Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 1: Isolated cellular RNA (ISO 20186-1:2019)

This International Standard recommends the handling, documentation, storage and processing of venous whole blood specimens intended for cellular RNA examination during the pre-examination phase before a molecular assay is performed. This International Standard covers specimens collected in venous whole blood collection tubes. This International Standard is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, but also pertains institutions and commercial organizations performing biomedical research, biobanks, and regulatory authorities.
Blood cellular RNA profiles can change significantly after blood collection. Therefore, special measures need to be taken to secure good quality blood samples for cellular RNA examination and storage.
Different dedicated measures need to be taken for stabilising blood cell free circulating RNA and RNA in exosomes circulating in blood, which are not described in this International Standard.
Different dedicated measures need to be 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 International Standard.
RNA in pathogens present in blood is not covered by this International Standard.
NOTE   International, national or regional regulations or requirements may also apply to specific topics covered in this International Standard.

Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für präanalytische Prozesse für venöse Vollblutproben - Teil 1: Isolierte zelluläre RNA (ISO 20186-1:2019)

Diese Internationale Norm gibt Empfehlungen zur Handhabung, Dokumentation, Lagerung und Verarbeitung von Proben venösen Vollbluts, die für die Untersuchung der zellulären RNA vorgesehen sind, während der präanalytischen Phase vor der Durchführung einer molekularen Analyse. 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 im Blut zirkulierender blutzellfreier RNA und RNA in Exosomen sind andere spezielle Maßnahmen erforderlich, die in dieser Internationalen Norm nicht beschrieben werden.
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 zellulärer RNA aus diesen Zellen.
Auch RNA 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 1: ARN cellulaire extrait (ISO 20186-1:2019)

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'ARN cellulaire durant la phase préanalytique précédant la réalisation d'un essai 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 sont prises pour stabiliser l'ARN libre circulant dans le sang et l'ARN des exosomes du sang. Ces mesures ne sont pas décrites dans le présent document.
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'ARN cellulaire qu'elles contiennent.
L'ARN 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 - 1. del: Izolirana celična RNK (ISO 20186-1:2019)

Ta mednarodni standard vsebuje priporočila za obravnavo, dokumentiranje, shranjevanje in obdelavo vzorcev venske polne krvi, namenjenih za analizo celične RNA 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, nanaša pa se tudi na institucije in komercialne organizacije, ki izvajajo biomedicinske raziskave, biobanke ter regulativne organe. Profili krvne celične RNA se lahko po odvzemu krvi bistveno spremenijo. Zato je treba sprejeti posebne ukrepe za pridobivanje vzorcev krvi dobre kakovosti za analizo in shrambo celične RNA. Sprejeti je treba različne namenske ukrepe za stabiliziranje krožeče RNA brez krvnih celic in RNA v eksosomih, ki kroži v krvi, kar ni opisano v tem mednarodnem standardu. 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. RNA v patogenih 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
Public Enquiry End Date
19-Feb-2017
Publication Date
03-Jun-2019
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
10-Apr-2019
Due Date
15-Jun-2019
Completion Date
04-Jun-2019

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SLOVENSKI STANDARD
SIST EN ISO 20186-1:2019
01-julij-2019
Nadomešča:
SIST-TS CEN/TS 16835-1:2015
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za vensko polno kri - 1. del: Izolirana celična RNK (ISO 20186-1:2019)

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

for venous whole blood - Part 1: Isolated cellular RNA (ISO 20186-1:2019)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für

präanalytische Prozesse für venöse Vollblutproben - Teil 1: Isolierte zelluläre RNA (ISO

20186-1:2019)

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus

préanalytiques pour le sang total veineux - Partie 1: ARN cellulaire extrait (ISO 20186-

1:2019)
Ta slovenski standard je istoveten z: EN ISO 20186-1:2019
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 20186-1:2019 en

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

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SIST EN ISO 20186-1:2019
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SIST EN ISO 20186-1:2019
EN ISO 20186-1
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2019
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 16835-1:2015
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for venous whole blood -
Part 1: Isolated cellular RNA (ISO 20186-1:2019)

