Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for frozen tissue - Part 1: Isolated RNA (ISO 20184-1:2018)

This document gives guidelines on the handling, documentation, storage and processing of frozen tissue specimens intended for RNA examination during the pre-examination phase before a molecular assay is performed.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories and molecular pathology laboratories that evaluate RNA extracted from frozen tissue. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
Tissues that have undergone chemical stabilization pre-treatment before freezing are not covered in this document.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für präanalytische Prozesse für schockgefrorene Gewebeproben - Teil 1: Isolierte RNS (ISO 20184-1:2018)

Dieses Dokument dient als Leitfaden zur Handhabung, Dokumentation, Lagerung und Verarbeitung von gefrorenen Gewebeproben, die für die RNA Untersuchung während der präanalytischen Phase vor Beginn der molekularen Analyse vorgesehen sind.
Dieses Dokument ist anwendbar auf molekulare in vitro diagnostische Untersuchungen, die von medizinischen Laboratorien und Laboratorien der molekularen Pathologie durchgeführt werden, die aus gefrorenem Gewebe extrahierte RNA auswerten. Es hat außerdem den Zweck, von Kunden des Laboratoriums, Entwicklern und Herstellern im Bereich der In vitro Diagnostik, Biobanken, Institutionen und kommerziellen Organisationen, die biomedizinische Forschungen durchführen, und von Arzneimittel-agenturen verwendet zu werden.
Gewebe, die vor dem Gefriervorgang einer chemischen Vorbehandlung zur Stabilisierung unterzogen wurden, sind nicht durch dieses Dokument abgedeckt.
ANMERKUNG   Internationale, nationale oder regionale Regelungen bzw. Anforderungen können ebenfalls für bestimmte Themen in diesem Dokument gelten.

Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus préanalytiques pour les tissus congelés - Partie 1: ARN extrait (ISO 20184-1:2018)

Le présent document fournit des lignes directrices pour la manipulation, la documentation, le stockage et le traitement de prélèvements de tissus congelés destinés à l'analyse de l'ARN durant la phase préanalytique précédant la réalisation d'un essai moléculaire.
Le présent document s'applique aux analyses de diagnostic moléculaire in vitro réalisées par des laboratoires de biologie médicale et des laboratoires de pathologie moléculaire qui évaluent l'ARN extrait de tissus congelés. 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.
Le cas des tissus ayant subi un prétraitement de stabilisation chimique avant la congélation n'est pas couvert par le présent document.
NOTE Des réglementations ou exigences internationales, nationales ou régionales peuvent également s'appliquer à des sujets spécifiques traités dans le présent document.

Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese za zamrznjena tkiva - 1. del: Izolirani RNK (ISO 20184-1:2018)

Ta mednarodni standard vsebuje priporočila za obravnavo, dokumentiranje, shranjevanje in obdelavo vzorcev zamrznjenih tkiv, namenjenih za analizo RNK med predpreiskovalno fazo, preden se izvede molekularni preskus. 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 RNK v tkivih se lahko močno spremenijo pred zbiranjem in po njem ter se različno spremenijo pri tkivih različnih darovalcev/bolnikov. Zato je nujno treba sprejeti posebne ukrepe, da se zmanjšajo opisane spremembe profila v tkivu za nadaljnje preiskave RNA. Tkiva, ki so pred zamrzovanjem prestala predobdelavo za kemično stabilizacijo, niso zajeta v tem dokumentu. 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
18-Dec-2018
Current Stage
6060 - Definitive text made available (DAV) - Publishing
Due Date
19-Dec-2018
Completion Date
19-Dec-2018

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SLOVENSKI STANDARD
SIST EN ISO 20184-1:2019
01-marec-2019
1DGRPHãþD
SIST-TS CEN/TS 16826-1:2015
0ROHNXODUQHGLDJQRVWLþQHSUHLVNDYHLQYLWUR6SHFLILNDFLMH]DSUHGSUHLVNRYDOQH
SURFHVH]D]DPU]QMHQDWNLYDGHO,]ROLUDQL51. ,62

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

for frozen tissue - Part 1: Isolated RNA (ISO 20184-1:2018)
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für

präanalytische Prozesse für schockgefrorene Gewebeproben - Teil 1: Isolierte RNS (ISO

