CEN ISO/TS 7552-3:2024

Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumour cells (CTCs) in venous whole blood - Part 3: Preparations for analytical CTC staining (ISO/TS 7552-3:2024)

This document specifies requirements and gives recommendations on the handling, storage, CTC enrichment, preparation for CTC staining, and documentation of venous whole blood specimens intended for staining of CTCs during the pre-examination phase before an 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.
Different dedicated measures are taken for stabilizing CTCs genomic DNA and RNA that are not described in this document; they are covered in ISO 7552-1 and ISO 7552-2.
NOTE 1        The requirements given in this document can also be applied to other circulating rare cells (e.g. foetal cells).
NOTE 2        International, national or regional regulations or requirements can also apply to specific topics covered in this document.

Spezifikationen für präanalytische Prozesse für zirkulierende Tumorzellen (CTC) in venösen Vollblutproben - Teil 3: Vorbereitungen für die analytische CTC‑Färbung (ISO/TS 7552‑3:2024)

Dieses Dokument legt Anforderungen fest und gibt Empfehlungen zur Handhabung, Lagerung, CTC Anreicherung, Vorbereitung für die CTC Färbung und Dokumentation von venösem Vollblut-Untersuchungsmaterial, das für die Färbung der CTC vorgesehen ist, während der präanalytischen Phase vor der Durchführung einer 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 betreiben, sowie durch Arzneimittelagenturen bestimmt.
Dieses Dokument behandelt nicht die Anforderungen an den präanalytischen Arbeitsablauf zur Kryokonservierung und Kultivierung lebensfähiger CTC.
Zur Stabilisierung der genomischen DNA und RNA von zirkulierenden Tumorzellen werden verschiedene spezielle Maßnahmen ergriffen, die in diesem Dokument nicht beschrieben werden; sie werden in ISO 7552 1  und ISO 7552 2  behandelt.
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) dans le sang total veineux - Partie 3: Préparations pour l’analyse par coloration des CTC (ISO/TS 7552-3:2024)

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 (ISO/DTS 7552-3:2024)

General Information

• Status: Published
• Publication Date: 12-Nov-2024
• ICS: 11.100.10 - In vitro diagnostic test systems
• Technical Committee: CEN/TC 140 - In vitro diagnostic systems
• Drafting Committee: CEN/TC 140/WG 3 - Quality management in the medical laboratory
• Current Stage: 6060 - Definitive text made available (DAV) - Publishing
• Start Date: 13-Nov-2024
• Completion Date: 13-Nov-2024
• Ref Project: KSIST-TS FprCEN ISO/TS 7552-3:2024 - Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumour cells (CTCs) in venous whole blood - Part 3: Preparations for analytical CTC staining (ISO/DTS 7552-3:2024)

Relations

• Replaces: CEN/TS 17390-3:2020 - 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
• Effective Date: 18-Jan-2023

Standards Content (Sample)

SLOVENSKI STANDARD
01-september-2024
Nadomešča:
SIST-TS CEN/TS 17390-3:2020
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 (ISO/DTS 7552-3:2024)
Molecular in vitro diagnostic examinations - Specifications for pre-examination processes
for circulating tumour cells (CTCs) in venous whole blood - Part 3: Preparations for
analytical CTC staining (ISO/DTS 7552-3:2024)
Spezifikationen für präanalytische Prozesse für zirkulierende Tumorzellen (CTC) in
venösen Vollblutproben - Teil 3: Vorbereitungen für die analytische CTC-Färbung
(ISO/DTS 7552-3:2024)
Titre manque - Partie 3: Titre manque (ISO/DTS 7552-3:2024)
Ta slovenski standard je istoveten z: FprCEN ISO/TS 7552-3
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.

FINAL DRAFT
Technical
Specification
ISO/DTS 7552-3
ISO/TC 212
Molecular in vitro diagnostic
Secretariat: ANSI
examinations — Specifications
Voting begins on:
for pre-examination processes for
2024-07-17
circulating tumour cells (CTCs) in
Voting terminates on:
venous whole blood —
2024-10-09
Part 3:
Preparations for analytical CTC
staining
RECIPIENTS OF THIS DRAFT ARE INVITED TO SUBMIT,
WITH THEIR COMMENTS, NOTIFICATION OF ANY
RELEVANT PATENT RIGHTS OF WHICH THEY ARE AWARE
AND TO PROVIDE SUPPOR TING DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/CEN PARALLEL PROCESSING LOGICAL, COMMERCIAL AND USER PURPOSES, DRAFT
INTERNATIONAL STANDARDS MAY ON OCCASION HAVE
TO BE CONSIDERED IN THE LIGHT OF THEIR POTENTIAL
TO BECOME STAN DARDS TO WHICH REFERENCE MAY BE
MADE IN NATIONAL REGULATIONS.
Reference number
ISO/DTS 7552-3:2024(en) © ISO 2024

