Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)

Atreya, Chintamani; Glynn, Simone; Busch, Michael; Kleinman, Steve; Snyder, Edward; Rutter, Sara; AuBuchon, James; Flegel, Willy; Reeve, David; Devine, Dana; Cohn, Claudia; Custer, Brian; Goodrich, Raymond; Benjamin, Richard J.; Razatos, Anna; Cancelas, Jose; Wagner, Stephen; Maclean, Michelle; Gelderman, Monique; Cap, Andrew; Ness, Paul

The second technology tested was PRT using amustaline (S-303). This approach to target nucleic acid-containing pathogens does not require photochemical activation through the use of a small molecule (amustaline, S-303) that reacts rapidly with nucleic acid and then decomposes into unreactive byproducts. Published PI results show that amustaline treatment of RBCs effectively inactivates multiple blood-borne pathogens (≥4 log) and residual WBCs. 147, [166] [167] [168] [169] To prevent nonspecific reactions of amustaline with RBC membrane proteins, GSH is used in conjunction with the amustaline treatment. In two different two-center studies we analyzed the viability of RBCs prepared with a second-generation process and stored for 35 days was evaluated in two different blood centers in a Phase I and II clinical trial design, respectively. Both were single-blind randomized, controlled, two-period crossover studies where amustaline or control RBCs were prepared in random sequence and stored for 35 days followed by 51 Cr tagging and 24-hour RBC posttransfusion recovery, mean life span, median lifespan (T 50 ), and life span AUC analyzed. The mean 24-hour posttransfusion recovery of test and control RBCs was comparable (83.2% AE 5.2% and 84.9% AE 5.9%, respectively; p = 0.06), and consistent with the FDA criteria for acceptable RBC viability. There were differences in the T 50 between test and control RBCs (33.5 and 39.7 days, 17% difference; p < 0.001) but it was within published reference ranges of 28 to 35 days. The AUC (percent surviving × days) for test and control RBCs was similar (22.6 and 23.1% surviving cells × days, respectively; p > 0.05). After infusion of test RBCs, there were no clinically relevant abnormal laboratory values or adverse events.