20184-1:2018)
Examens de diagnostic moléculaire in vitro - Spécifications pour les processus

d'examens préliminaires des tissus congelés - Partie 1: ARN isolé (ISO 20184-1:2018)

Ta slovenski standard je istoveten z: EN ISO 20184-1:2018
ICS:
11.100.10 'LDJQRVWLþQLSUHVNXVQL In vitro diagnostic test
VLVWHPLLQYLWUR systems
SIST EN ISO 20184-1:2019 en

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

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SIST EN ISO 20184-1:2019
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SIST EN ISO 20184-1:2019
EN ISO 20184-1
EUROPEAN STANDARD
NORME EUROPÉENNE
December 2018
EUROPÄISCHE NORM
ICS 11.100.10 Supersedes CEN/TS 16826-1:2015
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for frozen tissue - Part 1:
Isolated RNA (ISO 20184-1:2018)

Analyses de diagnostic moléculaire in vitro - Molekularanalytische in-vitro-diagnostische Verfahren

Spécifications relatives aux processus préanalytiques - Spezifikationen für präanalytische Prozesse für

pour les tissus congelés - Partie 1: ARN extrait (ISO schockgefrorene Gewebeproben - Teil 1: Isolierte RNS

20184-1:2018) (ISO 20184-1:2018)
This European Standard was approved by CEN on 30 November 2018.

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

© 2018 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 20184-1:2018 E

worldwide for CEN national Members.
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SIST EN ISO 20184-1:2019
EN ISO 20184-1:2018 (E)
Contents Page

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

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SIST EN ISO 20184-1:2019
EN ISO 20184-1:2018 (E)
European foreword

This document (EN ISO 20184-1:2018) 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 June 2019, and conflicting national standards shall be

withdrawn at the latest by June 2019.

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 16826-1:2015.

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 20184-1:2018 has been approved by CEN as EN ISO 20184-1:2018 without any

modification.
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SIST EN ISO 20184-1:2019
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SIST EN ISO 20184-1:2019
INTERNATIONAL ISO
STANDARD 20184-1
First edition
2018-11
Molecular in vitro diagnostic
examinations — Specifications for
pre-examination processes for frozen
tissue —
Part 1:
Isolated RNA
Analyses de diagnostic moléculaire in vitro — Spécifications relatives
aux processus préanalytiques pour les tissus congelés —
Partie 1: ARN extrait
Reference number
ISO 20184-1:2018(E)
ISO 2018
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2018

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 2018 – All rights reserved
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(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 ................................................................................................................................................................................... 5

5.1 Specimen collection ............................................................................................................................................................................ 5

5.1.1 General...................................................................................................................................................................................... 5

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

5.1.3 Information about the specimen ....................................................................................................................... 6

5.1.4 Specimen processing .................................................................................................................................................... 6

5.2 Fresh tissue transport requirements ................................................................................................................................... 7

5.2.1 General...................................................................................................................................................................................... 7

5.2.2 Preparations for the transport ............................................................................................................................. 7

5.2.3 During transport .............................................................................................................................................................. 7

6 Inside the laboratory ....................................................................................................................................................................................... 7

6.1 Information about the reception of the specimen .................................................................................................... 7

6.2 Evaluation of the pathology of the specimen and selection of the sample(s) .................................. 8

6.3 Freezing of the specimen or sample(s) .............................................................................................................................. 8

6.4 Storage requirements .....................................................................................................................................................................10

6.5 Isolation of RNA ..................................................................................................................................................................................11

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

6.5.2 Requirements and recommendations ........................................................................................................11

6.5.3 Using commercial kits ..............................................................................................................................................12

6.5.4 Using the laboratories own protocols ........................................................................................................12

6.6 Quantity and quality assessment of isolated RNA .................................................................................................12

6.7 Storage of isolated RNA ................................................................................................................................................................12

6.7.1 General...................................................................................................................................................................................12

6.7.2 Using commercially available kits for RNA isolation .....................................................................13

6.7.3 Using the laboratory's own protocols for RNA isolation ............................................................13

Annex A (informative) Impact of pre-examination variables on RNA profiles obtained from

frozen liver tissue samples collected during and after routine surgery .................................................14

Bibliography .............................................................................................................................................................................................................................18

© ISO 2018 – All rights reserved iii
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(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.
A list of all parts in the ISO 20184 can be found on the ISO website.

