CEN/TS 16835-1:2015
(Main)Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 1: Isolated cellular RNA
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 1: Isolated cellular RNA
This Technical Specification recommends the handling, documentation and processing of venous whole blood specimens intended for cellular RNA analysis during the preanalytical phase before a molecular assay is performed. This Technical Specification covers specimens collected by venous whole blood collection tubes. This Technical Specification is applicable to molecular in vitro diagnostic examinations (e.g. in vitro diagnostic laboratories, laboratory customers, in vitro diagnostics developers and manufacturers, institutions and commercial organizations performing biomedical research, biobanks, and regulatory authorities).
Blood cellular RNA profiles can change significantly after collection. Therefore, special measures need to be taken to secure good quality blood samples for cellular RNA analysis and storage.
Different dedicated measures need to be taken for stabilizing blood cell free circulating RNA and RNA in exosomes circulating in blood, which are not described in this Technical Specification.
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. These are not described in this Technical Specification.
RNA in pathogens present in blood is not covered by this Technical Specification.
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für präanalytische Prozesse für venöse Vollblutproben - Teil 1: Isolierte zelluläre RNS
Diese Technische Spezifikation gibt Empfehlungen zur Handhabung, Dokumentation und Verarbeitung von für die Analyse zellulärer RNS vorgesehenen venösen Vollblutproben während der präanalytischen Phase vor Beginn der molekularen Analyse. Diese Technische Spezifikation behandelt Untersuchungsmaterial, das mit Blutentnahmeröhrchen für venöses Vollblut entnommen wurde. Diese Technische Spezifikation gilt für molekulare in vitro diagnostische Untersuchungen (z. B. In vitro Diagnostik Labore, Kunden dieser Labore, Entwickler und Hersteller von In vitro Diagnostika, Einrichtungen und kommerzielle Organisationen, die in der biomedizinischen Forschung tätig sind, Biobanken und Aufsichtsbehörden).
Profile von zellulärer RNS in Blutzellen können sich nach der Entnahme signifikant verändern. Daher müssen besondere Maßnahmen getroffen werden, um eine gute Qualität der Blutproben für die Analyse der zellulären RNS und die Lagerung sicherzustellen.
Zur Stabilisierung frei zirkulierender Blutzellen RNS und im Blut zirkulierender RNS in Exosomen müssen gesonderte Maßnahmen getroffen werden, die nicht in dieser Technischen Spezifikation beschrieben sind.
Für die Entnahme, die Stabilisierung, den Transport und die Lagerung von Kapillarblut sowie für die Entnahme und die Lagerung von Blut mit auf Papier basierenden Technologien müssen gesonderte Maßnahmen getroffen werden. Diese Maßnahmen sind nicht in dieser Technischen Spezifikation beschrieben.
Nicht durch diese Technische Spezifikation abgedeckt ist RNS in im Blut vorhandenen Pathogenen.
Tests de diagnostic moléculaire in vitro - Spécifications relatives aux processus pré-analytiques pour le sang total veineux - Partie 1: ARN cellulaire extrait
La présente Spécification technique donne des recommandations pour la manipulation, la documentation et le traitement des spécimens de sang total veineux destinés à l’analyse de l’ARN cellulaire pendant la phase pré-analytique, avant d’effectuer un essai moléculaire. Elle concerne les spécimens collectés dans des tubes de prélèvement de sang total veineux. Elle est applicable aux tests de diagnostic moléculaire in vitro (par exemple laboratoires de diagnostic in vitro, clients de laboratoires, concepteurs et fabricants de tests de diagnostics in vitro, institutions et organisations commerciales travaillant dans la recherche biomédicale, les biobanques et les autorités réglementaires).
Les profils d’ARN cellulaire sanguin peuvent changer de manière significative après le prélèvement. Par conséquent, des mesures spécifiques doivent être prises pour assurer la bonne qualité des échantillons de sang en vue de l’analyse de l’ARN cellulaire et de son stockage.
Des mesures spécifiques, non décrites dans la présente Spécification technique, doivent être prises pour stabiliser l’ARN circulant et l’ARN des exosomes du sang.
Des mesures spécifiques doivent être prises pour prélever, stabiliser, transporter et stocker le sang capillaire, et pour prélever et stocker le sang par des technologies sur support papier. Ces mesures ne sont pas décrites dans la présente Spécification technique.
