Supervisor(s): Dr. David Latulippe

Project Description: Therapeutic viruses represent a promising new class of biotherapeutics with applications ranging from cancer treatment to novel vaccines. As demand for these products grows, efficient large-scale production and purification becomes critical. A current challenge during purification of some therapeutic viruses is the terminal sterile filtration step (required to ensure product safety and regulatory compliance), where a significant loss of product can occur due to membrane fouling. To address this, we have studied how different process and product variables can influence filtration performance and have identified various mechanisms which cause loss of virus. Through the use of a small-scale constant flux filtration system, we have performed filtration tests using various membrane types, different viruses, and under controlled solution conditions. Then, using analytical techniques such as transmembrane pressure measurement, virus titer assays, and post-filtration microscopy of the membrane we measured the degree to which membrane fouling and loss of virus occurred under the test conditions. From this data, we have identified key variables influencing the filtration process which include pore size, membrane material, impurities in solution, the type of virus, and more. A proper understanding of these variables is critical to enable efficient large-scale production, and will aid manufacturers or any other researchers working in the field of virus production.