History of plasma-product safety.

The evolution of transfusion or infusion therapies for diseases requiring specific protein replacements (e.g., hemophilia A and B and severe combined immunodeficiency syndrome) was dramatic over the second half of the 20th century. Unfortunately, it was accompanied by extreme manifestations of transfusion-transmitted diseases, such as human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. The milestones of both the replacement therapies and the associated diseases are discussed in this presentation, which focuses on the technologic advances that resulted in even more "pure" replacement therapies for plasma-protein diseases. From donor screening to the development of viral attenuation techniques, every facet of production for these products was impacted by the exigent push for viral safety created by HIV and hepatitis. Almost invariably, this negatively affects total product yield. At the beginning of the 21st century, success in making plasma products safe from recognized and potential pathogens has dramatically increased societal pressures to produce a zero-risk, plasma-derived protein therapy. However, past improvements and low theoretic risks for future pathogen contamination have increased product cost. This is associated with a possible decrease in the overall supply of these plasma proteins because of the reduced numbers of acceptable donors and the loss of protein from expanded attenuation technology. These impacts and the role of dynamic societal and scientific pressures on these decision processes are discussed.