Misleading nomenclature of units of WHO materials used for standardization of SARS COv-2 serology

Abstract

The mission of the Committee of Nomenclature for Properties and Units (C-NPU), a joint commission of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and International Union of Pure Applied Chemists (IUPAC), is to recommend an standardized laboratory terminology for reporting laboratory results that include proper kinds-of-properties (e.g. category, mass concentration) and measurement units. In this letter, we express our deep concerns of a new unit concept recently introduced by WHO. The necessary, and prompt work byWHO to establish an international standard (IS) labelled 20/136, as a Certified Reference Material (CRM) for measurement of the activity of SARS CoV-2 antibodies, is acknowledged. However, in the correspondence “WHO International Standard for anti-SARS CoV-2 immunoglobulin,”wewere puzzled by the newmetrological unit concept, referred as “Binding Antibody Unit” (BAU) [1]. In version 1.0 of the certificate for IS 20/136, the value “250 IU/ampoule” was assigned for both calibration of measurements of neutralizing antibodies and for (“binding”) antibodies [2]. In the second version, BAU was introduced as a unit concept for harmonization (n.b. not calibration) of results from binding antibody assays [3]. The reason was recently developed: “For example, it is inappropriate to assign a protective titre for vaccine efficacy in IU/mL when using an assay that is not measuring an antigen associated with protection. Such cases have arisen formeasles and rubella, and have led to amisplaced lack of confidence in the use of the International Standard” [4]. Hence, the reason to introduce separate units for results from “neutralising antibody” assays and results from “binding antibody” assays, was the lack of confidence to CRM when users had not clearly distinguished two different measurands. The use of separate unit names for the same kind-of-quantity (e.g. mass concentration), instead of separate names for the components (analytes), is a deviation from international nomenclature conventions used byWHO to assign International Units to CRM [5]. It is a concern that should cause alarms in scientific societies, standardisation bodies and health care organisations. Before the SI unit system, literally numerous different units for the same kind-of-quantity existed [6, 7]. This nontransparent practice created confusion in trade (exchanging goods with measurements) across geographically borders, even between close-by-cities. Same confusion can and will happen in health care with potentially mistreatment of patients if multiple international units are introduced for results of the same kind-of-quantity. Thus, a limited number of internationally recognized units (preferable SI units or international recognized nonSI units) has been recommended in laboratory medicine since 1966 [8]. However, it is acknowledged that it may not be possible to assign an SI unit to a measurand of a CRM, e.g. CRM for a biological activity. In these cases, WHO assigns an arbitrary value of the amount of a biological substance in a CRM expressed as multiples of International Units (IU). As example, CRMs for Hepatitis Virus All authors are members of C-NPU.