Virus Safety of Blood and Plasma Products: From Established Threats to Emerging Uncertainties

Following virus transmissions associated with plasma-derived medicinal products (PDMPs) particularly in the 1980s and 1990s, product safety was substantially improved through the "Safety Tripod": deferral of higher risk donors, testing of plasma for infectious disease markers, and, quantitatively most importantly, pathogen removal and inactivation steps within their industrial manufacturing processes. As a result, virus transmissions by PDMPs have not been reported for many years, including emerging viruses not even tested for. Blood components for transfusion also rely on donor deferral and donation testing, but unlike PDMPs they do not enjoy a manufacturing process that provides for robust virus reduction. Although sensitive nucleic acid tests have reduced HIV, HBV, and HCV transmission risks to below one in a million, additional screening has been required for emerging or newly recognized viruses such as West Nile virus or hepatitis E virus, yet transfusion-transmitted infections still occur. Advances in virology now indicate that known viruses represent only a small fraction of those in circulation, some of which may pose risks after long incubation periods or in immunocompromised patients. As medical progress, particularly in oncology, increases the population of immune-deficient individuals, more dependable blood and plasma safety margins are needed. Implementing virus reduction across PDMPs and blood components represents a science-based, economically reasonable strategy that should inform future regulatory requirements.