A Guide to Define Pool Size and Assay Cut-Off

Discovered in 1975, Parvo B19 virus was found to be highly contagious, causing a mild illness called the fifth disease or erythema infectiosum.It is primarily seen in children but can affect people of any age. While Parvo B19 doesn't cause life threatening illness in the population, exposure to Parvo B19 among immunocompromised patients can cause the development of chronic anemia.2

The Parvo B19 virus is known to be difficult to eliminate. It is a non-enveloped, small virus that is highly resistant to in-process inactivation (heat and detergents) and to filtration methods.Since many patients using plasma-derived products are immunocompromised, it became critical to identify plasma donations contaminated with parvo B19.

Mitigation strategies have been put in place to prevent high titer Parvo B19 from entering the fractionation pool. National regulatory authorities and the plasma industry have issued testing guidance for plasma for fractionation to lower the risk of Parvo B19 contamination.4 The Federal Drug Agency (FDA) guidance on Parvo B19 plasma screening tests was issued in 2009 and introduced in the European Pharmacopoeia. It recommends nucleic acid testing (NAT) be done on source and recovered plasma for fractionation.

In the United States and Europe, the FDA and European Medical Agency (EMA) require that the Parvo B19 concentration in manufacturing pools should not exceed 10000 IU/mL.5 A Parvo B19 cut-off value can be assigned to the screening test to identify donations exceeding the manufacturing threshold titer.

When defining the assay cut-off value, laboratories should consider the following:

Individual donation B19 titer, relative to the manufacturing pool size (specified maximum concentration determined by the plasma  manufacturer, which depend on the manufacturing pool size)

Pool size for screening

Quantitative range of assay cut-off

The following formula can be used to determine the assay cut-off:

Assay cut-off = Minimum B19 IU/mL to be flagged / screening pool size

However, in cases where the laboratory knows the required assay cut-off and needs to calculate the screening pool size, the formula would be:

Screening pool size = Minimum B19 IU/mL to be flagged / assay cut-off

Parvo B19 is a frequent contaminant in plasma donations. For the safety of plasma-derived products, the requirement for a universal B19 NAT screening as an in-process test for plasma was established in the US and Europe. While planning to start testing for it in your laboratory, it is important to establish a cut-off level for screening.

For more information on Parvo B19 Plasma screening and other best practices in pool size and assay cut-off, click here.

 

 

References

1. Juhl D, Hennig H. Parvovirus B19: What Is the Relevance in Transfusion Medicine? Front Med [Internet].2018 Feb;5(4): Link to article DOI: 10.3389/fmed.2018.00004

2. Florea AV, Ionescu DN, Melhem MF. Parvovirus B19 infection in the immunocompromised host. Arch Pathol Lab Med [Internet]. 2007 May;131(5):799-804. Link to article DOI: 10.1043/1543-2165(2007)131[799:PBIITI]2.0.CO;2

3. Marano G, Vaglio S, Pupella S, Facco G, Calizzani G, Candura F et al.Human Parvovirus B19 and blood product safety: a tale of twenty years of improvements. Blood Transfus.2015 Apr;13(12):184-96. Link to article DOI 10.2450/2014.0174.14

4. PPTA.QSEAL NAT Testing Standard. PPTA Global [Internet]. 2013 Jun; Version 2.0. Link to article

5. US Food & Drug Administration. Nucleic Acid Testing to Reduce the Possible Risk of Parvovirus B19 Transmission by Plasma-Derived Products. FDA [Internet].2009 Jul. Link to article

 

This information is intended for physicians and healthcare professionals only.

Product registration and availability vary by country. For more information on product availability, please contact us here.