The past, present and future of blood plasma fractionation.

Edwin Cohn, appointed to the Harvard Medical School in 1920, was commissioned by the United States military in 1940 to develop a stable albumin solution to treat blood/plasma loss from battlefield injury. Albumin was first produced at the Harvard pilot plant using Cohn's five variable, ethanol precipitation process which was rapidly transferred to private industry for industrial manufacture. For the past decades IgG has been used to treat multiple conditions and has become the industry driver whilst albumin is now a low-price commodity. The development of purification techniques, particularly chromatography, spurred the manufacture of coagulation factors for haemophilia and other proteins from Cohn fractions, leading to the current, unique roster of multiple, essential, plasma-derived medicines. The major cost in fractionation is for plasma, making recombinant and other non-factor alternatives a challenge for the industry. Plasma-derived haemophilia therapies are largely redundant in Western economies, although other products, including prothrombin complex, alpha-1 anti-trypsin, fibrin sealant, provide essential treatments. The established industry is also challenged by potential alternatives to IgG. Despite the plethora of alternative manufacturing technologies, Cohn fractionation in combination with "upstream" harvesting of other proteins through other technologies and "downstream processes" which incorporate unit operations for virus safety is the global industry standard.