(313a) 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.