In vitro diagnostics for screening the blood supply: the new European regulation for IVD and the WHO IVD prequalification programme.

Blood transfusion remains a routine life-saving medical procedure that helps replace blood lost due to surgery, injury or disease. The quality of transfused blood is crucial in this process as blood donors must be free of transfusion-transmissible infections and donated blood should be compatible to that of the recipient. The quality of donated blood could be affected by the quality of in vitro diagnostic medical devices (IVDs) used in the screening process. Consequently, the need for high-quality, safe and well-performing IVDs for use in transfusion medicine arises, accompanied by the need for tight regulations in this domain. In the European Union, the new IVD Regulation will replace the existing IVD Directive within a five-year transitional period. Manufacturers of IVDs are expected to fully comply with the new Regulation by 26 May 2022. In this review, we address the major differences relating to marketing authorization and testing between this new Regulation and its predecessor. We further present the main elements of the prequalification assessment introduced by the WHO for IVDs, including disease-specific IVDs for blood screening laboratories.

Evaluation of 17 CE-marked HBsAg assays with respect to clinical sensitivity, analytical sensitivity, and hepatitis B virus mutant detection.

Seventeen HBsAg assays, in use in the European market (CE-marked), were assessed for their diagnostic sensitivity using 38 commercially available seroconversion panels, and for their analytical sensitivity with the HBsAg ad and ay standards of the Paul-Ehrlich-Institut (PEI). In addition, the ability to detect HBsAg mutants was investigated by means of 21 recombinant HBsAg mutant samples and 5 natural mutants. Analysis of seroconversion data revealed that there were marked differences in the sensitivity among the CE-marked HBsAg assays. Differences in the window period between the most and the least sensitive assays were up to 2 weeks. Analytical sensitivities of the investigated assays ranged from 0.009 to 0.05 PEI-U/ml for HBsAg ad standard (relating to approximately 0.018 to 0.100 IU/ml of the 2nd WHO HBsAg standard) and 0.012 to 0.11 PEI-U/ml for the ay standard. Clinical and analytical sensitivities were basically correlated. The capacity to detect mutant HBsAg forms was influenced by the assay format and the properties of the monoclonal antibodies used for coating of the solid phase or in the conjugate. While some assays detected all mutants others exhibited weaknesses especially in recognising HBsAg mutations affecting loop 2 of the HBsAg a-determinant. The results obtained with the recombinant mutants were largely confirmed by the investigation of clinical samples. The study gives a broad overview of the current state of the art of about 70% of the HBsAg assays currently available in Europe. The overall sensitivity has not been improved further since 1995 when the most sensitive assay was introduced into the market. In addition, detection of HBsAg mutants seems problematic with several assays. It is concluded that there is potential to improve clinical sensitivity and mutant recognition of HBsAg assays.