Development of the S-303 Pathogen Inactivation Technology for Red Blood Cell Concentrates.

ABSTRACT

Pathogen inactivation systems are in use in many European countries as routine procedures. However, a pathogen inactivation system for erythrocytes is currently not available. Although significant improvements have been made to decrease the incidence of transfusion-transmitted infections, risks remain for infectious disease agents specific to red blood cell concentrates, such as parasitic infections resulting in babesiosis and malaria. The pathogen inactivation system for erythrocytes utilizes S-303 and glutathione for the treatment of red blood cell concentrates. Preclinical studies to assess the pathogen inactivation efficacy and toxicology as well as preliminary clinical studies have been completed. Preclinical studies have shown log reduction for leukocytes, several viruses and bacteria in excess of 4 to 6 logs. Preclinical toxicology studies were conducted to enable the initiation of two phase III clinical studies in the USA for support of acute and chronic anemia. A second-generation system was developed after observation of an unexpected immune response in two chronic anemia patients. Preclinical pathogen inactivation studies, serological evaluations and a clinical study to evaluate survival of S-303-treated erythrocytes have been completed to support advanced development of the S-303 pathogen inactivation system. A functional system for the inactivation of red blood cell concentrates has been completed and is reaching clinical application.