Regulation of blood-screening diagnostics in sub-Saharan African countries remains a challenge.

According to the World Health Organization, blood must be screened for major transmitted infections before transfusion to prevent the possibility of passing an infection to the recipient. For accurate detection of infectious disease pathogens in the blood of donors, diagnostic medical devices (IVDs) of high specificity and sensitivity should be used. In mature healthcare systems, the regulatory authorities authorize the usage of devices with the highest performance capabilities, which are also controlled through active market oversight.

Performance of 20 rapid antigen detection tests to detect SARS-CoV-2 B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants using a clinical specimen panel from January 2022, Berlin, Germany.

BackgroundThere are conflicting reports on the performance of rapid antigen detection tests (RDT) in the detection of the SARS-CoV-2 Omicron (B.1.1.

Antibody response to SARS-CoV-2 for more than one year - kinetics and persistence of detection are predominantly determined by avidity progression and test design.

Background: Antibody detection of SARS-CoV-2 requires an understanding of its variation, course, and duration.

Methods: Antibody response to SARS-CoV-2 was evaluated over 5-430 days on 828 samples across COVID-19 severity levels, for total antibody (TAb), IgG, IgA, IgM, neutralizing antibody (NAb), antibody avidity, and for receptor-binding-domain (RBD), spike (S), or nucleoprotein (N). Specificity was determined on 676 pre-pandemic samples.

Establishment of a specimen panel for the decentralised technical evaluation of the sensitivity of 31 rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021.

IntroductionThe detection of SARS-CoV-2 with rapid diagnostic tests (RDT) has become an important tool to identify infected people and break infection chains. These RDT are usually based on antigen detection in a lateral flow approach.AimWe aimed to establish a comprehensive specimen panel for the decentralised technical evaluation of SARS-CoV-2 antigen rapid diagnostic tests.

Comparative sensitivity evaluation for 122 CE-marked rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021.

IntroductionNumerous CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) are offered in Europe, several of them with unconfirmed quality claims.AimWe performed an independent head-to-head evaluation of the sensitivity of SARS-CoV-2 Ag RDT offered in Germany.MethodsWe addressed the sensitivity of 122 Ag RDT in direct comparison using a common evaluation panel comprised of 50 specimens.

Reliability of CE-marked NATs for HIV-1 subtype C detection and quantitation.

We compared seven CE-marked HIV-1 RNA nucleic acid amplification technology (NAT) based assays for their detection efficiency and quantitation concordance in regard to HIV-1 subtype C. We used 398 plasma samples from South African repeat blood donors identified as HIV positive at occasion of routine screening NAT performed mainly during the years 2010-2013, with most plasma samples reflecting recent HIV-1 infections. All HIV-1 subtype C specimens were detected, independent of mono- or dual-target assay design.

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.

Summary of the WHO hearing on the development of product-specific reference materials for coagulation factor VIII and factor IX products.

In recent years, several modified recombinant factor (F) VIII and FIX therapeutics with extended half-life have been licensed internationally for the treatment of haemophilia. Safe and effective use of these products requires monitoring of factor activity in patient plasma. The potency of all FVIII and FIX products is currently assigned in International Units (IU) which anchors the relationship between potency labelling, dosing and clinical monitoring.

WHO international standard for anti-rubella: learning from its application.

The WHO international standard for anti-rubella was first established in the 1960s when clinical diagnostics were in their infancy. Since the endorsement of the first international standard for anti-rubella IgG (RUBI-1-94), new rubella vaccines have been developed and global coverage of rubella vaccination has increased. Methods used to measure concentrations of anti-rubella IgG have also evolved to rapid, high-throughput binding assays, which have replaced often cumbersome and highly technical functional assays.

Standardization of Nucleic Acid Tests: the Approach of the World Health Organization.

The first World Health Organization (WHO) international standards (ISs) for nucleic acid amplification techniques were established two decades ago, with the initial focus on blood screening for three major viral targets, i.e., hepatitis C virus, hepatitis B virus, and human immunodeficiency virus 1.

Establishment of the Ph. Eur. Hepatitis A virus RNA for NAT testing BRP batch 1.

Detection of viral contamination in plasma donations is critical to prevent transmission of infectious diseases. The European Pharmacopoeia (Ph. Eur.

Comparative characterization of hepatitis B virus surface antigen derived from different hepatitis B virus genotypes.

For human hepatitis B virus eight distinct and two candidate genotypes are described. These genotypes differ with respect to geographic distribution, molecular virology and virus-associated pathogenesis. Comparative analysis of HBV genotypes revealed, with exception of HBV/G that shows impaired HBsAg release, that no fundamental disparities between genotypes exist regarding glycosylation, subcellular distribution, release of HBsAg and formation of subviral particles.

