CEN/TS 17390-3:2020
(Main)Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood - Part 3: Preparations for analytical CTC staining
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood - Part 3: Preparations for analytical CTC staining
This document gives guidelines on the handling, storage, processing and documentation of venous whole blood and the CTC (Circulating Tumor Cell) enrichment, CTC isolation and other preparations for analytical staining (i.e., conventional cytochemical and immunocytochemical staining) of CTCs during the pre-examination Phase before the cytopathological evaluation is performed.
This document 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, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
This document does not cover specific staining procedures.
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 zirkulierende Tumorzellen (CTC) in venösen Vollblutproben - Teil 3: Vorbereitungen für die analytische CTC Färbung
Dieses Dokument spezifiziert Empfehlungen zur Handhabung, Lagerung, Verarbeitung und Dokumentation von Proben venösen Vollbluts, die für die Färbung der zirkulierenden Tumorzellen (CTCs) vorgesehen sind, während der präanalytischen Phase vor der Durchführung einer molekularen Analyse.
Dieses Dokument ist anwendbar auf molekulare in vitro diagnostische Untersuchungen, die in medizinischen Laboratorien durchgeführt werden, einschließlich vom Laboratorium selbst entwickelter Verfahren. Es ist darüber hinaus für die Verwendung durch Kunden von Laboratorien, Entwickler und Hersteller von In vitro Diagnostika, durch Biobanken, Institutionen und kommerzielle Organisationen, die biomedizinische Forschungen durchführen, sowie durch Arzneimittelagenturen bestimmt.
Dieses Dokument behandelt nicht die Anforderungen an den präanalytischen Arbeitsablauf zur Kryokonser¬vierung und Kultivierung lebensfähiger CTCs.
ANMERKUNG 1 Die in diesem Dokument dargelegten Anforderungen können auch auf andere zirkulierende Zellen (z. B. fetale Zellen) angewendet werden.
ANMERKUNG 2 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 cellules tumorales circulantes (CTC) du sang total veineux - Partie 3 : Préparations pour l’analyse par coloration des CTC
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese za cirkulirajoče tumorske celice (CTC) v venski polni krvi - 3. del: Priprave za analitično barvanje CTC
General Information
Standards Content (Sample)
SLOVENSKI STANDARD
01-marec-2020
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese za cirkulirajoče tumorske celice (CTC) v venski polni krvi - 3. del: Priprave
za analitično barvanje CTC
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes
for circulating tumor cells (CTCs) in venous whole blood - Part 3: Preparations for
analytical CTC staining
Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für zirkulierende Tumorzellen (CTC) in venösen Vollblutproben
- Teil 3: Vorbereitungen für die analytische CTC-Färbung
Analyses de diagnostic moléculaire in vitro - Spécifications relatives aux processus
préanalytiques pour les cellules tumorales circulantes (CTC) du sang total veineux -
Partie 3 : Préparations pour l’analyse par coloration des CTC
Ta slovenski standard je istoveten z: CEN/TS 17390-3:2020
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 17390-3
TECHNICAL SPECIFICATION
SPÉCIFICATION TECHNIQUE
January 2020
TECHNISCHE SPEZIFIKATION
ICS 11.100.10
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for circulating tumor cells
(CTCs) in venous whole blood - Part 3: Preparations for
analytical CTC staining
Analyses de diagnostic moléculaire in vitro - Molekularanalytische in-vitro-diagnostische Verfahren
Spécifications relatives aux processus préanalytiques - Spezifikationen für präanalytische Prozesse für
pour les cellules tumorales circulantes (CTC) du sang zirkulierende Tumorzellen (CTC) in venösen
total veineux - Partie 3 : Préparations pour l'analyse Vollblutproben - Teil 3: Vorbereitungen für die
par coloration des CTC analytische CTC-Färbung
This Technical Specification (CEN/TS) was approved by CEN on 27 October 2019 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
© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN/TS 17390-3:2020 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 . 9
5 Outside the laboratory . 9
5.1 Specimen collection . 9
5.2 Transport requirements. 11
6 Inside the laboratory . 12
6.1 Specimen reception . 12
6.2 Storage requirements for the venous whole blood specimen . 12
6.3 Enrichment of the CTCs . 13
6.4 Storage of enriched CTCs . 13
6.5 Preparation for CTC staining . 14
Annex A (informative) Decision guideline for critical steps of the CTC pre-analytical
workflow for staining . 16
Bibliography . 18
European foreword
This document (CEN/TS 17390-3:2020) 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.
