Virus filtration of cell culture media

1. A method for removing a viral contaminant from a liquid preparation comprising the steps of:

supplying a liquid preparation to at least one replaceable virus filter having an effective pore size of 5-75 nm, wherein the virus filter is in fluid communication with a bioreactor; and

removing a viral contaminant by filtering the preparation through the virus filter, under pressure, for a minimum total run time of about 24 hours; and

collecting the filtered preparation;

wherein the preparation comprises a cell culture medium or at least one component thereof; the virus filter is not replaced during the minimum run time; the pressure is from about 100 mbar to about 4000 mbar; and filtration operates at a volumetric capacity of at least about 2000 L/m 2 .

2. The method of claim 1 , wherein the bioreactor is a chemostat reactor, a perfusion reactor, or a fed batch reactor.

3. The method of claim 1 , wherein the virus filter comprises two or more virus filters arranged in series, in parallel, or both.

4. The method of claim 3 , wherein the virus filter comprises two virus filters arranged in parallel in a system of feed lines comprising a Y-shaped junction and wherein each virus filter is in fluid communication with a branch of the Y-shaped junction.

5. The method of claim 1 , wherein the virus filter is autoclavable.

6. The method of claim 1 , wherein the preparation comprises a soy hydrolysate.

7. The method of claim 1 , wherein the preparation comprises animal derived components.

8. The method of claim 1 , wherein the volumetric capacity is at least about 3000 L/m 2 .

9. The method of claim 1 , wherein the total run time is at least about 48 hours.

10. The method of claim 1 , wherein the filtration is continuous filtration.

11. The method of claim 1 , wherein the filtering provides at least a 4 Log 10 reduction value (LRV) for the viral contaminant.

12. The method of claim 1 , wherein the filtration is performed at a pressure ranging from about 1000 mbar to about 3000 mbar.

13. The method of claim 1 , wherein the virus filter has an effective pore size of 15-75 nm.

14. The method of claim 13 , wherein the pressure is from about 1000 mbar to about 3000 mbar.

15. The method of claim 14 , wherein the filtering provides at least a 4 Log 10 reduction value (LRV) for the viral contaminant.

16. The method of claim 15 , wherein the filtration is continuous filtration.

17. The method of claim 15 , wherein the volumetric capacity is at least about 3000 L/m 2 .

18. The method of claim 16 , wherein the volumetric capacity is at least about 3000 L/m 2 .

19. The method of claim 1 , wherein the effective pore size is 15-35 nm.

20. The method of claim 14 , wherein the effective pore size is 15-35 nm.

21. A method for removing a viral contaminant from a liquid preparation comprising a cell culture medium or at least one component thereof, the method comprising the steps of:

supplying a liquid preparation to two or more replaceable virus filters arranged in series, in parallel, or both, wherein each virus filter is in fluid communication with a bioreactor and each virus filter has an effective pore size of 15-75 nm; and

removing a viral contaminant by filtering the preparation through the virus filters, under pressure, for a minimum total run time of at least about 24 hours per virus filter; and

collecting the filtered preparation;

wherein no virus filter is replaced during its minimum run time; the pressure is from about 100 mbar to about 2000 mbar; and filtration operates at a volumetric capacity of at least about 2000 L/m 2 .

22. The method of claim 21 , wherein the two or more replaceable virus filters comprises two virus filters arranged in parallel in a system of feed lines comprising a Y-shaped junction and wherein each virus filter is in fluid communication with a branch of the Y-shaped junction.

23. The method of claim 22 , wherein the system of feed lines is upstream of the bioreactor.

24. The method of claim 22 , wherein the filtration is continuous filtration.

25. The method of claim 22 , wherein the filtration is batch filtration.

26. The method of claim 21 , wherein the filtration is performed at a temperature of from about 10° C. to about 40° C.

27. The method of claim 21 , wherein the filtration is performed at ambient temperature.

28. The method of claim 21 , further comprising the step of replacing each virus filter that exceeds a predetermined pressure differential.

29. The method of claim 28 , wherein the predetermined pressure differential is about 2000 mbar.

30. The method of claim 21 , wherein the total run time of each virus filter is at least about 48 hours.

31. The method of claim 21 , wherein the total run time of each virus filter is at least about 72 hours.

32. The method of claim 21 , wherein the total run time of each virus filter is at least about 1 week.

33. The method of claim 21 , wherein the total run time of each virus filter is at least about 4 weeks.

34. The method of claim 21 , wherein the total run time of each virus filter is at least about 2 months.

35. The method of claim 21 , wherein a total volumetric capacity per virus filter, without replacement, is at least about 4000 L/m 2 .

36. The method of claim 21 , wherein a total volumetric capacity per virus filter, without replacement, is at least about 5000 L/m 2 .

37. The method of claim 21 , wherein a total volumetric capacity per virus filter, without replacement, is at least about 7500 L/m 2 .

38. The method of claim 21 , wherein a total volumetric capacity per virus filter, without replacement, is at least about 10,000 L/m 2 .

39. The method of claim 21 , wherein a total volumetric capacity per virus filter, without replacement, is at least about 20,000 L/m 2 .

40. The method of claim 1 , wherein a specific flow rate of each virus filter is from about 5 L/(m 2 ×hr) to about 500 L/(m 2 ×hr).

41. The method of claim 21 , wherein a specific flow rate of each virus filter is from about 5 L/(m 2 ×hr) to about 500 L/(m 2 ×hr).

42. The method of claim 1 , wherein at least two virus filters are arranged in parallel in a system of feed lines, the effective pore size of each virus filter is 15-35 nm, filtration is performed at a pressure of at least 100 mbar and a temperature of from about 10° C. to about 40° C., and a specific flow rate of each virus filter is from about 5 L/(m 2 ×hr) to about 500 L/(m 2 ×hr).

43. The method of claim 42 , wherein the system of feed lines is upstream of the bioreactor, the filtration is continuous filtration, the run time is at least about 4 weeks, the volumetric capacity is at least about 5000 L/m 2 , and the filtering provides at least a 4 Log 10 reduction value (LRV) for the viral contaminant.

44. The method of claim 21 , wherein at least two virus filters are arranged in parallel in a system of feed lines, the effective pore size of each virus filter is 15-35 nm, filtration is performed at a pressure of at least 100 mbar and a temperature of from about 10° C. to about 40° C., and a specific flow rate of each virus filter is from about 5 L (m 2 ×hr) to about 500 L (m 2 ×hr).

45. The method of claim 44 , wherein the system of feed lines is upstream of the bioreactor, the bioreactor has a capacity of at least about 2000 L, the filtration is continuous filtration, the run time is at least about 4 weeks, the volumetric capacity is at least about 5000 L/m 2 , and the filtering provides at least a 4 Log 10 reduction value (LRV) for the viral contaminant.

46. The method of claim 43 , wherein the filtration is crossflow filtration.

47. The method of claim 45 , wherein the filtration is crossflow filtration.

48. The method of claim 43 , wherein the filtration is dead end filtration.

49. The method of claim 45 , wherein the filtration is dead end filtration.