, disease type, concomitant

disease, demographics (e.g. age and gender)];

b) the information about medical treatment and special treatment prior to blood collection (e.g.

anaesthetics, medications);
c) the type and the purpose of the proposed examination requested;
d) the appropriate consent from the specimen donor/patient.
See also ISO 15189:2012, 5.4.4.
5.1.2  Selection of the venous whole blood collection tube by the laboratory

The quality of genomic DNA can be influenced (e.g. DNA fragmentation) by inadequate venous whole

blood collection procedures, inappropriate storage/shipping conditions as well as DNA isolation

[9][10][11][12][13][14][15][16]
procedures .

Blood should be collected in appropriate venous whole blood collection tubes containing an

[17]

anticoagulant such as EDTA or acid citrate dextrose (ACD) , and their catalogue and lot number

should be documented.

NOTE Blood collection tubes containing EDTA as an anticoagulant are preferable for most genomic DNA

examination. Blood collection tubes containing heparin as an anticoagulant can impact the purity of the isolated

genomic DNA, when using genomic DNA isolation methods not eliminating the heparin. Carrying

...

SLOVENSKI STANDARD
SIST EN ISO 20186-2:2019
01-julij-2019
Nadomešča:
SIST-TS CEN/TS 16835-2:2015
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za vensko polno kri - 2. del: Iz genoma izolirana DNA (ISO 20186-2:2019)

Molecular in vitro diagnostic examinations - Specifications for pre-examination processes

for venous whole blood - Part 2: Isolated genomic DNA (ISO 20186-2:2019)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für

präanalytische Prozesse für venöse Vollblutproben - Teil 2: Isolierte genomische DNA

(ISO 20186-2:2019)

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus

préanalytiques pour le sang total veineux - Partie 2: ARN cellulaire extrait (ISO 20186-

2:2019)
Ta slovenski standard je istoveten z: EN ISO 20186-2:2019
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
11.100.30 Analiza krvi in urina Analysis of blood and urine
SIST EN ISO 20186-2:2019 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 20186-2:2019
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SIST EN ISO 20186-2:2019
EN ISO 20186-2
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2019
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 16835-2:2015
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for venous whole blood -
Part 2: Isolated genomic DNA (ISO 20186-2:2019)

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 2: ADN génomique venöse Vollblutproben - Teil 2: Isolierte genomische

extrait (ISO 20186-2:2019) DNA (ISO 20186-2:2019)
This European Standard was approved by CEN on 2 February 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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,

Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, 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 20186-2:2019 E

worldwide for CEN national Members.
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SIST EN ISO 20186-2:2019
EN ISO 20186-2:2019 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

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SIST EN ISO 20186-2:2019
EN ISO 20186-2:2019 (E)
European foreword

This document (EN ISO 20186-2:2019) 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 September 2019, and conflicting national standards

shall be withdrawn at the latest by March 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 16835-2:2015.

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, Former Yugoslav Republic of Macedonia,

France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,

Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,

Turkey and the United Kingdom.
Endorsement notice

The text of ISO 20186-2:2019 has been approved by CEN as EN ISO 20186-2:2019 without any

modification.
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SIST EN ISO 20186-2:2019
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SIST EN ISO 20186-2:2019
INTERNATIONAL ISO
STANDARD 20186-2
First edition
2019-02
Molecular in vitro diagnostic
examinations — Specifications for
pre-examination processes for venous
whole blood —
Part 2:
Isolated genomic DNA
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour le sang total veineux —
Partie 2: ADN génomique extrait
Reference number
ISO 20186-2:2019(E)
ISO 2019
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(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

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
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved
---------------------- Page: 8 ----------------------
SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2  Normative references ...................................................................................................................................................................................... 1

3  Terms and definitions ..................................................................................................................................................................................... 1

4 General considerations .................................................................................................................................................................................. 5

5 Outside the laboratory ................................................................................................................................................................................... 6

5.1 Specimen collection ............................................................................................................................................................................ 6

5.1.1 Information about the specimen donor/patient .................................................................................. 6

5.1.2 Selection of the venous whole blood collection tube by the laboratory .......................... 6

5.1.3 Venous whole blood specimen 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 ................................................................................................................................................................. 8

