Removal of microorganisms from cell culture media

Abstract

Compositions and methods are provided for removing viral contaminants from a chemically defined cell culture medium. Compositions provided herein are resistant to or exhibit reduced fouling by one or more components in a chemically defined cell culture medium.

What is claimed is: 
     
         1 . A method of removing one or more viral contaminants from a chemically defined cell culture medium, the method comprising:
 a. providing a chemically defined cell culture medium; and   b. filtering the chemically defined cell culture medium through a porous membrane, prior to or during transfer of the medium into a bioreactor, wherein the porous membrane is a PES membrane, a PVDF membrane, or a cellulosic membrane and wherein the porous membrane has a surface treatment comprising a cross-linked polymer, the cross-linked polymer comprising a diacetone acrylamide and one or more non-acrylamides;   
       wherein the level of one or more viral contaminants in the chemically defined cell culture medium inside the bioreactor is lower than the level prior to filtering the medium through the membrane. 
     
     
         2 . The method of  claim 1 , wherein the porous membrane is an asymmetric membrane. 
     
     
         3 . The method of  claim 1 , wherein the one or more non-acrylamides is polyethylene glycol diacrylate. 
     
     
         4 . The method of  claim 1 , wherein the polymer is directly coated on a surface of the porous membrane using an energy source. 
     
     
         5 . The method of  claim 4 , wherein the energy source is selected from the group consisting of heat, electron beam, ultraviolet light and gamma radiation. 
     
     
         6 . The method of  claim 1 , wherein the porous membrane is incorporated into a device. 
     
     
         7 . The method of  claim 6 , wherein the device is in a format selected from a disc, a pleated cartridge, a spirally wound cartridge, and a multi-plate flat sheet. 
     
     
         8 . The method of  claim 1 , wherein the chemically defined cell culture medium is selected from the group consisting of Lonza Power CHO, CD Opti CHO, EMD Millipore Cellvento CHO 100 and Cellvento CHO 200. 
     
     
         9 . The method of  claim 1 , wherein level of one or more viral contaminants following step (b) is reduced by at least 1 Log 10  reduction value (LRV) or at least 4 Log 10  reduction value (LRV) or at least 6 Log 10  reduction value (LRV). 
     
     
         10 . The method of  claim 1 , wherein the filtering step is carried out for a period of less than 24 hours. 
     
     
         11 . The method of  claim 1 , wherein the filtering step is conducted at a temperature ranging from 20° C. to 25° C. 
     
     
         12 . The method of  claim 1 , wherein a normal flow filtering step is conducted at a temperature ranging from 20° C. to 25° C. 
     
     
         13 . The method of  claim 1 , wherein the filtering step is conducted at a pH ranging from 4 to 8. 
     
     
         14 . A method of reducing the fouling of a virus retentive membrane by one or more components in a chemically defined cell culture medium during filtration, the method comprising:
 a. providing a virus retentive membrane; and   b. modifying a surface of the virus retentive membrane with a polymer comprising crosslinked monomers of diacetone acrylamide and one or more non-acrylamides monomers,   
       wherein the fouling of the modified membrane by one or more components in a chemically defined cell culture medium is reduced relative to an unmodified membrane. 
     
     
         15 . The method of  claim 14 , wherein the virus retentive membrane is a PES membrane, a PVDF membrane, a cellulosic membrane or a nylon membrane. 
     
     
         16 . The method of  claim 14 , wherein the one or more non-acrylamide monomer is PEGDA.