Biochemical Characterization and Stability of a New Fibrinogen Concentrate (BT524) Manufactured Using an Innovative...

Human plasma is utilized in the production of life-saving pharmaceuticals, including fibrinogen, a key player in clot formation, tissue repair, and hemostasis. Fibrinogen deficiency results in impaired blood clotting and potentially severe hemorrhagic events. Fibrinogen concentrate or cryoprecipitate are the preferred options for fibrinogen replacement therapy. Both increase plasma fibrinogen levels, but utilization of fibrinogen concentrate is advantageous. It offers enhanced pathogen safety through manufacturing procedures that remove or inactivate viruses or prions potentially present in human plasma.

We developed a novel manufacturing process that yields a fibrinogen concentrate (BT524) and coagulation factor VIII (Haemoctin^® SDH) in one workflow. This process contains several virus inactivation steps, including an innovative UV-C irradiation and a cation exchange chromatography (CEX) step for prion removal.

While successfully inactivating potential viral contamination, UV-C irradiation showed no influence on fibrinogen structure and composition, and no formation of neoantigenic structures could be identified. Fibrinogen concentrate (BT524) contained almost exclusively fibrinogen with activity close to 100%, very low numbers of sub-visible particles and lacked measurable thrombogenic activity. The stability study of clinical material demonstrated a stable product for five years under several storage conditions. With a solubility at room temperature of 2-4 min upon reconstitution using the nextaro^®v transfer device, the fibrinogen concentrate is almost immediately ready to use. The reconstituted solution demonstrated physico-chemical stability for 24 h.

Fibrinogen concentrate (BT524) generated using the novel manufacturing process yielded a product of high quality, purity and virus safety. In addition, it offers excellent solubility, long-term stability and high activity. The integration of shared process steps with Haemoctin^® SDH facilitates a more ethical and efficient utilization of human blood plasma. In clinical trials, the potency, safety and tolerability of the manufactured fibrinogen concentrate were demonstrated.