The medical community feared that the formation of such inhibitors to the product would render the patient more difficult to treat effectively (Aledort, Dietrich, Levine interviews). Behringwerke's heat-treated product was also considerably more expensive, and German insurance companies covered its cost only for special circumstances (Weidmann and Hoechst 1993; Federal Minister of Health 1992). Behringwerke initiated testing the pasteurized product for inactivation of NANB hepatitis in 1985, and a successful clinical trial was completed during 1986–1987 (Weidmann and Hoechst 1993).

Studies by U.S. Plasma Fractionation Companies

There were basically three methods utilizing heat for viral inactivation used by U.S. manufacturers in the early 1980s: (1) In 1979, the Baxter Healthcare company initiated studies on heat inactivation of AHF concentrate using a "dry heat" process. The dry heat process involved the application of heat at a specified temperature and time to the concentrate in the lyophilized (freezedried) state (Persky pers. com. 1995); (2) the "wet heat" process, a term coined by Alpha Therapeutics, involved suspending powder of lyophilized concentrate in heptane solvent and heating at 60°C for 20 hours. Following the heating process, the solvent was removed and the concentrate revialed (McAuley pers. com. 1995); and (3) in liquid pasteurization, Factor VIII, albumin, or other proteins in the completely soluble liquid state were heated with the addition of various stabilizers.

By the early 1980s, all of the plasma fractionators had initiated studies on inactivation by application of various amounts of heat for different durations of time (McAuley pers. com. 1995; Persky pers. com. 1995; Leahy pers. com. 1995; Hammes pers. com. 1995). They also began experimenting with the addition of different stabilizers and organic solvents to protect the protein and enhance the heat effect. There was, however, little if any communication between the different manufacturers regarding the results of the ongoing experiments, because of antitrust laws, regulations, and the normal business consideration of competitive advantage (Bacich pers. com. 1994; Feldman pers. com. 1994; Hammes pers. com. 1995).

Problems of Viral Inactivation Development

As the Behringwerke experience illustrates, to some extent the possibility of using heat to inactivate viruses in AHF concentrate, as used in other plasma derivatives (e.g., albumin), would be accompanied by three major concerns that impeded progress. The first concern was that heat would denature the labile

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