Viral clearance is one of the important aspects in manufacturing of plasma and recombinant host-derived protein therapeutics. Manufacturers of biological drug products are required to demonstrate adequate viral clearance strategies during downstream purification to ensure patient safety and drug efficacy. Development of cost effective virus filtration process is an important goal of process development scientists. Single-use application and membrane cost due to unique sieving properties make virus filtration as of the most expensive unit operations at commercial scale manufacturing of therapeutic proteins. Throughput of virus filtration depends on two key features: Initial flux and flux decay. Membrane fouling due to presence of solutes in the load material leads to flux decay. Therefore, understanding the membrane fouling mechanism is critical to enhance virus filtration throughput.      Primary goal of this study was to better understand the impact of properties of product and product related impurities (e.g., high molecular weight species, charge variants) on the filtration capacity of widely used commercial VireSolve� Pro and PlanovaTM 20N virus filters. Work was focused on evaluating the impact of hydrophobic and electrostatic interactions between membrane and proteins on the membrane fouling. Monoclonal antibody (IgG1) and Fc-proteins were used as model proteins for this study. Solute properties were conditioned by varying protein composition and solution pH and conductivity of the load material. Filtration flux (L/m2/h) and throughput (kg/m2/h) were measured to evaluate filtration performance. The load material was characterized using SEC-HPLC, Dynamic light scattering, analytical ultracentrifugation, ELISA and quantitative PCR analysis.Key words: viral clearance, filtration, membrane fouling, antibody purification, electrostatic interaction, hydrophobicity

Understanding the interplay between antibody and membrane properties to enhance the filtration capacity of virus removal filters

247th National Meeting (2014)

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