CEN/TS 17742:2022
(Main)Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Isolated circulating cell free RNA from plasma
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Isolated circulating cell free RNA from plasma
This document specifies requirements and recommendations for the pre-examination phase of circulating cell free RNA (ccfRNA) from venous whole blood specimens, including but not limited to the collection, handling, storage, processing and documentation of venous whole blood specimens intended for ccfRNA examination. This document covers specimens collected in venous whole blood collection tubes.
The pre-examination process described in this document results in circulating cell free RNA isolated from blood plasma without prior enrichment of exosomes and other extracellular vesicles.
This document is applicable to molecular in vitro diagnostic examinations 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 need to be taken during the pre-examination phase for isolated RNA from enriched exosomes and other extracellular vesicles enriched from venous whole blood and for cellular RNA isolated from venous whole blood. These are not described in this document but are covered in CEN/TS 17747, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for exosomes and other extracellular vesicles in venous whole blood - Isolated DNA, RNA and proteins, and in EN ISO 20186 1, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 1: Isolated cellular RNA.
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 venöse Vollblutproben - Isolierte zirkulierende zellfreie RNA aus Plasma
Dieses Dokument legt Anforderungen und Empfehlungen für die präanalytische Phase der Untersuchung zirkulierender zellfreier RNA (ccfRNA) aus venösen Vollblutproben fest, unter anderem für die Entnahme, Handhabung, Lagerung, Verarbeitung und Dokumentation von venösen Vollblutproben, die für die ccfRNA Untersuchung vorgesehen sind. Dieses Dokument betrifft Untersuchungsmaterial, das mit Blutentnahmeröhrchen für venöses Vollblut entnommen wurde.
Mit dem in diesem Dokument beschriebenen präanalytischen Verfahren wird zirkulierende zellfreie RNA ohne vorherige Anreicherung von Exosomen und anderen extrazellulären Vesikeln aus dem Blutplasma isoliert.
Dieses Dokument ist anwendbar auf molekulare in vitro-diagnostische Untersuchungen, die in medizinischen Laboratorien durchgeführt werden. Es soll auch von Laborkunden, Entwicklern und Herstellern von In vitro-Diagnostika, Biobanken, Einrichtungen und kommerziellen Organisationen, die in der biomedizinischen Forschung tätig sind, sowie Aufsichtsbehörden eingesetzt werden.
Während der präanalytischen Phase müssen für RNA, die aus angereicherten Exosomen und aus anderen aus venösem Vollblut angereicherten extrazellulären Vesikeln isoliert wurde, und für aus venösem Vollblut isolierte zelluläre RNA verschiedene spezielle Maßnahmen getroffen werden. Diese sind in diesem Dokument nicht beschrieben, sondern werden in CEN/TS 17747, Molekularanalytische in‑vitro-diagnostische Verfahren — Spezifikationen für präanalytische Prozesse für Exosomen und andere extrazelluläre Vesikel im venösen Vollblut — Isolierte DNA, RNA und Proteine, und in EN ISO 20186 1, Molekularanalytische in vitro-diagnostische Verfahren — Spezifikationen für präanalytische Prozesse für venöse Vollblutproben — Teil 1: Isolierte zelluläre RNA, behandelt.
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 auc processus préanalytiques pour le sang total veineux — ARN libre circulant extrait du plasma
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese za vensko polno kri - Iz plazme izolirana cirkulirajoča brezcelična RNK
Ta dokument podaja smernice glede obravnave, shranjevanja, obdelave in dokumentiranja vzorcev venske polne krvi, namenjenih za analizo krožeče brezcelične RNK (ccfRNA) med predpreiskovalno fazo, preden se izvede molekularna preiskava. Ta dokument zajema vzorce, ki so zbrani s cevkami za zbiranje venske polne krvi.