6 Inside the laboratory ....................................................................................................................................................................................... 8

6.1 Specimen reception ............................................................................................................................................................................ 8

6.2 Storage requirements ........................................................................................................................................................................ 8

6.3 Isolation of the genomic DNA ..................................................................................................................................................10

6.3.1 General...................................................................................................................................................................................10

6.3.2 Examination provider's instructions available ...................................................................................10

6.3.3 Examination provider's instructions not available .........................................................................10

6.4 Quantity and quality assessment of isolated genomic DNA ..........................................................................11

6.5 Storage of isolated genomic DNA .........................................................................................................................................11

6.5.1 General...................................................................................................................................................................................11

6.5.2 Genomic DNA isolated with commercially available kits .................. .........................................11

6.5.3 Genomic DNA isolated with the laboratory's own protocols .................................................12

Annex A (informative) Impact of pre-examination process steps on venous whole blood

genomic DNA quality .....................................................................................................................................................................................13

Bibliography .............................................................................................................................................................................................................................19

© ISO 2019 – All rights reserved iii
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(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.

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.
A list of all parts in the ISO 20186 series can be found on the ISO website.
iv © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
Introduction

Molecular in vitro diagnostics has enabled significant progress in medicine. Further progress is

expected by new technologies analysing profiles of nucleic acids, proteins, and metabolites in human

tissues and body fluids. However, the profiles of these molecules can change drastically during the

pre-examination process, including the specimen collection, transport, storage and processing.

Consequently, this makes the outcome from diagnostics or research unreliable or even impossible,

because the subsequent examination might not determine the real situation in the patient but an

artificial profile generated during the pre-examination processes.

Genomic DNA can fragment or degrade after blood collection. Therefore, special measures need to be

taken to secure good quality specimens for genomic DNA examination. This is particularly relevant for

examination test procedures requiring high molecular weight DNA (HMW DNA).

Standardization of the entire workflow from specimen collection to the genomic DNA examination is

needed due to genomic DNA degradation and fragmentation after blood collection. Studies have been

undertaken to determine the important influencing factors. This document draws upon such work to

codify and standardize the steps for venous whole blood genomic DNA examination in what is referred

to as the pre-examination phase.
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.
© ISO 2019 – All rights reserved v
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SIST EN ISO 20186-2:2019
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SIST EN ISO 20186-2:2019
INTERNATIONAL STANDARD ISO 20186-2:2019(E)
Molecular in vitro diagnostic examinations —
Specifications for pre-examination processes for venous
whole blood —
Part 2:
Isolated genomic DNA
1 Scope

This document gives guidelines on the handling, storage, processing and documentation of venous

whole blood specimens intended for genomic DNA examination during the pre-examination phase

before a molecular examination 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 cell free circulating DNA, which are not

described in this document.
NOTE Circulating cell free DNA in blood is covered in ISO 20186-3.

Different dedicated measures are taken for collecting, stabilizing, transporting and storing capillary

blood as well as for collecting and storing blood by paper based technologies or other technologies

generating dried blood. These are not described in this document.

This document does not cover the isolation of specific blood cells and subsequent isolation of genomic

DNA therefrom.
DNA in pathogens present in blood is not covered by 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 15189:2012, Medical laboratories — Requirements for quality and competence
3  Terms and definitions
For the purposes of this document, the following terms and definitions 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/
© ISO 2019 – All rights reserved 1
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.1
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2003, 3.2]
3.2
backflow
flow of a liquid opposite to the usual or desired direction
3.3
blood collection set

intravenous device specialized for venepuncture consisting of a stainless steel bevelled needle and tube

(tubing) with attached plastic wings and fitting connector

Note 1 to entry: The connector attaches to an additional blood collection device, e.g. a blood collection tube (3.4).