Any feedback or questions on this document should be directed to the user’s national standards body. A

complete listing of these bodies can be found at www .iso .org/members .html.
iv © ISO 2018 – All rights reserved
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
Introduction

Molecular in vitro diagnostics, including molecular pathology, has enabled a significant progress in

medicine. Further progress is expected with new technologies analysing nucleic acids, proteins, and

metabolites in human tissues and body fluids. However, the profiles and/or integrity of these molecules

can change drastically during specimen collection, transport, storage, and processing thus making

the outcome from diagnostics or research unreliable or even impossible because the subsequent

examination assay will not determine the situation in the patient but an artificial profile generated

during the pre-examination process.

Therefore, a standardization of the entire process from specimen collection to the 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 frozen tissue with regard to RNA

examination in what is referred to as the pre-examination phase.

RNA profiles in tissues can change drastically before, during and after collection (due to e.g. gene

induction or gene down regulation). RNA species can change differently in different donor's patients’

tissues.

Therefore, it is essential to take special measures to minimize the described RNA profile changes and

modifications within the tissue for subsequent examination.
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 2018 – All rights reserved v
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SIST EN ISO 20184-1:2019
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SIST EN ISO 20184-1:2019
INTERNATIONAL STANDARD ISO 20184-1:2018(E)
Molecular in vitro diagnostic examinations —
Specifications for pre-examination processes for frozen
tissue —
Part 1:
Isolated RNA
1 Scope

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

tissue specimens intended for RNA examination during the pre-examination phase before a molecular

assay is performed.

This document is applicable to any molecular in vitro diagnostic examination performed by medical

laboratories and molecular pathology laboratories that evaluate RNA extracted from frozen tissue. It is

also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers,

biobanks, institutions and commercial organisations performing biomedical research, and regulatory

authorities.

Tissues that have undergone chemical stabilization pre-treatment before freezing are not covered in

this document.

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

covered in this document.
2  Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

ISO 15189:2012, Medical laboratories — Requirements for quality and competence
3  Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 15189 and 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
aliquot

portion of a larger amount of homogenous material, assumed to be taken with negligible sampling error

Note 1 to entry: The term is usually applied to fluids. Tissues are heterogeneous and therefore cannot be

aliquoted.
Note 2 to entry: The definition is derived from References [22], [23] and [24].
© ISO 2018 – All rights reserved 1
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
3.2
ambient temperature
unregulated temperature of the surrounding air
3.3
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2003, 3.2]
3.4
analytical test performance

accuracy, precision, and sensitivity of a test to measure the analyte of interest

Note 1 to entry: Other test performance characteristics such as robustness, repeatability can apply as well.

3.5
cold ischemia

condition after removal of the tissue from the body until stabilization or fixation

3.6
diagnosis

identification of a health or disease state from its signs and/or symptoms, where the diagnostic process

can involve examinations and tests for classification of an individual's condition into separate and

distinct categories or subclasses that allow medical decisions about treatment and prognosis to be made

3.7
DNA
deoxyribonucleic acid

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 catalyzes 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 and include all kinds of parameter testing or

chemical manipulation for quantitative or qualitative examination.

[SOURCE: ISO 15189:2012, 3.7, modified — Notes to entry 1 to 3 have been removed, Note 1 to entry has

been added and “analytical test” has been added as a preferred term.]
3.10
grossing
gross examination

inspection of pathology specimens with the bare eye to obtain diagnostic information, while being

processed for further microscopic examination
3.11
homogeneous
uniform in structure and composition
2 © ISO 2018 – All rights reserved
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
3.12
interfering substances

endogenous substances of a specimen/sample or exogenous substances (e.g. stabilization solution) that

can alter an examination result
3.13
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), transportation

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

examination begins

Note 1 to entry: The pre-examination phase includes preparative processes that influence the outcome of the

intended examination.

[SOURCE: ISO 15189:2012, 3.15, modified — “pre-analytical workflow” has been added as a preferred

term, Note 1 to entry has been added and the definition has been extended.]
3.14
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 1 to 3 have been removed.]

3.15
proficiency test

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

comparisons

[SOURCE: ISO 17043:2010, 3.7, modified — Notes to entry 1 and 2 have been removed.]

