Pathogen inactivation - defining 'adequate' bacterial protection

Background and Objectives Clinical acceptance of pathogen inactivation technologies depends on the demonstration of product safety, a minimal effect on product efficacy and the range and degree of pathogen inactivation. The major rationale for pathogen inactivation of platelets is the prevention of transfusion-associated bacterial sepsis, a persistent problem despite multiple innovations to minimize and detect contamination. Materials and Methods Recent reports and an empirical model are used to describe our current understanding of the efficacy of pathogen inactivation in improving platelet transfusion safety. Results Optimized in vitro testing evaluated the efficacy of riboflavin/UV light (Mirasol (TM)), amotosalen/UVA (Intercept (TM)) and UVC irradiation (THERAFLEX (TM) UV platelets) systems to effect a 10(2) - > 10(6) fold reduction of a variety of bacterial species. All systems are less effective at inactivating bacterial spores. Reviewing reports on the level of pathogen inactivation at very low and high bacterial concentrations identifies areas for further scrutiny. Conclusions Clinical trials of pathogen inactivated platelets have focused on safety and clinical efficacy in terms of count increments and the prevention and treatment of bleeding. Little attention has been paid to efficacy in reducing the risk of bacterial transmission. Pathogen inactivation is expected to significantly reduce transfusion of contaminated platelet units, especially ones that are the result of low initial bacterial titres that are a systemic issue with the current testing methodology. Nevertheless, available data suggest that breakthrough cases of sepsis are likely and that their rates will vary substantially by technology.