Effective poxvirus removal by sterile filtration during manufacture of plasma derivatives.

As a consequence of the September 2001 terrorist events, programs to protect against further such acts including potentially the use of biological warfare agents have been launched in the USA and elsewhere. As part of these initiatives, Vaccinia virus was procured for the pre-emptive vaccination of key personnel against smallpox as well as population-wide protection after an eventual exposure. The introduction of this live virus into a population at a relatively large scale represents a theoretical challenge for the safety of the blood supply, and potentially for plasma for fractionation. To strengthen further the demonstration of safety margins for plasma derived products against Vaccinia virus, the capacity of sterile filtration procedures to remove the virus was investigated. An infectivity assay for the Vaccinia virus strain which represents the majority of smallpox vaccine stocks available currently was used to investigate the potential removal of this virus by sterile filtration processes during the manufacture of plasma derivatives. Vaccinia virus behaves as predicted based on its size, i.e., an artificially added virus load is removed about 10,000-fold by the sterile filtration procedures tested. As the current investigation covered a range of different protein concentrations, filter materials and filters from different manufacturers, the results obtained are considered to be widely applicable. The current investigation supports further the high safety margins of plasma derivatives against any potential Vaccinia virus content of plasma for fractionation. As the large size is a general feature of Orthopox viruses, the results would also provide assurance against poxviruses identified more recently, for example, Monkeypox virus. (c) 2005 Wiley-Liss, Inc.