3.4
blood collection tube

tube used for blood collection, usually in a vacuum which forces blood from the vein through the needle

into the tube
3.5
blood genomic DNA stabilizers

compounds, solutions or mixtures that are designed to minimize degradation and fragmentation of

genomic DNA (3.12) in blood
3.6
closed system

non-modifiable system provided by the vendor including all necessary components for the examination

(i.e. hardware, software, procedures and reagents)
3.7
deoxyribonucleic acid
DNA

polymer of deoxyribonucleotides occurring in a double-stranded (dsDNA) or single-stranded

(ssDNA) form
[SOURCE: ISO 22174:2005, 3.1.2]
3.8
DNase
deoxyribonuclease
enzyme that catalyses the degradation of DNA into smaller components
3.9
examination
analytical test

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 (3.1) and include all kinds of parameter testing or

chemical manipulation for quantitative or qualitative examination.

[SOURCE: ISO 15189:2012, 3.7, modified — Term and definition are used here without the original

notes; an additional term was added.]
2 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.10
examination performance
analytical test performance
analytical performance

ability of an examination procedure to measure or detect a particular analyte (3.1)

Note 1 to entry: Analytical performance is determined from analytical performance studies used to assess the

ability of an in vitro diagnostic examination procedure to measure or detect a particular analyte.

Note 2 to entry: Analytical performance includes such characteristics as analytical sensitivity, detection limit,

analytical specificity (interference and cross-reactivity), trueness, precision and linearity.

[SOURCE: ISO/TS 17822-1:2014, 3.2, modified — Two terms have been added.]
3.11
examination provider
analytical test provider
entity that provides the specific analytical test
3.12
genomic DNA

DNA from the nuclear and mitochondrial genomes containing all coding (exon) and non-coding (intron

and other) sequences

Note 1 to entry: In this document, reference is only made to genomic DNA present in cells in blood, excluding

circulating cell free DNA.
3.13
high molecular weight DNA
HMW DNA

DNA with an average double strand size larger than 50 kb on a pulsed field electrophoresis gel for the

purpose of this document
3.14
interfering substances

endogenous or exogenous substances in clinical specimens (3.17)/samples (3.23) that can alter an

examination result

Note 1 to entry: Examples of endogenous substances are blood components and acidic polysaccharides.

Note 2 to entry: Examples of exogenous substances are talc and anticoagulant.
3.15
needle holder

barrel used in routine venepuncture procedures to hold the blood collection tube (3.4) in place and to

protect the phlebotomist from direct contact with blood
3.16
pre-examination processes
preanalytical phase
preanalytical workflow

processes that start, in chronological order, from the clinician’s request and include the examination

request, preparation and identification of the patient, collection of the primary sample(s) (3.17),

transportation to and within the medical laboratory, isolation of analytes, and end when the analytical

examination begins

Note 1 to entry: The pre-examination phase includes preparative processes, e.g. DNA isolation procedures, which

influence the outcome of the intended examination.

[SOURCE: ISO 15189:2012, 3.15, modified — An additional term has been added and more details have

been included.]
© ISO 2019 – All rights reserved 3
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.17
primary sample
specimen

discrete portion of a body fluid, breath, hair or tissue taken for examination, study or analysis of one or

more quantities or properties assumed to apply for the whole
[SOURCE: ISO 15189:2012, 3.16, modified — Notes to entry have been omitted.]
3.18
primary sample collection device

apparatus specifically intended by an IVD manufacturer to obtain, contain and preserve a body fluid or

tissue for in vitro diagnostic examination
[SOURCE: ISO 18113-1:2009, 3.55]

Note 1 to entry: Includes devices intended to store a specimen prior to examination.

Note 2 to entry: Includes both vacuum and non-vacuum specimen collection devices.

3.19
proficiency testing

evaluation of participant performance against pre-established criteria by means of inter-laboratory

comparisons

[SOURCE: ISO 17043:2010, 3.7, modified — Term and definition are used here without the original notes.]

3.20
RNA
ribonucleic acid

polymer of ribonucleotides occurring in a double-stranded or single-stranded form

[SOURCE: ISO 22174:2005, 3.1.3]
3.21
RNase
ribonuclease
enzyme that catalyses the degradation of RNA into smaller components
3.22
room temperature
temperature in the range of 18 °C to 25 °C
Note 1 to entry: Local or national regulations can have different definitions.
3.23
sample
one or more parts taken from a primary sample (3.17)
[SOURCE: ISO 15189:2012, 3.24, modified — The example has been omitted.]
3.24
stability

ability of a sample material, when stored under specified conditions, to maintain a stated property

value within specified limits for a specified period of time

[SOURCE: ISO Guide 30:2015, 2.1.15, modified — The words “reference material” were replaced by

“sample material”.]
4 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)
3.25
validation

confirmation, through the provision of objective evidence, that the requirements for a specific intended

use or application have been fulfilled

Note 1 to entry: The term “validated” is used to designate the corresponding status.

