Virus filtration of cell culture media

Abstract

The invention relates to a method for removing a viral contaminant from a preparation, being a cell culture medium or at least a component of a cell culture medium. The method comprises subjecting said preparation to filtration for at least about 24 hours through a virus filter having an effective pore size of maximum about 75 nm. Further, the invention relates to the use of a virus filter in filtration of at least about 24 hours, wherein the virus filter has an effective pore size of maximum about 75 nm for the removal of viral contaminant from a preparation, being a cell culture medium or at least a component of a cell culture medium. In some embodiments the filtration according to the invention operates at a volumetric capacity of at least about 2000 L/m 2 . Further, the invention relates to the use of a preparation, being a cell culture medium or at least a component of a cell culture medium obtainable according to method of the invention for cell culture; pharmaceutical, diagnostic and/or cosmetic preparations as well as in food preparations.

1 .- 14 . (canceled) 
     
     
         15 . An apparatus comprising a bioreactor and a virus filter, wherein the virus filter is inline of the medium feed line of the bioreactor, wherein the virus filter has an effective pore size of maximum 75 nm, and wherein the virus filter is for removing a viral contaminant from a preparation, said preparation being a cell culture medium or at least one component of a cell culture medium. 
     
     
         16 . The apparatus of  claim 15 , wherein the bioreactor is a chemostat reactor, a perfusion reactor, or a fed batch reactor. 
     
     
         17 . The apparatus of  claim 15 , wherein the filter comprises two or more filters arranged in series, in parallel, or both. 
     
     
         18 . The apparatus of  claim 17 , wherein the filter comprises two filters arranged in parallel in a system of tubes comprising a Y-shaped junction and wherein each filter is in fluid communication with a branch of the Y-shaped junction and a preparation supply source. 
     
     
         19 . The apparatus of  claim 15 , wherein the virus filter is autoclavable. 
     
     
         20 . The apparatus of  claim 15 , wherein the cell culture medium is a cell culture medium comprising a soy hydrolysate or a cell culture medium comprising animal derived components. 
     
     
         21 . A cell culture medium prepared by a method comprising
 a) subjecting a preparation to filtration for at least about 24 hours through a virus filter having an effective pore size of maximum 75 nm, wherein the preparation is a cell culture medium or at least one component of a cell culture medium, and wherein the filtration operates at a volumetric capacity of at least about 2000 L/m 2 .   
     
     
         22 . The cell culture medium of  claim 21 , wherein the filtration operates at a volumetric capacity of at least about 3000 L/m 2 , or at least about 5000 L/m 2 . 
     
     
         23 . The cell culture medium of  claim 21 , wherein the preparation is subjected to filtration for at least about 48 hours to about 7 months, or for at least about 72 hours to about 3 months, or for at least about 10 days to about 2 months. 
     
     
         24 . The cell culture medium of  claim 21 , further comprising
 b) feeding the filtrate to a cell culture medium or to at least one component of a cell culture medium.   
     
     
         25 . The cell culture medium of  claim 21 , wherein the filtration is a continuous filtration. 
     
     
         26 . The cell culture medium of  claim 21 , wherein the filtration is performed at a temperature of from about 2° C. to about 60° C., or from about 10° C. to about 40° C., or from about 15° C. to about 37° C. 
     
     
         27 . The cell culture medium of  claim 21 , wherein the virus filter achieves at least a 1 Log 10  reduction value (LRV) for a viral contaminant, or at least a 4 Log 10  reduction value (LRV) for a viral contaminant, or at least a 6 Log 10  reduction value (LRV) for a viral contaminant. 
     
     
         28 . The cell culture medium of  claim 27 , wherein the viral contaminant is a member of the viral family of Orthomyxoviridae, Arenaviridae, Paramyxoviridae, Rhabdoviridae, Coronaviridae, Flaviviridae, Picornaviridae, Togaviridae, Arteriviridae, RetParvoviridae, Bunyaviridae, Caliciviridae, Retroviridae, Reoviridae, Circoviridae, Adenoviridae, Poxviridae, Herpesviridae, Iridoviridae or Reoviridae. 
     
     
         29 . The cell culture medium of  claim 21 , wherein the filtration is performed using two or more filters arranged in series, in parallel, or both. 
     
     
         30 . The cell culture medium of  claim 29 , wherein the filtration is performed using two filters arranged in parallel in a system of tubes comprising a Y-shaped junction and wherein each filter is in fluid communication with a branch of the Y-shaped junction and a preparation supply source. 
     
     
         31 . The cell culture medium of  claim 21 , wherein the filtration is performed at a pressure ranging from about 100 mbar to about 4000 mbar, or from about 100 mbar to about 3500 mbar, or from about 1000 mbar to about 3000 mbar, or from about 1000 mbar to about 2000 mbar. 
     
     
         32 . The cell culture medium of  claim 21 , wherein the virus filter is autoclavable. 
     
     
         33 . The cell culture medium of  claim 21 , wherein the cell culture medium comprises soy hydrolysate. 
     
     
         34 . A method comprising utilizing the cell culture medium of  claim 21  for preparing a cell culture, a pharmaceutical preparation, a diagnostic preparation, a cosmetic preparation or a food preparation.