Clinical application of ISO and CEN/TS standards for liquid biopsies

In their recent publication, researchers from partner Medical University of Graz evaluated the applicability of ISO and CEN/TS standards for the pre-analytical quality of whole venous blood for circulation cell free DNA (ccfDNA) and for circulating tumor cells (CTC).

A family of international ISO quality standards exists that specifies requirements and give recommendation on how to correctly handle different types of human specimens and what to consider during the preanalytical phase in order to achieve high sample quality and thus reliable and reproducible analysis results.
Among the standards are those for liquid biopsy samples, i.e.


  • ISO 20186-3:2019: Molecular in vitro diagnostic examinations – Specifications for pre-examination processes for venous whole blood – Part 3: Isolated circulating cell free DNA (ccfDNA) from plasma.
  • 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. representatives from the Medical University of Graz participated to the development of these and other standards for pre-analytical sample quality (most of) which were generated in the context of the EU project SPIDIA4P.

The authors of this publication show that 92% of 659 peripheral blood clinical samples that were included in their study, met the requirements of the respective standards. This included for example tube filling level, time from collection to storage of the samples, transport conditions, exposure to temperature variations and tube draw order. In the samples that did not align with ISO and CEN/TS standards, the most common mistake was a lack of documentation of the identity of the person who collected the blood, followed by missing tube inversion. Furthermore, the study shows that hemolysis is common, even when pre-analytical errors were avoided in compliance with the standards.

For biobanks, compiling with pre-analytical ISO and CEN/TS standards is especially important, as it enables the foundation of new liquid biopsy cohorts and the further use of these samples for research projects.