Guidelines on estimation of residual risk of HIV, HBV or HCV infections via cellular blood components and plasma, Annex 4, TRS No 1004

Overview

Blood-screening assays are differentiated by distinct categories. The residual risk of missing viral infections using any screening assay is mainly due to the viraemic phase of the diagnostic window period (vDWP) for each assay – the mean size of which varies between different assay categories. Another component of the residual risk is the virus epidemiology of the donor population (consisting of repeat and first-time donors) with the rate of new infections (incidence) in donors determining the probability of window-period donations. The residual risk per donation from the repeatdonor subpopulation may be used to extrapolate the respective risk for the firsttime donor subpopulation, for which incidence data are often unavailable. The residual risk affects recipients of non-pathogen-inactivated blood components to whom viruses may be transmitted. It also determines the potential viral load of plasma pools used for the manufacturing of plasma-derived medicinal products (PDMPs); this potential contamination level needs to be assessed against the viral inactivation or reduction strategies in the manufacturing process.

These WHO Guidelines provide advice on estimating the residual risk of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) being present in cellular blood components and plasma. This estimation has implications for the safety of non- (or incompletely) pathogeninactivated blood components or plasma products. These WHO Guidelines therefore aim to enable the approximate estimation of residual risks based on limited data, while recognizing that more precise models have been published in the scientific literature. Nevertheless, it is hoped that this document can help in rationalizing decisionmaking on the use of plasma units for fractionation.

Since the performance of screening assays is one of the key elements in minimizing the residual risk of blood components and guaranteeing the safety of plasma products, these WHO Guidelines also contain advice on the assessment of in vitro diagnostics (IVDs) in studies using specimen panels from the region (Appendix 1). Such targeted performance evaluations for new assays may be performed prior to the acceptance of a new blood-screening assay in a country.