The Food and Drug Administration's perspective on plasma safety.

Abstract

The balance between acceptable plasma-product safety and the demand for those products involves a finite (but very low) level of risk for transmitting infectious diseases. The Food and Drug Administration (FDA) has focused on the use of a triple safety net to provide safe plasma products. This safety net includes donor selection, plasma testing, and inventory hold (look back and retrieval). Although each part of this safety net contributes to reducing the overall viral load in plasma products, each part may not contribute equally to a safe product in all cases. Donor selection is not universally reliable, and plasma antibody testing can be negative for a disease during its seroconversion window period. However, inventory hold (especially for first-time donors) has added to the usefulness of the other safety-net components. This review article provides a brief overview of each safety component and subsequent related improvements, including advances in antibody testing for donor screening and the addition of PCR testing for donor minipools and viral inactivation procedures during plasma-product manufacturing. Dilemmas created by this safety approach are also discussed, including the debate over zero risk of product versus cost and the impact on donors when they test positive for the various diagnostic tests used. Other dilemmas include the decision to include or exclude currently used plasma tests with the advent of polymerase chain reaction (PCR) testing, expanded use of PCR to test for other plasma-transmitted diseases that impart limited risk to recipients, and the role of antigen/antibody interactions in plasma products, especially as the latter relate to plasma-pool and final-product testing.