3.16
RNA profile

amounts of the individual RNA molecules that are present in a sample and that can be measured in the

absence of any losses, inhibition and interference
3.17
RNA
ribonucleic acid

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

[SOURCE: ISO 22174:2005, 3.1.3]
3.18
RNase
ribonuclease
enzyme that catalyses the degradation of RNA into smaller components
3.19
room temperature
for the purposes of this document, temperature in the range of 18 °C to 25 °C
Note 1 to entry: Local or national regulations can have different definitions.
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
3.20
sample
one or more parts taken from a primary sample
[SOURCE: ISO 15189:2012, 3.24, modified — EXAMPLE has been removed.]
3.21
stability

characteristic of a sample material, when stored under specified conditions, to maintain a specified

property value within specified limits for a specified period of time
Note 1 to entry: The analyte for the purpose of this document is isolated RNA.

[SOURCE: ISO Guide 30:2015, 2.1.15, modified — “reference material” has been replaced by “sample

material”, “characteristic” has been replaced by “ability” and Note 1 to entry has been changed.]

3.22
storage

prolonged interruption of the pre-analytical workflow of a sample or analyte respectively, or of their

derivatives e.g., stained sections or tissue blocks, under appropriate conditions in order to preserve

their properties

Note 1 to entry: Long-term storage typically occurs in laboratory archives or in biobanks.

3.23
validation

confirmation, throughout 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 — Notes to entry 1 and 3 have been removed.]

3.24
verification

confirmation, through 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 where not taken over.]

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.
3.25
warm ischemia

condition before the tissue is removed from the body, but where it is deprived of its normal blood supply

3.26
workflow
series of activities necessary to complete a task
4 © ISO 2018 – All rights reserved
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
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, Clause 8 and 7.2. The requirements on

laboratory equipment, reagents, and consumables in accordance with 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 analytical test result. Thus, the entire

workflow including biomolecule stability and sample storage conditions shall be verified and validated.

Workflow steps which cannot always be controlled (e.g. warm ischemia) shall be documented. A risk

assessment of non-controllable workflow steps including their potential impact on the analytical test

performance shall be performed and mitigation measures shall be established to enable the required

analytical test performance.

Before or during the design of an analytical test, it should therefore be investigated and assured that the

RNA profile(s) intended to be analysed is/are not compromised in a manner impacting the analytical

test performance (e.g. by performing a time course experiment or study; see also Annex A).

Before tissues are stabilized by freezing, the RNA profile(s) can change e.g. by gene induction, gene

down regulation and RNA degradation. These effects depend on the warm and cold ischemia duration

and the ambient temperature before freezing. In addition, the described effects can vary in different

donors'/patients' tissues.

Generally, the longer the duration of warm and cold ischemia and the higher the ambient temperature

before freezing the tissue specimen, the higher is the risk that changes in the RNA profile can occur.

NOTE Intraoperative warm ischemia can result in more pronounced changes of RNA profiles than during

[7][8]

postoperative cold ischemia . RNA profiles can also vary, depending on the origin and type of tissue, the

underlying disease, the surgical procedure, the drug regimen, and drugs administered for anaesthesia or

treatment of concomitant disease and on the different environmental conditions after the tissue removal from

the body.

As warm ischemia cannot be easily standardized, its duration shall be documented. When it is not

possible to avoid cold ischemia, duration shall be documented and temperatures of the specimen

container's surroundings should be documented. Where the specimen is transported to another facility

for freezing, the transport duration shall be documented and the ambient conditions should also be

documented.

Safety instructions 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 specimens/samples, 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 use and performance lies with the user.
5 Outside the laboratory
5.1 Specimen collection
5.1.1 General

For the collection of the specimen, the requirements (e.g. disease condition, specimen size) for the

intended molecular examination (see also Clause 6) should be considered.
See also ISO 15189:2012, 5.4.4.
© ISO 2018 – All rights reserved 5
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SIST EN ISO 20184-1:2019
ISO 20184-1:2018(E)
5.1.2  Information about the specimen donor/patient

The documentation shall include the ID of the specimen donor/patient, which can be in the form of a code.

The documentation should include, but is not limited to:

a) the relevant health status of the specimen donor/patient (e.g. healthy, disease type, concomitant

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

b) the information about routine medical treatment and special treatment prior to tissue collection

(e.g. anaesthetics, medications, surgical or diagnostic procedures);
c) the appropriate consent from the specimen donor/patient.
5.1.3  Information about the specimen
The documentat
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