Development of a pharmaceutical apotransferrin product for iron binding therapy

High-dose chemotherapy of patients with haematological malignancies results in extracellular iron accumulation and appearance of non-transferrin-bound iron, which is thought to predispose the patients to septic infections and contribute to organ toxicity. We describe the development of a human plasm a-derived apotransferrin product for iron binding therapy. The product is p urified from Cohn fraction IV of human plasma by two ion exchange chromatog raphy steps and ultrafiltration. The process comprises solvent detergent tr eatment as the main virus inactivation step and 15 nm virus filtration and polyethylene glycol precipitation as removal steps for physico-chemically r esistant infectious agents. Product characterization by electrospray and MA LDI-TOF mass spectrometry indicated no other chemical modifications than N- linked glycan chains and disulphide bonds, except minor oxidation. The puri ty of the product was more than 98%, main impurities being IgG, IgA and hem opexin. The product had intact iron binding capacity and native conformatio n. A stable liquid formulation for the finished product was developed. The product has proved safe and well tolerated in early clinical trials in iron binding therapy. (C) 2001 The International Association for Biologicals.