[SOURCE: ISO 9000:2015, 3.8.13, modified — Note 1 and 3 have been omitted.]
3.26
venous whole blood

blood collected after directly puncturing a vein, usually with a needle and syringe, or other

collection device
3.27
verification

confirmation, through the provision of objective evidence, that specified requirements have been

fulfilled

Note 1 to entry: The term “verified” is used to designate the corresponding status.

[SOURCE: ISO 9000: 2015, 3.8.12, modified — Note 1 and Note 2 have been omitted.]

Note 2 to entry: Confirmation can comprise activities such as
— performing alternative calculations;

— comparing a new design specification with a similar proven design specification;

— undertaking tests and demonstrations; and
— reviewing documents prior to issue.
3.28
workflow
series of activities necessary to complete a task
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 15189:2012, 4.2, 5.4.4, 5.4.6 or ISO/IEC 17020:2012, 7.2 and Clause 8. The requirements on

laboratory equipment, reagents, and consumables according to ISO 15189:2012, 5.3 shall be followed;

ISO 15189:2012, 5.5.1.2 and 5.5.1.3 and ISO/IEC 17020:2012, 6.2 can also apply.

All steps of a diagnostic workflow can influence the final examination result. Thus, the entire workflow,

including specimen/sample storage and transport conditions, and its impact on the stability of

biomolecules intended to be examined shall be verified and validated. Workflow steps which cannot

always be controlled shall be documented and their impact on the examination performance shall

be investigated and mitigation measures shall be established to enable the required examination

performance. In these cases, risk assessment is recommended.

The stability of the genomic DNA should be investigated throughout the complete pre-examination

[8]

workflow. Additional post-collection effects can also occur, e.g. genomic DNA fragmentation .

Before or during the design of an examination, it should be investigated and ensured that the genomic

DNA minimum amount and size required for the examination are not affected by the envisioned entire

pre-examination workflow.

Safety procedures for handling and transport shall be in place. Safety regulations on transport and

handling shall be considered (see ISO 15189:2012, 5.2.3 and 5.4.5, and ISO 15190).

© ISO 2019 – All rights reserved 5
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SIST EN ISO 20186-2:2019
ISO 20186-2:2019(E)

During the whole pre-examination process, precautions shall be taken to avoid cross contamination

between different samples/specimens, e.g. by using single-use material whenever feasible or

appropriate cleaning procedures between processing of different specimens/samples.

If a commercial product is not used in accordance with the manufacturer's instructions, responsibility

for its validation, verification, use and performance lies with the user.

NOTE International, national or regional regulations or requirements can also apply to specific topics

covered in this document.
5 Outside the laboratory
5.1 Specimen collection
5.1.1  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 relevant health status of the specimen donor or patient [e.g. healthy, disease type, concomitant

disease, demographics (e.g. age and gender)];

b) the information about medical treatment and special treatment prior to blood collection (e.g.

anaesthetics, medications);
c) the type and the purpose of the proposed examination requested;
d) the appropriate consent from the specimen donor/patient.
See also ISO 15189:2012, 5.4.4.
5.1.2  Selection of the venous whole blood collection tube by the laboratory

The quality of genomic DNA can be influenced (e.g. DNA fragmentation) by inadequate venous whole

blood collection procedures, inappropriate storage/shipping conditions as well as DNA isolation

[9][10][11][12][13][14][15][16]
procedures .

Blood should be collected in appropriate venous whole blood collection tubes containing an

[17]

anticoagulant such as EDTA or acid citrate dextrose (ACD) , and their catalogue and lot number

should be documented.

NOTE Blood collection tubes containing EDTA as an anticoagulant are preferable for most genomic DNA

examination. Blood collection tubes containing heparin as an anticoagulant can impact the purity of the isolated

genomic DNA, when using genomic DNA isolation methods not
...

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