Method for removing viruses from high concentration monoclonal antibody solution

1. A method for producing a preparation containing a monoclonal antibody, which comprises a step of removing viruses by filtering viruses in a monoclonal antibody solution using a virus-removing membrane, wherein

(1) the monomer content of the monoclonal antibody accounts for 90% or more;

(2) the monoclonal antibody concentration in the monoclonal antibody solution ranges from 20 mg/ml to 100 mg/ml;

(3) the monoclonal antibody solution contains at least a basic amino acid; and

(4) the parvovirus removal rate of the virus-removing membrane satisfies the following conditions:

LRV (Log Reduction Value: logarithmic reduction value)≧4;

wherein the antibody throughput is 2 kg/m 2/3 hours/bar (based on pressure) or more; and

wherein filtration using the virus-removing membrane is dead-end filtration.

2. The method according to claim 1 , wherein the monoclonal antibody solution is prepared by cell culture.

3. The method according to claim 1 , wherein the pH of the monoclonal antibody solution ranges from 4 to 7.

4. The method according to claim 1 , wherein the material of the virus-removing membrane is cellulose.

5. The method according to claim 1 , wherein the material of the virus-removing membrane is a hydrophilized synthetic polymer.

6. The method according to claim 5 , wherein the synthetic polymer is polyvinylidene fluoride, polyether sulfone, polysulfone, or polyethylene.

7. The method according to claim 1 , wherein the basic amino acid is arginine, histidine, lysine or a derivative thereof, or a salt thereof.

8. The method according to claim 1 , wherein the basic amino acid content in the monoclonal antibody solution ranges from 0.1 mmol/g to 20 mmol/g with respect to the antibody.

9. The method according to claim 1 , wherein the monoclonal antibody solution contains one or more types of member selected from among an inorganic salt, a buffer ingredient, a surfactant, and a saccharide.

10. The method according to claim 1 , wherein the step of removing viruses by filtering a monoclonal antibody solution using a virus-removing membrane is performed after chromatography, concentration, or buffer exchange.

11. The method according to claim 1 , wherein the step of removing viruses by filtering a monoclonal antibody solution using a virus-removing membrane is performed after concentration or buffer exchange.

12. A method for removing viruses in a monoclonal antibody solution, which comprises a step of removing viruses by filtering viruses in a monoclonal antibody solution using a virus-removing membrane, wherein

(1) the monomer content of the monoclonal antibody accounts for 90% or more;

(2) the monoclonal antibody concentration in the monoclonal antibody solution ranges from 20 mg/ml to 100 mg/ml;

(3) the monoclonal antibody solution contains at least a basic amino acid; and

(4) the parvovirus removal rate of the virus-removing membrane satisfies the following conditions:

LRV (Log Reduction Value: logarithmic reduction value)≧4;

wherein the antibody throughput is 2 kg/m 2 /3 hours/bar (based on pressure) or more; and

wherein filtration using the virus-removing membrane is dead-end filtration.

13. A method for producing a preparation containing a monoclonal antibody, which comprises a step of removing viruses by filtering viruses in a monoclonal antibody solution using a virus-removing membrane, wherein

(1) the monomer content of the monoclonal antibody accounts for 90% or more;

(2) the monoclonal antibody concentration in the monoclonal antibody solution ranges from 20 mg/ml to 100 mg/ml;

(3) the monoclonal antibody solution contains at least a basic amino acid; and

(4) the zeta potential Ei1 (mV) of the monoclonal antibody in the solution satisfies the following conditions:

a) 0 mV≦Ei1−Em≦20 mV, with respect to the zeta potential Em (mV) of the virus-removing membrane; and satisfies the following conditions:

b) 10 mV≦Ei0−Ei1≦40 mV, with respect to the zeta potential Ei0 (mV) of the monoclonal antibody in the solution (pH=4 and ionic strength of 0.1 mM) containing the monoclonal antibody.

14. The method according to claim 13 , wherein the zeta potential Ei1 (mV) of the monoclonal antibody in the monoclonal antibody solution satisfies the following conditions:

−4%×Em≦Ei1≦−550%×Em, with respect to the zeta potential Em (mV) of the virus-removing membrane.

15. The method according to claim 13 , wherein the zeta potential Ei0 (mV) of the monoclonal antibody contained in a solution (pH=4 and ionic strength of 0.1 mM) containing the monoclonal antibody is +25 mV or higher.

16. The method according to claim 13 , wherein the antibody throughput is 2 kg/m 2 /3 hours/bar (based on pressure) or more.

17. The method according to claim 13 , wherein filtration using the virus-removing membrane is dead-end filtration.

18. A method for removing viruses by filtering a monoclonal antibody solution containing a monoclonal antibody using a virus-removing membrane, wherein:

(1) the monomer content of the monoclonal antibody accounts for 90% or more;

(2) the monoclonal antibody concentration in the monoclonal antibody solution ranges from 20 mg/ml to 100 mg/ml;

(3) the monoclonal antibody solution contains at least a basic amino acid; and

(4) the zeta potential Ei1 (mV) of the monoclonal antibody in the solution satisfies the following conditions:

a) 0 mV≦Ei1−Em≦20 mV, with respect to the zeta potential Em (mV) of the virus-removing membrane; and satisfies the following conditions:

b) 10 mV≦Ei0−Ei1≦40 mV, with respect to the zeta potential Ei0 (mV) of the monoclonal antibody in a solution (pH=4 and ionic strength of 0.1 mM) containing the monoclonal antibody.