L’ARN des pathogènes présents dans le sang n’est pas couvert par la présente Spécification technique.
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese za vensko polno kri - 1. del: Izolirana celična RNA
Ta tehnična specifikacija vsebuje priporočila za obravnavo, dokumentiranje in obdelavo vzorcev venske polne krvi, namenjenih za analizo celične RNA med predanalizno fazo, preden se izvede molekularni preskus. Ta tehnična specifikacija zajema vzorce, ki so zbrani s cevkami za zbiranje venske polne krvi. Ta tehnična specifikacija se uporablja za molekularne diagnostične preiskave in vitro (npr. diagnostični laboratoriji in vitro, laboratorijske stranke, razvijalci in proizvajalci diagnostike in vitro, institucije in komercialne organizacije, ki izvajajo biomedicinske raziskave, biobanke ter regulativni organi).
Profili krvne celične RNA se lahko po odvzemu 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 tehničnem poročilu.
Sprejeti je treba različne namenske ukrepe za zbiranje, stabiliziranje, prevoz in shrambo kapilarne krvi ter za zbiranje in shrambo krvi s tehnologijami, ki temeljijo na papirju. To ni opisano v tej tehnični specifikaciji.
RNA v patogenih v krvi ni obravnavana v tej tehnični specifikaciji.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-september-2015
0ROHNXODUQHGLDJQRVWLþQHSUHLVNDYHLQYLWUR6SHFLILNDFLMH]DSUHGSUHLVNRYDOQH
SURFHVH]DYHQVNRSROQRNULGHO ,]ROLUDQDFHOLþQD51$
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes
for venous whole blood - Part 1: Isolated cellular RNA
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für venöse Vollblutproben - Teil 1: Isolierte zelluläre RNS
Tests de diagnostic moléculaire in vitro - Spécifications relatives aux processus
préanalytiques pour le sang veineux total - Partie 1 : ARN cellulaire isolé
Ta slovenski standard je istoveten z: CEN/TS 16835-1:2015
ICS:
11.100.10 'LDJQRVWLþQLSUHVNXVQL In vitro diagnostic test
VLVWHPLLQYLWUR systems
11.100.30 Analiza krvi in urina Analysis of blood and urine
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
TECHNICAL SPECIFICATION
CEN/TS 16835-1
SPÉCIFICATION TECHNIQUE
TECHNISCHE SPEZIFIKATION
July 2015
ICS 11.100.10
English Version
Molecular in vitro diagnostic examinations - Specifications for
pre-examination processes for venous whole blood - Part 1:
Isolated cellular RNA
Tests de diagnostic moléculaire in vitro - Spécifications Molekularanalytische in-vitro-diagnostische Verfahren -
relatives aux processus préanalytiques pour le sang Spezifikationen für präanalytische Prozesse für venöse
veineux total - Partie 1 : ARN cellulaire isolé Vollblutproben - Teil 1: Isolierte zelluläre RNS
This Technical Specification (CEN/TS) was approved by CEN on 30 May 2015 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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, 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: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN/TS 16835-1:2015 E
worldwide for CEN national Members.
Contents Page
Foreword .3
Introduction .4
1 Scope .5
2 Normative references .5
3 Terms and definitions .5
4 General considerations .6
5 Outside the laboratory .7
5.1 Primary venous whole blood collection manual .7
5.1.1 Information about the primary sample donor .7
5.1.2 Selection of the venous blood collection tube by the laboratory .7
5.1.3 Primary venous whole blood collection from the patient and stabilization procedures .7
5.1.4 Information on the primary blood sample and storage requirements at the blood
collection facility .8
5.2 Transport requirements .9
6 Inside the laboratory .9
6.1 Sample reception .9
6.2 Storage requirements .9
6.3 Isolation of the cellular RNA . 10
6.4 Quality assessment of isolated cellular RNA . 11
6.5 Storage of isolated cellular RNA . 11
Annex A (informative) Impact of preanalytical workflow steps on venous whole blood cellular
RNA profiles . 12
A.1 General information on operated experiments in Annex A and Annex B. 12
A.2 Influence of blood collection tube type (with or without blood cellular RNA profile
stabilizer) on the analysis of specific blood cellular RNA profiles . 12
A.2.1 Unstable blood cellular RNA profiles . 12
A.2.2 Stable blood cellular RNA profiles . 14
Annex B (informative) Influence of blood storage temperature on blood cellular RNA profiles . 16
Bibliography . 19
Foreword
This document (CEN/TS 16835-1:2015) 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 [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to announce this Technical Specification: 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, 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 analyzing signatures of nucleic acids, proteins, and metabolites in human tissues and body
fluids. However, the profiles of these molecules can change drastically during primary sample collection,
transport, storage, and processing thus making the outcome from diagnostics or research unreliable or even
impossible because the subsequent analytical 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 sample collection to RNA analysis is needed. Studies have been undertaken to determine the
important influencing factors. This Technical Specification draws upon such work to codify and standardize the
steps for venous whole blood cellular RNA analysis in what is referred to as the preanalytical phase.
