Methods for the Production of Clinically Effective Intermediate and High‐Purity Factor‐VIII Concentrates

S ummary . An intermediate‐ and a high‐purity factor‐VIII concentrate for clinical use have been prepared on a large scale by cryoethanol precipitation, extraction of the precipitate with tris buffer, and fractionation with polyethylene glycol. With bench‐scale fractionation, the intermediate material is 22‐fold purified on the average and the mean yield is 63%, while the high‐purity factor VIII is 274‐fold purified with a mean yield of 62%. With fractionation of 100 1. or more of fresh frozen plasma, the intermediate material shows a 30% yield and 14‐30‐fold purification; the high‐purity factor VIII shows an 18% yield and 125–350‐fold purification using 5.8 g/100 ml polyethylene glycol (PEG). A yield of nearly 30% should be possible with PEG, 4–5 g/100 ml. Both factor‐VIII preparations are stable for over a year in the lyophilized state at 4°C. Other plasma proteins can be fractionated from the residual plasma by routine Cohn procedures.