Predpreiskovalni proces, opisan v tem dokumentu, vključuje cirkulirajočo brezcelično RNK, izolirano iz krvne plazme brez predhodne obogatitve eksosomov in drugih zunajceličnih veziklov.
Ta dokument se uporablja za molekularne diagnostične preiskave in vitro, ki jih izvajajo v medicinskih laboratorijih. Namenjen je tudi temu, da ga uporabljajo laboratorijske stranke, razvijalci in proizvajalci diagnostike in vitro, biobanke, institucije in komercialne organizacije, ki izvajajo biomedicinske raziskave, ter regulativni organi.
V predpreiskovalnem procesu se izvajajo različni namenski ukrepi za izolirano RNK iz obogatenih eksosomov in drugih zunajceličnih veziklov, obogatenih iz venske polne krvi, in za celično RNK, izolirano iz venske polne krvi. Ti niso opisani v tem dokumentu, vendar so zajeti v standardu CEN/PWI, Molekularne diagnostične preiskave in vitro – Specifikacije za predpreiskovalne procese za eksosome in druge zunajcelične vezikle v vensko polni krvi – Izolirana DNK, RNK in beljakovine ter v standardu ISO 20186-1, Molekularne diagnostične preiskave in vitro – Specifikacije za predpreiskovalne procese za vensko polno kri – 1. del: Izolirana celična RNK.
OPOMBA: Za določene teme, ki so zajete v tem dokumentu, lahko veljajo tudi mednarodni, nacionalni ali regionalni predpisi ali zahteve.
General Information
Standards Content (Sample)
SLOVENSKI STANDARD
01-junij-2022
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za vensko polno kri - Iz plazme izolirana cirkulirajoča brezcelična RNK
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes
for venous whole blood - Isolated circulating cell free RNA from plasma
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für venöse Vollblutproben - Isolierte zirkulierende zellfreie RNA
aus Plasma
Analyses de diagnostic moléculaire in vitro — Spécifications relatives auc processus
préanalytiques pour le sang total veineux — ARN libre circulant extrait du plasma
Ta slovenski standard je istoveten z: CEN/TS 17742:2022
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
CEN/TS 17742
TECHNICAL SPECIFICATION
SPÉCIFICATION TECHNIQUE
March 2022
TECHNISCHE SPEZIFIKATION
ICS 11.100.10
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for venous whole blood -
Isolated circulating cell free RNA from plasma
Molekularanalytische in-vitro-diagnostische Verfahren
- Spezifikationen für präanalytische Prozesse für
venöse Vollblutproben - Isolierte zirkulierende
zellfreie RNA aus Plasma
This Technical Specification (CEN/TS) was approved by CEN on 14 February 2022 for provisional application.
The period of validity of this CEN/TS is limited initially to three years. After two years the members of CEN will be requested to
submit their comments, particularly on the question whether the CEN/TS can be converted into a European Standard.
CEN members are required to announce the existence of this CEN/TS in the same way as for an EN and to make the CEN/TS
available promptly at national level in an appropriate form. It is permissible to keep conflicting national standards in force (in
parallel to the CEN/TS) until the final decision about the possible conversion of the CEN/TS into an EN is reached.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2022 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN/TS 17742:2022 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
Introduction . 4
1 Scope . 5
2 Normative references . 5
3 Terms and definitions . 5
4 General considerations . 10
5 Outside the laboratory . 11
5.1 Specimen collection . 11
5.1.1 General . 11
5.1.2 Information about the patient/specimen donor . 11
5.1.3 Selection of the venous whole blood collection tube by the laboratory . 12
5.1.4 Venous whole blood specimen collection from the patient/donor . 12
5.2 Specimen storage and transport . 13
5.2.1 General . 13
5.2.2 Storage and transport using blood collection tubes with stabilizers . 13
5.2.3 Storage and transport using blood collection tubes without stabilizers . 14
6 Inside the laboratory . 14
6.1 Specimen reception . 14
6.2 Storage requirements for blood specimens . 14
6.3 Plasma preparation . 15
6.4 Storage requirements for plasma samples . 15
6.5 Isolation of ccfRNA . 16
6.5.1 General . 16
6.5.2 Using a commercial ccfRNA isolation kit intended for diagnostic use . 16
6.5.3 Using a laboratory developed ccfRNA isolation procedure . 17
6.6 Quantity and quality assessment of isolated ccfRNA . 17
6.6.1 General . 17
6.6.2 Quantity assessment . 18
6.6.3 Quality assessment . 18
6.7 Storage of isolated ccfRNA . 18
Annex A (informative) Impact of pre-examination process steps on circulating cell free RNA
profiles in venous whole blood plasma . 20
Bibliography . 23
European foreword
This document (CEN/TS 17742:2022) has been prepared by Technical Committee CEN/TC 140 “In vitro
diagnostic medical devices”, the secretariat of which is held by DIN.
