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

Speaker's summary: Despite the implementation of improved diagnostic screening and donor selection, the residual risk of transmission of new emerging pathogens and bacterial contamination persists. PR of blood components may be capable of proactively reducing and/or eliminating the chance of disease transmission by transfusion. PR could replace the current paradigm of serial introduction of diagnostic tests as new microorganisms with potential TT are recognized. PR for RBC and WB products remains a major challenge in the development of safe blood products for transfusion and it is of major interest in the context of chronic transfusion protocols. The first technology evaluated was the use of riboflavin/UV (80 J/mL RBC) light (Mirasol) system for PR of WB. The riboflavin/UV light PR technology (Mirasol PRT system, or Mirasol) method is based on irreversible nucleic acid damage mediated by electron transfer processes at sites where riboflavin-guanine base chemistry occurs. 153, 154 Our group and others have already published significant information on the RBC viability of PR WB-derived RBCs in vitro in the context of high-dose illumination resulting in significant PR. 84, [154] [155] [156] [157] [158] [159] [160] [161] [162] [163] [164] These sets of data indicate that PR of WB is possible albeit at a loss of RBC viability in vitro as assessed by hemolysis, ATP levels, and potassium leakage and in vivo as assessed by 24-hour recovery and survival analyses. 155, 156 Through a two-center clinical trial, our combined data consistently support that riboflavin/UV light-treated RBCs stored for 21 days after being generated from Mirasol-treated WB maintain adequate levels of 24-hour recovery as assessed by 51 Crtagged circulatory RBC survival analysis. As anticipated, there was decreased in vivo viability of poststorage riboflavin/UV light RBCs compared to data obtained from the same donors similarly stored untreated RBCs. The overall 24-hour recovery, survival, T 50 , and area under the curve (AUC) of Mirasol RBCs were reduced by 9.9, 25.9, 36.9, and 16.5%, respectively, compared to the subjects untreated control RBCs. 165 As expected, the percentage of RBC hemolysis significantly correlated with the 24-hour recoveries of the control RBCs but not with their T 50 survivals, suggesting that both hemolysis and 24-hour recoveries measured the destruction of a population of cells that did not survive storage. In contrast, there was no similar correlation between percent hemolysis and recoveries of Mirasol RBCs nor between their T 50 and percent hemolysis. However, for the Mirasol RBCs, there was a significant correlation between ATP levels and 24-hour recoveries, but a similar association was not found for control RBCs.