1 Scope
This Technical Specification recommends the handling, documentation and processing of venous whole blood
specimens intended for cellular RNA analysis during the preanalytical phase before a molecular assay is
performed. This Technical Specification covers specimens collected by venous whole blood collection tubes.
This Technical Specification is applicable to molecular in vitro diagnostic examinations (e.g. in vitro diagnostic
laboratories, laboratory customers, in vitro diagnostics developers and manufacturers, institutions and
commercial organizations performing biomedical research, biobanks, and regulatory authorities).
Blood cellular RNA profiles can change significantly after collection. Therefore, special measures need to be
taken to secure good quality blood samples for cellular RNA analysis and storage.
Different dedicated measures need to be taken for stabilizing blood cell free circulating RNA and RNA in
exosomes circulating in blood, which are not described in this Technical Specification.
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. These are not described in this
Technical Specification.
RNA in pathogens present in blood is not covered by this Technical Specification.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated references,
the latest edition of the referenced document (including any amendments) applies.
EN ISO 15189:2012, Medical laboratories - Requirements for quality and competence (ISO 15189:2012,
Corrected version 2014-08-15)
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 15189:2012 and the following
apply.
3.1
ambient temperature
unregulated temperature of the surrounding air
3.2
analytical phase
processes that start with the isolated analyte and include all kind of parameter testing or chemical
manipulation for quantitative or qualitative analysis
3.3
blood cellular RNA
cellular RNA
RNA molecules present in blood cells
3.4
blood cellular RNA profile\s
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
3.5
blood cellular RNA profile stabilizers
compounds, solutions or mixtures that are designed to minimize changes of the blood cellular RNA profile
3.6
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), temporary storage,
transportation to and within the analytical laboratory, aliquotting, retrieval, isolation of analytes, and end when
the analytical examination begins
[SOURCE: EN ISO 15189:2012, 3.15, modified — An additional term was added and more details were
included.]
Note 1 to entry: The preanalytical phase may include preparative processes that may influence the outcome of the
intended examination.
3.7
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: EN ISO 15189:2012, 3.16, modified — The term and definition is used here without the original
notes.]
3.8
RNA
ribonucleic acid
polymer of ribonucleotides occurring in a double-stranded or single-stranded form
[SOURCE: EN ISO 22174:2005, 3.1.3]
3.9
room temperature
temperature which is defined as 18 °C to 25 °C for the purposes of this document
3.10
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 30:1992, 2.7]
Note 1 to entry: The measured constituent for the purpose of this document is blood cellular RNA.
4 General considerations
For general statements on primary sample collection and handling (including avoidance of cross
contaminations), see EN ISO 15189:2012, 5.2.6, 5.4.4. Consumables including kits shall be verified before
use in examination (see EN ISO 15189:2012, 5.3.2.3); EN ISO 15189:2012, 5.5.1.2 and 5.5.1.3 can also
apply.
As all steps of a diagnostic workflow can influence the final analytical performance, the entire workflow
comprising the preanalytical steps, including information on sample stability and storage conditions, and the
analytical steps should be verified and validated (see EN ISO 15189).
Blood cellular RNA profiles can change significantly after collection (e.g. gene induction, gene down
regulation, RNA degradation) [3], [4], [5], [6]. These changes can vary individually in different blood dono
...
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