ISO/TS 7552-1:2024
(Main)Molecular in vitro diagnostic examinations — Specifications for pre-examination processes for circulating tumour cells (CTCs) in venous whole blood — Part 1: Isolated RNA
Molecular in vitro diagnostic examinations — Specifications for pre-examination processes for circulating tumour cells (CTCs) in venous whole blood — Part 1: Isolated RNA
This document specifies requirements and gives recommendations on the handling, storage, CTC enrichment and isolation, RNA isolation and storage, and documentation of venous whole blood specimens intended for the examination of RNA isolated from 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 the isolation of cellular RNA directly from venous whole blood containing CTCs. This is covered in ISO 20186-1. This document does not cover the isolation of specific white blood cells and subsequent isolation of cellular RNA therefrom. 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. foetal cells). NOTE 2 International, national or regional regulations or requirements can also apply to specific topics covered in this document.
Analyses de diagnostic moléculaire in vitro — Spécifications relatives aux processus préanalytiques pour les cellules tumorales circulantes (CTC) dans le sang total veineux — Partie 1: ARN isolé
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ISO/TS 7552-1
First edition
Molecular in vitro diagnostic
2024-11
examinations — Specifications
for pre-examination processes for
circulating tumour cells (CTCs) in
venous whole blood —
Part 1:
Isolated RNA
Analyses de diagnostic moléculaire in vitro — Spécifications
relatives aux processus préanalytiques pour les cellules tumorales
circulantes (CTC) dans le sang total veineux —
Partie 1: ARN isolé
Reference number
© ISO 2024
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ii
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 .7
5.1.4 Venous whole blood specimen collection from the patient/donor .7
5.2 Specimen storage and transport .8
5.2.1 General .8
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 .9
6 Activities inside the laboratory . 9
6.1 Specimen reception .9
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 .10
6.3.3 Using the laboratory-developed CTC enrichment procedure.10
6.4 Quality of enriched CTCs .11
6.5 Storage of enriched CTCs .11
6.6 Isolation of CTCs .11
6.6.1 General .11
6.6.2 Using a commercial CTC isolation system intended for diagnostic use .11
6.6.3 Using the laboratory-developed CTC isolation procedure . 12
6.7 Isolation of RNA from an enriched CTC sample . 12
6.7.1 General . 12
6.7.2 Using a commercial RNA isolation kit intended for diagnostic use . 12
6.7.3 Using a laboratory-developed CTC RNA isolation procedure . 13
6.8 Quantity and quality assessment of isolated RNA from enriched or isolated CTCs . 13
6.8.1 General . 13
6.8.2 Quantity assessment of CTC RNA . 13
6.8.3 Quality assessment CTC RNA .14
6.9 Storage of isolated RNA from enriched CTCs .14
6.9.1 General .14
6.9.2 Storage of RNA isolated with a commercially available kit intended for
diagnostic use . 15
6.9.3 Storage of RNA isolated with the laboratory-developed procedure . 15
Annex A (informative) Decision guideline for critical steps of the CTC pre-analytical workflow .16
Bibliography .18
iii
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
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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 not received notice of (a)
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this may not represent the latest information, which may be obtained from the patent database available at
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This document was prepared by Technical Committee ISO/TC 212, Medical laboratories and in vitro diagnostic
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
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
[20,21]
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
[41]
tumour progression, with distinct genetic, epigenetic and gene expression biomarkers.
Besides the prognostic role of CTC identification and enumeration in cancer progression, CTC molecular
characterization can improve disease outcome prediction, therapeutic guidance and post-treatment
[39]
monitoring of the patient.
CTCs are now considered as a surrogate of tumour tissue in cancer early development, progression and
[23]
metastatic phase .
Molecular characterization of CTCs can provide a strategy for monitoring cancer genotypes during systemic
[24]
therapies, identifying mechanisms of disease progression, identifying novel targets for biological
[25] [39]
treatment and selecting targeted therapies .
Moreover, CTC single-cell sequencing is emerging as an important tool for tumour genomic heterogeneity
[26-28]
analysis. 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 examination.
RNA profiles of CTCs resemble gene expression profiles of tumours. For RNA profile analysis, measures to
remove the WBCs are necessary in order to obtain sufficiently enriched CTC-specific RNA.
RNA profiles can change significantly after blood collection, during CTC enrichment and isolation. Therefore,
special measures are necessary to obtain CTC samples of adequate quality and isolated RNA of appropriate
[29]
quality for ensuring the specified RNA examination performance.
Standardization includes all steps of the pre-examination process, including blood collection and stabilization,
transport, storage, CTC enrichment, CTC isolation (if included), and RNA isolation. This pre-examination
standardization is crucial to ensure reliable examination results in current clinical use and is also critical to
[30]
develop new CTC based diagnostic examinations and to establish these in clinical healthcare.
An illustration of critical steps of the CTC pre-analytical workflow is pro
...
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