Effects Of Solution Conditions On Virus Retention In A Commercial Virus Removal Filter

Open Access
Author:
Micklin, Matthew Robert
Area of Honors:
Chemical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Andrew Zydney, Thesis Supervisor
  • Andrew Zydney, Honors Advisor
  • Wayne Roger Curtis, Faculty Reader
Keywords:
  • chemical
  • engineering
  • virus
  • filtration
  • pharmaceutical
  • biotech
  • downstream
  • purification
Abstract:
Virus filtration is an essential part of the downstream purification process in the production of biotherapeutics and is used to remove small parvoviruses from the product solution. Virus filtration is typically thought to be strictly a size-based exclusion process; the possibility of adsorptive effects on virus retention has been given little attention. The objective of this study was to examine the effects of solution pH and ionic strength on virus retention using the Viresolve® NFP membrane. Bacteriophage ϕX-174 was used as a model parvovirus. The solution conditions were controlled by using appropriate buffers (acetate, phosphate, and carbonate) with different concentrations to prepare the virus feed solution. Virus retention was greatest at low pH and low ionic strength, conditions where there is a significant electrostatic attraction between the positively charged virus and the negatively charged membrane. In addition, these conditions showed very robust virus retention; there was no transient increase in virus transmission in response to a pressure disruption, a phenomenon which is known to occur at neutral pH due to diffusion of previously captured virus out of the membrane pores. Virus retention was also a function of protein fouling, likely due to changes in the underlying pore size distribution. These results provide new insights into the factors governing virus filtration for the preparation of safe biotherapeutics.