Virus Filtration Optimization
“The pore size of a virus filter must allow the mAb, or other target molecules, to pass through, which limits the minimum pore size possible for viral removal filters,” said Anika Meyer, product manager, viral clearance, Sartorius Stedim Biotech.
Virus filters and Protein A resins are the most costly components in a bill of materials for a mAb production batch. Filters must be optimized to achieve the highest throughput without compromising the flow rate, and the desired log retention value for virus removal.
The virus filter, or inactivation method, must get adjusted to the hydrophilic or hydrophobic properties of the antibody, the isoelectric point, the tendency to aggregate, as well as to the viscosity under the conditions the filtration or inactivation will be performed. There is not one filter or method that does it all.
In practice the most robust solution, not necessarily the most economical solution, gets established. A robust solution allows the establishment of a platform process, which has its own economic impacts.
New generation virus filters have improved performance and robustness, however testing and validation can become more costly as larger volumes of more highly purified virus spike material are needed. Overall, the most important aspect is the positive impact the filters have on the production process cost of goods.
“High titer processes are posing new challenges for final virus filters as product concentration and viscosity increases. The identification of viruses smaller than 20 nm also will challenge the currently used viral clearance strategies.
“Additional economic challenges are related to the discussion of extending viral clearance strategies upstream to raw materials and cell culture media. In this scenario, a filter or inactivation method does not need to balance between virus removal efficiency and target protein transmission. New, cost-efficient virus filters specifically designed for these applications will help to overcome economic constraints.”