FINAL DRAFT
ISO/DTS 7552-3:2024(en)
Technical
Specification
ISO/DTS 7552-3
ISO/TC 212
Molecular in vitro diagnostic
Secretariat: ANSI
examinations — Specifications
Voting begins on:
for pre-examination processes for
circulating tumour cells (CTCs) in
Voting terminates on:
venous whole blood —
Part 3:
Preparations for analytical CTC
staining
RECIPIENTS OF THIS DRAFT ARE INVITED TO SUBMIT,
WITH THEIR COMMENTS, NOTIFICATION OF ANY
RELEVANT PATENT RIGHTS OF WHICH THEY ARE AWARE
AND TO PROVIDE SUPPOR TING DOCUMENTATION.
© ISO 2024
IN ADDITION TO THEIR EVALUATION AS
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
LOGICAL, COMMERCIAL AND USER PURPOSES, DRAFT
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
INTERNATIONAL STANDARDS MAY ON OCCASION HAVE
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
TO BE CONSIDERED IN THE LIGHT OF THEIR POTENTIAL
or ISO’s member body in the country of the requester.
TO BECOME STAN DARDS TO WHICH REFERENCE MAY BE
MADE IN NATIONAL REGULATIONS.
ISO copyright office
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Phone: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland Reference number
ISO/DTS 7552-3:2024(en) © ISO 2024

ii
ISO/DTS 7552-3:2024(en)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3  Terms and definitions . 1
4 General Considerations . 5
5 Activities outside the laboratory. 6
5.1 Specimen collection .6
5.1.1 General .6
5.1.2 Information about the specimen donor/patient.6
5.1.3 Selection of the venous whole blood collection tube by the laboratory .6
5.1.4 Venous whole blood specimen collection from the patient/donor .7
5.2 Specimen storage and transport .7
5.2.1 General .7
5.2.2 Storage and transport using blood collection tubes with stabilizers .8
5.2.3 Storage and transport using blood collection tubes without stabilizers .8
6 Activities inside the laboratory . 8
6.1 Specimen reception .8
6.2 Specimen storage after transport and reception .9
6.3 Enrichment of CTCs .9
6.3.1 General .9
6.3.2 Using a commercial CTC enrichment system intended for diagnostic use .9
6.3.3 Using the laboratory developed CTC enrichment procedure .10
6.4 Quality of enriched CTCs .10
6.5 Storage of enriched CTCs .10
6.6 Preparation for CTC staining .10
6.6.1 General .10
6.6.2 Pretreatment for different staining techniques (antibody, colour staining, in
situ techniques) .11
Annex A (informative)  Decision guideline for critical steps of the CTC pre-analytical workflow .12
Bibliography . 14

iii
ISO/DTS 7552-3:2024(en)
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).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
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, in collaboration with the European Committee for Standardization (CEN) Technical
Committee CEN/TC 140, In vitro diagnostic medical devices, in accordance with the Agreement on technical
cooperation between ISO and CEN (Vienna Agreement).
A list of all parts in the ISO 7552 series 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/DTS 7552-3:2024(en)
Introduction
Solid tumours release cells and bioanalytes into blood and other body fluids. This has opened the option
of utilizing such body fluids (liquid biopsies) for a minimally-invasive procedure for tumour detection,
diagnosis and characterization. Liquid biopsies can enable earlier detection and diagnosis of cancers and
[19,20]
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 can reflect the disease complexity that evolves during
[21]
tumour progression, with distinct genetic, epigenetic and expression features.
Besides the prognostic role of CTC identification and enumeration in cancer progression, CTC identification
and analysis can improve disease outcome prediction, therapeutic guidance and post-treatment monitoring
[19]
of the patient.
CTCs are now considered as a surrogate of tumour tissue in cancer early development, progression and
[22]
metastatic phase.
Molecular characterization of CTCs can provide a strategy for monitoring cancer during systemic
[23] [24]
therapies, identifying mechanisms of disease progression, identifying novel targets for treatment and
[19]
selecting targeted therapies .
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 approximately 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. This 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 of the CTCs, such
as expression of surface mole
...