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 1: ARN cellulaire venöse Vollblutproben - Teil 1: Isolierte zelluläre RNA

extrait (ISO 20186-1:2019) (ISO 20186-1:2019)
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 20186-1:2019 E

worldwide for CEN national Members.
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SIST EN ISO 20186-1:2019
EN ISO 20186-1:2019 (E)
Contents Page

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

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SIST EN ISO 20186-1:2019
EN ISO 20186-1:2019 (E)
European foreword

This document (EN ISO 20186-1:2019) 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 16835-1:2015.

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 20186-1:2019 has been approved by CEN as EN ISO 20186-1:2019 without any

modification.
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SIST EN ISO 20186-1:2019
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SIST EN ISO 20186-1:2019
INTERNATIONAL ISO
STANDARD 20186-1
First edition
2019-02
Molecular in vitro diagnostic
examinations — Specifications for
pre-examination processes for venous
whole blood —
Part 1:
Isolated cellular RNA
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour le sang total veineux —
Partie 1: ARN cellulaire extrait
Reference number
ISO 20186-1:2019(E)
ISO 2019
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(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 20186-1:2019
ISO 20186-1:2019(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 cellular RNA........................................................................................................................................................ 9

6.3.1 General...................................................................................................................................................................................... 9

6.3.2 Using blood collection tubes with RNA profile stabilizers .......................................................... 9

6.3.3 Using blood collection tubes without RNA profile stabilizers ...............................................10

6.4 Quantity and quality assessment of isolated cellular RNA ............................................................................10

6.5 Storage of isolated cellular RNA ............................................................................................................................................11

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

6.5.2 Cellular RNA isolated with commercially available kits .............................................................11

6.5.3 Cellular RNA isolated with the laboratory's own protocols ....................................................11

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

cellular RNA profiles ......................................................................................................................................................................................12

Annex B (informative) Influence of blood storage temperature on blood cellular RNA profiles .......16

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

© ISO 2019 – All rights reserved iii
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(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 20186-1:2019
ISO 20186-1:2019(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 process.

Blood cellular RNA profiles can change significantly after blood collection. Therefore, special measures

need to be taken to secure good quality blood samples for cellular RNA examination and storage.

Standardization of the entire workflow from specimen collection to the cellular RNA examination is

needed. 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 cellular RNA

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 20186-1:2019
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SIST EN ISO 20186-1:2019
INTERNATIONAL STANDARD ISO 20186-1:2019(E)
Molecular in vitro diagnostic examinations —
Specifications for pre-examination processes for venous
whole blood —
Part 1:
Isolated cellular RNA
1 Scope

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

whole blood specimens intended for cellular RNA 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 RNA and RNA in

exosomes circulating in blood. These are not described in this document.

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 cellular

RNA therefrom.
RNA 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/
3.1
ambient temperature
unregulated temperature of the surrounding air
© ISO 2019 – All rights reserved 1
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.2
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2003, 3.2]
3.3
backflow
flow of a liquid opposite to the usual or desired direction
3.4
blood cellular RNA
cellular RNA
RNA molecules present in blood cells
3.5
blood cellular RNA profile

amounts of different RNA molecules, that are present in blood cells and that can be measured in the

absence of any losses, inhibition and interference
3.6
blood cellular RNA profile stabilizers

compounds, solutions or mixtures that are designed to minimize changes of the blood cellular RNA

profile (3.5)
3.7
blood collection set

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

(tubing) with attached plastic wings and fitting connector

Note 1 to entry: The connector attaches to an additional blood collection device, such as a blood collection tube (3.8).

3.8
blood collection tube

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

into the tube
3.9
closed system

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

(i.e. hardware, software, procedures and reagents)
3.10
deoxyribonucleic acid
DNA

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

(ssDNA) form
[SOURCE: ISO 22174:2005, 3.1.2]
3.11
deoxyribonuclease
DNase
enzyme that catalyzes the degradation of DNA into smaller components
2 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.12
examination
analytical test

set of operations having the object of determining the value or characteristics of a property

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

notes; an additional term was added.]

