Viral safety of C1-inhibitor NF.

Abstract We studied the efficacy of virus reduction by three process steps (polyethylene glycol 4000 (PEG) precipitation, pasteurization, and 15 nm virus filtration) in the manufacturing of C1-inhibitor NF. The potential prion removing capacity in this process was estimated based on data from the literature. Virus studies were performed using hepatitis A virus (HAV) and human immunodeficiency virus (HIV) as relevant viruses and bovine viral diarrhea virus (BVDV), canine parvovirus (CPV) and pseudorabies virus (PRV) as model viruses, respectively. In the PEG precipitation step, an average reduction in infectious titer of 4.5 log 10 was obtained for all five viruses tested. Pasteurization resulted in reduction of infectious virus of >6 log 10 for BVDV, HIV, and PRV; for HAV the reduction factor was limited to 2.8 log 10 and for CPV it was zero. Virus filtration (15 nm) reduced the infectious titer of all viruses by more than 4.5 log 10 . The overall virus reducing capacity was >16 log 10 for the LE viruses. For the NLE viruses CPV and HAV, the overall virus reducing capacities were >8.7 and >10.5 log 10 , respectively. Based on literature and theoretical assumptions, the prion reducing capacity of the C1-inhibitor NF process was estimated to be >9 log 10 .