viruses in AHF concentrate. Each plasma fractionation company subjected the AHF concentrate to varying temperatures and conditions for different durations.

Each company used stabilizers to protect the Factor VIII against the heat, but there was uncertainty whether the stabilizers also provided protection for pathogens as well. Using stabilizers such as sucrose resulted in a less than 20 percent loss of potency (Hwang 1982). Each of the manufacturers also initiated chimpanzee studies to determine if the hepatitis virus had been inactivated. Alpha Therapeutics reported that they had also looked for evidence of neoantigenicity but found none after heat treatment (McAuley 1994).

Testing for the Effectiveness of the Inactivation Process

As stated above, the major rationale for developing a viral inactivation procedure for AHF concentrate was to eliminate the hepatitis viruses. Proof that hepatitis had been inactivated, however, required inoculating the treated AHF concentrate into chimpanzees, a time-consuming, expensive, and resource-intensive effort. From 1981 through 1984 each of the plasma fractionators initiated chimpanzee studies to determine whether their viral inactivation processes inactivated HBV and NANB hepatitis virus. The results of initial studies conducted by Armour Pharmaceutical indicated that HBV was not completely inactivated by their heat treatment process, but that NANB was (Feldman pers. com. 1994). Armour Pharmaceutical was licensed for a process in January 1984 that was proven to inactivate NANB hepatitis in chimpanzee studies; but the company was unable to successfully inactivate HBV with their initial heat treatment process (Leahy pers. com. 1995; Rodell interview).

FDA Approval and Licensing of Treated Factor VIII

Table 4.1 summarizes the dates of license application and the FDA's approval of each plasma fractionator's heat-treated Factor VIII concentrate. Baxter's licensing was accomplished in only 8 months and licensing for the other fractionators took about 12 months from initial application. All plasma fractionators were licensed for sale of Factor VIII concentrate by February 1984. Upon licensure of the change in processing of the AHF concentrate products, the plasma fractionators immediately began producing a proportion of their production output using the added heat treatment step (Hammes pers. com. 1995; Leahy pers. com. 1995; McAuley pers. com. 1995; Persky pers. com. 1995). The four relevant plasma fractionators claim to have begun processing and distributing heat-treated AHF concentrate immediately after obtaining FDA licensure. However, none of the companies had entirely converted their



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