Note 1 to entry: Processes that start with the isolated analyte (3.2) and include all kinds of parameter testing or

chemical manipulation for quantitative or qualitative examination.
3.13
examination performance
analytical test performance
analytical performance

ability of an examination procedure to measure or detect a particular analyte (3.2)

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.]
3.14
examination provider
analytical test provider
entity that provides the specific analytical test
3.15
interfering substance

endogenous or exogenous substances in clinical specimens (3.18)/samples (3.24) that can alter an

examination (3.12) 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.
3.16
needle holder

barrel used in routine venepuncture procedures to hold the blood collection tube (3.8) in place and to

protect the phlebotomist from direct contact with blood
3.17
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) (3.18),

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. RNA isolation procedures, which

influence the outcome of the intended examination.

[SOURCE: ISO 15189:2012, 3.15, modified — An additional term was added and more detail was

included.]
© ISO 2019 – All rights reserved 3
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.18
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.]
3.19
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

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.

[SOURCE: ISO 18113-1:2009, 3.55]
3.20
proficiency testing

evaluation of participant performance against pre-established criteria by means of interlaboratory

comparisons
[SOURCE: ISO 17043:2010, 3.7, modified — Notes to entry have been omitted.]
3.21
ribonucleic acid
RNA

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

[SOURCE: ISO 22174:2005, 3.1.3]
3.22
ribonuclease
RNase
enzyme that catalyses the degradation of RNA into smaller components
3.23
room temperature
temperature in the range of 18 °C to 25 °C

Note 1 to entry: The definition is given for the purposes of this document. Local or national regulations can have

different definitions.
3.24
sample
one or more parts taken from a primary sample (3.18)
[SOURCE: ISO 15189:2012, 3.24, modified — The example has been omitted.]
3.25
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 phrase “reference material” has been replaced by

“sample material”.]
4 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.26
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 Note 3 have been omitted.]
3.27
venous whole blood

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

collection device
3.28
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.

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;
— reviewing documents prior to issue.

[SOURCE: ISO 9000:2015, 3.8.12, modified — Note 1 and Note 2 were not taken over.]

3.29
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.

Cellular RNA profiles can change significantly after blood collection, for example by gene induction, gene

[8][9][10][11]

down regulation or RNA degradation . These changes can vary individually in blood from

[8][12][13][14][15]

different donors or patients , and can impact the validity and reliability of examination

results.

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

specific blood cellular RNA profile(s) intended to be analysed is/are not compromised by the envisioned

pre-examination process in a manner impacting the examination performance. This can, for example,

© ISO 2019 – All rights reserved 5
---------------------- Page: 17 ----------------------
SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)

be done by performing time-course studies examining the post collection stability of the specific RNA

profile intended to by analysed.

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).

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

between different samples/specimens, for example 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, fasting status);
c) the type and 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

Due to the high instability of blood cellular RNA profiles in specimens collected from individual

[8][12][13][14][15]

patients/donors commercially available venous whole blood collection tubes containing

[12][13][15][16][17]

blood cellular RNA profile stabilizers should be used and their catalogue and lot

number should be documented. See also Figure A.1.

Blood collection tubes not containing any blood cellular RNA profile stabilizer should only be used, if

the specific blood cellular RNA molecule or the blood cellular RNA profile to be
...