Hepatitis E viral loads in plasma pools for fractionation.

Background: It is now recognized that blood donors may be silently infected with hepatitis E virus (HEV) and that plasma pools used in the manufacture of plasma-derived medicinal products may also contain detectable virus RNA. The occurrence of HEV-infected blood and plasma donors can vary considerably depending on local epidemiology.

Study Design And Methods: Manufacturing plasma pools from North America, Europe, the Middle East, and Asia were examined for the presence of HEV using transcription-mediated amplification of HEV RNA; confirmatory testing was performed using real-time reverse transcription polymerase chain reaction and sequencing.

Viral nucleic acids in human plasma pools.

Background: The identification of viruses in human blood is required for epidemiologic surveillance and to detect potentially emerging threats to blood transfusion safety.

Study Design And Methods: Viral nucleic acids in plasma fractionation pools assembled from blood donors in the United States and Europe were analyzed by viral metagenomics.

Results: Anelloviruses were detected in each of the 10 plasma pools.

Standardization of NAT for Blood-Borne Pathogens.

Assays based on nucleic acid amplification technology (NAT) are increasingly used for screening of blood and for diagnosis or monitoring of patients. Both regulatory requirements for blood screening and international recommendations for the treatment of patients are based on common reference materials available globally for the standardization of NAT assays. World Health Organization International Standards (WHO ISs) and International Reference Panels (WHO IRPs) are primary reference materials.

World Health Organization International Standard To Harmonize Assays for Detection of Mycoplasma DNA.

Nucleic acid amplification technique (NAT)-based assays (referred to here as NAT assays) are increasingly used as an alternative to culture-based approaches for the detection of mycoplasma contamination of cell cultures. Assay features, like the limit of detection or quantification, vary widely between different mycoplasma NAT assays. Biological reference materials may be useful for harmonization of mycoplasma NAT assays.

Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples.

Background: Hepatitis C virus (HCV) antigen and antibody combination assays have been launched as a cost-effective alternative to nucleic acid testing (NAT) for reducing the antibody-negative window period (WP). Later, a HCV antigen chemiluminescence immunoassay (CLIA) became available.

Study Design And Methods: A panel composed of 337 HCV NAT-yield samples that were characterized for viral load (VL) and genotype was used to compare the sensitivity of two combination enzyme-linked immunosorbent assays (Monolisa, Bio-Rad; and Murex, formerly Abbott) and a HCV antigen CLIA (Abbott).

[Legal basis and practice of examination of critical in vitro diagnostic devices].

In vitro diagnostic devices (IVD) are categorized into different risk classes depending on the potential consequences of false test results in transfusion medicine or on the individual patient. Test systems of higher risk may be assessed and examined by a third party in addition to the manufacturer's evaluation. The preapproval examination of essential performance features can assure minimum quality features prior to marketing of the IVDs.

Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany.

Background: Several publications describe HIV-1 RNA false-negative results or viral load underquantitation associated with Communauté Européenne(CE)-marked qualitative or quantitative nucleic acid amplification technique (NAT) assays. 6 cases occurred during blood screening in Germany, with 2 of them causing HIV-1 transmissions to recipients of blood components. The implicated NAT assays were mono-target assays amplifying in different viral genome regions (gag or long terminal repeat).

Performance of hepatitis B surface antigen tests with the first WHO international hepatitis B virus genotype reference panel.

Background: Standardization of hepatitis B surface antigen (HBsAg) tests is indispensable for consistent quality and comparability. Ideally, the assays should detect all known hepatitis B virus (HBV) genotypes equally well.

Objective: Development of an HBV genotype reference panel for HBsAg assays representing the most prevalent HBV subgenotypes to address commutability and traceability of the heat-inactivated 2nd WHO International Standard (IS) for HBsAg in relation to native HBsAg and to HBV genotypes.

[The ways of harmonization of clinical laboratory measurement techniques].

The results of implementation of different clinical laboratory techniques are to be equal in clinically significant limits to be optimally applied in diagnostics of diseases and treatment of patients. When the results of laboratory tests are not standardized and harmonized for the very same clinical assay the results can be expressed by unmatched numbers. Unfortunately, in some handbooks the values are presented based on the results of application of specific laboratory techniques without considering possibility or likelihood of differences between various techniques.

How safe is safe: new human immunodeficiency virus Type 1 variants missed by nucleic acid testing.

Background: Nucleic acid amplification techniques (NAT) in routine blood donor screening considerably reduce the diagnostic window phase period. Nevertheless, several reports of false-negative NAT results were published. Here, four cases of human immunodeficiency virus Type 1 (HIV-1) RNA-positive blood donations that escaped detection by NAT screening are described.