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

Most PRT methods that have been implemented and are approved for use in the United States and outside the United States are based on the use of chemical additives to the blood products, which can be activated in specific ways to prevent nucleic acid replication of targeted pathogens and white blood cells (WBCs) in these products. 25 The nature of the compounds used in these approaches varies considerably based on method and include the use of riboflavin 134 and vitamin B2 as well as synthetically derived compounds such as amotosalen and amustaline, which are based on psoralen, acridine, and mustard hydrochloride derivatives, respectively. 135 In many cases, these agents and their breakdown products exhibit considerable toxicity and genotoxicity that must be considered in terms of likely patient population and effectiveness of both handling and removal methods intended to reduce exposure to patients and health care workers. 136 Processing requirements necessitated by the nature of the agents used have complicated the practical logistics of delivering blood products to patients. 118 Not all pathogens will be eliminated by the application of these processes Variable levels of PR are observed for bacteria and enveloped viruses depending on the method that is being applied. 137 Knowledge about what levels of inactivation are necessary to prevent disease transmission are not clear or uniform for all agents. 138, 139 Examples are now available from completed and ongoing routine use studies that suggest that while disease transmission may be significantly curtailed, some breakthrough events may still be anticipated including cases where pathogen loads in donated products may exceed inactivation potential 123 or where the PRT method may prove ineffective against specific types of resistant agents such as nonenveloped viruses. 140 Not all methods will deliver the same outcomes in pathogen load reduction capabilities; hence continued field evaluation of what is needed to significantly reduce the probability of disease transmission in areas where such diseases are endemic will be necessary to fully determine the extent of effectiveness. 131 Process control will be essential to assure reproducibility and reliability of these methods Significant efforts have been made by manufacturers to develop techniques that can be practically applied to treatment of PLT and plasma products in the routine blood bank setting. Such devices and processes need to account for practical factors including throughput, product specifications, media, product losses, timing of process steps, record keeping, and costs to manufacture disposables and equipment. Validation of these methods has required significant investment on the part of manufacturers yet concerns in each of these categories related to implementation remain and continue to be identified as these methods enter routine clinical use. 142 These processes will add cost Routine implementation in high-income countries where endemic disease and exposure are rare is likely to continue to be debated on the basis of cost and benefit. Advances in adoption are likely to result when these processes can serve low-income nations with significant blood safety concerns with affordable products made with high quality and low cost. Questions about implementation with patients who are most vulnerable and thus may benefit the most from these methods need to be asked. Such groups may include those receiving chronic transfusion suppo