Efficacy of viral clearance methods used in the manufacture of activated prothrombin complex concentrates: focus on AUTOPLEX (R) T

Various methods are described for the elimination of infectious viruses fro m activated prothrombin complex concentrates (aPCCs) and for the analysis o f the final products (AUTOPLEX(R) T and FEIBA(R) VH). Viruses of concern in human plasma-derived products are enveloped (hepatitis B and C, cytomegalo virus, Epstein-Barr virus, and human immunodeficiency virus [HIV]) and none nveloped (hepatitis A and parvovirus B19). Donated blood used for AUTOPLEX( R) T is screened for antihepatitis C, HBsAg, anti-HIV types 1 and 2, and p2 4 antigen. Plasma pools utilized for raw materials are also tested by PCR f or HIV and hepatitis C virus. Partial virus inactivation and partitioning a re achieved by purification of the aPCC. Further reduction of virus infecti vity is accomplished by lyophilization and dry-hear treatment. Each step un dergoes virus elimination validation studies in which a relevant sample is 'spiked' with the appropriate virus or model virus. The total reduction in virus from raw material to final product can then be calculated. For AUTOPL EX(R) T the cumulative log(10) reduction factors for several viruses vary f rom 4.2 to 14.3. This ensures an exceptionally high margin of safety. Defin itive evidence for product safety was obtained by clinical observation of t reated patients. The viral inactivation process of AUTOPLEX(R) T involves a four-tier viral safety program, including Cohn alcohol fractionation and d ry-heat treatment, in place of the two-stage vapour-heating process for FEI BA(R).