Removal of small nonenveloped viruses by antibody-enhanced nanofiltration during the manufacture of plasma derivatives.

Background: Filters with nominal pore sizes in the nanometer range are well-established tools for enhancing the virus safety margins of plasma-derived products, yet intrinsically less successful for smaller viruses such as hepatitis A virus (HAV) and human parvovirus B19 (B19V). The formation of virus-antibody complexes increases the effective size of these smaller viruses and would thus improve their removal by nanofiltration. While the principle of virus removal by antibody-dependent nanofiltration has been demonstrated with animal antisera and viruses spiked into human plasma product intermediates, the significance of these results remains unclear due to the potential contributions of xenoanti-bodies and/or heteroagglutination in such heterologous systems.