SLOVENSKI STANDARD
SIST EN ISO 20186-1:2019
01-julij-2019
Nadomešča:
SIST-TS CEN/TS 16835-1:2015
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za vensko polno kri - 1. del: Izolirana celična RNA (ISO 20186-1:2019)

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

for venous whole blood - Part 1: Isolated cellular RNA (ISO 20186-1:2019)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für

präanalytische Prozesse für venöse Vollblutproben - Teil 1: Isolierte zelluläre RNA (ISO

20186-1:2019)

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus

préanalytiques pour le sang total veineux - Partie 1: ARN cellulaire extrait (ISO 20186-

1:2019)
Ta slovenski standard je istoveten z: EN ISO 20186-1:2019
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 20186-1:2019 en

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

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SIST EN ISO 20186-1:2019
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SIST EN ISO 20186-1:2019
EN ISO 20186-1
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2019
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 16835-1:2015
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for venous whole blood -
Part 1: Isolated cellular RNA (ISO 20186-1:2019)

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 1: ARN cellulaire venöse Vollblutproben - Teil 1: Isolierte zelluläre RNA

extrait (ISO 20186-1:2019) (ISO 20186-1:2019)
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 20186-1:2019 E

worldwide for CEN national Members.
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SIST EN ISO 20186-1:2019
EN ISO 20186-1:2019 (E)
Contents Page

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

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SIST EN ISO 20186-1:2019
EN ISO 20186-1:2019 (E)
European foreword

This document (EN ISO 20186-1:2019) 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 16835-1:2015.

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 20186-1:2019 has been approved by CEN as EN ISO 20186-1:2019 without any

modification.
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SIST EN ISO 20186-1:2019
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SIST EN ISO 20186-1:2019
INTERNATIONAL ISO
STANDARD 20186-1
First edition
2019-02
Molecular in vitro diagnostic
examinations — Specifications for
pre-examination processes for venous
whole blood —
Part 1:
Isolated cellular RNA
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour le sang total veineux —
Partie 1: ARN cellulaire extrait
Reference number
ISO 20186-1:2019(E)
ISO 2019
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(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 20186-1:2019
ISO 20186-1:2019(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 cellular RNA........................................................................................................................................................ 9

6.3.1 General...................................................................................................................................................................................... 9

6.3.2 Using blood collection tubes with RNA profile stabilizers .......................................................... 9

6.3.3 Using blood collection tubes without RNA profile stabilizers ...............................................10

6.4 Quantity and quality assessment of isolated cellular RNA ............................................................................10

6.5 Storage of isolated cellular RNA ............................................................................................................................................11

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

6.5.2 Cellular RNA isolated with commercially available kits .............................................................11

6.5.3 Cellular RNA isolated with the laboratory's own protocols ....................................................11

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

cellular RNA profiles ......................................................................................................................................................................................12

Annex B (informative) Influence of blood storage temperature on blood cellular RNA profiles .......16

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

© ISO 2019 – All rights reserved iii
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(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 20186-1:2019
ISO 20186-1:2019(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 process.

Blood cellular RNA profiles can change significantly after blood collection. Therefore, special measures

need to be taken to secure good quality blood samples for cellular RNA examination and storage.

Standardization of the entire workflow from specimen collection to the cellular RNA examination is

needed. 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 cellular RNA

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 20186-1:2019
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SIST EN ISO 20186-1:2019
INTERNATIONAL STANDARD ISO 20186-1:2019(E)
Molecular in vitro diagnostic examinations —
Specifications for pre-examination processes for venous
whole blood —
Part 1:
Isolated cellular RNA
1 Scope

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

whole blood specimens intended for cellular RNA 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 RNA and RNA in

exosomes circulating in blood. These are not described in this document.

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 cellular

RNA therefrom.
RNA 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/
3.1
ambient temperature
unregulated temperature of the surrounding air
© ISO 2019 – All rights reserved 1
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.2
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2003, 3.2]
3.3
backflow
flow of a liquid opposite to the usual or desired direction
3.4
blood cellular RNA
cellular RNA
RNA molecules present in blood cells
3.5
blood cellular RNA profile

amounts of different RNA molecules, that are present in blood cells and that can be measured in the

absence of any losses, inhibition and interference
3.6
blood cellular RNA profile stabilizers

compounds, solutions or mixtures that are designed to minimize changes of the blood cellular RNA

profile (3.5)
3.7
blood collection set

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

(tubing) with attached plastic wings and fitting connector

Note 1 to entry: The connector attaches to an additional blood collection device, such as a blood collection tube (3.8).

