(571f) Effect of Feed Solution Properties On Viral Filtration Performance

Viral safety is an essential component of biopharmaceutical products derived from cell lines of animal origin. One aspect of viral safety is the incorporation of viral clearance capability into the manufacturing process.  For example, nano-filtration is commonly employed to provide removal of a variety of large (e.g., retrovirus) and small (e.g., parvovirus) virus types. Parvovirus’s have a diameter of 18-26 nm, whereas a typical IgG antibody has a hydrodynamic diameter of 8-12 nm.  In order to achieve robust removal of these viruses while maintaining product throughput and minimal filtration area, viral filters are required to have a very narrow pore size distribution and are often sensitive to operating conditions.  Therefore, careful optimization of operating parameters will ensure a robust, economical and scalable virus removal step.

Scaled-down systems were utilized to model and optimize the performance of a variety of commercial viral filters.  Studies were performed evaluating the individual and combined effects of protein concentration, pH, ionic strength, and impurity levels on filter capacity, flux performance, and product recovery.  In addition, these results were used to determine the optimal location of a viral filtration step in the purification process.