Dr Véronique Saada
PharmSCiD, Specialist in Hematology, Institut Gustave Roussy, Paris, France
Off-the-shelf antibody testing has revolutionised flow cytometry testing in the haematology laboratory.
Off-the-shelf flow cytometry testing can enable smaller haematology laboratories to maximise their workforce capacity, save time and money, and achieve faster, more detailed and more accurate immunophenotyping for their clients. It is also a powerful tool used in immunophenotyping for haematological malignancies, such as chronic lymphocytic leukaemia (CLL), as well as in basic research and in clinical trials.
Flow cytometry is said to have several advantages over immunohistochemistry (IHC) in cancer including: the ability to define distinct cell populations by their size and granularity; the capacity to gate out dead cells detection of weakly expressed surface antigens; and multi-colour analysis to measure several antigens simultaneously. At the heart of the test is a panel of antibodies that detect markers or antigens on the cells, aiding laboratorians in the identification of cell lineage.
Fulfilling potential return on investment
Although widely used, to date, flow cytometry testing has not fulfilled its potential to provide laboratories with maximum return on the high capital cost associated with the purchase of a flow cytometer: methodology and data interpretation, clinical data sharing and education have all been hindered by the complexity and variability of test set-up and results analysis.
For manually prepared and designed panels, each of the required number of antibodies must be titrated and validated and then revalidated when combined with other antibodies– a process which itself may require further technical adjustment in order to achieve accurate results. Quality assurance of the reagent cocktail demands rigorous documentation (dating, etc) at each step, including regular, ongoing testing to assess the quality of each batch. Lot variations, as well as stability issues, converge to add to the administrative burden. Manual antibody cocktail preparation is a process that is inherently fraught with the potential for errors.
Dr Veronique Saada is a specialist practitioner in hematology at leading cancer research centre, the Institut Gustave Roussy in Paris. She says: “There can be missing markers and the wrong antibodies can be added, raising the spectre of potential misinterpretation of the patient sample and an incorrect clinical conclusion that can have serious consequences for the patient.”
In words that will resonate with lab technicians throughout the world, Dr Saada says: “Cocktail preparation is a complex, time consuming process involving individual pipetting of antibodies into the batch.”
Cocktail preparation is a complex, time consuming process involving individual pipetting of antibodies into the batch.
Technological development to detect cancers
Since June 2017, labs have benefited from US Food and Drug Administration authorised technology, designed to detect a range of leukaemias and lymphomas, including chronic leukaemia, acute leukaemia, non-Hodgkin lymphoma, myeloma, myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The new technology, Beckman Coulter ClearLLab Reagents, have been authorised through the de novo premarket review pathway, a regulatory pathway for novel, low- to moderate- risk devices that are not substantially equivalent to an already marketed device. The authorisation was supported by a study designed to demonstrate the test’s performance, which was conducted on 279 samples at four independent clinical sites.
Lower costs, less time and greater patient and professional satisfaction
For labs around the world, the availability of FDA and Bethesda International Consensus recommendations compliant panels, containing premixed and optimised multi-colour antibodies assay, has important implications.
Like many other ideas that are intended to improve existing products or procedures, the new European IVD Regulation (IVD-R) 2017/746 road is paved with good intentions. However, some of these intentions may potentially render the daily life of clinical flow cytometry laboratories more complex than what they are now, due to the impact these latest regulations will have for laboratory-developed tests (LDTs).
As an organisation, Beckman Coulter Life Sciences continues to devote time and resources to ensure their extensive CE-IVD portfolio of single colour reagents and off-the-shelf testing remains compliant and meets the higher safety and performance requirements outlined in the new EU Regulation.