Comparison of Bacterial Risk in Cryo AHF and Pathogen Reduced Cryoprecipitated Fibrinogen Complex

Abstract

Until November 2020, cryoprecipitated antihaemophilic factor (cryo AHF) was the only United States Food and Drug Administration (FDA)-approved fibrinogen source to treat acquired bleeding. The post-thaw shelf life of cryo AHF is limited, in part, by infectious disease risk. Concerns over product wastage demand that cryo AHF is thawed as needed, with thawing times delaying the treatment of coagulopathic patients. In November 2020, the FDA approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex for the treatment and control of bleeding, including massive hemorrhage, associated with fibrinogen deficiency. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (also known as INTERCEPT® Fibrinogen Complex, IFC) has a five-day post-thaw room-temperature shelf life. Unlike cryo AHF, manufacturing of IFC includes broad spectrum pathogen reduction (Amotosalen + UVA), enabling this extended post-thaw shelf life. In this study, we investigated the risk of bacterial contamination persisting through the cryoprecipitation manufacturing process of cryo AHF and IFC. Experiments were performed which included spiking plasma with bacteria prior to cryoprecipitation, and bacterial survival was analyzed at each step of the manufacturing process. The results show that while bacteria survive cryo AHF manufacturing, IFC remains sterile through to the end of shelf life and beyond. IFC, with a five-day post-thaw shelf life, allows the product to be sustainably thawed in advance, facilitating immediate access to concentrated fibrinogen and other key clotting factors for the treatment of bleeding patients.