3.8
blood collection tube

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

into the tube
3.9
closed system

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

(i.e. hardware, software, procedures and reagents)
3.10
deoxyribonucleic acid
DNA

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

(ssDNA) form
[SOURCE: ISO 22174:2005, 3.1.2]
3.11
deoxyribonuclease
DNase
enzyme that catalyzes the degradation of DNA into smaller components
2 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.12
examination
analytical test

set of operations having the object of determining the value or characteristics of a property

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

notes; an additional term was added.]

Note 1 to entry: Processes that start with the isolated analyte (3.2) and include all kinds of parameter testing or

chemical manipulation for quantitative or qualitative examination.
3.13
examination performance
analytical test performance
analytical performance

ability of an examination procedure to measure or detect a particular analyte (3.2)

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.]
3.14
examination provider
analytical test provider
entity that provides the specific analytical test
3.15
interfering substance

endogenous or exogenous substances in clinical specimens (3.18)/samples (3.24) that can alter an

examination (3.12) 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.
3.16
needle holder

barrel used in routine venepuncture procedures to hold the blood collection tube (3.8) in place and to

protect the phlebotomist from direct contact with blood
3.17
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) (3.18),

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. RNA isolation procedures, which

influence the outcome of the intended examination.

[SOURCE: ISO 15189:2012, 3.15, modified — An additional term was added and more detail was

included.]
© ISO 2019 – All rights reserved 3
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.18
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.]
3.19
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

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.

[SOURCE: ISO 18113-1:2009, 3.55]
3.20
proficiency testing

evaluation of participant performance against pre-established criteria by means of interlaboratory

comparisons
[SOURCE: ISO 17043:2010, 3.7, modified — Notes to entry have been omitted.]
3.21
ribonucleic acid
RNA

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

[SOURCE: ISO 22174:2005, 3.1.3]
3.22
ribonuclease
RNase
enzyme that catalyses the degradation of RNA into smaller components
3.23
room temperature
temperature in the range of 18 °C to 25 °C

Note 1 to entry: The definition is given for the purposes of this document. Local or national regulations can have

different definitions.
3.24
sample
one or more parts taken from a primary sample (3.18)
[SOURCE: ISO 15189:2012, 3.24, modified — The example has been omitted.]
3.25
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 phrase “reference material” has been replaced by

“sample material”.]
4 © ISO 2019 – All rights reserved
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SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)
3.26
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 Note 3 have been omitted.]
3.27
venous whole blood

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

collection device
3.28
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.

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;
— reviewing documents prior to issue.

[SOURCE: ISO 9000:2015, 3.8.12, modified — Note 1 and Note 2 were not taken over.]

3.29
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.

Cellular RNA profiles can change significantly after blood collection, for example by gene induction, gene

[8][9][10][11]

down regulation or RNA degradation . These changes can vary individually in blood from

[8][12][13][14][15]

different donors or patients , and can impact the validity and reliability of examination

results.

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

specific blood cellular RNA profile(s) intended to be analysed is/are not compromised by the envisioned

pre-examination process in a manner impacting the examination performance. This can, for example,

© ISO 2019 – All rights reserved 5
---------------------- Page: 17 ----------------------
SIST EN ISO 20186-1:2019
ISO 20186-1:2019(E)

be done by performing time-course studies examining the post collection stability of the specific RNA

profile intended to by analysed.

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).

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

between different samples/specimens, for example 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, fasting status);
c) the type and 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

Due to the high instability of blood cellular RNA profiles in specimens collected from individual

[8][12][13][14][15]

patients/donors commercially available venous whole blood collection tubes containing

[12][13][15][16][17]

blood cellular RNA profile stabilizers should be used and their catalogue and lot

number should be documented. See also Figure A.1.

Blood collection tubes not containing any blood cellular RNA profile stabilizer should only be used, if

the specific blood cellular RNA molecule or the
...

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