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

Proactive surveillance and research to evaluate responses to potential EID threats to blood safety have been adopted through collaborative initiatives of NIH, FDA, CDC, AABB, and blood research organizations. [5] [6] [7] An unintended consequence has been the identification of agents found through viral discovery programs using metagenomics technologies that can theoretically be transmitted by transfusion but which, upon subsequent investigation, prove not to be (Fig. 1 ). The most striking example of this was xenotrophic murine leukemia-related virus, which was reported to be associated with prostate cancer and later chronic fatigue syndrome and to be present in the blood of asymptomatic blood donors. 17 Intensive research consuming much time and money subsequently determined that xenotrophic murine leukemiarelated virus did not affect humans and was a laboratory contaminant from cell lines that contained this murine virus. 18 These experiences led to the US National Heart, Lung and Blood Institute (NHLBI) and FDA to convene workshops focused on proactive but rational and systematic responses to EIDs. 6, 7 The Alliance of Blood Operators developed a "riskbased decision-making" process that includes formalized methods for quantifying risk and evaluating interventions. 19 The 2015 to 2017 ZIKV pandemic is illustrative of the ongoing challenge of balancing timely and precautionary responses to emerging TTI threats with logistic and economic considerations. As the epidemic expanded in the Americas and the association of ZIKV with severe fetal outcomes emerged along with several cases of probable TT, the FDA mandated implementation of individual-donation (ID)-NAT or PRT of PLTs throughout the United States in 2016. 11, 12 After 2 years of ID-NAT with very low yield at an annual cost of $137 million, the FDA ZIKV policy was revised to allow for minipool NAT with ID-NAT triggered during future epidemics, similar to successful screening for WNV. Nonetheless, ZIKV testing now represents a theoretical benefit at a high cost, precipitating consideration of regional screening policies and an urgent need to further define "tolerable risk" in the blood safety arena. 20 Pathogen reduction: an overview of policy issues-Steve Kleinman, MD Speaker's summary: Pathogen inactivation and/or reduction should be viewed in the context of shifting the blood safety paradigm from reactive to proactive thereby providing insurance against known and unknown pathogens that may enter the blood supply or are currently un(der)recognized. Based on the positive experience of PI for plasma derivatives (e.g., no HIV, HCV, or HBV transmission since 1987), it seems reasonable to apply this safety paradigm to blood components. Of note, a consensus conference held in Canada in 2007 issued recommendations in favor of rapid adoption of a PI technology even if it could not be applied to the full range of blood components. Despite these recommendations, PI technology for PLTs has been slow to be adopted in the United States. As described in Table 1 , the reasons for this are many but it appears that the predominant impediment has been cost.