Stored red blood cell viability is maintained after treatment with a second-generation S-303 pathogen inactivation process

BACKGROUND: Transfusion‐transmitted infections and immunologic effects of viable residual lymphocytes remain a concern in red blood cell (RBC) transfusion. Pathogen reduction technologies for RBC components are under development to further improve transfusion safety. S‐303 is a frangible anchor‐linker‐effector with labile alkylating activity and a robust pathogen reduction profile. This study characterized the viability of RBCs prepared with a second‐generation S‐303 process and stored for 35 days. STUDY DESIGN AND METHODS: This was a two‐center, single‐blind randomized, controlled, crossover study in 27 healthy subjects. S‐303 (test) or control RBCs were prepared in random sequence and stored for 35 days, at which time an aliquot of radiolabeled RBCs was transfused. The 24‐hour recovery, RBC life span, and in vitro metabolic and viability variables were analyzed. RESULTS: The mean 24‐hour RBC recovery and hemolysis of test RBCs were similar to control RBCs and were consistent with the Food and Drug Administration (FDA) guidance for RBC viability. The mean differences in life span and median life span (T50) of circulating test RBCs were 13.7 and 6.8 days, while the mean difference in the area under the curve of surviving RBCs was 1.38%, in favor of control RBCs. There were no clinically relevant abnormal laboratory values after the infusion of test RBCs. All crossmatch assays of autologous S‐303 RBCs were nonreactive. CONCLUSIONS: RBCs prepared using the S‐303 pathogen inactivation process were physiologically and metabolically suitable for transfusion after 35 days of storage, met the FDA guidance criteria for 24‐hour recovery, and did not induce antibody formation.