Pathogen inactivation of platelets with a photochemical treatment with amotosalen HCl and ultraviolet light: process used in the SPRINT trial

BACKGROUND: A photochemical treatment (PCT) system has been developed to inactivate a broad spectrum of pathogens and white blood cells in platelet (PLT) products. The system comprises PLT additive solution (PAS III), amotosalen HCl, a compound adsorption device (CAD), a microprocessor-controlled ultraviolet A light source, and a commercially assembled system of interconnected plastic containers. STUDY DESIGN AND METHODS: A clinical prototype of the PCT system was used in a large, randomized, controlled, double-blind, Phase III clinical trial (SPRINT) that compared the efficacy and safety of PCT apheresis PLTs to untreated apheresis PLTs. The ability of multiple users was assessed in a blood center setting to perform the PCT and meet target process specifications. RESULTS: Each parameter was evaluated for 2237 to 2855 PCT PLT products. PCT requirements with respect to mean PLT dose, volume, and plasma content were met. Transfused PCT PLT products contained a mean of 3.6 x 10(11) +/- 0.7 x 10(11) PLTs. The clinical process, which included trial-specific samples, resulted in a mean PLT loss of 0.8 x 10(11) +/- 0.6 x 10(11) PLTs per product. CAD treatment effectively reduced the amotosalen concentration from a mean of 31.9 +/- 5.3 mu mol per L after illumination to a mean of 0.41 +/- 0.56 mu mol per L after CAD. In general, there was little variation between sites for any parameter. CONCLUSIONS: The PCT process was successfully implemented by 12 blood centers in the United States to produce PCT PLTs used in a prospective, randomized trial where therapeutic efficacy of PCT PLTs was demonstrated. Process control was achieved under blood bank operating conditions.