Parvoviral Filtration: Step Order Matters! Including Tools to Ensure Success of Worst-Case Process Characterization Studies

Title: Parvoviral Filtration: Step Order Matters!

Including Tools to Ensure Success of Worst-Case Process Characterization Studies

Parvovirus filtration is rapidly replacing retrovirus filtration as the industry standard for virus removal in monoclonal antibody cell culture manufacturing processes. The mass and volumetric throughput of monoclonal antibodies (mAbs) in parvoviral filters has been found to be significantly lower than on retroviral filters due primarily to the smaller pore size. A variety of solutions have been tested to improve throughput with some success. One seemingly easy solution is to place the parvovirus filtration step at the end of the purification process such that the feed is the most highly purified pool. However it may be the mode of separation of the chromatography step immediately preceding the filter that gives this improvement rather than the number of upstream purification steps. In addition, while the step order change can improve throughput, it does not rid the parvoviral filter of its inherent sensitivity to changes in product concentration, flow rate, and operating temperature. These parameters are tested at worst-case during process characterization studies, which can result in failure due to this sensitivity. Here we present strategies for implementation of a new virus filter type as well as a new location in a downstream process and for success when testing worst-case parameters during the process characterization of a parvovirus filtration step. Through case studies we also address the question of whether it is the mode of separation of the upstream chromatography step or the number of purification steps preceding the filter that has the greater effect on throughput improvement.