CEN/TS 17390 consists of the following parts, under the general title Molecular in vitro diagnostic
examinations — Specifications for pre-examination processes for Circulating Tumor Cells (CTCs) in venous
whole blood:
— Part 1: Isolated RNA
— Part 2: Isolated DNA
— Part 3: Preparations for analytical CTC staining
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
Solid tumours release cells and bioanalytes into blood and other body fluids. This has opened the option
of minimally-invasive tumour detection, diagnosis and characterization from venous whole blood
(liquid biopsies). Liquid biopsies are expected to enable earlier detection and diagnosis of cancers and
advance personalized patient treatment. These applications have become one of the fastest growing
segments of the entire diagnostic market.
Circulating tumour cells (CTCs) in venous whole blood reflect the disease complexity that evolves
during tumour progression, with distinct genetic, epigenetic and expression features. Besides the
prognostic role of CTC identification and/or enumeration in cancer progression, CTC identification and
analysis can improve e.g. disease outcome prediction, therapeutic guidance and post-treatment
monitoring of the patient.
CTCs are now considered as a surrogate sample of tumour tissue, both in cancer early development and
metastatic phase.
Molecular characterization of CTCs can provide for example a strategy for monitoring cancer genotypes
during systemic therapies [1], identification of mechanisms of disease progression, identification of
novel targets for treatment [2] and to select targeted therapies. Moreover, CTC single-cell sequencing is
emerging as an important tool for tumour genomic heterogeneity analysis [3] [4] [5].
CTCs are fragile and tend to degrade within a few hours when collected in conventional blood collection
tubes, e.g. EDTA containing tubes, without dedicated CTC stabilizers. CTCs are extremely rare, especially
in early disease, e.g. less than 10 cells per 10 ml of blood, representing a ratio of approx. 1:10 CTCs to
white blood cells (WBCs). This low ratio represents a significant challenge to CTC enrichment required
for identification and examination as tumour-derived cells.
Furthermore, CTC morphology and biomolecules can change during the pre-examination process. These
can lead to changes in protein quantity, integrity, modification, conformation and localization within the
cell. This can impact the validity and reliability of the examination result.
CTC examination usually requires a CTC enrichment step (e.g. based on biological properties, such as
expression of surface molecules, or physical properties, such as size and density, of the CTCs or their
combination) prior to cytomorphological examination or immunofluorescent staining. CTC enrichment
technologies can provide CTCs attached on a solid surface, ready for cytological examination, or CTCs in
suspension requiring extra processing steps prior to the examination. This can lead to potential cell
loss. [6]
CTC enrichment is usually followed by their identification by conventional cytochemical or protein-
targeted staining procedures that allow detection of the cell traits.
Standardization of all steps of the pre-examination process is required. This includes blood collection
and stabilization, transport, storage, CTC enrichment, and CTC isolation (if required). A decision
guideline for the critical steps of the pre-analytical workflow for CTC staining is provided in Annex A.
This document describes measures to standardize the pre-examination process to obtain appropriate
CTC staining.
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 guidelines on the handling, storage, processing and documentation of human
venous whole blood specimens intended for staining of circulating tumour cells (CTCs) during the pre-
examination phase before a molecular examination is performed.
This document 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, biobanks, institutions and commercial
organizations performing biomedical research, and regulatory authorities.
This document does not cover pre-analytical workflow requirements for viable CTC cryopreservation
and culturing.
NOTE 1 The requirements given in this document can also be applied to other circulating rare cells (e.g. fetal
cells).
NOTE 2 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 15189:2012, 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 following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http://www.electropedia.org/
— ISO Online browsing platform: available at https://www.iso.org/obp
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 bibliographical references [7], [8] and [9].
[SOURCE: EN ISO 20166-3:2019, 3.1]
3.2
ambient temperature
unregulated temperature of the surrounding air
[SOURCE: EN ISO 20166-3:2019, 3.2]
3.3
analyte
component represented in the name of a measurable quantity
[SOURCE: EN ISO 17511:2003, 3.2, modified — EXAMPLE has been removed.]
3.4
analytical test performance
accuracy, precision, specificity 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.
[SOURCE: EN ISO 20184-1:2018, 3.4, modified — “specificity” was added.]
3.5
blood collection set
intravenous device specialized for venipuncture consisting of a stainless steel bevelled needle and tube
(tubing) with attached plastic wings and fitting connector
Note 1 to entry: The connector attaches to an additional blood collection device, e.g. a blood collection tube.
3.6
blood collection tube
tube used for blood collection, usually in a vacuum which f
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