(97a) Improving Virus Filter Performance through Pretreatment By Membrane Adsorbers

Validation of adequate virus clearance is essential in the manufacture of biopharmaceutical products. Virus filtration is routinely used to ensure the high level of virus clearance required for products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The for-mation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hy-drophobic interaction membrane adsorber was the most effective in minimizing flux de-cline during virus filtration. Ion exchange membranes may also be effective if the mono-clonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when com-pared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. Understanding the concentration dependence on the formation of reversible aggregates is important during the purification of monoclonal antibodies.