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.
Any feedback and questions on this document should be directed to the users’ national standards body.
A complete listing of these bodies can be found on the CEN website.
According to the CEN/CENELEC Internal Regulations, the national standards organisations of the
following countries are bound to announce this Technical Specification: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United
Kingdom.
Introduction
Molecular in vitro diagnostics has enabled a 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, as the
subsequent examination might not determine the real situation in the patient, but an artificial profile
generated during the pre-examination processes.
Besides circulating cell free DNA (ccfDNA), circulating tumour cells (CTCs) and other rare cells,
circulating cell free RNA (ccfRNA) represents another key component of liquid biopsies. Therefore, there
is a strongly increasing interest in emerging diagnostics and research in ccfRNA.
In blood, ccfRNA is composed of extracellular RNA present both in and outside of exosomes and other
extracellular vesicles. The pre-examination process described in this document results in total ccfRNA
isolated from blood plasma.
ccfRNA profiles and quantity can change significantly after blood collection, e.g. by release and/or uptake
of RNA containing extracellular vesicles by cells present in the blood specimen as well as by ccfRNA
degradation. Therefore, special measures have to be taken to secure good quality specimens for ccfRNA
examination.
Standardization of the entire workflow from specimen collection to the ccfRNA examination is therefore
needed. Studies have been undertaken to determine the important influencing factors. This document
draws upon such work to codify and standardize the steps of ccfRNA 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.
1 Scope
This document specifies requirements and recommendations for the pre-examination phase of
circulating cell free RNA (ccfRNA) from venous whole blood specimens, including but not limited to the
collection, handling, storage, processing and documentation of venous whole blood specimens intended
for ccfRNA examination. This document covers specimens collected in venous whole blood collection
tubes.
The pre-examination process described in this document results in circulating cell free RNA isolated from
blood plasma without prior enrichment of exosomes and other extracellular vesicles.
This document is applicable to molecular in vitro diagnostic examinations 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 need to be taken during the pre-examination phase for isolated RNA from
enriched exosomes and other extracellular vesicles enriched from venous whole blood and for cellular
RNA isolated from venous whole blood. These are not described in this document but are covered in
CEN/TS 17747, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes
for exosomes and other extracellular vesicles in venous whole blood - Isolated DNA, RNA and proteins, and
in EN ISO 20186-1, Molecular in vitro diagnostic examinations - Specifications for pre-examination
processes for venous whole blood - Part 1: Isolated cellular RNA.
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.
EN ISO 15189, Medical laboratories - Requirements for quality and competence (ISO 15189)
ISO 15190, Medical laboratories — Requirements for safety
3 Terms and definitions
For the purposes of this document, the terms and definitions given in EN ISO 15189 and the following
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 https://www.electropedia.org/
Under preparation. Stage at the time of publication: FprCEN/TS 17747.
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 the Compendium of Chemical Terminology Gold Book.
International Union of Pure and Applied Chemistry. Version 2.3.3., 2014; the PAC, 1990,62,1193 (Nom
...
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