An Industry Standard Today, 30 Years in the Making
Following the HIV crisis of the 1980s, the plasma industry actively engaged in strategies to improve plasma safety. By the mid-1980s, the first serologic test was available to screen for HIV but the window period between infection and detection could be 6-12 weeks.1 Earlier detection of the virus was needed. Researchers were using nucleic acid testing (NAT) in the laboratory for confirmation testing but use of NAT to screen individually large number of plasma donations was costly and difficult to implement.
By the mid-90s, several manufacturers had launched HIV and HCV assays making plasma pool testing possible. The European Union issued a directive in 1998 and the Food and Drug Administration shortly after, in 1999, requiring all plasma donations to be tested for HCV with NAT. In 2002, Procleix became the first commercial molecular assay to receive FDA approval for HIV and HCV in individual donations and in pools. By 2007, fully automated triplex assays (HIV, HBV, HCV) such as Procleix Ultrio were approved by both European and US regulators.
A good assay relies on several factors in order to be robust enough for use in pools: a solid design, in process control systems, and an high clinical sensitivity and specificity.
The ability of a NAT assay to detect reactive samples depends on several factors: the clinical sensitivity of the assay, the pool size used for screening, and the viral load in the donation. Testing plasma pools of 96 samples or more requires a highly sensitive and reproducible NAT assay.
The assay should have a limit of detection allowing detection of low viral load even in high pool size. The Paul Ehrlich Institute (PEI) requires minimal sensitivity limits of 5000 IU HCV‐RNA/mL and 10 000 IU HIV‐1 RNA/mL for the individual donation. The assay must also detect all known subtypes and genotypes of the targeted virus and have features to allow the detection of the potential mutations. In 2019, the European Council mandated the detection of two independent HIV target regions2 thus reducing the possible occurrence of a false negative result due to viral mutation.
Another important factor is the assay specificity, which is the ability to assess unequivocally the targeted virus in the presence of other pathogens or other components. The higher the assay specificity is, the less unnecessary retesting will be needed for plasma pools and their individual constituents. A false reactive result caused by poor specificity could cause all donations in that pool to be held back until complete resolution.
Grifols was the first company to receive approval for its assay used in pools of plasma. The Transcription-Mediated Amplification (TMA) assays have proven high sensitivity and specificity. The Procleix Ultrio Elite Assay, the first of its kind, approaches 100% sensitivity.3
For information on Procleix assays in plasma pools testing, click here.
1. Alexander TS.Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution. Clinical and Vaccine Immunology.2016 Apr;23 (4):249-253. Link to article
2. European commission. Commission Implementing Decision (EU) 2019/1244 of 1 July 2019 amending Decision 2002/364/EC as regards requirements for HIV and HCV antigen and antibody combined tests and as regards requirements for nucleic acid amplification techniques with respect to reference materials and qualitative HIV assays (notified under document C (2019) (4632) ( 1 ). Official Journal of the European Union. Link to article
3. Ultrio Elite Package insert GDSS-IFU-000006 v. 5.0. Link to article
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